Clinical and Molecular Hepatology

"Medicine"

Review Article

Cardiovascular and Hepatic Outcomes: Prognostic Differences Across MASLD-MetALD-ALD Continuum: Han Ah Lee, Gi-Ae Kim, Won Kim; Received March 25, 2026 Accepted April 29, 2026 Published online May 8, 2026; DOI: https://doi.org/10.3350/cmh.2026.0367 [Accepted]

Abstract
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A paradigm shift in fatty liver disease nomenclature has introduced steatotic liver disease (SLD) as an umbrella term, encompassing metabolic dysfunction–associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-associated liver disease (ALD). These SLD subtypes exist along a dynamic continuum shaped by the synergistic interplay of metabolic dysfunction and alcohol exposure. Accumulating evidence indicates that SLD exhibits distinct outcome-based clusters reflecting heterogeneity in pathogenic drivers and clinical trajectories. Cardiometabolic clusters, most prominently observed in MASLD, are characterized by systemic metabolic dysfunction and confer increased risks of cardiovascular disease (CVD). In contrast, liver-specific clusters demonstrate progressive fibrosis and cirrhosis, hepatic decompensation, and hepatocellular carcinoma. In large-scale cohorts, CVD accounts for 40-50% of deaths in MASLD, while liver-related mortality predominates in ALD (>60%). The relative dominance of cardiometabolic versus liver-specific clusters shifts progressively across the MASLD-MetALD-ALD spectrum. While CVD remains a major driver of mortality, particularly in MASLD, hepatic outcomes increase stepwise with advancing fibrosis and greater alcohol exposure. Advanced fibrosis is the predominant shared determinant amplifying both CVD and hepatic risks across subtypes. This review synthesizes cardiovascular and hepatic outcome patterns across the MASLD-MetALD-ALD spectrum, highlighting the prognostic reorientation across the continuum, in which hepatic outcomes rise stepwise with alcohol exposure while cardiovascular risk remains an important but less subtype-differentiated burden. These findings advocate outcome-oriented risk stratification integrating noninvasive fibrosis assessment, alcohol biomarkers (PEth), and cardiovascular risk calculators within the Cardiovascular-Kidney-Metabolic framework. Understanding SLD as a modifiable continuum enables individualized management to optimize multisystem outcomes.

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Reply to Correspondence

Reply to correspondence: Sodium-Glucose Cotransporter-2 Inhibitors and Liver Outcomes in Metabolic Dysfunction-associated Steatotic Liver Disease: Yang-Hsiang Lin, Ching-Chih Hu, Chih-Lang Lin; Received January 25, 2026 Accepted February 2, 2026 Published online February 5, 2026; DOI: https://doi.org/10.3350/cmh.2026.0123 [Accepted]

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Editorial

Challenges and Innovations in MASLD and T2DM: Strengthening Personalized Medicine with SGLT2 Inhibitors: Yang-Hsiang Lin, Ching-Chih Hu, Chih-Lang Lin; Received January 2, 2026 Accepted January 17, 2026 Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2026.0002 [Accepted]

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Reviews

Clinical applications of immunogenomics in hepatocellular carcinoma: James K. Carter, Daniel C. Cameron, Augusto Villanueva; Clin Mol Hepatol 2026;32(2):511-535.
Published online January 6, 2026; DOI: https://doi.org/10.3350/cmh.2025.1323

Abstract
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Liver cancer is one of the deadliest malignancies, with increasing incidence worldwide. Recent advances in immunotherapy have expanded the options for systemic therapy against advanced hepatocellular carcinoma (HCC), but there are no biomarkers currently available to predict which patients will respond, leading to suboptimal patient selection strategies. Understanding of the genetic and immunologic features of HCC is accelerating rapidly through the use of single cell and spatial transcriptomic techniques. However, there is a need to translate insights gained through these new studies to improve treatment options and improve patient selection. In this review we summarize knowledge of the immunogenomics of HCC, emphasizing recent advances, and discuss progress toward clinical translation.

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Association of NUDT1 expression with the clinical outcomes of primary hepatocellular carcinoma
Yingda Xie, Xiaochen Ding, Fuqiang Ma
Asian Journal of Surgery.2026;[Epub] CrossRef

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Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders: Yun Kyung Cho, Chang Hee Jung; Clin Mol Hepatol 2026;32(2):464-486.
Published online November 26, 2025; DOI: https://doi.org/10.3350/cmh.2025.0744

Abstract
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Obesity and its related metabolic comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease, are increasingly recognized as heterogeneous and multisystemic disorders. Despite the significant benefits in glycemic control and weight loss exhibited by GLP-1 receptor agonists (GLP-1RAs), their limitations have initiated the development of engineered multi-agonist therapies targeting additional nutrient-stimulated hormonal (NUSH) pathways. Dual and triple peptide-based co-agonists combining glucagon-like peptide-1 (GLP-1) with glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, or peptide YY have demonstrated superior metabolic efficacy in preclinical and clinical studies. Tirzepatide (GLP-1/GIP dual agonist), CagriSema (GLP-1/amylin dual agonist), and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented levels of weight loss and glycemic improvement, with certain agents also demonstrating hepatic, cardiovascular, and inflammatory benefits. Non-peptidyl oral GLP-1 RAs such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence. Multi-agonist incretin-based therapies represent a paradigm shift in the management of obesity and metabolic diseases. These agents offer broad clinical utility beyond glucose lowering by mimicking the pleiotropic hormonal responses observed after bariatric surgery. These therapies are poised to emerge as key components of precision metabolic medicine. This review article explores the mechanistic basis, pharmacological characteristics, and clinical data supporting the use of engineered NUSH-based peptide therapies for obesity and its related metabolic disorders, with particular emphasis on recent progress in the development and clinical application of dual and triple agonists.

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Glucagon-like peptide-1 and dual/triple receptor agonists in the treatment of metabolic dysfunction-associated steatotic liver disease: advances in mechanistic research
Xinyi Lu, Li Yang
Frontiers in Medicine.2026;[Epub] CrossRef

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Novel biomarkers for alcohol-associated liver disease and their implications across clinical settings: Kaanthi Rama, Vinay Jahagirdar, Francisco Idalsoaga, Hanna Blaney, S. Fisher Rhoads, Luis Antonio Díaz, Marco Arrese, Juan Pablo Arab; Clin Mol Hepatol 2026;32(2):443-463.
Published online November 25, 2025; DOI: https://doi.org/10.3350/cmh.2025.0921

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Alcohol-associated liver disease (ALD) is a leading cause of preventable cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality, yet current laboratory and imaging tools detect only late-stage disease. This narrative review synthesizes emerging evidence on novel biomarkers that capture the multidimensional pathophysiology of ALD and discusses their utility for routine clinical practice. Traditional serum-based liver fibrosis markers (e.g., cytokeratin-18 fragments, Pro-C3, the enhanced liver fibrosis test) improve non-invasive staging risk beyond aminotransferases, while elastography techniques, such as vibration-controlled transient elastography and magnetic resonance elastography, can also quantify liver stiffness with high precision. Among novel mechanistic biomarkers, genetic polymorphisms in PNPLA3, TM6SF2, MBOAT7, HSD17B13, and polygenic risk scores define lifetime risk, whereas sex-specific hormonal milieus also modify susceptibility and progression. Moreover, gut dysbiosis signatures, including reduced Faecalibacterium prausnitzii, Akkermansia muciniphila, and a lower Firmicutes/Bacteroidetes ratio, and their metabolites (short-chain fatty acids, and bile acids, trimethylamine N-oxide) correlate with liver inflammation and fibrosis. Endocrine imbalances of cortisol, testosterone, and thyroid hormones further stratify metabolic vulnerability. Ultimately, multi-omics platforms (i.e., transcriptomics, lipidomics, proteomics, metabolomics, and epigenomics) can reveal distinct molecular signatures that predict steatohepatitis, fibrogenesis, and early HCC. Integrating these biomarkers enables phase-specific enrichment strategies, earlier intervention windows, adaptive dose-finding, and mechanismbased endpoints in ALD trials. Remaining challenges include assay standardization, validation across diverse cohorts, and incorporation into regulatory frameworks. Future work could evaluate cost-effectiveness and feasibility in routine clinical practice. Widespread adoption promises earlier diagnosis, personalized risk reduction, and more efficient drug development for this globally prevalent disorder.

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Immune Determinants of MASLD Progression: From Immunometabolic Reprogramming to Fibrotic Transformation
Senping Xu, Zhaoshan Zhang, Zhongquan Zhou, Jiawei Guo
Biology.2026; 15(2): 148. CrossRef
Review Article on: AI-Driven Precision Medicine in Liver Disease: Microbiome and Nanotechnology Integration
Rahul Kumar, Amritesh Kumar, Aayush Kumar Tiwari, MD Nasiruddin Khan, Mohit Kumar, Moidul Islam Judder
Pan-African Journal of Health and Psychological Sciences.2026;[Epub] CrossRef
N-acetylcysteine for patients with alcohol use disorder, post-traumatic stress disorder, and their co-occurrence: a systematic review of placebo-controlled randomized trials
Mohamed Awad E. Ahmed, Mufreh Amin, Yomna Emad Abdalla, Amr Abdelghani, Nourhan Eid, Aya Samy, Omar Kassar, Khalid Radwan Alsaadany, Mohamed Ezzat M. Mansour
BMC Psychiatry.2026;[Epub] CrossRef

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Special Review

Liver disease trends in the Asia-Pacific region for the next 50 years: Shuichiro Shiina, Javkhlan Maikhuu, Qing Deng, Terguunbileg Batsaikhan, Lariza Marie Canseco, Maki Tobari, Hitoshi Maruyama, Hiroaki Nagamatsu, Diana Alcantara-Payawal, Rino Gani, Yi-Hsiang Huang, Tawesak Tanwandee, Giovanni Galati, Yoon Jun Kim; Clin Mol Hepatol 2025;31(3):671-684.
Published online March 4, 2025; DOI: https://doi.org/10.3350/cmh.2025.0043

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Liver disease has emerged as a critical and escalating public health concern worldwide, with the Asia-Pacific region at the forefront of this challenge due to its vast population and diverse socioeconomic landscape. Over the coming five decades, this region will experience profound changes in liver disease patterns, shaped by rapid urbanization, lifestyle modifications, advancements in medical technologies, and evolving public health strategies. This article offers an in-depth analysis of six transformative areas defining the trajectory of liver disease in the region. First, it highlights the alarming rise of metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis, diseases driven by modern lifestyle factors and inherent metabolic susceptibilities. Concurrently, it celebrates the declining burden of viral hepatitis, underscoring the success of sustained public health interventions. However, new challenges are emerging, such as the growing impact of environmental and occupational exposures on liver health. Breakthroughs in genomic and epigenetic research promise to advance precision medicine, offering targeted therapeutic solutions. Additionally, the integration of artificial intelligence, big data, and telemedicine is poised to revolutionize liver disease management, improving accessibility and personalized care. Finally, the article emphasizes the critical role of robust health policies, preventive strategies, and cross-border collaboration in shaping a healthier future. By synthesizing these insights, the study aims to guide innovative and effective responses to the evolving liver disease landscape in the Asia-Pacific region.

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Reviews

Artificial intelligence, epidemiology, methodology, or others

Liver organoids: Current advances and future applications for hepatology: Yohan Kim, Minseok Kang, Michael Girma Mamo, Michael Adisasmita, Meritxell Huch, Dongho Choi; Clin Mol Hepatol 2025;31(Suppl):S327-S348.
Published online December 26, 2024; DOI: https://doi.org/10.3350/cmh.2024.1040

Abstract
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The creation of self-organizing liver organoids represents a significant, although modest, step toward addressing the ongoing organ shortage crisis in allogeneic liver transplantation. However, researchers have recognized that achieving a fully functional whole liver remains a distant goal, and the original ambition of organoid-based liver generation has been temporarily put on hold. Instead, liver organoids have revolutionized the field of hepatology, extending their influence into various domains of precision and molecular medicine. These 3D cultures, capable of replicating key features of human liver function and pathology, have opened new avenues for human-relevant disease modeling, CRISPR gene editing, and high-throughput drug screening that animal models cannot accomplish. Moreover, advancements in creating more complex systems have led to the development of multicellular assembloids, dynamic organoid-on-chip systems, and 3D bioprinting technologies. These innovations enable detailed modeling of liver microenvironments and complex tissue interactions. Progress in regenerative medicine and transplantation applications continues to evolve and strives to overcome the obstacles of biocompatibility and tumorigenecity. In this review, we examine the current state of liver organoid research by offering insights into where the field currently stands, and the pivotal developments that are shaping its future.

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Steatotic liver disease

Microbiome-centered therapies for the management of metabolic dysfunction-associated steatotic liver disease: Huma Saeed, Luis Antonio Díaz, Antonio Gil-Gómez, Jeremy Burton, Jasmohan S. Bajaj, Manuel Romero-Gomez, Marco Arrese, Juan Pablo Arab, Mohammad Qasim Khan; Clin Mol Hepatol 2025;31(Suppl):S94-S111.
Published online November 28, 2024; DOI: https://doi.org/10.3350/cmh.2024.0811

Abstract
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies’ potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.

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Probiotic-Derived Strain-Specific Metabolites Ameliorate Metabolic Dysfunction–Associated Steatotic Liver Disease through Modulation of the Gut-Liver Axis
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Probiotics and Antimicrobial Proteins.2026; 18(3): 4353. CrossRef
Sarcopenia and MASLD: novel insights and the future
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Editorial

Hepatic neoplasm

Personalized approaches to the treatment of hepatocellular carcinoma using immune checkpoint inhibitors: Editorial on “Genomic biomarkers to predict response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma: Insights from the IMbrave150 trial”: Naoshi Nishida; Clin Mol Hepatol 2025;31(1):311-315.
Published online September 3, 2024; DOI: https://doi.org/10.3350/cmh.2024.0739

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Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to editorial on “Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis”: Jiaorong Qu, Le Wang, Xiaojiaoyang Li; Clin Mol Hepatol 2024;30(4):1002-1004.
Published online May 17, 2024; DOI: https://doi.org/10.3350/cmh.2024.0357

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Artificial intelligence, epidemiology, methodology, or others

Correspondence on Letter 2 regarding “Assessing the performance of ChatGPT in answering questions regarding cirrhosis and hepatocellular carcinoma”: Yee Hui Yeo, Jamil S. Samaan, Wee Han Ng; Clin Mol Hepatol 2023;29(3):823-824.
Published online May 31, 2023; DOI: https://doi.org/10.3350/cmh.2023.0182

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Original Article

Artificial intelligence, epidemiology, methodology, or others

Assessing the performance of ChatGPT in answering questions regarding cirrhosis and hepatocellular carcinoma: Yee Hui Yeo, Jamil S. Samaan, Wee Han Ng, Peng-Sheng Ting, Hirsh Trivedi, Aarshi Vipani, Walid Ayoub, Ju Dong Yang, Omer Liran, Brennan Spiegel, Alexander Kuo; Clin Mol Hepatol 2023;29(3):721-732.
Published online March 22, 2023; DOI: https://doi.org/10.3350/cmh.2023.0089

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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Calcified Tissue International.2026;[Epub] CrossRef
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Healthcare Informatics Research.2026; 32(2): 179. CrossRef
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The Journal of Clinical Endocrinology & Metabolism.2025; 110(3): e841. CrossRef
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The American Surgeon™.2025; 91(1): 94. CrossRef
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Virchows Archiv.2025; 486(4): 663. CrossRef
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Journal of Hepatology.2025; 82(1): e15. CrossRef
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JMIR Medical Informatics.2025; 13: e63924. CrossRef
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American Journal of Health-System Pharmacy.2025; 82(8): 448. CrossRef
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Orbit.2025; 44(3): 295. CrossRef
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Journal of Clinical Medicine.2025; 14(9): 2942. CrossRef
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Journal of Endodontics.2025; 51(11): 1617. CrossRef
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The New Journal of Urology.2025; 20(1): 21. CrossRef
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Steatotic liver disease

Eating, diet, and nutrition for the treatment of non-alcoholic fatty liver disease: Georg Semmler, Christian Datz, Michael Trauner; Clin Mol Hepatol 2023;29(Suppl):S244-S260.
Published online December 14, 2022; DOI: https://doi.org/10.3350/cmh.2022.0364

Abstract
PDF

Nutrition and dietary interventions are a central component in the pathophysiology, but also a cornerstone in the management of patients with non-alcoholic fatty liver disease (NAFLD). Summarizing our rapidly advancing understanding of how our diet influences our metabolism and focusing on specific effects on the liver, we provide a comprehensive overview of dietary concepts to counteract the increasing burden of NAFLD. Specifically, we emphasize the importance of dietary calorie restriction independently of the macronutrient composition together with adherence to a Mediterranean diet low in added fructose and processed meat that seems to exert favorable effects beyond calorie restriction. Also, we discuss intermittent fasting as a type of diet specifically tailored to decrease liver fat content and increase ketogenesis, awaiting future study results in NAFLD. Finally, personalized dietary recommendations could be powerful tools to increase the effectiveness of dietary interventions in patients with NAFLD considering the genetic background and the microbiome, among others.

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Deep learning-based prediction of molecular cancer biomarkers from tissue slides: A new tool for precision oncology: Sung Hak Lee, Hyun-Jong Jang; Clin Mol Hepatol 2022;28(4):754-772.
Published online April 21, 2022; DOI: https://doi.org/10.3350/cmh.2021.0394

Molecular tests are necessary to stratify cancer patients for targeted therapy. However, high cost and technical barriers limit the application of these tests, hindering optimal treatment. Recently, deep learning (DL) has been applied to predict molecular test results from digitized images of tissue slides. Furthermore, treatment response and prognosis can be predicted from tissue slides using DL. In this review, we summarized DL-based studies regarding the prediction of genetic mutation, microsatellite instability, tumor mutational burden, molecular subtypes, gene expression, treatment response, and prognosis directly from hematoxylin- and eosin-stained tissue slides. Although performance needs to be improved, these studies clearly demonstrated the feasibility of DL-based prediction of key molecular features in cancer tissues. With the accumulation of data and technical advances, the performance of the DL system could be improved in the near future. Therefore, we expect that DL could provide cost- and time-effective alternative tools for patient stratification in the era of precision oncology.

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Steatotic liver disease

Precision medicine in nonalcoholic fatty liver disease: New therapeutic insights from genetics and systems biology: Silvia Sookoian, Carlos J. Pirola; Clin Mol Hepatol 2020;26(4):461-475.
Published online September 10, 2020; DOI: https://doi.org/10.3350/cmh.2020.0136

Despite more than two decades of extensive research focusing on nonalcoholic fatty liver disease (NAFLD), no approved therapy for steatohepatitis—the severe histological form of the disease—presently exists. More importantly, new drugs and small molecules with diverse molecular targets on the pathways of hepatocyte injury, inflammation, and fibrosis cannot achieve the primary efficacy endpoints. Precision medicine can potentially overcome this issue, as it is founded on extensive knowledge of the druggable genome/proteome. Hence, this review summarizes significant trends and developments in precision medicine with a particular focus on new potential therapeutic discoveries modeled via systems biology approaches. In addition, we computed and simulated the potential utility of the NAFLD polygenic risk score, which could be conceptually very advantageous not only for early disease detection but also for implementing actionable measures. Incomplete knowledge of the druggable NAFLD genome severely impedes the drug discovery process and limits the likelihood of identifying robust and safe drug candidates. Thus, we close this article with some insights into emerging disciplines, such as chemical genetics, that may accelerate accurate identification of the druggable NAFLD genome/proteome.

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Viral hepatitis

Personalized treatment of hepatitis B: Anna S. Lok; Clin Mol Hepatol 2015;21(1):1-6.
Published online March 25, 2015; DOI: https://doi.org/10.3350/cmh.2015.21.1.1

Abstract
PDF

There are seven approved drugs for treatment of hepatitis B. Professional guidelines provide a framework for managing patients but these guidelines should be interpreted in the context of the individual patient's clinical and social circumstances. Personalized management of hepatitis B can be applied based on prediction of the individual patient's risk of cirrhosis and hepatocellular carcinoma to guide the frequency and intensity of monitoring and urgency of treatment. It can also be applied to decisions regarding when to start treatment, which drug to use, and when to stop based on the individual patient's disease characteristics, preference, comorbidities and other mitigating circumstances.

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Case Report

Autoimmune liver disease

Co-development of autoimmune hepatitis and Sjögren's syndrome triggered by the administration of herbal medicines: Hyo Jeong Oh, Young Mi Mok, Moon Seong Baek, Ji Kyeong Lee, Bong Soo Seo, Tae Hyeon Kim, Keum Ha Choi, In Kyeom Hwang, Ji Eun Ra, Yong-Reol Oh, Yong Sung Kim, Eun Young Cho, Haak Cheoul Kim, Young Woo Sohn; Clin Mol Hepatol 2013;19(3):305-308.
Published online September 30, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.3.305

Abstract
PDF

Autoimmune hepatitis (AIH) has been reported in association with Sjögren's syndrome (SS). Drug-induced AIH has been rarely reported. A rare case of the co-development of AIH and SS in a 53-year-old woman after the consumption of herbal medicines is described. After admission, the patient complained of dryness in her mouth, and she was subsequently diagnosed with SS, which had not been detected previously. The patient's bilirubin and aminotransferase levels initially decreased following conservative management; however, they later began to progressively increase. A diagnosis of AIH was made based on the scoring system proposed by the International Autoimmune Hepatitis Group. The patient was administered a combination of prednisolone and azathioprine, and the results of follow-up liver-function tests were found to be within the normal range. This is an unusual case of AIH and SS triggered simultaneously by the administration of herbal medicines.

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Review

Drug induced liver injury

Drug-induced liver injury: present and future: Ki Tae Suk, Dong Joon Kim; Korean J Hepatol 2012;18(3):249-257.
Published online September 25, 2012; DOI: https://doi.org/10.3350/cmh.2012.18.3.249

Abstract
PDF

Liver injury due to prescription and nonprescription medications is a growing medical, scientific, and public health problem. Worldwide, the estimated annual incidence rate of drug-induced liver injury (DILI) is 13.9-24.0 per 100,000 inhabitants. DILI is one of the leading causes of acute liver failure in the US. In Korea, the annual extrapolated incidence of cases hospitalized at university hospital is 12/100,000 persons/year. Most cases of DILI are the result of idiosyncratic metabolic responses or unexpected reactions to medication. There is marked geographic variation in relevant agents; antibiotics, anticonvulsants, and psychotropic drugs are the most common offending agents in the West, whereas in Asia, 'herbs' and 'health foods or dietary supplements' are more common. Different medical circumstances also cause discrepancy in definition and classification of DILI between West and Asia. In the concern of causality assessment, the application of the Roussel Uclaf Causality Assessment Method (RUCAM) scale frequently undercounts the cases caused by 'herbs' due to a lack of previous information and incompatible time criteria. Therefore, a more objective and reproducible tool that could be used for the diagnosis of DILI caused by 'herbs' is needed in Asia. In addition, a reporting system similar to the Drug-Induced Liver Injury Network (DILIN) in the US should be established as soon as possible in Asia.

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10.1016/b978-0-323-26339-9.00019-6

CrossRef Listing of Deleted DOIs.2000;[Epub] CrossRef

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Original Article

The value of serum retinol-binding protein 4 Levels for determining disease severity in patients with chronic Liver disease: Jung Hyun Kwon, M.D., Seong Tae Park1, Gi Dae Kim, Ph.D.1, Chan Ran You, M.D., Jin Dong Kim, M.D., Hyun Young Woo, M.D., Jeong Won Jang, M.D.1, Chang Wook Kim, M.D., Si Hyun Bae, M.D., Jong Young Choi, M.D., Seung Kew Yoon, M.D.; Korean J Hepatol 2009;15(1):59-69.
Published online March 31, 2009; DOI: https://doi.org/10.3350/kjhep.2009.15.1.59

Abstract
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Backgrounds/Aims
Serum retinol-binding protein 4 (RBP4) is known to be a specific transport protein for retinol, and has recently been reported to be associated with insulin resistance. Hyaluronic acid (HA) is a well-known marker of liver fibrosis. In this study, the degree to which serum RBP4 levels can be used to predict disease severity in patients with chronic liver disease (CLD) was evaluated. Methods: Serum levels of RBP4 and HA were measured in 573 CLD patients [235 with chronic hepatitis (CH), 230 with liver cirrhosis Child-Pugh grade (Child) A, and 108 with liver cirrhosis with Child B and C] and 40 normal controls. Results: The mean age of the whole cohort was 53.1 years and the causes of CLD were hepatitis B virus (61.9%), hepatitis C virus (9.8%), alcohol (9.0%), and nonalcoholic steatohepatitis (3.8%). Serum levels of RBP4 significantly reduced and HA increased with disease condition, from none (normal controls) to advanced cirrhosis (normal control: RBP4 4.3±0.1 mg/dL, HA 25.3±28.1 ng/mL; CH: RBP4 3.6±0.1 mg/dL, HA 75.5±7.8 ng/mL; cirrhosis with Child A: RBP4 2.6±0.1 mg/dL, HA 184.4±14.5 ng/mL; and cirrhosis with Child B and C: RBP4 1.6±0.1 mg/dL, HA 656.5±86.7 ng/mL; P<0.001, respectively). Serum RBP4 level was a distinguishing factor at the early stage of CLD between CH and Child A cirrhosis (post-hoc test; P<0.001) and was correlated with histological fibrosis score (n=80, P<0.05) and several biochemical factors. Antiviral therapy (n=45, median interval 1,205 days) resulted in an improvement in serum RBP4 levels (P=0.001). Conclusions: The results of our study suggest that RBP4 is a serologic marker for disease severity in patients with CLD. It could also be useful as an early marker of CLD and of the relative success of antiviral therapy. (Korean J Hepatol 2008;15:59-69)

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Case Report

Four cases of toxic Liver injury associated with Dictamnus dasycarpus: Jong Soon Jang, M.D., Eui Geun Seo, M.D., Cheol Han, M.D., Hee Bok Chae, M.D., Soon Je Kim, M.D.1, Jae Dong Lee, M.D.1, Joon Ho Wang, M.D.1; Korean J Hepatol 2008;14(2):206-212.
Published online June 20, 2008; DOI: https://doi.org/10.3350/kjhep.2008.14.2.206

Abstract
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We report four cases of toxic hepatitis that occurred after taking a decoction made by boiling down the root of Dictamnus dasycarpus. The four patients had a median age of 60 years, common symptoms of jaundice and general weakness, and stated that they had not consumed alcohol for at least 5 years. The markers of hepatitis A, B, and C were all negative in the patients. Abdominal ultrasonography revealed common bile ducts with normal diameters. Two of the cases were a mother and daughter, and the other two were sporadic. All of them had consumed a decoction made by boiling down the root of Dictamnus dasycarpus five or six times daily until several days before admission. Dictamnus dasycarpus induced liver injury presenting with a benign course lasting less than 1 month after cessation of the causative agent. We suggest that this natural product can cause acute hepatitis in rural areas. (Korean J Hepatol 2008;14:206-212)

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Original Article

The Survey for the Actual Condition of Drug Medication and Development of Health Care Cost Associated with Toxic Liver Injury in Korean; A Multicenter Study for the Detection and the Development of Nationwide Reporting System of Toxic Liver Injury: Tae Woo Yoo, M.D., Byung Ik Kim, M.D., Jin Bong Kim, M.D.1, Dong Joon Kim, M.D.1, Jae Woo Kim.2, Soon Koo Baik.2, Kwang Seok Kim, M.D.3, Gab Jin Cheon, M.D.3; Korean J Hepatol 2007;13(1):34-43.

Abstract
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Backgrounds/Aims
In Korea, interests in health and health care costs have been increased along with the increase of mean survival rate and income level. The aim of this study is to investigate the actual condition of drug medication and burden of health care cost. Methods: A total of 1,434 subjects in four tertiary medical centers were enrolled in this study. The questionnaires were obtained between March 2005 and September 2005. Based on this information, the actual condition of drug medication and health care cost were analyzed.
Results
The mean age of the subjects was 55.0±11.4 years (16-87 years). The male and female ratio was 1.74:1. The subjects with drug medication except for doctor’s prescription are presently 26.6% and were 40.9% in the past. Traditional medicine (39.6%) and health food (29.9%) are more frequently used than herbal medicine (5.8%) and medical supplies (4.2%) now. In the past, herbal medicine (14.6%) was more frequently used compared with the present. The side effects of drug medication were developed in 90 subjects (7.5%). The total mean health care costs were 895,000 won/year, the herbal medicine, 834,000 won/year, the health food, 950,000 won/year, and the traditional medicine, 324,000 won/year. Conclusions: In this study, the subjects with other drug medications without doctor’s prescription were as high as ever. The frequency of the use of the herbal medicine was decreased. However, the frequency for the use of the health food and traditional medicine have relatively increased. The side effects and additional large amounts of health care costs were occurred. (Korean J Hepatol 2007;13:34-43)