Hepatology

Introduction
Hepatoblastoma accounts for most pediatric liver cancers, but accounts for only 1% of all malignancies in children. Rates of hepatoblastoma have increased gradually over the past 20 years for unclear reasons, but it remains a rare malignancy. In the 1970s, only a small percentage of patients survived long-term. Today, 5-year survival rates range from 65% to over 90%, depending on risk factors, thanks to recent advancements in the understanding and treatment of hepatoblastoma.^1-5 Improved risk stratification has led to better staging and more personalized treatment approaches. To further improve survival, current research is concentrated on improving outcomes in the most challenging patient subsets, such as those with metastatic disease and patients with disease relapse.

Background
Hepatoblastoma is typically diagnosed in the first 2 years of life.⁶ Accounting for more than 60% of pediatric hepatic malignancies worldwide, the incidence of hepatoblastoma is increasing. Results from a study evaluating the incidence between 2001 and 2017 showed a 2% annual increase documented in children aged from birth to 4 years in the United States, climbing to 5.8% annually among children aged 5 to 9 years.² Risk factors for hepatoblastoma include maternal preeclampsia, premature birth, and parental smoking.⁷ The degree to which each of these factors plays a role is uncertain. A genetic etiology is suspected in a minority of hepatoblastoma cases, but it is associated with several genetic diseases, including Beckwith-Weidemann syndrome, familial adenomatous polyposis, and Prader-Willi syndrome.⁸ Genetic mutations in the Wnt signaling pathway that result in the accumulation of beta-catenin have also been found in sporadic, nonfamilial cases.⁹

Although this condition generally presents as a single abdominal mass in the right lobe of the liver, multifocal hepatoblastoma at diagnosis does occur.¹⁰ In most patients, alpha-fetoprotein (AFP) is significantly elevated.¹¹ An estimated 20% of patients present with metastases, which are most commonly found in the lung.¹² While ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) can be used to define the extent of the tumor in the liver, a chest CT is appropriate to look for metastases beyond the liver.¹³

Of the 2 broad histological categories commonly used to characterize hepatoblastoma, the more common epithelial form consists of fetal or embryonal liver cells. The mixed epithelial-mesenchymal form that accounts for 20% to 30% of hepatoblastomas features epithelial and primitive mesenchymal tissue, often with osteoid tissue or cartilage⁶; both have numerous histological subtypes. For example, the epithelial type can be further characterized by a well- or poorly-differentiated appearance, while the mixed type can be subdivided by the presence or absence of teratoid features.

Prior to 2017, there was considerable disparity in the way hepatoblastomas were characterized and staged among the major research consortiums. This issue was addressed when a consortium was established in which pediatric oncology groups pooled their data. The Children’s Hepatic tumors International Collaboration (CHIC) released the PRETEXT (PRETreatment EXTent of disease) approach.^7,14 Based on comprehensive data from 1605 children participating in multicenter trials, the CHIC risk stratification defines and provides risk trees for very low-, low-, intermediate-, and high-risk groups. The most important predictors included AFP levels, patient age, extent of disease in the liver (particularly involving major hepatic veins), and the presence of metastases.

Further improvements to the diagnosis and staging of hepatoblastoma are credited to consensus-based recommendations for imaging that were created in the context of the PRETEXT staging system.¹³ While ultrasound is recommended for the initial approach to diagnosis, this consensus calls for MRI with hepatobiliary contrast to better characterize the lesion and detect satellite lesions. This form of imaging is also recommended for follow-up after treatment, but results should be interpreted in the context of biomarkers, such as AFP levels, pathologic grading, and tumor subtypes.

In patients with the most common familial disorders associated with a predisposition for hepatoblastoma, such as adenomatous polyposis, Beckwith-Weidemann spectrum, or trisomy 18, regular surveillance for hepatoblastoma is recommended during the early years of life.⁸ Characterization of the genetic and molecular features of patients who present with hepatoblastoma might be useful in determining prognosis. Of genetic features, mutations in the CTNNB1 gene are the most common, but several genes in the Wnt pathway are also linked to hepatoblastoma formation.⁹

Along with the progress in subtyping patients by genetics, epigenetics, and molecular features, there is a growing appreciation for the heterogeneity of hepatoblastoma and the likelihood that treatment strategies can be better individualized to improve outcomes in high-risk patients. This progress is expected to accelerate further when results from the results from the Pediatric Hepatic International Tumor Trial (PHITT) are published. These data are expected to be available in 2025, and may help with prognostication and understanding the biology of hepatoblastoma in relation to outcomes.

Treatment Strategies in Hepatoblastoma
For low-grade hepatoblastoma, the first-line therapy is surgery, which can be sufficient for cure without relapse in selected patients with PRETEXT group 1 disease. Although only 40% to 60% of patients have resectable disease at diagnosis,¹⁰ there are several strategies to shrink tumor bulk, particularly chemotherapy due to the relatively high sensitivity of hepatoblastoma to cytotoxic therapies. The intensity of chemotherapy is increased relative to risk.¹¹ For example, cisplatin-based regimens are considered for low-risk patients, while additional therapies, such as doxorubicin, irinotecan, or both, are added in patients at higher risk. Cure is common if these regimens permit a margin-free resection, although relapse does occur in a subset of patients.

If adequate debulking of the tumor cannot be achieved with conventional surgery, liver transplantation is typically offered for patients without extrahepatic disease or after distant metastases have been successfully excised. With liver transplantation and combination therapies to inhibit relapse associated with seeding, long-term survival rates of 80% have been reported.³ Judicious use of transplantation in patients with high-risk disease that raises the potential for relapse has been credited with rates of long-term survival that exceed 80% in some series. However, there is concern of offering transplantation when it is not necessary. In patients who are high risk with multiple lesions in the liver, there is a general agreement that transplantation reduces the likelihood of subsequent relapse; however, as the precision of aggressive resection coupled with effective chemotherapy has improved, there are more patients in whom the optimal choice might not be debated by experts.

Review articles typically cite the likelihood of an overall 5-year survival in patients with hepatoblastoma as being on the order of 80%.¹ This rate includes children with late-onset disease, which is generally associated with a worse prognosis, and patients who eventually experience disease relapse. Survival rates are now likely to be substantially higher, with progress developing better treatment protocols for both groups. In the absence of high-risk features, long-term survival rates of 90% or higher are now being reported in some centers with high relative volumes of hepatoblastoma, regardless of baseline risks. 

PHITT
The rarity of hepatoblastoma poses a significant challenge to conducting prospective studies with sufficient sample sizes to evaluate the overall efficacy of treatments and their effectiveness in patient subgroups based on specific clinical characteristics and disease severity. PHITT is the first international collaborative liver tumors trial to use a consensus approach. Centers in Europe, Japan, and the United States are participating through regional cancer study consortia. The Cincinnati Children’s Hospital and Medical Center, a leader in hepatoblastoma management in the United States, is anchoring this effort for the Children’s Oncology Group. 

In addition to assessing treatment strategies in larger patient cohorts, PHITT is expanding the data available to correlate outcomes across different stages and risk categories based on histological and biological classifications. Hepatoblastoma and hepatocellular carcinoma are being addressed in PHITT, but the design schema for these malignancies differs. For patients enrolled with hepatoblastoma, 4 risk groups have been defined, ranging from very low to high. Within these risk categories, flow charts provide guide selection of treatments based on clinical and disease features.

Cincinnati Children’s Hospital and Medical Center is one of the most active centers for the treatment of hepatoblastoma in the Unites States but manages only 15 to 20 cases of this rare disease per year. PHITT is expected to play a critical role in achieving a high level of valuable data, and the first sets of outcomes from this collaboration are anticipated to be available in early 2025. As the study progresses, meaningful data are expected for the most challenging and some of the rarest hepatoblastoma risk groups.

Summary
The rates of cure are now approaching 100% with surgery and chemotherapy in patients with localized or locally advanced hepatoblastoma. For more advanced, unresectable disease, liver transplantation is effective in most patients, providing high rates of long-term survival. For patients with relapsed disease, advanced treatment protocols at centers with high relative volumes
of hepatoblastoma are now regularly achieving a second remission—many of which are durable. Although prognosis is less favorable in patients who experience a second relapse, long-term survival is achieved even in a proportion of these children. Substantial rates of response and long-term survival have been common in hepatoblastoma diagnosed at early stages, but the recent progress in advanced hepatoblastoma is credited to more aggressive therapies based on a better understanding of the disease characteristics that allows for individualized therapy. There is hope that the larger pool of data becoming available in 2025 from PHITT will prove to be an additional source of information that guides further advances in managing this rare disease.

Read more from the 2024 Rare Diseases Report: Hematology and Oncology.

Introduction
Hepatoblastoma accounts for most pediatric liver cancers, but accounts for only 1% of all malignancies in children. Rates of hepatoblastoma have increased gradually over the past 20 years for unclear reasons, but it remains a rare malignancy. In the 1970s, only a small percentage of patients survived long-term. Today, 5-year survival rates range from 65% to over 90%, depending on risk factors, thanks to recent advancements in the understanding and treatment of hepatoblastoma.^1-5 Improved risk stratification has led to better staging and more personalized treatment approaches. To further improve survival, current research is concentrated on improving outcomes in the most challenging patient subsets, such as those with metastatic disease and patients with disease relapse.

Background
Hepatoblastoma is typically diagnosed in the first 2 years of life.⁶ Accounting for more than 60% of pediatric hepatic malignancies worldwide, the incidence of hepatoblastoma is increasing. Results from a study evaluating the incidence between 2001 and 2017 showed a 2% annual increase documented in children aged from birth to 4 years in the United States, climbing to 5.8% annually among children aged 5 to 9 years.² Risk factors for hepatoblastoma include maternal preeclampsia, premature birth, and parental smoking.⁷ The degree to which each of these factors plays a role is uncertain. A genetic etiology is suspected in a minority of hepatoblastoma cases, but it is associated with several genetic diseases, including Beckwith-Weidemann syndrome, familial adenomatous polyposis, and Prader-Willi syndrome.⁸ Genetic mutations in the Wnt signaling pathway that result in the accumulation of beta-catenin have also been found in sporadic, nonfamilial cases.⁹

Although this condition generally presents as a single abdominal mass in the right lobe of the liver, multifocal hepatoblastoma at diagnosis does occur.¹⁰ In most patients, alpha-fetoprotein (AFP) is significantly elevated.¹¹ An estimated 20% of patients present with metastases, which are most commonly found in the lung.¹² While ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) can be used to define the extent of the tumor in the liver, a chest CT is appropriate to look for metastases beyond the liver.¹³

Of the 2 broad histological categories commonly used to characterize hepatoblastoma, the more common epithelial form consists of fetal or embryonal liver cells. The mixed epithelial-mesenchymal form that accounts for 20% to 30% of hepatoblastomas features epithelial and primitive mesenchymal tissue, often with osteoid tissue or cartilage⁶; both have numerous histological subtypes. For example, the epithelial type can be further characterized by a well- or poorly-differentiated appearance, while the mixed type can be subdivided by the presence or absence of teratoid features.

Prior to 2017, there was considerable disparity in the way hepatoblastomas were characterized and staged among the major research consortiums. This issue was addressed when a consortium was established in which pediatric oncology groups pooled their data. The Children’s Hepatic tumors International Collaboration (CHIC) released the PRETEXT (PRETreatment EXTent of disease) approach.^7,14 Based on comprehensive data from 1605 children participating in multicenter trials, the CHIC risk stratification defines and provides risk trees for very low-, low-, intermediate-, and high-risk groups. The most important predictors included AFP levels, patient age, extent of disease in the liver (particularly involving major hepatic veins), and the presence of metastases.

Further improvements to the diagnosis and staging of hepatoblastoma are credited to consensus-based recommendations for imaging that were created in the context of the PRETEXT staging system.¹³ While ultrasound is recommended for the initial approach to diagnosis, this consensus calls for MRI with hepatobiliary contrast to better characterize the lesion and detect satellite lesions. This form of imaging is also recommended for follow-up after treatment, but results should be interpreted in the context of biomarkers, such as AFP levels, pathologic grading, and tumor subtypes.

In patients with the most common familial disorders associated with a predisposition for hepatoblastoma, such as adenomatous polyposis, Beckwith-Weidemann spectrum, or trisomy 18, regular surveillance for hepatoblastoma is recommended during the early years of life.⁸ Characterization of the genetic and molecular features of patients who present with hepatoblastoma might be useful in determining prognosis. Of genetic features, mutations in the CTNNB1 gene are the most common, but several genes in the Wnt pathway are also linked to hepatoblastoma formation.⁹

Along with the progress in subtyping patients by genetics, epigenetics, and molecular features, there is a growing appreciation for the heterogeneity of hepatoblastoma and the likelihood that treatment strategies can be better individualized to improve outcomes in high-risk patients. This progress is expected to accelerate further when results from the results from the Pediatric Hepatic International Tumor Trial (PHITT) are published. These data are expected to be available in 2025, and may help with prognostication and understanding the biology of hepatoblastoma in relation to outcomes.

Treatment Strategies in Hepatoblastoma
For low-grade hepatoblastoma, the first-line therapy is surgery, which can be sufficient for cure without relapse in selected patients with PRETEXT group 1 disease. Although only 40% to 60% of patients have resectable disease at diagnosis,¹⁰ there are several strategies to shrink tumor bulk, particularly chemotherapy due to the relatively high sensitivity of hepatoblastoma to cytotoxic therapies. The intensity of chemotherapy is increased relative to risk.¹¹ For example, cisplatin-based regimens are considered for low-risk patients, while additional therapies, such as doxorubicin, irinotecan, or both, are added in patients at higher risk. Cure is common if these regimens permit a margin-free resection, although relapse does occur in a subset of patients.

If adequate debulking of the tumor cannot be achieved with conventional surgery, liver transplantation is typically offered for patients without extrahepatic disease or after distant metastases have been successfully excised. With liver transplantation and combination therapies to inhibit relapse associated with seeding, long-term survival rates of 80% have been reported.³ Judicious use of transplantation in patients with high-risk disease that raises the potential for relapse has been credited with rates of long-term survival that exceed 80% in some series. However, there is concern of offering transplantation when it is not necessary. In patients who are high risk with multiple lesions in the liver, there is a general agreement that transplantation reduces the likelihood of subsequent relapse; however, as the precision of aggressive resection coupled with effective chemotherapy has improved, there are more patients in whom the optimal choice might not be debated by experts.

Review articles typically cite the likelihood of an overall 5-year survival in patients with hepatoblastoma as being on the order of 80%.¹ This rate includes children with late-onset disease, which is generally associated with a worse prognosis, and patients who eventually experience disease relapse. Survival rates are now likely to be substantially higher, with progress developing better treatment protocols for both groups. In the absence of high-risk features, long-term survival rates of 90% or higher are now being reported in some centers with high relative volumes of hepatoblastoma, regardless of baseline risks. 

PHITT
The rarity of hepatoblastoma poses a significant challenge to conducting prospective studies with sufficient sample sizes to evaluate the overall efficacy of treatments and their effectiveness in patient subgroups based on specific clinical characteristics and disease severity. PHITT is the first international collaborative liver tumors trial to use a consensus approach. Centers in Europe, Japan, and the United States are participating through regional cancer study consortia. The Cincinnati Children’s Hospital and Medical Center, a leader in hepatoblastoma management in the United States, is anchoring this effort for the Children’s Oncology Group. 

In addition to assessing treatment strategies in larger patient cohorts, PHITT is expanding the data available to correlate outcomes across different stages and risk categories based on histological and biological classifications. Hepatoblastoma and hepatocellular carcinoma are being addressed in PHITT, but the design schema for these malignancies differs. For patients enrolled with hepatoblastoma, 4 risk groups have been defined, ranging from very low to high. Within these risk categories, flow charts provide guide selection of treatments based on clinical and disease features.

Cincinnati Children’s Hospital and Medical Center is one of the most active centers for the treatment of hepatoblastoma in the Unites States but manages only 15 to 20 cases of this rare disease per year. PHITT is expected to play a critical role in achieving a high level of valuable data, and the first sets of outcomes from this collaboration are anticipated to be available in early 2025. As the study progresses, meaningful data are expected for the most challenging and some of the rarest hepatoblastoma risk groups.

Summary
The rates of cure are now approaching 100% with surgery and chemotherapy in patients with localized or locally advanced hepatoblastoma. For more advanced, unresectable disease, liver transplantation is effective in most patients, providing high rates of long-term survival. For patients with relapsed disease, advanced treatment protocols at centers with high relative volumes
of hepatoblastoma are now regularly achieving a second remission—many of which are durable. Although prognosis is less favorable in patients who experience a second relapse, long-term survival is achieved even in a proportion of these children. Substantial rates of response and long-term survival have been common in hepatoblastoma diagnosed at early stages, but the recent progress in advanced hepatoblastoma is credited to more aggressive therapies based on a better understanding of the disease characteristics that allows for individualized therapy. There is hope that the larger pool of data becoming available in 2025 from PHITT will prove to be an additional source of information that guides further advances in managing this rare disease.

Read more from the 2024 Rare Diseases Report: Hematology and Oncology.

Introduction
Hepatoblastoma accounts for most pediatric liver cancers, but accounts for only 1% of all malignancies in children. Rates of hepatoblastoma have increased gradually over the past 20 years for unclear reasons, but it remains a rare malignancy. In the 1970s, only a small percentage of patients survived long-term. Today, 5-year survival rates range from 65% to over 90%, depending on risk factors, thanks to recent advancements in the understanding and treatment of hepatoblastoma.^1-5 Improved risk stratification has led to better staging and more personalized treatment approaches. To further improve survival, current research is concentrated on improving outcomes in the most challenging patient subsets, such as those with metastatic disease and patients with disease relapse.

Background
Hepatoblastoma is typically diagnosed in the first 2 years of life.⁶ Accounting for more than 60% of pediatric hepatic malignancies worldwide, the incidence of hepatoblastoma is increasing. Results from a study evaluating the incidence between 2001 and 2017 showed a 2% annual increase documented in children aged from birth to 4 years in the United States, climbing to 5.8% annually among children aged 5 to 9 years.² Risk factors for hepatoblastoma include maternal preeclampsia, premature birth, and parental smoking.⁷ The degree to which each of these factors plays a role is uncertain. A genetic etiology is suspected in a minority of hepatoblastoma cases, but it is associated with several genetic diseases, including Beckwith-Weidemann syndrome, familial adenomatous polyposis, and Prader-Willi syndrome.⁸ Genetic mutations in the Wnt signaling pathway that result in the accumulation of beta-catenin have also been found in sporadic, nonfamilial cases.⁹

Although this condition generally presents as a single abdominal mass in the right lobe of the liver, multifocal hepatoblastoma at diagnosis does occur.¹⁰ In most patients, alpha-fetoprotein (AFP) is significantly elevated.¹¹ An estimated 20% of patients present with metastases, which are most commonly found in the lung.¹² While ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) can be used to define the extent of the tumor in the liver, a chest CT is appropriate to look for metastases beyond the liver.¹³

Of the 2 broad histological categories commonly used to characterize hepatoblastoma, the more common epithelial form consists of fetal or embryonal liver cells. The mixed epithelial-mesenchymal form that accounts for 20% to 30% of hepatoblastomas features epithelial and primitive mesenchymal tissue, often with osteoid tissue or cartilage⁶; both have numerous histological subtypes. For example, the epithelial type can be further characterized by a well- or poorly-differentiated appearance, while the mixed type can be subdivided by the presence or absence of teratoid features.

Prior to 2017, there was considerable disparity in the way hepatoblastomas were characterized and staged among the major research consortiums. This issue was addressed when a consortium was established in which pediatric oncology groups pooled their data. The Children’s Hepatic tumors International Collaboration (CHIC) released the PRETEXT (PRETreatment EXTent of disease) approach.^7,14 Based on comprehensive data from 1605 children participating in multicenter trials, the CHIC risk stratification defines and provides risk trees for very low-, low-, intermediate-, and high-risk groups. The most important predictors included AFP levels, patient age, extent of disease in the liver (particularly involving major hepatic veins), and the presence of metastases.

Further improvements to the diagnosis and staging of hepatoblastoma are credited to consensus-based recommendations for imaging that were created in the context of the PRETEXT staging system.¹³ While ultrasound is recommended for the initial approach to diagnosis, this consensus calls for MRI with hepatobiliary contrast to better characterize the lesion and detect satellite lesions. This form of imaging is also recommended for follow-up after treatment, but results should be interpreted in the context of biomarkers, such as AFP levels, pathologic grading, and tumor subtypes.

In patients with the most common familial disorders associated with a predisposition for hepatoblastoma, such as adenomatous polyposis, Beckwith-Weidemann spectrum, or trisomy 18, regular surveillance for hepatoblastoma is recommended during the early years of life.⁸ Characterization of the genetic and molecular features of patients who present with hepatoblastoma might be useful in determining prognosis. Of genetic features, mutations in the CTNNB1 gene are the most common, but several genes in the Wnt pathway are also linked to hepatoblastoma formation.⁹

Along with the progress in subtyping patients by genetics, epigenetics, and molecular features, there is a growing appreciation for the heterogeneity of hepatoblastoma and the likelihood that treatment strategies can be better individualized to improve outcomes in high-risk patients. This progress is expected to accelerate further when results from the results from the Pediatric Hepatic International Tumor Trial (PHITT) are published. These data are expected to be available in 2025, and may help with prognostication and understanding the biology of hepatoblastoma in relation to outcomes.

Treatment Strategies in Hepatoblastoma
For low-grade hepatoblastoma, the first-line therapy is surgery, which can be sufficient for cure without relapse in selected patients with PRETEXT group 1 disease. Although only 40% to 60% of patients have resectable disease at diagnosis,¹⁰ there are several strategies to shrink tumor bulk, particularly chemotherapy due to the relatively high sensitivity of hepatoblastoma to cytotoxic therapies. The intensity of chemotherapy is increased relative to risk.¹¹ For example, cisplatin-based regimens are considered for low-risk patients, while additional therapies, such as doxorubicin, irinotecan, or both, are added in patients at higher risk. Cure is common if these regimens permit a margin-free resection, although relapse does occur in a subset of patients.

If adequate debulking of the tumor cannot be achieved with conventional surgery, liver transplantation is typically offered for patients without extrahepatic disease or after distant metastases have been successfully excised. With liver transplantation and combination therapies to inhibit relapse associated with seeding, long-term survival rates of 80% have been reported.³ Judicious use of transplantation in patients with high-risk disease that raises the potential for relapse has been credited with rates of long-term survival that exceed 80% in some series. However, there is concern of offering transplantation when it is not necessary. In patients who are high risk with multiple lesions in the liver, there is a general agreement that transplantation reduces the likelihood of subsequent relapse; however, as the precision of aggressive resection coupled with effective chemotherapy has improved, there are more patients in whom the optimal choice might not be debated by experts.

Review articles typically cite the likelihood of an overall 5-year survival in patients with hepatoblastoma as being on the order of 80%.¹ This rate includes children with late-onset disease, which is generally associated with a worse prognosis, and patients who eventually experience disease relapse. Survival rates are now likely to be substantially higher, with progress developing better treatment protocols for both groups. In the absence of high-risk features, long-term survival rates of 90% or higher are now being reported in some centers with high relative volumes of hepatoblastoma, regardless of baseline risks. 

PHITT
The rarity of hepatoblastoma poses a significant challenge to conducting prospective studies with sufficient sample sizes to evaluate the overall efficacy of treatments and their effectiveness in patient subgroups based on specific clinical characteristics and disease severity. PHITT is the first international collaborative liver tumors trial to use a consensus approach. Centers in Europe, Japan, and the United States are participating through regional cancer study consortia. The Cincinnati Children’s Hospital and Medical Center, a leader in hepatoblastoma management in the United States, is anchoring this effort for the Children’s Oncology Group. 

In addition to assessing treatment strategies in larger patient cohorts, PHITT is expanding the data available to correlate outcomes across different stages and risk categories based on histological and biological classifications. Hepatoblastoma and hepatocellular carcinoma are being addressed in PHITT, but the design schema for these malignancies differs. For patients enrolled with hepatoblastoma, 4 risk groups have been defined, ranging from very low to high. Within these risk categories, flow charts provide guide selection of treatments based on clinical and disease features.

Cincinnati Children’s Hospital and Medical Center is one of the most active centers for the treatment of hepatoblastoma in the Unites States but manages only 15 to 20 cases of this rare disease per year. PHITT is expected to play a critical role in achieving a high level of valuable data, and the first sets of outcomes from this collaboration are anticipated to be available in early 2025. As the study progresses, meaningful data are expected for the most challenging and some of the rarest hepatoblastoma risk groups.

Summary
The rates of cure are now approaching 100% with surgery and chemotherapy in patients with localized or locally advanced hepatoblastoma. For more advanced, unresectable disease, liver transplantation is effective in most patients, providing high rates of long-term survival. For patients with relapsed disease, advanced treatment protocols at centers with high relative volumes
of hepatoblastoma are now regularly achieving a second remission—many of which are durable. Although prognosis is less favorable in patients who experience a second relapse, long-term survival is achieved even in a proportion of these children. Substantial rates of response and long-term survival have been common in hepatoblastoma diagnosed at early stages, but the recent progress in advanced hepatoblastoma is credited to more aggressive therapies based on a better understanding of the disease characteristics that allows for individualized therapy. There is hope that the larger pool of data becoming available in 2025 from PHITT will prove to be an additional source of information that guides further advances in managing this rare disease.

Read more from the 2024 Rare Diseases Report: Hematology and Oncology.

TOPLINE:

Up to one in seven young adults with obesity and type 2 diabetes (T2D) have clinically significant hepatic fibrosis, signaling the crucial need for screening in this population to aid early detection and intervention.

METHODOLOGY:

• Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
• Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
• All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
• Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.

TAKEAWAY:

• Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
• There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
• The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
• In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
• The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).

IN PRACTICE:

“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.

SOURCE:

This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.

LIMITATIONS:

The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.

DISCLOSURES:

This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Up to one in seven young adults with obesity and type 2 diabetes (T2D) have clinically significant hepatic fibrosis, signaling the crucial need for screening in this population to aid early detection and intervention.

METHODOLOGY:

• Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
• Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
• All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
• Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.

TAKEAWAY:

• Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
• There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
• The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
• In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
• The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).

IN PRACTICE:

“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.

SOURCE:

This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.

LIMITATIONS:

The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.

DISCLOSURES:

This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Up to one in seven young adults with obesity and type 2 diabetes (T2D) have clinically significant hepatic fibrosis, signaling the crucial need for screening in this population to aid early detection and intervention.

METHODOLOGY:

• Researchers aimed to assess the prevalence of hepatic steatosis and clinically significant fibrosis (stage ≥ 2) in young adults without a history of metabolic dysfunction–associated steatotic liver disease (MASLD), hypothesizing that the rates would be comparable with those in older adults, especially in the presence of cardiometabolic risk factors.
• Overall, 1420 participants aged 21-79 years with or without T2D (63% or 37%, respectively) were included from outpatient clinics at the University of Florida, Gainesville, Florida, and divided into two age groups: < 45 years (n = 243) and ≥ 45 years (n = 1177).
• All the participants underwent assessment of liver stiffness via transient elastography, with magnetic resonance elastography (MRE) or liver biopsy recommended when indicated.
• Participants also underwent a medical history review, physical examination, and fasting blood tests to rule out secondary causes of liver disease.

TAKEAWAY:

• Overall, 52% of participants had hepatic steatosis, and 9.5% had clinically significant fibrosis.
• There were no significant differences in the frequencies of hepatic steatosis (50.2% vs 52.7%; P = .6) or clinically significant hepatic fibrosis (7.5% vs 9.9%; P = .2) observed between young and older adults.
• The presence of either T2D or obesity was linked to an increased prevalence of both hepatic steatosis and fibrosis in both the age groups (P < .01).
• In young and older adults, the presence of both T2D and obesity led to the highest rates of both hepatic steatosis and clinically significant fibrosis, with the latter rate being statistically similar between the groups (15.7% vs 17.3%; P = .2).
• The presence of T2D and obesity was the strongest risk factors for hepatic fibrosis in young adults (odds ratios, 4.33 and 1.16, respectively; P < .05 for both).

IN PRACTICE:

“The clinical implication is that young adults with obesity and T2D carry a high risk of future cirrhosis, possibly as high as older adults, and must be aggressively screened at the first visit and carefully followed,” the authors wrote.

SOURCE:

This study, led by Anu Sharma, University of Florida College of Medicine, Gainesville, was published online in Obesity.

LIMITATIONS:

The diagnosis of clinically significant hepatic fibrosis was confirmed via MRE and/or liver biopsy in only 30% of all participants. The study population included a slightly higher proportion of young adults with obesity, T2D, and other cardiometabolic risk factors than that in national averages, which may have limited its generalizability. Genetic variants associated with MASLD were not included in this study.

DISCLOSURES:

This study was funded partly by grants from the National Institutes of Health and Echosens. One author disclosed receiving research support and serving as a consultant for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

SAN DIEGO — Since the adoption of the most recent Model for End-Stage Liver Disease (MELD 3.0) scoring system by the federal Organ Procurement and Transplantation Network (OPTN) in July 2023, the gender gap in liver transplants has narrowed, according to new research.

In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.

“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 

“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 

 

Changes in MELD and Transplant Numbers

MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium. 

“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 

“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 

Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 

MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 

To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.

After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.

In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.

The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 

However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.

 

Disparities Continue to Exist 

Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.

“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”

Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 

Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.

“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”

In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.

This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 

It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”

Kwong, Krag, and Taddei reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Since the adoption of the most recent Model for End-Stage Liver Disease (MELD 3.0) scoring system by the federal Organ Procurement and Transplantation Network (OPTN) in July 2023, the gender gap in liver transplants has narrowed, according to new research.

In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.

“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 

“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 

 

Changes in MELD and Transplant Numbers

MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium. 

“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 

“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 

Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 

MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 

To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.

After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.

In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.

The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 

However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.

 

Disparities Continue to Exist 

Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.

“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”

Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 

Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.

“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”

In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.

This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 

It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”

Kwong, Krag, and Taddei reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Since the adoption of the most recent Model for End-Stage Liver Disease (MELD 3.0) scoring system by the federal Organ Procurement and Transplantation Network (OPTN) in July 2023, the gender gap in liver transplants has narrowed, according to new research.

In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.

“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 

“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 

 

Changes in MELD and Transplant Numbers

MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium. 

“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 

“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 

Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 

MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 

To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.

After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.

In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.

The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 

However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.

 

Disparities Continue to Exist 

Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.

“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”

Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 

Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.

“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”

In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.

This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 

It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”

Kwong, Krag, and Taddei reported no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.

METHODOLOGY:

• Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
• Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
• International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.

TAKEAWAY:

• Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
• Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
• American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
• The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.

IN PRACTICE:

“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.

SOURCE:

The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.

LIMITATIONS:

According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.

DISCLOSURES:

The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.

METHODOLOGY:

• Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
• Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
• International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.

TAKEAWAY:

• Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
• Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
• American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
• The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.

IN PRACTICE:

“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.

SOURCE:

The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.

LIMITATIONS:

According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.

DISCLOSURES:

The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

US alcohol-related mortality rates increased from 10.7 to 21.6 per 100,000 between 1999 and 2020, with the largest rise of 3.8-fold observed in adults aged 25-34 years. Women experienced a 2.5-fold increase, while the Midwest region showed a similar rise in mortality rates.

METHODOLOGY:

• Analysis utilized the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to examine alcohol-related mortality trends from 1999 to 2020.
• Researchers analyzed data from a total US population of 180,408,769 people aged 25 to 85+ years in 1999 and 226,635,013 people in 2020.
• International Classification of Diseases, Tenth Revision, codes were used to identify deaths with alcohol attribution, including mental and behavioral disorders, alcoholic organ damage, and alcohol-related poisoning.

TAKEAWAY:

• Overall mortality rates increased from 10.7 (95% CI, 10.6-10.8) per 100,000 in 1999 to 21.6 (95% CI, 21.4-21.8) per 100,000 in 2020, representing a significant twofold increase.
• Adults aged 55-64 years demonstrated both the steepest increase and highest absolute rates in both 1999 and 2020.
• American Indian and Alaska Native individuals experienced the steepest increase and highest absolute rates among all racial groups.
• The West region maintained the highest absolute rates in both 1999 and 2020, despite the Midwest showing the largest increase.

IN PRACTICE:

“Individuals who consume large amounts of alcohol tend to have the highest risks of total mortality as well as deaths from cardiovascular disease. Cardiovascular disease deaths are predominantly due to myocardial infarction and stroke. To mitigate these risks, health providers may wish to implement screening for alcohol use in primary care and other healthcare settings. By providing brief interventions and referrals to treatment, healthcare providers would be able to achieve the early identification of individuals at risk of alcohol-related harm and offer them the support and resources they need to reduce their alcohol consumption,” wrote the authors of the study.

SOURCE:

The study was led by Alexandra Matarazzo, BS, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. It was published online in The American Journal of Medicine.

LIMITATIONS:

According to the authors, the cross-sectional nature of the data limits the study to descriptive analysis only, making it suitable for hypothesis generation but not hypothesis testing. While the validity and generalizability within the United States are secure because of the use of complete population data, potential bias and uncontrolled confounding may exist because of different population mixes between the two time points.

DISCLOSURES:

The authors reported no relevant conflicts of interest. One coauthor disclosed serving as an independent scientist in an advisory role to investigators and sponsors as Chair of Data Monitoring Committees for Amgen and UBC, to the Food and Drug Administration, and to Up to Date. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Intermittent calorie restriction (CR) diet is more effective in reducing liver fat content than a standard-of-care diet in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), especially in those with obesity.

METHODOLOGY:

• Intermittent CR, which involves alternating periods of energy restriction and regular energy intake, has been proposed as a dietary intervention for MASLD.
• Researchers conducted a 12-week randomized controlled trial to compare the effects of a 5:2 intermittent CR and standard-of-care diet in nondiabetic patients with MASLD with or without obesity at an outpatient clinic in Korea.
• Intermittent CR comprised a reduced calorie consumption (500 kcal/d for women and 600 kcal/d for men) on 2 nonconsecutive days a week and, on the remaining 5 days/wk, following the Korean Dietary Reference Intakes (2000 kcal/d for women and 2500 kcal/d for men).
• The standard diet involved the consumption of 80% of the recommended calories (1200-1500 kcal/d for women and 1500-1800 kcal/d for men, or reducing 500-1000 kcal/d).
• The primary outcome was a relative reduction of ≥ 30% in the liver fat content measured by MRI-proton density fat fraction after 12 weeks.
• The secondary outcomes included changes in liver fibrosis, body weight, and body composition from baseline to week 12.

TAKEAWAY:

• Researchers enrolled 72 participants (36 patients with obesity and 36 without), with 63 completing the trial; of these, 32 received an intermittent CR diet (median age, 47.0 years; 58.8% men) and 31 received a standard-of-care diet (median age, 53.0 years; 36.4% men).
• A higher proportion of patients in the intermittent CR group achieved a relative reduction of ≥ 30% in the liver fat content at 12 weeks than the standard-of-care group (72.2% vs 44.4%; P = .033).
• These findings were even more prominent among those with obesity (61.1% in the intermittent CR group vs 27.7% in the standard-of-care group; P = .030).
• Patients with obesity in the intermittent CR group also showed a greater relative reduction in body weight than those in the standard-of-care group (–5.5% vs –2.9%; P = .022).
• Intermittent CR had no apparent effects on body composition, liver enzymes, or the lipid and glucose profiles of those with or without obesity.

IN PRACTICE:

“These results support the recommendation of a 5:2 [intermittent CR] diet as a useful dietary strategy for patients with MASLD,” the authors wrote.

SOURCE:

The study, led by Han Ah Lee, PhD, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, South Korea, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The intervention period of 12 weeks was relatively short, limiting the ability to observe long-term effects. The study did not reveal the effects of intermittent CR on histologic metabolic dysfunction–associated steatohepatitis or significantly advanced fibrosis. The study was conducted at a single center located in an urban, metropolitan area in Korea, which may limit the applicability of the findings to other populations.

DISCLOSURES:

This study was supported in part by a grant from the National Research Foundation of Korea funded by the Ministry of Science and ICT. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Intermittent calorie restriction (CR) diet is more effective in reducing liver fat content than a standard-of-care diet in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), especially in those with obesity.

METHODOLOGY:

• Intermittent CR, which involves alternating periods of energy restriction and regular energy intake, has been proposed as a dietary intervention for MASLD.
• Researchers conducted a 12-week randomized controlled trial to compare the effects of a 5:2 intermittent CR and standard-of-care diet in nondiabetic patients with MASLD with or without obesity at an outpatient clinic in Korea.
• Intermittent CR comprised a reduced calorie consumption (500 kcal/d for women and 600 kcal/d for men) on 2 nonconsecutive days a week and, on the remaining 5 days/wk, following the Korean Dietary Reference Intakes (2000 kcal/d for women and 2500 kcal/d for men).
• The standard diet involved the consumption of 80% of the recommended calories (1200-1500 kcal/d for women and 1500-1800 kcal/d for men, or reducing 500-1000 kcal/d).
• The primary outcome was a relative reduction of ≥ 30% in the liver fat content measured by MRI-proton density fat fraction after 12 weeks.
• The secondary outcomes included changes in liver fibrosis, body weight, and body composition from baseline to week 12.

TAKEAWAY:

• Researchers enrolled 72 participants (36 patients with obesity and 36 without), with 63 completing the trial; of these, 32 received an intermittent CR diet (median age, 47.0 years; 58.8% men) and 31 received a standard-of-care diet (median age, 53.0 years; 36.4% men).
• A higher proportion of patients in the intermittent CR group achieved a relative reduction of ≥ 30% in the liver fat content at 12 weeks than the standard-of-care group (72.2% vs 44.4%; P = .033).
• These findings were even more prominent among those with obesity (61.1% in the intermittent CR group vs 27.7% in the standard-of-care group; P = .030).
• Patients with obesity in the intermittent CR group also showed a greater relative reduction in body weight than those in the standard-of-care group (–5.5% vs –2.9%; P = .022).
• Intermittent CR had no apparent effects on body composition, liver enzymes, or the lipid and glucose profiles of those with or without obesity.

IN PRACTICE:

“These results support the recommendation of a 5:2 [intermittent CR] diet as a useful dietary strategy for patients with MASLD,” the authors wrote.

SOURCE:

The study, led by Han Ah Lee, PhD, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, South Korea, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The intervention period of 12 weeks was relatively short, limiting the ability to observe long-term effects. The study did not reveal the effects of intermittent CR on histologic metabolic dysfunction–associated steatohepatitis or significantly advanced fibrosis. The study was conducted at a single center located in an urban, metropolitan area in Korea, which may limit the applicability of the findings to other populations.

DISCLOSURES:

This study was supported in part by a grant from the National Research Foundation of Korea funded by the Ministry of Science and ICT. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Intermittent calorie restriction (CR) diet is more effective in reducing liver fat content than a standard-of-care diet in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), especially in those with obesity.

METHODOLOGY:

• Intermittent CR, which involves alternating periods of energy restriction and regular energy intake, has been proposed as a dietary intervention for MASLD.
• Researchers conducted a 12-week randomized controlled trial to compare the effects of a 5:2 intermittent CR and standard-of-care diet in nondiabetic patients with MASLD with or without obesity at an outpatient clinic in Korea.
• Intermittent CR comprised a reduced calorie consumption (500 kcal/d for women and 600 kcal/d for men) on 2 nonconsecutive days a week and, on the remaining 5 days/wk, following the Korean Dietary Reference Intakes (2000 kcal/d for women and 2500 kcal/d for men).
• The standard diet involved the consumption of 80% of the recommended calories (1200-1500 kcal/d for women and 1500-1800 kcal/d for men, or reducing 500-1000 kcal/d).
• The primary outcome was a relative reduction of ≥ 30% in the liver fat content measured by MRI-proton density fat fraction after 12 weeks.
• The secondary outcomes included changes in liver fibrosis, body weight, and body composition from baseline to week 12.

TAKEAWAY:

• Researchers enrolled 72 participants (36 patients with obesity and 36 without), with 63 completing the trial; of these, 32 received an intermittent CR diet (median age, 47.0 years; 58.8% men) and 31 received a standard-of-care diet (median age, 53.0 years; 36.4% men).
• A higher proportion of patients in the intermittent CR group achieved a relative reduction of ≥ 30% in the liver fat content at 12 weeks than the standard-of-care group (72.2% vs 44.4%; P = .033).
• These findings were even more prominent among those with obesity (61.1% in the intermittent CR group vs 27.7% in the standard-of-care group; P = .030).
• Patients with obesity in the intermittent CR group also showed a greater relative reduction in body weight than those in the standard-of-care group (–5.5% vs –2.9%; P = .022).
• Intermittent CR had no apparent effects on body composition, liver enzymes, or the lipid and glucose profiles of those with or without obesity.

IN PRACTICE:

“These results support the recommendation of a 5:2 [intermittent CR] diet as a useful dietary strategy for patients with MASLD,” the authors wrote.

SOURCE:

The study, led by Han Ah Lee, PhD, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, South Korea, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

The intervention period of 12 weeks was relatively short, limiting the ability to observe long-term effects. The study did not reveal the effects of intermittent CR on histologic metabolic dysfunction–associated steatohepatitis or significantly advanced fibrosis. The study was conducted at a single center located in an urban, metropolitan area in Korea, which may limit the applicability of the findings to other populations.

DISCLOSURES:

This study was supported in part by a grant from the National Research Foundation of Korea funded by the Ministry of Science and ICT. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.