Clinical and Molecular Hepatology

"Liver failure"

Editorials

Rethinking ACLF Prognosis: Can Machine Learning Outperform Conventional Scores? Editorial on: Predictive Machine Learning Model in ICU Patients with Acute-on-Chronic Liver Failure and Two or More Organ Failures: Jung Hee Kim; Received September 15, 2025 Accepted September 17, 2025 Published online September 23, 2025; DOI: https://doi.org/10.3350/cmh.2025.1053 [Accepted]

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An editorial on “Human cytomegalovirus reactivation in cirrhosis patients with acute decompensation” by Hong et al. Title: Human cytomegalovirus reactivation in decompensated cirrhosis: marker of immunosuppression or contributor to severity?: Zhujun Cao, Richard Moreau; Received August 27, 2025 Accepted August 29, 2025 Published online September 1, 2025; DOI: https://doi.org/10.3350/cmh.2025.0962 [Accepted]

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Research Letter

Early oxidative protein modifications and gut damage/leakiness contribute to drug-induced acute liver failure: Wiramon Rungratanawanich, Ying Qu, Andrew Holmes, Neil Kaplowitz, Byoung-Joon Song; Received July 8, 2025 Accepted July 30, 2025 Published online August 4, 2025; DOI: https://doi.org/10.3350/cmh.2025.0748 [Accepted]

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Original Article

Human cytomegalovirus reactivation in cirrhosis patients with acute decompensation: Changze Hong, Zuxiong Huang, Yingli He, Rongqi Wang, Jiaying Lin, Yushan Liu, Baicheng Liu, Xiaoqin Lan, Qinjun He, Wenfan Luo, Qintao Lai, Ling Zhou, Tingting Qi, Yali Ji, Miaoxia Liu, Qiaoping Wu, Yichen Yao, Weihao Liang, Xianbo Wang, Guohong Deng, Yanhang Gao, Yan Huang, Feng Liu, Xiaobo Lu, Zhongji Meng, Yuemin Nan, Hai Li, Beiling Li, Rajiv Jalan, Jinjun Chen; Clin Mol Hepatol 2025;31(4):1316-1332.
Published online July 4, 2025; DOI: https://doi.org/10.3350/cmh.2025.0332

Background/Aims
The role of reactivation of human cytomegalovirus (HCMV) in determining outcomes of cirrhotic patients with acute decompensation (AD) is unknown. We aimed to investigate HCMV incidence and potential correlation with hepatic outcomes in AD patients.
Methods
Two prospective multicentre cohorts with AD patients were investigated. Patients in cohort 1 were recruited from 4 centres, while patients in cohort 2 were randomly selected from a second multicentre cohort. HCMV reactivation was established with quantitative real-time polymerase chain reaction assay in seropositive patients.
Results
HCMV reactivation was found in 35 patients from cohort 1 (n=722) and 14 from cohort 2 (n=291), with an incidence of 4.8% in both cohorts. Bacterial infection and liver failure were independently correlated with HCMV reactivation. HCMV reactivation was an independent predictor of 90-day mortality. Among bacterial infection populations in these two cohorts, patients with HCMV reactivation had worse prognosis compared to those without. Incidence of acute-on-chronic liver failure (ACLF) was higher in patients with HCMV reactivation compared to those without and was also independently correlated with development of ACLF. In a total of 49 HCMV reactivation cases, 8 patients were treated with ganciclovir, in whom a significantly lower 90-day mortality compared with those not treated was observed. All 3 patients who underwent liver transplantation with reactivation of HCMV died.
Conclusions
In AD patients, HCMV reactivation was common, especially in those with bacterial infection or liver failure, and they were more prone to having ACLF and 90‑day mortality. The data propose the need for active surveillance for HCMV infection in AD patients.

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Review

Tracking the trajectory of kidney dysfunction in cirrhosis: the acute kidney injury: chronic kidney disease spectrum: Vishnu Girish, Rakhi Maiwall; Clin Mol Hepatol 2025;31(3):730-752.
Published online March 26, 2025; DOI: https://doi.org/10.3350/cmh.2024.1060

Abstract
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Kidney disease in cirrhosis is now viewed as a continuum encompassing acute kidney injury (AKI), acute kidney disease (AKD), and chronic kidney disease (CKD), rather than three different disorders. Contemporary diagnostic criteria for AKI integrate urine output (UO) parameters and acknowledge the intricate relationship and possibility of overlap between functional and structural as well as acute and chronic entities, including hepatorenal syndrome (HRS). AKI demonstrates a propensity for progression to AKD and CKD, particularly in the context of recurrent and severe insults. The diagnostic complexity is further compounded by limitations in serum creatinine measurements, prompting the integration of novel biomarkers and the need to accurately estimate glomerular filtration rate. The diagnosis, phenotyping, and management of AKI should be prompt and early; the initial step should always be volume and UO assessment. A personalized approach is needed and the possibility of co-existing structural or functional kidney disease should be borne in mind. The earlier concept of waiting for 48 hours to diagnose HRS has evolved and early diagnosis and prompt treatment are advised now. Kidney replacement therapy and simultaneous liver and kidney transplantation may be required in resistant cases.

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Association between the C-reactive protein–triglyceride–glucose index (CTI) and the risk of acute kidney injury in critically ill patients with cirrhosis
Lu-Huai Feng, Tianbao Liao, Tingting Su, Xuefei Zhou, Yang Lu, Lina Huang, Zhenhua Yang
BMC Nephrology.2025;[Epub] CrossRef

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Original Article

Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures for early mortality in acute liver failure: Neha Sharma, Sushmita Pandey, Gaurav Tripathi, Manisha Yadav, Nupur Sharma, Babu Mathew, Abhishak Gupta, Vasundhra Bindal, Sadam H. Bhat, Yash Magar, Rimsha Saif, Sanju Yadav, Amritpal Kaur, Rakhi Maiwall, Shvetank Sharma, Shiv Kumar Sarin, Jaswinder Singh Maras; Clin Mol Hepatol 2025;31(4):1233-1251.
Published online December 13, 2024; DOI: https://doi.org/10.3350/cmh.2024.0554

Background/Aims
Acute liver failure (ALF) has high mortality predominantly due to compromised immune system and increased vulnerability to bacterial and fungal infections.
Methods
Plasma lipidome and fungal peptide-based community (mycobiome) analysis were performed in discovery cohort (ALF=40, healthy=5) and validated in a validation cohort of 230 patients with ALF using high-resolution-mass-spectrometry, artificial neural network (ANN) and machine learning (ML).
Results
Untargeted lipidomics identified 2,013 lipids across 8 lipid group. 5 lipid-species—phosphatidylcholine (PC)[15:0/17:0], PC[20:1/14:1], PC[26:4/10:0], PC[32:0] and TG[4:0/10:0/23:6]—significantly differentiated ALF-NS (FC>10, P<0.05, FDR<0.01). Mycobiome alpha/beta diversity was significantly higher and showed 4 phyla and >20 species significantly dysregulated in ALF-NS linked with lipid metabolism, fatty acid elongation in ER, and others (P<0.05). Lipid and mycobiome diversity values in ALF-NS were strongly correlated (r²>0.7, P<0.05). Multi-modular correlation network showed striking associations between lipid, fungal peptide modules, and clinical parameters specific to ALF-NS (P<0.05). Cryptococcus amylolentus CBS6039 and Penicillium oxalicum 1142 directly correlated with phosphatidylcholine, triglycerides, and severity in ALF-NS (r²>0.85, P<0.05). POD-fungus and POD-lipids showed direct association with infection, necrosis, and hepatic encephalopathy (Beta>1.2, P<0.05). POD-lipid (AUC=0.969 and HR=1.99 [1.02–2.04]) superseded POD-fungus and severity indices for early-mortality prediction. Finally, significant increase in PC (15:0/17:0) level showed highest normalized importance, and ANNs and ML predicted early mortality with >95% accuracy, sensitivity, and specificity. Interestingly, fungal surveillance protein Clec7a was significantly downregulated (>2-fold), leading to a notable increase in fungal infection-mediated choline/phosphatidylcholine and associated enzymes (FC>1.5; Kennedy cycle). This contributed to phosphatidic acid-mediated hyper-inflammation in ALF-NS.
Conclusions
In ALF, the plasma lipidome and mycobiome are dysregulated. Increased circulating phosphatidylcholine could stratify ALF predisposed to early mortality or require emergency liver transplantation.

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Reviews

Liver Transplantation

Prediction and management of small-for-size syndrome in living donor liver transplantation: Jia-hao Law, Alfred Wei-Chieh Kow; Clin Mol Hepatol 2025;31(Suppl):S301-S326.
Published online December 10, 2024; DOI: https://doi.org/10.3350/cmh.2024.0870

Abstract
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Small-for-size syndrome (SFSS) remains a critical challenge in living donor liver transplantation (LDLT), characterized by graft insufficiency due to inadequate liver volume, leading to significant postoperative morbidity and mortality. As the global adoption of LDLT increases, the ability to predict and manage SFSS has become paramount in optimizing recipient outcomes. This review provides a comprehensive examination of the pathophysiology, risk factors, and strategies for managing SFSS across the pre-, intra-, and postoperative phases. The pathophysiology of SFSS has evolved from being solely volume-based to incorporating portal hemodynamics, now recognized as small-for-flow syndrome. Key risk factors include donor-related parameters like age and graft volume, recipient-related factors such as MELD score and portal hypertension, and intraoperative factors related to venous outflow and portal inflow modulation. Current strategies to mitigate SFSS include careful graft selection based on graft-to-recipient weight ratio and liver volumetry, surgical techniques to optimize portal hemodynamics, and novel interventions such as splenic artery ligation and hemiportocaval shunts. Pharmacological agents like somatostatin and terlipressin have also shown promise in modulating portal pressure. Advances in 3D imaging and artificial intelligence-based volumetry further aid in preoperative planning. This review emphasizes the importance of a multifaceted approach to prevent and manage SFSS, advocating for standardized definitions and grading systems. Through an integrated approach to surgical techniques, hemodynamic monitoring, and perioperative management, significant strides can be made in improving the outcomes of LDLT recipients. Further research is necessary to refine these strategies and expand the application of LDLT, especially in challenging cases involving small-for-size grafts.

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Simultaneous Splenic Artery Ligation During Adult Orthotopic Liver Transplantation Improves Surgical Outcomes
Zichen Wang, Zhan Qu, Fan Mu, Lexuan Xu, Liangshuo Hu, Bo Wang, Jianhua Shi
World Journal of Surgery.2025; 49(10): 2909. CrossRef

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Hepatitis E as a trigger for acute-on-chronic liver failure: Maria Buti, Juan Carlos Ruiz-Cobo, Rafael Esteban, Mar Riveiro-Barciela; Clin Mol Hepatol 2025;31(Suppl):S196-S204.
Published online November 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0758

Abstract
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Acute hepatitis E virus (HEV) infection is typically self-limiting and has a favourable prognosis. However, certain populations such as patients with pre-existing chronic liver disease may experience severe manifestations, including progression to acute-on-chronic liver failure (ACLF). Among viral hepatitis types, hepatitis A, E, and B are major causes of ACLF. Active screening and early diagnosis of HEV infection in patients with cirrhosis, especially those who develop ACLF, can improve management and enable timely antiviral therapy. Preventive measures, including HEV vaccination for high-risk groups, could reduce the morbidity and mortality associated with hepatitis E.

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Efficacy and safety of mesenchymal stem cell therapy in acute on chronic liver failure: a systematic review and meta-analysis of randomized controlled clinical trials
Wenming Lu, Longxiang Yan, Lulu Peng, Xuesong Wang, Xingkun Tang, Jing Du, Jing Lin, Zhengwei Zou, Lincai Li, Junsong Ye, Lin Zhou
Stem Cell Research & Therapy.2025;[Epub] CrossRef
Hepatitis A and E Viruses Are Important Agents of Acute Severe Hepatitis in Asia: A Narrative Review
Reina Sasaki-Tanaka, Tatsuo Kanda, Takeshi Yokoo, Hiroyuki Abe, Kazunao Hayashi, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai
Pathogens.2025; 14(5): 454. CrossRef
The role of bacterial outer membrane vesicles in inflammatory response of acute-on-chronic liver failure
Xiaojing Qin, Shuang Wang, Zhanyao Yan, Ninghui Zhao, Jia Yao
Frontiers in Microbiology.2025;[Epub] CrossRef
Ribavirina como tratamiento de hepatitis E aguda grave sobre hepatopatía crónica: experiencia clínica
Alba Rabadán Mata, María Dolores Antón Conejero, José María Paredes Arquiola
Medicina Clínica.2025; 165(6): 107187. CrossRef
Ribavirin as a treatment for severe acute hepatitis E on chronic liver disease: Clinical experience
Alba Rabadán Mata, María Dolores Antón Conejero, José María Paredes Arquiola
Medicina Clínica (English Edition).2025; : 107187. CrossRef

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Correspondence

Acute liver injury and Acute liver failure

Correspondence to editorial on “Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment”: Do Seon Song, Dong Joon Kim; Clin Mol Hepatol 2024;30(4):1012-1015.
Published online June 18, 2024; DOI: https://doi.org/10.3350/cmh.2024.0448

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Editorial

Acute liver injury and Acute liver failure

Modified quick-SOFA score: Can it enhance prognostic assessment for hospitalized patients with chronic liver diseases?: Editorial on “Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment”: Simone Incicco, Salvatore Piano; Clin Mol Hepatol 2024;30(4):695-697.
Published online June 3, 2024; DOI: https://doi.org/10.3350/cmh.2024.0409

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RAC1 as a novel therapeutic target for acute liver failure
Barbara Bueloni, Esteban Fiore, María José Cantero, Lucia Lameroli, Catalina Atorrasagasti, Matías Ciarlantini, Andrea Barquero, Lucía Gandolfi Donadio, Daiana Ganiewich, Francisco Orozco, Martín Fauda, Julieta Comin, Ali Canbay, Juan Bayo, Guillermo Mazz
JHEP Reports.2025; 7(11): 101547. CrossRef
Correspondence to editorial on “Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment”
Do Seon Song, Dong Joon Kim
Clinical and Molecular Hepatology.2024; 30(4): 1012. CrossRef

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Original Article

Acute liver injury and Acute liver failure

Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment: Do Seon Song, Hee Yeon Kim, Young Kul Jung, Tae Hyung Kim, Hyung Joon Yim, Eileen L Yoon, Ki Tae Suk, Jeong-ju Yoo, Sang Gyune Kim, Moon Young Kim, Young Chang, Soung Won Jeong, Jae Young Jang, Sung-Eun Kim, Jung-Hee Kim, Jung Gil Park, Won Kim, Jin Mo Yang, Dong Joon Kim, Korean Acute-on-Chronic Liver Failure (KACLiF) study group, Ashok Kumar Choudhury, Vinod Arora, Shiv Kumar Sarin, APASL ACLF Research Consortium (AARC) for APASL ACLF working party; Clin Mol Hepatol 2024;30(3):388-405.
Published online April 11, 2024; DOI: https://doi.org/10.3350/cmh.2023.0563

Background/Aims
Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF).
Methods
We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high.
Results
Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353–5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484– 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC).
Conclusions
Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.

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Emergency living donor liver transplantation
Jongman Kim
Annals of Liver Transplantation.2025; 5(1): 27. CrossRef
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Hankil Lee, Sang Hoon Ahn, Beom Kyung Kim
Yonsei Medical Journal.2025; 66(11): 713. CrossRef
Living versus deceased donor liver transplantation in highly urgent patients using Korean national data
Jongman Kim, Sang Jin Kim, Kyunga Kim, YoungRok Choi, Geun Hong, Jun Yong Park, Young Seok Han, Nam-Joon Yi, Soon-Young Kim, Jung-Bun Park, Youngwon Hwang, Dong-Hwan Jung
Annals of Liver Transplantation.2025; 5(2): 115. CrossRef
Predicting risk factors for waiting mortality in adult emergent living donor liver transplantation based on Korean national data
Sang Jin Kim, Jongman Kim, Kyunga Kim, Soon-Young Kim, Jung-Bun Park, Youngwon Hwang, Dong-Hwan Jung
Annals of Liver Transplantation.2025; 5(2): 107. CrossRef
Correspondence to editorial on “Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment”
Do Seon Song, Dong Joon Kim
Clinical and Molecular Hepatology.2024; 30(4): 1012. CrossRef
Modified quick-SOFA score: Can it enhance prognostic assessment for hospitalized patients with chronic liver diseases?: Editorial on “Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure a
Simone Incicco, Salvatore Piano
Clinical and Molecular Hepatology.2024; 30(4): 695. CrossRef
Revisiting septic shock in cirrhosis: a call for personalized management
Vishnu Girish, Rakhi Maiwall
Expert Review of Gastroenterology & Hepatology.2024; 18(12): 795. CrossRef

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7 Web of Science
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Review

Acute liver injury and Acute liver failure

Acute-on-chronic liver failure: Terminology, mechanisms and management: Vinay Kumar BR, Shiv Kumar Sarin; Clin Mol Hepatol 2023;29(3):670-689.
Published online March 20, 2023; DOI: https://doi.org/10.3350/cmh.2022.0103

Abstract
PDF

Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the "Golden Window" period of 7 days, gives an opportunity for reversal of the syndrome. Scores like the Asian Pacific Association for the Study of the Liver (APASL) ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF-C ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade hepatic encephalopathy, and in the absence of >2 organ failure or overt sepsis to improve survival of up to 80% at five years. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation.

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Original Article

Decreased vitamin D-binding protein level portends poor outcome in acute-on-chronic liver failure caused by hepatitis B virus: Daxian Wu, Qunfang Rao, Zhongyang Xie, Xiaoqing Zhu, Yuanmei Che, Jian Wu, Hainv Gao, Jingyu Zhang, Zhouhua Hou, Xiaoyu Cheng, Zeyu Sun; Clin Mol Hepatol 2022;28(4):912-925.
Published online July 28, 2022; DOI: https://doi.org/10.3350/cmh.2022.0121

Background/Aims
Acute-on-chronic liver failure (ACLF) is a catastrophic illness. Few studies investigated the prognostic value of vitamin D-binding protein (VDBP) for hepatitis B virus (HBV)-related ACLF (HBV-ACLF) resulted in conflicting results.
Methods
Two prospective HBV-ACLF cohorts (n=287 and n=119) were enrolled to assess and validate the prognostic performance of VDBP.
Results
VDBP levels in the non-survivors were significantly lower than in the survivors (P<0.001). Multivariate Cox regression demonstrated that VDBP was an independent prognostic factor for HBV-ACLF. The VDBP level at admission gradually decreased as the number of failed organs increased (P<0.001), and it was closely related to coagulation failure. The areas under the receiver operating characteristic curve (AUCs) of the Child-Pugh-VDBP and chronic liver failuresequential organ failure assessment (CLIF–SOFA)-VDBP scores were significantly higher than those of Child-Pugh (P<0.001) and CLIF-SOFA (P=0.0013). The AUCs of model for end-stage liver disease (MELD)-VDBP were significantly higher than those of MELD (P= 0.0384) only in the case of cirrhotic HBV-ACLF patients. Similar results were validated using an external multicenter HBV-ACLF cohort. By longitudinal observation, the VDBP levels gradually increased in survivors (P=0.026) and gradually decreased in non-survivors (P<0.001). Additionally, the VDBP levels were found to be significantly decreased in the deterioration group (P=0.012) and tended to be decreased in the fluctuation group (P=0.055). In contrast, they showed a significant increase in the improvement group (P=0.036).
Conclusions
The VDBP was a promising prognostic biomarker for HBV-ACLF. Sequential measurement of circulating VDBP shows value for the monitoring of ACLF progression.

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Liver fibrosis, cirrhosis, and portal hypertension

Acute on chronic liver failure in cirrhosis: Marta Tonon, Salvatore Piano; Clin Mol Hepatol 2022;28(2):273-275.
Published online February 14, 2022; DOI: https://doi.org/10.3350/cmh.2022.0036

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Editorial

Acute liver injury and Acute liver failure

Acute-on-chronic liver failure: A predictor of poor prognosis in patients with variceal bleeding or a risk factor for variceal bleeding?: Nae-Yun Heo; Clin Mol Hepatol 2020;26(4):487-488.
Published online October 1, 2020; DOI: https://doi.org/10.3350/cmh.2020.0209

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Clinical and Molecular Hepatology.2022; 28(3): 540. CrossRef

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Original Article

Acute liver injury and Acute liver failure

Acute-on-chronic liver failure as a major predictive factor for mortality in patients with variceal bleeding: Jongbeom Shin, Jung Hwan Yu, Young-Joo Jin, Hyung Joon Yim, Young Kul Jung, Jin Mo Yang, Do Seon Song, Young Seok Kim, Sang Gyune Kim, Dong Joon Kim, Ki Tae Suk, Eileen L. Yoon, Sang Soo Lee, Chang Wook Kim, Hee Yeon Kim, Jae Young Jang, Soung Won Jeong, on Behalf of the Korean Acute-onChronic Liver Failure (KACLiF) Study Group; Clin Mol Hepatol 2020;26(4):540-553.
Published online September 17, 2020; DOI: https://doi.org/10.3350/cmh.2020.0034

Background/Aims
This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients.
Methods
This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium.
Results
Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P<0.001), and patients with higher ACLF grades had a lower OS rate (P<0.001). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score was identified as a significant prognostic factor in patients hospitalized with variceal bleeding (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.30–1.50; P<0.001), even in ACLF patients with variceal bleeding (HR, 1.32; 95% CI, 1.19–1.46, P<0.001). Concerning the prediction of the mortality risk at 28- and 90-day using CLIF-SOFA scores, c-statistics were 0.895 (95% CI, 0.829–0.962) and 0.897 (95% CI, 0.842–0.951), respectively, and the optimal cut-off values were 6.5 and 6.5, respectively.
Conclusions
In cirrhotic patients hospitalized with variceal bleeding, the prognosis was poor when accompanied by ACLF, especially depending upon CLIF-SOFA score. CLIF-SOFA model well predicted the 28-day or 90-day mortality for cirrhotic patients who experienced variceal bleeding.

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Reviews

Acute liver injury and Acute liver failure

The fibrogenic process and the unleashing of acute-on-chronic liver failure: Guillermo Nahúm López-Sánchez, Mayra Dóminguez-Pérez, Misael Uribe, Natalia Nuño-Lámbarri; Clin Mol Hepatol 2020;26(1):7-15.
Published online June 14, 2019; DOI: https://doi.org/10.3350/cmh.2019.0011

Abstract
PDF

Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by a rapid deterioration of previously well-compensated chronic liver diseases. One of the main obstacles in ACLF is the lack of knowledge of the pathogenesis and specific broad-spectrum treatments. An excessive systemic inflammatory response has been proposed to explain the pathogenesis of ACLF; this hypothesis involves stellate cells, which are implicated in many liver homeostatic functions that include vitamin A storage, regulation of sinusoidal blood flow, local inflammation, maintenance of the hepatocyte phenotype and extracellular matrix remodeling. However, when there is damage to the liver, these cells are the main target of the inflammatory stimulus, as a result, the secretion of the extracellular matrix is altered. Activated hepatic stellate cells raise the survival of neutrophils by the stimulation of granulocytes colonies and macrophages, which exacerbates liver inflammation and promotes damage to hepatocytes. Elevation of pathogen-associated molecular patterns is related to liver damage by different pathophysiological mechanisms of decompensation, showing ballooning degeneration and cell death with a predominance of cholestatic infection. Moreover, patients with ACLF present a marked elevation of C-reactive protein together with an elevation of the leukocyte count. Chronic liver disease is a complex pathological state with a heterogeneous pathophysiology in which genetic factors of the host and external triggers interact and culminate in hepatic insufficiency. The better understanding of such interactions should lead to a better comprehension of the disease and to the discovery of new treatment targets that will make acute decompensations preventable and even decrease mortality.

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Alcohol-related liver disease

Severe acute alcoholic hepatitis and liver transplant: A never-ending mournful story: Aiman Obed, Abdalla Bashir, Steffen Stern, Anwar Jarrad; Clin Mol Hepatol 2018;24(4):358-366.
Published online October 24, 2018; DOI: https://doi.org/10.3350/cmh.2018.0044

Abstract
PDF

Severe acute alcoholic liver disease (SAAH) unresponsive to medical therapy shows one-year-mortality rates of up to 90%. Most transplant centers request six months of alcohol abstinence prior to transplantation, the so-called “6-month rule.” This regulation is not based on strong evidence, repeatedly making it a topic of controversial debates. The majority of patients with SAAH will die before fulfilling the 6-month rule. Therefore, liver transplantation (LT) protocols are becoming more flexible towards the rigid abstinence regulation, especially concerning SAAH patients. We conducted a literature review regarding LT in SAAH and its outcomes, including post-transplant mortality and recidivism. We studied available data on PubMed from 2011 and onwards whilst including articles dealing with genetic components, medical therapy and historic snapshots of alcoholism. Emerging studies recommend LT in SAAH not responding to medical therapies even without realizing the required abstinence period, since the majority of these patients would die within 6 months. SAAH without response to medical therapy has one-year-mortality rates of up to 90%. The 6-month rule is not based on strong evidence and is repeatedly a topic of controversial debates. There is genetic linkage to alcoholism and medical therapy is not as effective as estimated, yet. The 6-months-regulation has not shown to evidently decrease the risk of recidivism post-LT, which is a lifesaving treatment in SAAH patients. Insisting on rigid sobriety rules results in excluding patients with a low risk of recidivism from being transplanted. Moreover, the genetic linkage of alcoholism must be recognized.

Citations

Citations to this article as recorded by

Early liver transplantation for severe alcohol-associated hepatitis: A single-center experience
A Asgharpour, RK Sterling, E Smirnova, N Duong, K Houston, H Khan, Keller Nicole, S Matherly, J Wedd, H Lee, MS Siddiqui, V Patel, S Bullock, S Weinland, V Kumaran, S Lee, A Sharma, D Imai, A Kahn, M Levy, D Bruno
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Trasplante en la enfermedad hepática por alcohol
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Hepatología.2021; : 199. CrossRef
Outcome of patients with severe alcoholic hepatitis after Model for End-Stage Liver Disease-based allocation system implementation in Korea
Tae Jin Kwon, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Dong Hyun Sinn, Seung Woon Paik
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Early Liver Transplantation for Severe Alcoholic Hepatitis
Jessica L. Mellinger, Jonathan G. Stine
Digestive Diseases and Sciences.2020; 65(6): 1608. CrossRef
Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope
Khushboo S. Gala, Vatsalya Vatsalya
Cells.2020; 9(3): 524. CrossRef
Das „framing“ der sechsmonatigen Karenzregel in der Lebertransplantation. Ein Beispiel für sprachlich vermittelte Deutungsmuster zur Eingrenzung des Indikationsgebietes
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Ethik in der Medizin.2020; 32(3): 239. CrossRef

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Case Report

Viral hepatitis

Favorable effect of corticosteroids in treating acute-on-chronic liver failure underlying chronic hepatitis B: Hyeji Kim, Jung Hyun Kwon, Yong Hee Kim, Soon Woo Nam, Jong Yul Lee, Jeong Won Jang; Clin Mol Hepatol 2018;24(4):430-435.
Published online November 27, 2017; DOI: https://doi.org/10.3350/cmh.2017.0016

Abstract
PDF

Acute-on-chronic liver failure (ACLF) occurs in the presence of a chronic liver disease or cirrhosis, and often results from exacerbation of chronic hepatitis B (CHB). The efficacy of corticosteroid treatment in ACLF patients with underlying CHB remains unclear. We report the case of a 50-year-old woman who experienced ACLF due to CHB exacerbation and was treated with a combination of corticosteroids and nucleot(s)ide analogue (NUC). The patient showed rapid decompensation due to CHB exacerbation. Three months of antiviral therapy produced no improvement in liver function. Combination therapy with corticosteroids and NUC was started, which did result in improvement of liver function. This case shows that the combined therapy of corticosteroids and NUC can be effective in treating ACLF due to CHB exacerbation.

Citations

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Parag Jain, Akanksha Jain, Rohitas Deshmukh, Pradeep Samal, Trilochan Satapathy, Ajazuddin
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Hypomethylation of thymosin β4 promoter is associated with glucocorticoid therapy in patients with acute-on-chronic hepatitis B-induced liver failure
He Wang, Yu Qian, Jing-Wen Wang, Yu Fang, Yu-Chen Fan, Hui-Hui Liu, Kai Wang
International Health.2023; 15(1): 19. CrossRef
Critically Ill COVID-19 Patient with Chronic Liver Disease - Insights into a Comprehensive Liver Intensive Care
Cyriac Abby Philips, Kamna Kakkar, Moby Joseph, Praveen Kumar Yerol, Rizwan Ahamed, Sasidharan Rajesh, Philip Augustine
Journal of Clinical and Translational Hepatology.2021; 000(000): 000. CrossRef

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Original Article

Viral hepatitis

Static and dynamic prognostic factors for hepatitis-B-related acute-on-chronic liver failure: Jung Min Ha, Won Sohn, Ju Yeon Cho, Jeung Hui Pyo, Kyu Choi, Dong Hyun Sinn, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Chul Koh, Seung Woon Paik, Byung Chul Yoo, Yong-Han Paik; Clin Mol Hepatol 2015;21(3):232-241.
Published online September 30, 2015; DOI: https://doi.org/10.3350/cmh.2015.21.3.232

Abstract
PDF

Background/Aims

Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission.

Methods

Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals.

Results

A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (≥28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (≥grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016).

Conclusions

Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.

Citations

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Plasma galectin-3 can be considered as a non-invasive marker to predict the prognosis of ACLF patients with new typing
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KASL clinical practice guidelines for management of chronic hepatitis B

Clinical and Molecular Hepatology.2022; 28(2): 276. CrossRef
A dynamic prediction model for prognosis of acute-on-chronic liver failure based on the trend of clinical indicators
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KASL clinical practice guidelines for management of chronic hepatitis B

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A Dynamic Model for Predicting Outcome in Patients with HBV Related Acute-On-Chronic Liver Failure
Wei Lin, Jing Zhang, Xiaohui Liu, Hongqun Liu, Jinqiu He, Ming Li, Shuqin Zhang, Hong Chen, Changqing Zhang, Wenfang Wu, Chenggang Jin, Samuel S. Lee, Zhongping Duan, Yuexin Zhang
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Review

Acute liver injury and Acute liver failure

Acute-on-chronic liver failure: Tae Yeob Kim, Dong Joon Kim; Clin Mol Hepatol 2013;19(4):349-359.
Published online December 28, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.4.349

Abstract
PDF

Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with chronic liver disease. Although there are no widely accepted diagnostic criteria for ACLF, the Asia.Pacific Association for the Study of the Liver (APASL) and the American Association for the Study of Liver Disease and the European Association for the Study of the Liver (AASLD/EASL) consensus definitions are commonly used. It is obvious that the APASL and the AASLD/EASL definitions are based on fundamentally different features. Two different definitions in two different parts of the world hamper the comparability of studies. Recently, the EASL-Chronic Liver Failure Consortium proposed new diagnostic criteria for ACLF based on analyses of patients with organ failure. There are areas of uncertainty in defining ACLF, such as heterogeneity of ACLF, ambiguity in qualifying underlying liver disease, argument for infection or sepsis as a precipitating event, etc. Although the exact pathogenesis of ACLF remains to be elucidated, alteration of host response to injury, infection, and unregulated inflammation play important roles. The predisposition, infection/inflammation, response, organ failure (PIRO) concept used for sepsis might be useful in describing the pathophysiology and clinical categories for ACLF. Treatment strategies are limited to organ support but better understanding of the pathophysiology is likely to lead to discovery of novel biomarkers and therapeutic strategies in the future.

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Sara Blasco-Algora
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Case Reports

Liver Transplantation

Liver transplantation for acute-on-chronic liver failure from erythropoietic protoporphyria: Pyoung-Jae Park, Shin Hwang, Young-Il Choi, Young-Dong Yu, Gil-Chun Park, Sung-Won Jung, Sam-Youl Yoon, Gi-Won Song, Tae-Yong Ha, Sung-Gyu Lee; Korean J Hepatol 2012;18(4):411-415.
Published online December 21, 2012; DOI: https://doi.org/10.3350/cmh.2012.18.4.411

Abstract
PDF

Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway that is characterized by accumulation of protoporphyrin in the blood, erythrocytes, and tissues, and cutaneous manifestations of photosensitivity, all resulting from abnormalities in ferrochelatase (FECH) activity due to mutations in the FECH gene. Protoporphyrin is excreted by the liver, and excess protoporphyrin leads to cholelithiasis with obstructive episodes and chronic liver disease, finally progressing to liver cirrhosis. Patients with end-stage EPP-associated liver disease require liver transplantation. We describe here a 31-year-old male patient with EPP who experienced acute-on-chronic liver failure and underwent deceased-donor liver transplantation. Surgical and postoperative care included specific shielding from exposure to ultraviolet radiation to prevent photosensitivity-associated adverse effects. The patient recovered uneventfully and was doing well 24 months after transplantation. Future prevention and treatment of liver disease are discussed in detail.

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Treatment strategy for erythropoietic protoporphyria accompanied by severe abdominal pain and liver injury
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Antonio Fontanellas, Matías A. Ávila, Karl E. Anderson, Jean-Charles Deybach
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Naoyuki Fujimori, Michiharu Komatsu, Naoki Tanaka, Mai Iwaya, Hajime Nakano, Ayumi Sugiura, Tomoo Yamazaki, Soichiro Shibata, Yugo Iwaya, Takashi Muraki, Yuki Ichikawa, Takefumi Kimura, Satoru Joshita, Takeji Umemura, Akihiro Matsumoto, Eiji Tanaka
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Les porphyries héréditaires : anomalies du métabolisme de l’hème
K. Peoc’h, C. Martin-Schmitt, N. Talbi, J.-C. Deybach, L. Gouya, H. Puy
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Porphyrias: A 2015 update
Zoubida Karim, Said Lyoumi, Gael Nicolas, Jean-Charles Deybach, Laurent Gouya, Hervé Puy
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Viral hepatitis

A fatal case of hepatitis B virus (HBV) reactivation during long-term, very-low-dose steroid treatment in an inactive HBV carrier: Joong Ho Bae, Joo Hyun Sohn, Hye Soon Lee, Hye Sun Park, Yil Sik Hyun, Tae Yeob Kim, Chang Soo Eun, Yong Cheol Jeon, Dong Soo Han; Korean J Hepatol 2012;18(2):225-228.
Published online June 26, 2012; DOI: https://doi.org/10.3350/cmh.2012.18.2.225

Abstract
PDF

Hepatitis B virus (HBV) may be reactivated after chemotherapy or immunosuppressive therapy, and therefore administration of antiviral agents before such treatment is recommended. Most reported cases of reactivation are associated with high doses of immunosuppressive agents or combination therapy. We present a case of a previously inactive HBV carrier with an acute severe flare-up during a long-term, very-low-dose (2.5 mg/day) steroid treatment for rheumatoid arthritis. We suggest that even a minimal dose of single-regimen oral steroid can cause reactivation of indolent, inactive HBV.

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Effect of Low-Dose Corticosteroid Use on HBV Reactivation in HBsAg-positive Rheumatoid Arthritis Patients
Wooseong Jeong, Jung-Yoon Choe, Byung-Cheol Song, Chang-Keun Lee, Hoon-Suk Cha, Byeongzu Ghang, Jinseok Kim
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Anil Arora, Anil C. Anand, Ashish Kumar, Shivaram P. Singh, Rakesh Aggarwal, Radha K. Dhiman, Shyam Aggarwal, Seema Alam, Pradeep Bhaumik, Vinod K. Dixit, Ashish Goel, Bhabadev Goswami, Ashok Kumar, Manoj Kumar, Kaushal Madan, Natarajan Murugan, Aabha Nag
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Original Article

Factors influencing the severity of acute viral hepatitis A: Joo Il Kim, Yun Soo Kim, Young Kul Jung, Oh Sang Kwon, Yeon Suk Kim, Yang Suh Ku, Duck Joo Choi, Ju Hyun Kim; Korean J Hepatol 2010;16(3):295-300.
Published online September 30, 2010; DOI: https://doi.org/10.3350/kjhep.2010.16.3.295

Abstract
PDF

Background/Aims

Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A.

Methods

We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups.

Results

The incidence of fulminant hepatitis was 1.4% (10/713) in patients with acute hepatitis A. Thirty-three (4.6%) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers.

Conclusions

While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection.

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Review

Acute Liver failure in Korea: etiology, prognosis and treatment: Young Suk Lim; Korean J Hepatol 2010;16(1):5-18.
Published online March 26, 2010; DOI: https://doi.org/10.3350/kjhep.2010.16.1.5

Abstract
PDF

Acute liver failure (ALF) is a rare condition in which rapid deterioration of liver function results in altered mentation and coagulopathy in individuals without previously recognized liver disease. The outcomes of patients with ALF vary greatly according to etiology, and the etiology of ALF varies markedly by geographical region. In Korea, about 90% of ALF are associated with etiologies that usually result in poor outcomes, including hepatitis B virus (HBV) infection and herbal remedies. The main causes of death in patients with ALF are increased intracranial pressure, systemic infection, and multi-organ failure. Recent advances in the intensive care of patients with ALF have contributed to a marked improvement in their overall survival. Emergency adult to adult living-donor liver transplantation (LDLT) can be performed expeditiously and safely for patients with ALF, and greatly improves survival rate as well as deceased-donor transplantation. As the window during which transplantation is possible is limited, emergency adult LDLT should be considered to be one of the first-line treatment options in patients with ALF, especially in regions in which ALFs are caused by etiologies associated with poor outcome and the supply of organs is very limited. (Korean J Hepatol 2010;16:5-18)

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Original Article

Clinical features of patients with fulminant hepatitis A requiring emergency Liver transplantation: comparison with acute Liver failure due to other causes: Jin Dong Kim, M.D., Jong Young Choi, M.D., Chung-Hwa Park, M.D., Myeong Jun Song, M.D., Jeong Won Jang, M.D., Si Hyun Bae, M.D., Seung Kew Yoon, M.D., Young Sok Lee, M.D., Young Kyoung You, M.D.1, Dong Goo Kim, M.D.1; Korean J Hepatol 2010;16(1):19-28.
Published online March 26, 2010; DOI: https://doi.org/10.3350/kjhep.2010.16.1.19

Abstract
PDF

Background/Aims
According to recent prevalence of hepatitis A virus (HAV) infection, acute liver failure ALF) due to HAV infection is observed frequently in parallel. The aim of this study was to elucidate the clinical, laboratory, and pathologic features of patients who have undergone emergency liver transplantation (LT) due to fulminant HAV infection. Methods: Clinical, laboratory, and pathologic data of 11 transplant recipients with anti-HAV IgM-positive ALF between December 2007 and May 2009 were analyzed, and compared with data of 10 recipients who underwent LT for the management of ALF due to other causes. Results: The median age of the patients with HAV-related ALF was 34 years (range: 15-43 years). The levels of hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were higher and the level of bilirubin was lower in the HAV-related ALF group than in the other group (P=0.005, 0.001, 0.001, 0.010, and 0.003, respectively). The time from the onset of initial symptoms to the development of encephalopathy was shorter in the HAV-related ALF group than in the other group (median 5 days, range: 4-13 days; P<0.001). In patients with HAV-related ALF, laboratory findings and clinical prognostic parameters including the Acute Liver Failure Study Group prognostic index, King`s College criteria, and model for endstage liver disease (MELD) and Child-Pugh scores were not associated with the grade of hepatic encephalopathy or time of progression to encephalopathy. Conclusions: The results of this study indicate that the clinical condition of patients with HAV-related ALF requiring emergency LT aggravates rapidly. Prognostic parameters are not sufficient for discriminating transplant candidates in patients with fulminant hepatitis A. (Korean J Hepatol 2010;16:19-28)

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Current status of Liver diseases in Korea: Toxic and alcoholic Liver diseases: Kyung Ah Kim; Korean J Hepatol 2009;15(60):29-33.
Published online December 31, 2009; DOI: https://doi.org/10.3350/kjhep.2009.15.S6.S29

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Case Report

A Case of Fulminant Hepatic Failure Secondary to Hepatic Metastasis of Small Cell Lung Carcinoma: Young Tae Hwang, M.D.1, Jung Woo Shin, M.D.1, Jun Ho Lee, M.D.1, Dae Sung Hwang, M.D.1, Jun Bum Eum, M.D.1, Hye Jeong Choi, M.D.2, Neung Hwa Park, M.D.1; Korean J Hepatol 2007;13(4):565-570.
Published online December 20, 2007; DOI: https://doi.org/10.3350/kjhep.2007.13.4.565

Abstract
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Although liver metastasis is commonly found in cancer patients, fulminant hepatic failure secondary to diffuse cancer infiltration into the liver is rare. Liver metastasis-induced fulminant hepatic failure has been reported in patients with primary cancer of the gastrointestinal tract, breast and uroepithelium, and in patients with melanoma and hematologic malignancy. Small cell lung cancer is so highly invasive that hepatic metastasis is common, but rapid progression to fulminant hepatic failure is extremely rare. We report here on a case of a patient who died because of rapid progression to fulminant hepatic failure as a result of hepatic metastasis of small cell lung carcinoma. (Korean J Hepatol 2007;13:565-570)

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Reviews

Nonsurgical Management of Fulmninant Hepatic Failure - Hepatocyte transplantation and bioartificial liver -: Byung Ho Kim; Korean J Hepatol 1996;2(2):116-128.

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Background
Fulminant hepatic failure is a devastating process associated with high mortality, but no sequele after recovep. At the moment, there are no specific therapeutic modalities except for the orthotopic liver transplantation(OLT) which is limited to a small number of patients due to a lack of donor organ. Recently, several nonsurgical managements have been investigated to overcome the donor shortage and to bridge patients to OLT. These include artificial hepatic support systems, hepatocyte transplantation and extracorporeal liver support. Xenotransplantation is also being investigated to circumbent the donor shortage. Hepatocyte transplantation:The application of liver cell transplantation has been envisioned for temporary metabolic support during liver failure, provision of specific liver functions in inherited metabolic diseases of the liver and as a vehicle for ex vivo gene therapy. Potential advantages over OLT are that the procedure is simple, hepatoyctes can be cryopreserved for immediate use in need, the cost is less expensive and abrogation of allograft rejection may be easier by the modification of antigenicity during culture. Moreover, donor shortage can be overcome by the use of fetal hepatocytes, conditionally immortalized hepatocytes and possibly liver progenitor cells. However, the optimum route and the method are still being investigated. Recently, biodegradable matrix or cotransplantation with non-parencymal liver cells is used to improve and prolong the survival of transplanted hepatocytes in the peritoneum, and injection of donor type splenocytes into the thymus along with ablation of the peripheral lymphocytes with antilymphocyte globulin is adopted to tolerize the recipient to allogeneic hepatocytes. BioartiTicial liver:Presently, several bioartificial liver systems use mammalian hepatocytes held within cartridges, mostly hollow- fiber bioreactor perfused by plasma or whole blood. Plasma is separated from patient blood using Background:Fulminant hepatic failure is a devastating process associated with high mortality, but no sequele after recovep. At the moment, there are no specific therapeutic modalities except for the orthotopic liver transplantation(OLT) which is limited to a small number of patients due to a lack of donor organ. Recently, several nonsurgical managements have been investigated to overcome the donor shortage and to bridge patients to OLT. These include artificial hepatic support systems, hepatocyte transplantation and extracorporeal liver support. Xenotransplantation is also being investigated to circumbent the donor shortage. Hepatocyte transplantation:The application of liver cell transplantation has been envisioned for temporary metabolic support during liver failure, provision of specific liver functions in inherited metabolic diseases of the liver and as a vehicle for ex vivo gene therapy. Potential advantages over OLT are that the procedure is simple, hepatoyctes can be cryopreserved for immediate use in need, the cost is less expensive and abrogation of allograft rejection may be easier by the modification of antigenicity during culture. Moreover, donor shortage can be overcome by the use of fetal hepatocytes, conditionally immortalized hepatocytes and possibly liver progenitor cells. However, the optimum route and the method are still being investigated. Recently, biodegradable matrix or cotransplantation with non-parencymal liver cells is used to improve and prolong the survival of transplanted hepatocytes in the peritoneum, and injection of donor type splenocytes into the thymus along with ablation of the peripheral lymphocytes with antilymphocyte globulin is adopted to tolerize the recipient to allogeneic hepatocytes. BioartiTicial liver:Presently, several bioartificial liver systems use mammalian hepatocytes held within cartridges, mostly hollow- fiber bioreactor perfused by plasma or whole blood. Plasma is separated from patient blood using

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Artificial Liver Assist Devices: Won Choong Choi; Korean J Hepatol 2000;6(4):411-420.

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Original Article

Clinical Features of Fulminant Hepatic Failure in a Tertiary Hospital with a Liver Transplant Center in Korea: Nae Yun Heo , Young Suk Lim , Jeong Min Kang , Se Il Oh , Chan Sun Park , Seok Won Jung , Yoon Sun Lee , Kang Mo Kim , Han Chu Lee , Young Hwa Chung , Yung Sang Lee ,; Korean J Hepatol 2006;12(1):82-92.

Abstract
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Background/Aims: Striking geographic differences have been noted in the etiology of fulminant hepatic failure (FHF). The prognosis of patients with FHF who do not receive liver transplantation in a timely manner is quite dismal. This study intended to identify the etiology and outcome of FHF in Korean adults and to examine the role of urgent living-donor liver transplantation (LDLT) for treating this unique situation. Methods: We identified all the adult FHF patients who were referred to our unit between 1999 and 2004. FHF was defined as severe acute hepatitis complicated by the rapid development of hepatic encephalopathy within 8 weeks of the initial symptoms in the patients without a previous history of liver disease. Results: One hundred fourteen patients (47 males and 67 females) were identified. The mean age was 39.5±15.3 years. Drugs were the most common cause (28.1%) of FHF (herbal medications, 9.6%), and acute viral infection accounted for 23.7% (HBV accounted for 15.8%). Indeterminate etiologies were noted in 34%. The 90-day survival rate of the nontransplant group was only 15%. Fourteen patients received liver transplants (13 right- lobe LDLT, 1 cadaveric whole liver), and 12 of these (85.7%) survived and showed good graft function during 22 months of median follow-up. Conclusions: Although the causes of FHF in Korea were diverse, HBV infection and herbal medications were responsible for a significant proportion of the cases. Since urgent LDLT improved the overall survival rate of patients with FHF, this should be considered as an important treatment option for patients suffering with FHF. (Korean J Hepatol 2006;12:82-92)

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