Clinical and Molecular Hepatology

"Amit G. Singal"

Correspondences

Correspondence to letter to the editor on "Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States": Pojsakorn Danpanichkul, Luis Antonio Diaz, Juan Pablo Arab, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2026;32(3):e399-e401.
Published online September 1, 2025; DOI: https://doi.org/10.3350/cmh.2025.0948

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Correspondence to letter to the editor on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”: Pojsakorn Danpanichkul, Luis Antonio Diaz, Juan Pablo Arab, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2026;32(2):e246-e248.
Published online June 17, 2025; DOI: https://doi.org/10.3350/cmh.2025.0594

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Citations to this article as recorded by

Reply to correspondence 2 on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”
Dibin Liu
Clinical and Molecular Hepatology.2026; 32(2): e264. CrossRef
Sex chromosomes/hormones and the tumor microenvironment of non-reproductive cancers
Chun-Miao Zhang, Zhong-Bo Ge, Hai-Hong Zhou, Meng-Xiao Wei, Xin-Yuan Ding, Zhe-Zheng Lin, Ming-Yu Wang, Cai-Juan Bai
Frontiers in Immunology.2025;[Epub] CrossRef
Rising burden of steatotic liver disease in women of childbearing age and projections till 2035
Youxin Wang, Ruiqiu Chen, Shi Yan Lee, Eunice X.X. Tan, Mark Muthiah, Zhou Yu, Margaret L.P. Teng, Jazleen Leo, Cheng Han Ng, Ashok Choudhury, Daniel Q. Huang
JHEP Reports.2025; : 101646. CrossRef
Stable Nationwide Sepsis-Related Mortality Does Not Extend to Individuals with Alcohol-Associated Liver Disease
Pojsakorn Danpanichkul, Kwanjit Duangsonk, Claire S. Faulkner, Supapitch Sirimangklanurak, Tulaton Sodsri, Natchaya Polpichai, Shu-Yen Chan, Yanfang Pang, Omar Y. Mousa, Donghee Kim, Suthat Liangpunsakul, Karn Wijarnpreecha
Digestive Diseases and Sciences.2025;[Epub] CrossRef

3,224 View
34 Download
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Advancing policy and practice in alcohol-associated liver disease and alcohol-attributable cancer: Correspondence to the editorial on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”: Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2026;32(1):e96-e98.
Published online May 15, 2025; DOI: https://doi.org/10.3350/cmh.2025.0527

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Reply to correspondence 1 on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States”
Sung-Eun Kim
Clinical and Molecular Hepatology.2026; 32(1): e125. CrossRef

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26 Download
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Original Article

Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States: Pojsakorn Danpanichkul, Yanfang Pang, Tanuj Mahendru, Primrose Tothanarungroj, Luis Antonio Díaz, Juan Pablo Arab, Pimtawan Jatupornpakdee, Mark D. Muthiah, Kwanjit Duangsonk, Won-Mook Choi, Daniel Q. Huang, Donghee Kim, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2025;31(3):1058-1070.
Published online April 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0169

Background/Aims
Harmful alcohol use is a substantial contributor to liver diseases, liver cancer, and extrahepatic neoplasms. Patterns of alcohol consumption have shifted over recent decades. This study evaluates trends in alcohol-associated liver disease (ALD) and alcohol-attributable cancers in the United States (US) from 2000 to 2021.
Methods
Using the methodological framework of the Global Burden of Disease Study 2021, we analyzed trends in incidence, prevalence, and mortality from ALD and alcohol-attributable cancers in the US.
Results
In 2021, there were 28,340 new cases of ALD, 227,730 prevalent cases, and 21,860 deaths attributed to ALD in the US. From 2000 to 2021, ALD incidence, prevalence, and mortality increased by 43%, 36%, and 79%, respectively. The age-standardized incidence and death rate of ALD rose disproportionately among females compared to males. For alcohol-attributable cancers, primary liver cancer, colorectal cancer, and esophageal cancer accounted for the largest share of deaths in 2021. Age-standardized death rates increased significantly for primary liver cancer (annual percent change [APC] 2.21%, 95% confidence interval [CI] 1.70–2.73%) and other pharyngeal cancer (APC 1.35%, 95% CI 1.08–1.62%).
Conclusions
The burden of ALD is substantial and continues to rise in the US, with a particularly notable increase among females. Mortality from alcohol-attributable cancers is also increasing, mainly driven by primary liver cancer and pharyngeal cancer. However, system-wise, gastrointestinal cancer had the highest death attributable to alcohol. These findings highlight the urgent need for public health strategies to tackle ALD, primary liver cancer, and alcoholattributable extrahepatic malignancies.

Citations

Citations to this article as recorded by

Advancing policy and practice in alcohol-associated liver disease and alcohol-attributable cancer: Correspondence to the editorial on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the Unite
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Amit G. Singal, Ju Dong Yang
Clinical and Molecular Hepatology.2026; 32(1): e96. CrossRef
Rising burden of steatotic liver disease in women of childbearing age and projections to 2035
Youxin Wang, Ruiqiu Chen, Shi Yan Lee, Eunice X.X. Tan, Mark Muthiah, Zhou Yu, Margaret L.P. Teng, Jazleen Leo, Cheng Han Ng, Ashok Choudhury, Daniel Q. Huang
JHEP Reports.2026; 8(1): 101646. CrossRef
Stable Nationwide Sepsis-Related Mortality Does Not Extend to Individuals with Alcohol-Associated Liver Disease
Pojsakorn Danpanichkul, Kwanjit Duangsonk, Claire S. Faulkner, Supapitch Sirimangklanurak, Tulaton Sodsri, Natchaya Polpichai, Shu-Yen Chan, Yanfang Pang, Omar Y. Mousa, Donghee Kim, Suthat Liangpunsakul, Karn Wijarnpreecha
Digestive Diseases and Sciences.2026; 71(6): 2165. CrossRef
Improved survival and reduced alcohol‐associated hepatitis risk with renin‐angiotensin‐aldosterone system inhibitors in alcohol‐associated liver disease
Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Andrew F. Ibrahim, Primrose Tothanarungroj, Omar Al Ta'ani, Narathorn Kulthamrongsri, Kwanjit Duangsonk, Robert J. Wong, Daniel Q. Huang, Karn Wijarnpreecha, Mazen Noureddin, Suthat Liangpunsakul
Alcohol, Clinical and Experimental Research.2026;[Epub] CrossRef
Spatiotemporal trends, demographic disparities, and predictions to 2040 in gastrointestinal cancer mortality in the United States
Maolang He, Jingyi Zhang, Shangqi Wang, Kainan Xing, Yanxin Zhao, Jianzhen Chen, Xi Zhang, Yong Zheng, Shuxin Tian
BMC Public Health.2026;[Epub] CrossRef
Global burden of esophageal cancer attributable to smoking and alcohol, 1990–2021, with projections to 2040: a population-based analysis of the global burden of disease study 2021
Hui Zhou, Jiao Wu, Yuan Yin
Annals of Medicine.2026;[Epub] CrossRef
The global epidemiology of alcohol-associated liver disease
Pojsakorn Danpanichkul, Francisco Idalsoaga, Frank Murray, Juan Pablo Arab, Luis Antonio Díaz
Hepatology Communications.2026;[Epub] CrossRef
History of Alcohol‐Related Cancers and ADH1B/ALDH2 Genotypes in a Large Japanese Cohort of Male Patients With Alcohol Dependence
Akira Yokoyama, Tetsuji Yokoyama
Cancer Medicine.2026;[Epub] CrossRef
MetALD: new insights and unraveling therapeutic potential
Yue Feng, PanShiLi Han, Tao Liu, YanHang Gao
Metabolism and Target Organ Damage.2025;[Epub] CrossRef
Sex Disparity in Major Adverse Liver Outcome and Major Adverse Cardiac Event in Alcohol‐Associated Liver Disease
Pojsakorn Danpanichkul, Donghee Kim, Karn Wijarnpreecha, Mark D. Muthiah, Suthat Liangpunsakul
Liver International.2025;[Epub] CrossRef
Effect of varenicline on major adverse liver outcomes in alcohol‐associated liver disease: An exploratory analysis
Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Thanathip Suenghataiphorn, Donghyun Ko, Andrew F. Ibrahim, Vitchapong Prasitsumrit, Kwanjit Duangsonk, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul
Alcohol, Clinical and Experimental Research.2025; 49(11): 2451. CrossRef
Consumo de alcohol y cirrosis en mujeres: un riesgo subestimado
P. Huerta, J.P. Arab, L.A. Díaz
Revista de Gastroenterología de México.2025; 90(4): 509. CrossRef
Alcohol use and cirrhosis in women: An underestimated risk
P. Huerta, J.P. Arab, L.A. Díaz
Revista de Gastroenterología de México (English Edition).2025; 90(4): 509. CrossRef
Etiology of cirrhosis is associated with risk of hepatic decompensation and hepatocellular carcinoma
Michelle Ng, Olgert Bardhi, Krystal Lai, Eden Koo, Sruthi Yekkaluri, Kevin Bass, Guruveer Bhamra, Pojsakorn Danpanichkul, Lisa Quirk, Ju Dong Yang, Jeremy Louissaint, Thomas A. Kerr, Amit G. Singal
BMC Gastroenterology.2025;[Epub] CrossRef

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Review

Hepatic neoplasm

Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment: Soo Young Hwang, Pojsakorn Danpanichkul, Vatche Agopian, Neil Mehta, Neehar D. Parikh, Ghassan K. Abou-Alfa, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2025;31(Suppl):S228-S254.
Published online December 26, 2024; DOI: https://doi.org/10.3350/cmh.2024.0824

Abstract
PDF

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.

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Original Article

Hepatic neoplasm

Factors associated with unrecognized cirrhosis in patients with hepatocellular carcinoma: Yi-Te Lee, Mohammad A. Karim, Hye Chung Kum, Sulki Park, Nicole E. Rich, Mazen Noureddin, Amit G. Singal, Ju Dong Yang; Clin Mol Hepatol 2023;29(2):453-464.
Published online February 1, 2023; DOI: https://doi.org/10.3350/cmh.2022.0450

Background/Aims
Cirrhosis is the most important risk factor of hepatocellular carcinoma (HCC), and patients with cirrhosis are recommended to receive semiannual surveillance for early HCC detection. However, early cirrhosis is often asymptomatic and can go undiagnosed for years, leading to underuse of HCC surveillance in clinical practice. We characterized the frequency and associated factors of unrecognized cirrhosis in a national sample of patients with HCC from the United States.
Methods
HCC patients aged 68 years and older, diagnosed during 2011 to 2015 were included from the SEERMedicare Linked Database. If cirrhosis was diagnosed within 6 months immediately preceding HCC diagnosis or after HCC diagnosis, cases were categorized as unrecognized cirrhosis. Factors associated with unrecognized cirrhosis were identified using logistic regression analyses. Factors associated with overall survival were evaluated using Cox regression analyses.
Results
Among 5,098 HCC patients, 74.8% patients had cirrhosis. Among those with cirrhosis, 57.4% had unrecognized cirrhosis, with the highest proportion (76.3%) among those with NAFLD-related HCC. Male sex (aOR: 2.12, 95% CI: 1.83–2.46), non-Hispanic Black race (aOR: 1.93, 95% CI: 1.45–2.57), and NAFLD etiology (aOR: 4.46, 95% CI: 3.68–5.41) were associated with having unrecognized cirrhosis. Among NAFLD-related HCC patients, male sex (aOR: 2.32, 95% CI: 1.71–3.14) was associated with unrecognized cirrhosis. Unrecognized cirrhosis was independently associated with worse overall survival (aHR: 1.17, 95% CI: 1.08–1.27) compared to recognized cirrhosis.
Conclusions
Unrecognized cirrhosis is common in NAFLD-related HCC, particularly among male and Black patients, highlighting these groups as important intervention targets to improve HCC surveillance uptake and outcomes.

Citations

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Reviews

Hepatic neoplasm

Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease: Karim Seif El Dahan, Darine Daher, Amit G. Singal; Clin Mol Hepatol 2023;29(Suppl):S207-S219.
Published online September 14, 2022; DOI: https://doi.org/10.3350/cmh.2022.0247

Abstract
PDF

Non-alcoholic fatty liver disease (NAFLD) may progress to cirrhotic or non-cirrhotic hepatocellular carcinoma (HCC), and is currently recognized as the fastest growing cause of HCC worldwide. Accordingly, professional society guidelines recommend HCC surveillance in patients with cirrhosis from any etiology, and some may consider it beneficial in subgroups with non-cirrhotic NAFLD at higher risk for HCC. Notably, patients with NAFLD-related HCC are more likely to have HCC diagnosed at more advanced stages and have poorer outcomes when compared to other etiologies, and suboptimal effectiveness of HCC surveillance programs is a major culprit. In this review, we summarize the current guidelines for HCC surveillance and discuss its benefits versus potential harms for NAFLD patients. We also address the unique challenges of HCC surveillance in NAFLD, including higher proportion of NAFLD-related HCC without cirrhosis, poor recognition of at-risk patients, lack of consensus regarding the value of surveillance in non-cirrhotic NAFLD, subpar effectiveness of surveillance tools related to NAFLD phenotype, and preponderant surveillance underuse among NAFLD patients. Finally, we examine the effectiveness of currently used surveillance tools (i.e., ultrasound and alpha fetoprotein) and outline future perspectives including emerging risk stratification tools, imaging surveillance strategies (e.g., abbreviated magnetic resonance imaging protocols), blood-based biomarkers (e.g., GALAD and circulating tumor DNA panels), and interventions to improve surveillance adherence.

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Hepatic neoplasm

Hepatocellular carcinoma surveillance in the 21st century: Saving lives or causing harm?: Ibrahim A. Hanouneh, Naim Alkhouri, Amit G. Singal; Clin Mol Hepatol 2019;25(3):264-269.
Published online March 4, 2019; DOI: https://doi.org/10.3350/cmh.2019.1001

Abstract
PDF

Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide. Prognosis and treatment options largely depend on tumor stage at diagnosis, with curative treatments only available if detected at an early stage. However, two thirds of patients with HCC are diagnosed at a late stage and not eligible for cure. Therefore several liver professional societies recommend HCC surveillance using abdominal ultrasound with or without alpha fetoprotein in at-risk populations, including patients with cirrhosis and subsets of those with chronic hepatitis B. Available data suggest HCC surveillance can significantly improve early tumor detection, curative treatment eligibility, and overall survival. However, the potential benefits of HCC surveillance must be considered in light a shifting HCC demographic from a viral-mediated cancer to an increasing proportion of patients having non-alcoholic steatohepatitis, which has been shown to limit ultrasound sensitivity and may mitigate observed benefits. Further, benefits of HCC surveillance must be weighed against potential physical, financial and psychological harms. Continued data for both benefits and harms of HCC surveillance in contemporary populations are necessary. In the interim, providers should continue to strive for high quality HCC surveillance in at-risk patients.

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Hye Won Lee, Soo Young Park, Yu Rim Lee, Hyein Lee, Jae Seung Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Beom Kyung Kim
American Journal of Gastroenterology.2022; 117(2): 288. CrossRef
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Digestive Diseases and Sciences.2022; 67(7): 3412. CrossRef
Changes in general and central fatness are associated with hepatocellular carcinoma: A Korean nationwide longitudinal study
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Achievement of textbook outcomes and comparisons with benchmark values after laparoscopic left lateral sectionectomy
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Updates in Surgery.2022; 74(4): 1299. CrossRef
Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma
Hyo Jung Cho, Young Hwan Ahn, Min Suh Sim, Jung Woo Eun, Soon Sun Kim, Bong Wan Kim, Jimi Huh, Jei Hee Lee, Jai Keun Kim, Buil Lee, Jae Youn Cheong, Bohyun Kim
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Postresection Period-Specific Hazard of Recurrence as a Framework for Surveillance Strategy in Patients with Hepatocellular Carcinoma: A Multicenter Outcome Study
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Deubiquitylating Enzyme OTUB2 Promotes the Progress of Liver Cancer Cells by Stabilizing TRIM54
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Validation of risk prediction scores for hepatocellular carcinoma in patients with chronic hepatitis B treated with entecavir or tenofovir
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Improved Outcomes of Laparoscopic Liver Resection for Hepatocellular Carcinoma Located in Posterosuperior Segments of the Liver
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The Prognostic Role of On-Treatment Liver Stiffness for Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B
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External validation of CAGE‐B and SAGE‐B scores for Asian chronic hepatitis B patients with well‐controlled viremia by antivirals
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An MRI-guided targeting dual-responsive drug delivery system for liver cancer therapy
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Change in the Recurrence Pattern and Predictors over Time after Complete Cure of Hepatocellular Carcinoma
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Factors Associated with Poor Self-Rated Health in Cancer Patients
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Immunological Markers, Prognostic Factors and Challenges Following Curative Treatments for Hepatocellular Carcinoma
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Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1
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Clinical characteristics and prognostic value of MEX3A mRNA in liver cancer
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Prognosis of Early-Stage Hepatocellular Carcinoma: Comparison between Trans-Arterial Chemoembolization and Radiofrequency Ablation
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Improved outcomes of major laparoscopic liver resection for hepatocellular carcinoma
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New advances in the diagnosis and management of hepatocellular carcinoma
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Reactive oxygen species-induced activation of Yes-associated protein-1 through the c-Myc pathway is a therapeutic target in hepatocellular carcinoma
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Hepatocellular Carcinoma Risk According to Regimens for Eradication of Hepatitis C Virus; Interferon or Direct Acting Antivirals
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Adjuvant cytokine-induced killer cell immunotherapy for hepatocellular carcinoma: a propensity score-matched analysis of real-world data
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