Clinical and Molecular Hepatology

"Jin Mo Yang"

Correspondence

Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”: Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang; Clin Mol Hepatol 2026;32(1):e55-e57.
Published online April 15, 2025; DOI: https://doi.org/10.3350/cmh.2025.0379

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Original Articles

Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial: Hyung Joon Yim, Yeon Seok Seo, Ji Hoon Kim, Won Kim, Young Kul Jung, Jae Young Jang, Sae Hwan Lee, Yun Soo Kim, Chang Wook Kim, Hyoung Su Kim, Jae-Jun Shim, Eun-Young Cho, In Hee Kim, Byung Seok Lee, Jeong-Hoon Lee, Byung Seok Kim, Jeong Won Jang, Hyun Woong Lee, Jung Hyun Kwon, Moon Young Kim, Do Seon Song, Jung Gil Park, Yoon Seok Lee, Eileen L. Yoon, Han Ah Lee, Seong Hee Kang, Jin Mo Yang; Clin Mol Hepatol 2025;31(3):810-822.
Published online January 17, 2025; DOI: https://doi.org/10.3350/cmh.2024.0819

Background/Aims
Besifovir (BSV) showed comparable antiviral activity and superior safety profiles to tenofovir disoproxil fumarate (TDF) in treatment-naïve chronic hepatitis B (CHB). However, no data are available regarding the antiviral efficacy and safety of BSV in patients with CHB who switched from long-term TDF to BSV. This study aimed to evaluate the outcome of a 48-week BSV therapy in patients with CHB who switched from long-term TDF treatment.
Methods
In this non-inferiority trial, 153 CHB patients treated with TDF for ≥48 weeks who had hepatitis B virus (HBV) DNA <20 IU/mL were randomized to receive either BSV 150 mg or TDF 300 mg for 48 weeks.
Results
The per-protocol analysis included 130 patients (BSV group, 64; TDF group, 66). The median duration of TDF use before enrollment was 4.14 years. After 48 weeks, 100.0% and 98.5% patients in the BSV and TDF groups, respectively, met the primary endpoint (HBV DNA <20 IU/mL), demonstrating the non-inferior antiviral efficacy of BSV to TDF (95% confidence interval –0.01 to 0.04; P>0.999), with a predefined margin of –0.18. The mean percentage changes in estimated glomerular filtration rates were slightly better in the BSV group (1.67±11.73%) than in the TDF group (–1.24±11.02%). The BSV group showed a significant improvement in bone turnover biomarkers compared to the TDF group; accordingly, hip and spine bone mineral density increased in the BSV group.
Conclusions
In patients with CHB receiving long-term TDF, switching to BSV may improve renal and bone safety with non-inferior antiviral efficacy compared to that of maintaining TDF.

Citations

Citations to this article as recorded by

Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
Clinical and Molecular Hepatology.2026; 32(1): e55. CrossRef
Besifovir: a viable option for long-term disease control in chronic hepatitis B: Editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Wai-Kay Seto
Clinical and Molecular Hepatology.2026; 32(1): 374. CrossRef
Tenofovir amibufenamide in chronic hepatitis B: Lipid changes and 144-week safety with tenofovir disoproxil fumarate-to-tenofovir amibufenamide switch
Zhi-Hao Zeng, Jin-Qing Liu, Min Zhang, Cai-Liang Qiu, Zhen-Yu Xu
World Journal of Gastroenterology.2025;[Epub] CrossRef

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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.

Citations

Citations to this article as recorded by

Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management
S. K. Sarin, Ashok Choudhury, Anupam Kumar, Nadim Mahmud, G. H. Lee, Qin Ning, Soek-Siam Tan, Kessarin Thanapirom, Vinod Arora, Nobuaki Nakayama, Jun Li, Constantine J. Karvellas
Nature Reviews Gastroenterology & Hepatology.2026;[Epub] CrossRef
Outcomes of Highly Urgent ABO-Incompatible Living Donor Liver Transplantation in National Databases
Jongman Kim, Sang Jin Kim, Boram Park, Kyunga Kim, YoungRok Choi, Geun Hong, Jun Yong Park, Young Seok Han, Nam-Joon Yi, Seung Heui Hong, Soon-Young Kim, Jungbun Park, Youngwon Hwang, Dong-Hwan Jung
Journal of Korean Medical Science.2026;[Epub] CrossRef
Emergency living donor liver transplantation
Jongman Kim
Annals of Liver Transplantation.2025; 5(1): 27. CrossRef
Oral Branched-Chain Amino Acids as a Cost-Effective Option for Managing Hepatic Encephalopathy
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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Letter to the Editor

Liver fibrosis, cirrhosis, and portal hypertension

Letter regarding “Impacts of muscle mass dynamics on prognosis of outpatients with cirrhosis”: Do Seon Song, U Im Chang, Jin Mo Yang; Clin Mol Hepatol 2023;29(1):165-167.
Published online October 31, 2022; DOI: https://doi.org/10.3350/cmh.2022.0339

Citations

Citations to this article as recorded by

Correspondence on Letter regarding “Impacts of muscle mass dynamics on prognosis of outpatients with cirrhosis”
Tae Hyung Kim, Young Kul Jung, Hyung Joon Yim
Clinical and Molecular Hepatology.2023; 29(1): 173. CrossRef

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Original Articles

Liver fibrosis, cirrhosis, and portal hypertension

Association between serum tumor necrosis factor-α and sarcopenia in liver cirrhosis: Ji Won Han, Da In Kim, Hee Chul Nam, U Im Chang, Jin Mo Yang, Do Seon Song; Clin Mol Hepatol 2022;28(2):219-231.
Published online July 20, 2021; DOI: https://doi.org/10.3350/cmh.2021.0082

Background/Aims
Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear.
Methods
Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease.
Results
LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues.
Conclusions
These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

Citations

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Shuangshuang Zhang, Tian Zhou, Mingbo Wu, Xuanxuan Xiong
European Journal of Gastroenterology & Hepatology.2025; 37(1): 100. CrossRef
Changes in serum myostatin levels among patients with type C liver cirrhosis treated with direct‐acting antivirals
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He Sun, Kai Song, Ze-Yu Zhou, Bin Tu, Yang Zhou, Li-Chan Lin, Zhi-Yan Liu, Zhen-Yu Liu, Ji-Ming Sha, Yan Shi, Jing-Jing Yang, Dong Lu, Jian-Yuan Zhao, Hui Tao
JACC: Basic to Translational Science.2025; 10(5): 612. CrossRef
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Thomas Worland, Penelope Hey, Darren Wong, Ross Apostolov, Roseanne Kimberley Chan, Marie Sinclair, Paul Gow
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npj Gut and Liver.2025;[Epub] CrossRef
Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCC
Hee Sun Cho, Soon Kyu Lee, Ji Won Han, Jung Hyun Kwon, Soon Woo Nam, Jaejun Lee, Keungmo Yang, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, Jong Young Choi
Frontiers in Immunology.2025;[Epub] CrossRef
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Qi Zhou, Peiyan Liu, Lixiang Li, Tengfei Yin, Hao Bai, Yanqing Li
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Interaction between sarcopenia and nonalcoholic fatty liver disease
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Viral hepatitis

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial: Do Seon Song, Won Kim, Sang Hoon Ahn, Hyung Joon Yim, Jae Young Jang, Young Oh Kweon, Yong Kyun Cho, Yoon Jun Kim, Gun Young Hong, Dong Joon Kim, Young Kul Jung, Joo Hyun Sohn, Jin-Woo Lee, Sung Jae Park, Byung Seok Lee, Ju Hyun Kim, Hong Soo Kim, Seung Kew Yoon, Moon Young Kim, Kwan Sik Lee, Young Suk Lim, Wan Sik Lee, Jin Mo Yang, Kyun-Hwan Kim, Kwang-Hyub Han, Soon Ho Um; Clin Mol Hepatol 2021;27(2):346-359.
Published online January 25, 2021; DOI: https://doi.org/10.3350/cmh.2020.0307

Background/Aims
Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients.
Methods
Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV).
Results
Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group.
Conclusions
BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Citations

Citations to this article as recorded by

Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
Clinical and Molecular Hepatology.2026; 32(1): e55. CrossRef
Prodrug strategies in developing antiviral nucleoside analogs
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RSC Medicinal Chemistry.2026; 17(1): 105. CrossRef
Comparison of hepatocellular carcinoma incidence after long-term treatment with besifovir vs. tenofovir AF
Hyuk Kim, Jae-Young Kim, Yoon E. Shin, Hye-Jin Yoo, Jeong-Ju Yoo, Sang Gyune Kim, Young-Seok Kim
Scientific Reports.2025;[Epub] CrossRef
Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial
Hyung Joon Yim, Yeon Seok Seo, Ji Hoon Kim, Won Kim, Young Kul Jung, Jae Young Jang, Sae Hwan Lee, Yun Soo Kim, Chang Wook Kim, Hyoung Su Kim, Jae-Jun Shim, Eun-Young Cho, In Hee Kim, Byung Seok Lee, Jeong-Hoon Lee, Byung Seok Kim, Jeong Won Jang, Hyun Wo
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Juhee Won, Ah Ram Lee, Mehrangiz Dezhbord, Da Rae Lee, Seong Ho Kim, Jong Chul Kim, Soree Park, Nayeon Kim, Byengjune Jae, Kyun-Hwan Kim
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Expert Opinion on Pharmacotherapy.2021; 22(18): 2427. CrossRef
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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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Steatotic liver disease

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease: Young Seok Kim, Eun Sun Jung, Wonhee Hur, Si Hyun Bae, Jong Young Choi, Myeong Jun Song, Chang Wook Kim, Se Hyun Jo, Chang Don Lee, Young Sok Lee, Sang Wook Choi, Jin Mo Yang, Jeong Won Jang, Sang Gyune Kim, Seung Won Jung, Hee Kyung Kim, Hee Bok Chae, Seung Kew Yoon; Clin Mol Hepatol 2013;19(2):120-130.
Published online June 27, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.2.120

Abstract
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Background/Aims

The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.

Methods

One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.

Results

According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.

Conclusions

Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.

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