Background/Aims Prediction of short-term mortality in patients with acute-on-chronic liver failure (ACLF) admitted to the intensive care unit (ICU) may enhance effective management.
Methods To develop, explain, and validate a predictive machine learning (ML) model for short-term mortality in patients with ACLF with two or more organ failures (OFs). Utilizing a large ICU cohort with detailed clinical information, we identified ACLF patients with two or more OFs according to the EASL-CLIF and NACSELD definitions. ML model was developed for each definition to predict 30-day mortality. The Shapley value was estimated to explain the models. Validation and calibration of these models were performed.
Results Of 5,994 patients with cirrhosis admitted to ICU, 1,511 met NACSELD criteria, and 1,692 met EASL-CLIF grade II or higher criteria. The CatBoost ACLF (CBA) model had the greatest accuracy in the NACSELD cohort (area under curve [AUC] of 0.87), while the Random Forest ACLF (RFA) model performed best in the EASL-CLIF cohort (AUC of 0.83). Both models showed robust calibration. The models were explained by SHAP score analysis, yielding a rank list, and the top twelve predictors were selected. Both simplified models demonstrated similar performance (CBA model: AUC 0.89, RFA model: AUC 0.81) and significantly outperformed contemporary scoring systems, including CLIF-C ACLF and MELD 3.0. The models were validated in both internal and external cohorts. A simple-to-use online tool was created to predict mortality rates.
Conclusions We presented explainable, well-validated, and calibrated predictive models for ACLF patients with two or more OFs, which outperformed existing predictive scores.
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
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
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.
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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
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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
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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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Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function. These advances have led to improvement in survival outcomes, with expected survival of greater than 18 months, in those with sensitive tumors, adequate liver function, and those functionally fit to receive sequential therapies. Several ongoing and promising trials are now evaluating combinational strategies with novel systemic agents and combinations of systemic therapy with locoregional therapy. In view of these trials, further advances in the treatment of HCC are foreseen in the near future.
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Background/Aims Patients with cirrhosis and hepatocellular carcinoma (HCC) require extensive and personalized care to improve outcomes. ChatGPT (Generative Pre-trained Transformer), a large language model, holds the potential to provide professional yet patient-friendly support. We aimed to examine the accuracy and reproducibility of ChatGPT in answering questions regarding knowledge, management, and emotional support for cirrhosis and HCC.
Methods ChatGPT’s responses to 164 questions were independently graded by two transplant hepatologists and resolved by a third reviewer. The performance of ChatGPT was also assessed using two published questionnaires and 26 questions formulated from the quality measures of cirrhosis management. Finally, its emotional support capacity was tested.
Results We showed that ChatGPT regurgitated extensive knowledge of cirrhosis (79.1% correct) and HCC (74.0% correct), but only small proportions (47.3% in cirrhosis, 41.1% in HCC) were labeled as comprehensive. The performance was better in basic knowledge, lifestyle, and treatment than in the domains of diagnosis and preventive medicine. For the quality measures, the model answered 76.9% of questions correctly but failed to specify decision-making cut-offs and treatment durations. ChatGPT lacked knowledge of regional guidelines variations, such as HCC screening criteria. However, it provided practical and multifaceted advice to patients and caregivers regarding the next steps and adjusting to a new diagnosis.
Conclusions We analyzed the areas of robustness and limitations of ChatGPT’s responses on the management of cirrhosis and HCC and relevant emotional support. ChatGPT may have a role as an adjunct informational tool for patients and physicians to improve outcomes.
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Assessing ChatGPT’s ability to answer questions
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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.
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Very early stage hepatocellular carcinoma (HCC) is defined as a single tumor with the largest diameter of the lesion measuring 2 cm or less according to Barcelona Liver Cancer staging system. Detection of very early stage HCC is clinically important as it confers an excellent prognosis with the 5-year survival rates over 60 to 80% after patients receive curative treatments. While diagnosing HCC at a very early stage is crucial, it is technically challenging and may come with the physical or psychosocial harms related to diagnostic tests. It is further complicated by the fact that patients with very early stage HCC are not prioritized for liver transplant (LT) in the United States organ allocation system. When LT-eligible patients present with an indeterminate lesion measuring between 1 and 2 cm on the multiphasic computed tomography or magnetic resonance imaging, clinicians often observe patients carefully until the lesion grows up to 2 cm so that patients can be eligible to receive a Model for End-Stage Liver Disease (MELD) exception score for HCC in the United States. The European guideline recommends a routine biopsy of such lesion. In conclusion, attempting to detect very early stage HCC is difficult to achieve and controversial. Clinicians should take into account of the risk and the benefit of diagnostic tests, LT candidacy of patients and the local organ allocation system.
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Spontaneous Regression of Hepatocellular Carcinoma From Autoinfarction and Implications on Liver Transplantation Kevin Singh ACG Case Reports Journal.2022; 9(7): e00825. CrossRef
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Targeted Next-Generation Sequencing of Plasma Cell-Free DNA in Korean Patients with Hepatocellular Carcinoma Hyojin Chae, Pil Soo Sung, Hayoung Choi, Ahlm Kwon, Dain Kang, Yonggoo Kim, Myungshin Kim, Seung Kew Yoon Annals of Laboratory Medicine.2021; 41(2): 198. CrossRef
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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 Jung Hyun Ji, Soo Young Park, Won Jeong Son, Hye Jung Shin, Hyein Lee, Hye Won Lee, Jae Seung Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Beom Kyung Kim Journal of Viral Hepatitis.2021; 28(6): 951. CrossRef
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