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"Liver fibrosis"

Original Articles

Histological severity and hepatic outcomes in patients with MASLD and discrepant FIB-4 and liver stiffness measurement
Joseph Rabbat, Boyu Yang, Hye Won Lee, Huapeng Lin, Emmanuel Tsochatzis, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Ming-Hua Zheng, Hannes Hagström, Jérôme Boursier, José Luis Calleja, George Boon-Bee Goh, Wah-Kheong Chan, Rocio Gallego-Durán, Arun J. Sanyal, Victor de Lédinghen, Philip N Newsome, Jian-Gao Fan, Laurent Castéra, Michelle Lai, Céline Fournier-Poizat, Grace Lai-Hung Wong, Mirko Zoncape, Grazia Pennisi, Angelo Armandi, Atsushi Nakajima, Wen-Yue Liu, Ying Shang, Marc de Saint-Loup, Elba Llop, Kevin Kim Jun Teh, Carmen Lara-Romero, Amon Asgharpour, Sara Mahgoub, Mandy Sau-Wai Chan, Clemence M Canivet, Manuel Romero-Gomez, Vincent Wai-Sun Wong, Seung Up Kim, Terry Cheuk-Fung Yip
Received August 6, 2025  Accepted November 2, 2025  Published online November 11, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0888    [Accepted]
Background/Aims
Current guidelines recommend a 2-step approach for identifying advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), using FIB-4 followed by liver stiffness measurement (LSM) via vibration-controlled transient elastography. However, some patients may exhibit discordant results. This study evaluates the histological severity and outcomes in patients with discordant FIB-4 and LSM results.
Methods
This secondary analysis of the VCTE-Prognosis study included 12,950 patients evaluated for MASLD at 16 tertiary centers, of whom 2,915 underwent liver biopsy. Patients were categorized into four groups based on established FIB-4 (1.3) and LSM (8 kPa) cutoffs.
Results
F3-F4 fibrosis was observed in 6.4%, 13.7%, 30.6%, and 62.4% in low-FIB-4-low-LSM (n=6,403), high-FIB-4-low-LSM (n=3,017), low-FIB-4-high-LSM (n=1,363), and high-FIB-4-high-LSM (n=2,167) groups, respectively. During a median follow-up of 47.4 months, 248 patients experienced hepatic decompensation, hepatocellular carcinoma, liver transplantation, or liver-related death. The incidence rates of liver-related events (LREs) were 0.67, 1.19, 2.58, and 21.30 per 1,000 person-years, respectively. Compared to low-FIB-4-low-LSM patients, those with low-FIB-4-high-LSM (adjusted subdistribution hazard ratio [aSHR] 4.2) and high-FIB-4-high-LSM (aSHR 21.3) had a significantly higher risk of LREs, while high-FIB-4-low-LSM patients did not. Similar findings were observed when hepatic decompensation and hepatocellular carcinoma were analyzed separately.
Conclusions
Approximately 30% of patients in tertiary centers exhibit discordant FIB-4 and LSM results, with LSM more likely reflecting true severity. While some patients with discordant results may have advanced fibrosis, the overall incidence of LREs remains low.
  • 749 View
  • 99 Download
Comparative Risk of Fibrosis Progression with SGLT2 vs. DPP-4 Inhibitors in MASLD and T2DM with Low-to-Intermediate Fibrosis
Jonggi Choi, Daniel Fulop, Vy H. Nguyen, Eric Przybyszewski, Jiunn Song, Allison Carroll, Megan Michta, Erik Almazan, Tracey G. Simon, Raymond T. Chung
Received July 23, 2025  Accepted November 4, 2025  Published online November 11, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0825    [Accepted]
Background and Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of cirrhosis and its complications. Given its close association with type 2 diabetes mellitus (T2DM), evaluating whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) can mitigate the progression of liver fibrosis is clinically important. We examined the association between SGLT2i use and liver fibrosis progression in patients diagnosed with MASLD and T2DM.
Methods
We conducted a target trial emulation study using a retrospective, active comparator new-user design among adults with MASLD, T2DM, and low-to-intermediate Fibrosis-4 (FIB-4 ≤2.67) scores who initiated treatment with either SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is) at Mass General Brigham or Asan Medical Center from 2013 to 2023. The primary outcome was the progression to advanced fibrosis (FIB-4 >2.67), confirmed on ≥2 occasions within 1 year. The secondary outcome was the development of major adverse liver outcomes (MALO), including incident cirrhosis, decompensation events, hepatocellular carcinoma, or liver transplantation.
Results
Among 16,901 eligible patients, 2,571 propensity score-matched pairs were identified with balanced baseline characteristics. During follow-up (median, 3.7 years), fibrosis progression occurred at a rate of 3.46/100 person-years in SGLT2i users and 4.44 in DPP4i users. SGLT2i use was associated with a lower risk of fibrosis progression (HR, 0.78; 95% CI, 0.67–0.89; p<0.001). No significant difference in MALO incidence was observed. Subgroup analyses showed a consistent association among users of metformin, statins, and aspirin.
Conclusions
SGLT2i use was associated with reduced risk of fibrotic progression compared to DPP4i use in adults with MASLD and T2DM.
  • 852 View
  • 95 Download

Letter to the Editor

Letter to the editor on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023”
Sisi Yang, Zhenxuan Ma
Received February 11, 2025  Accepted March 6, 2025  Published online March 7, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0153    [Epub ahead of print]
  • 3,510 View
  • 29 Download

Correspondence

Viral hepatitis

Correspondence to editorial on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”
Tom Ryu, Young Chang, Seung Up Kim, Jae Young Jang
Clin Mol Hepatol 2025;31(2):e203-e205.
Published online February 24, 2025
DOI: https://doi.org/10.3350/cmh.2025.0179

Citations

Citations to this article as recorded by  Crossref logo
  • Reply to correspondence on “Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C”
    Chen-Hua Liu, Yu-Ping Chang
    Clinical and Molecular Hepatology.2025; 31(2): e232.     CrossRef
  • 3,617 View
  • 25 Download
  • 1 Web of Science
  • Crossref

Original Article

Viral hepatitis

Adverse impact of metabolic dysfunction on fibrosis regression following direct-acting antiviral therapy: A multicenter study for chronic hepatitis C
Tom Ryu, Young Chang, Soung Won Jeong, Jeong-Ju Yoo, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Hong Soo Kim, Seung Up Kim, Jae Young Jang
Clin Mol Hepatol 2025;31(2):548-562.
Published online January 9, 2025
DOI: https://doi.org/10.3350/cmh.2024.0904
Background/Aims
Direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus. This study investigated whether metabolic dysfunction influences the likelihood of fibrosis regression after DAA treatment in patients with chronic hepatitis C (CHC).
Methods
This multicenter, retrospective study included 8,819 patients diagnosed with CHC who were treated with DAAs and achieved a sustained virological response (SVR) between January 2014 and December 2022. Fibrosis regression was defined as a 20% reduction in noninvasive surrogates for liver fibrosis, such as liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) and the fibrosis-4 (FIB-4) score. Hypercholesterolemia (h-TC) was defined as >200 mg/dL.
Results
The median age of the study population was 59.6 years, with a predominance of male patients (n=4,713, 57.3%). Genotypes 1, 2, and others were confirmed in 3,872 (46.2%), 3,487 (41.6%), and 1,024 (12.2%) patients, respectively. Diabetes mellitus (DM) was present in 1,442 (17.2%) patients and the median LS was 7.50 kPa (interquartile range, 5.30–12.50). Multivariate analysis revealed that the presence of DM and pre-DAA h-TC were independently associated with a decreased probability of fibrosis regression by VCTE. Additionally, pre-DAA h-TC was independently associated with a decreased probability of fibrosis regression by the FIB-4.
Conclusions
Metabolic dysfunction has an unfavorable influence on fibrosis regression in patients with CHC who achieve SVR after DAA treatment.

Citations

Citations to this article as recorded by  Crossref logo
  • Editorial: Risk of Incident Type 2 Diabetes and Prediabetes in Patients With Direct Acting Antiviral‐Induced Cure of Hepatitis C Virus Infection—Authors' Reply
    Yu‐Ping Chang, Jia‐Horng Kao, Chen‐Hua Liu
    Alimentary Pharmacology & Therapeutics.2025; 61(9): 1553.     CrossRef
  • Epidemiologic Characteristics of Chronic Hepatitis B and Coinfections with Hepatitis C Virus or Human Immunodeficiency Virus in South Korea: A Nationwide Claims-Based Study Using the Korean Health Insurance Review and Assessment Service Database
    Hyunwoo Oh, Won Sohn, Na Ryung Choi, Hyo Young Lee, Yeonjae Kim, Seung Woo Nam, Jae Yoon Jeong
    Pathogens.2025; 14(7): 715.     CrossRef
  • 6,972 View
  • 143 Download
  • 5 Web of Science
  • Crossref

Correspondence

Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to letter to the editor on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”
Hee Yeon Kim, Miyoung Choi, Dae Won Jun
Clin Mol Hepatol 2025;31(1):e105-e107.
Published online November 4, 2024
DOI: https://doi.org/10.3350/cmh.2024.0937
  • 4,288 View
  • 27 Download

Letter to the Editor

Liver fibrosis, cirrhosis, and portal hypertension

Letter regarding “Prevalence of clinically significant liver fibrosis in the general population”
Wei Feng, Qile Wang, Qingwang Ye
Clin Mol Hepatol 2025;31(1):e21-e22.
Published online October 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0887
  • 5,043 View
  • 35 Download
  • 1 Web of Science

Correspondence

Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to editorial on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”
Hee Yeon Kim, Miyoung Choi, Dae Won Jun
Clin Mol Hepatol 2025;31(1):e48-e51.
Published online September 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0777
  • 4,728 View
  • 34 Download

Original Article

Autoimmune liver disease

Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver diseases: A systematic review and meta-analysis
Jihyun An, Young Eun Chon, Gunho Kim, Mi Na Kim, Hee Yeon Kim, Han Ah Lee, Jung Hwan Yu, Miyoung Choi, Dae Won Jun, Seung Up Kim, Ji Won Han, Young-Joo Jin
Clin Mol Hepatol 2024;30(Suppl):S134-S146.
Published online August 21, 2024
DOI: https://doi.org/10.3350/cmh.2024.0586
Background/Aims
The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease.
Methods
Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, according to liver biopsy.
Results
Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87, 0.89, and 0.99 for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88, 0.88, and 0.92, respectively, while in PSC, they were 0.88, 0.95, and 0.92, respectively. The cutoff values for AF were 7.5–17.9 kPa in PBC, 8.18–12.1 kPa in AIH, and 9.6 kPa in PSC.
Conclusions
VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases. This non-invasive method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.

Citations

Citations to this article as recorded by  Crossref logo
  • Transient elastography for assessing liver fibrosis in autoimmune liver diseases: Excellent performance but limited details: Editorial on “Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver di
    Kyung-Ah Kim
    Clinical and Molecular Hepatology.2025; 31(1): 275.     CrossRef
  • Diagnostic value of serum Golgi protein 73 in liver fibrosis and inflammation in patients with autoimmune hepatitis
    Yazhen Zhang, Aifang Xu, Yujiao Jin, Jing Gao, Jiahui He
    Medicine.2025; 104(26): e43064.     CrossRef
  • Targeting endoplasmic reticulum proteostasis in liver fibrosis: From signaling mechanisms to therapeutic opportunities
    Yawei Kong, Zhengyang Chen, Zhentian Nie, Wei Chen
    Pharmacological Research.2025; 217: 107823.     CrossRef
  • Diagnostic Performance of SWE and Predictive Models Based on SWE for Post-Hepatectomy Liver Failure: A Systematic Review and Meta-analysis
    Jiaxu Liang, Fukun Shi, Lan Zhang, Suo Yin, Yong Chen
    Current Medical Imaging Formerly Current Medical Imaging Reviews.2025;[Epub]     CrossRef
  • Hidden weaknesses and biological insights in machine learning models of fibrosis in autoimmune hepatitis
    Shiuan-Chih Chen, Chun-Chieh Chen
    QJM: An International Journal of Medicine.2025;[Epub]     CrossRef
  • 7,436 View
  • 165 Download
  • 6 Web of Science
  • Crossref

Special Issue

Liver fibrosis, cirrhosis, and portal hypertension

KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease
Mi Na Kim, Ji Won Han, Jihyun An, Beom Kyung Kim, Young-Joo Jin, Seung-seob Kim, Minjong Lee, Han Ah Lee, Yuri Cho, Hee Yeon Kim, Yu Rim Shin, Jung Hwan Yu, Moon Young Kim, YoungRok Choi, Young Eun Chon, Eun Ju Cho, Eun Joo Lee, Sang Gyune Kim, Won Kim, Dae Won Jun, Seung Up Kim, on behalf of The Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2024;30(Suppl):S5-S105.
Published online August 19, 2024
DOI: https://doi.org/10.3350/cmh.2024.0506

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to editorial on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”
    Hee Yeon Kim, Miyoung Choi, Dae Won Jun
    Clinical and Molecular Hepatology.2025; 31(1): e48.     CrossRef
  • Non-Invasive Liver Fibrosis Test Using Shear Wave Elastography
    Ji Won Han
    The Korean Journal of Medicine.2025; 100(1): 26.     CrossRef
  • Influence of Sex in the Development of Liver Diseases
    Jie-Wen Zhang, Nan Zhang, Yi Lyu, Xu-Feng Zhang
    Seminars in Liver Disease.2025; 45(01): 015.     CrossRef
  • KASL clinical practice guidelines for the management of metabolic dysfunction-associated steatotic liver disease 2025
    Won Sohn, Young-Sun Lee, Soon Sun Kim, Jung Hee Kim, Young-Joo Jin, Gi-Ae Kim, Pil Soo Sung, Jeong-Ju Yoo, Young Chang, Eun Joo Lee, Hye Won Lee, Miyoung Choi, Su Jong Yu, Young Kul Jung, Byoung Kuk Jang
    Clinical and Molecular Hepatology.2025; 31(Suppl): S1.     CrossRef
  • Noninvasive identification of metabolic dysfunction–associated steatohepatitis (INFORM MASH): a retrospective cohort and disease modeling study
    G. Craig Wood, Anthony Hoovler, Rakesh Luthra, Christopher D. Still, Hamzah Shariff, Matthew Still, Jonathan Hayes, Peter Benotti, Chioma Uzoigwe
    Expert Review of Gastroenterology & Hepatology.2025; 19(4): 427.     CrossRef
  • Age serves as the silent architect of FIB-4’s precision in unveiling advanced hepatic fibrosis in MASLD with T2DM: Correspondence to letter to the editor on “Diagnostic accuracy of the fibrosis-4 index for advanced liver fibrosis in nonalcoholic fatty liv
    Ji Won Han, Dae Won Jun
    Clinical and Molecular Hepatology.2025; 31(2): e152.     CrossRef
  • The association between modified cardiometabolic index with non-alcoholic fatty liver disease and liver fibrosis: a cross-sectional study
    Yanjun Guo, Wei Su, Lulong Tao, Guoxin Zhang, Kun Wang
    BMC Gastroenterology.2025;[Epub]     CrossRef
  • Future Perspectives of Liver Research in the Asia‐Pacific Region: Focus on Hepatitis B and C
    Beom Kyung Kim
    Journal of Gastroenterology and Hepatology.2025; 40(8): 1855.     CrossRef
  • Novel Insights into Noninvasive Assessment of Liver Fibrosis in Chronic Hepatitis C Patients
    Guanlan Liu, Li Liu, Xing Yang, Qihao Wang, Mingqin Qian
    Journal of Clinical and Experimental Hepatology.2025; 15(6): 102610.     CrossRef
  • A Case Report of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) with Improved Cardiometabolic Risk Factors Following Treatment with Saenggangunbi-tang
    Eun Kyung Lee, Min Jeong Park, Youngchul Kim, Jang-Hoon Lee
    The Journal of Internal Korean Medicine.2025; 46(2): 303.     CrossRef
  • Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease
    Hye Won Lee, Jae Seung Lee, Mi Na Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Seung Up Kim
    Clinical and Molecular Hepatology.2025; 31(3): 1018.     CrossRef
  • Performance of APRI and FIB-4 Scores Compared to FibroScan: A Cross-Sectional Study in a Black Sub-Saharan African Population
    Jean-Bonny Nsumbu, Jean-Robert Makulo, Trésor Mutombo Tshiswaka, Christian Kisoka Lusunsi, Charles Nlombi Mbendi
    Hepatic Medicine: Evidence and Research.2025; Volume 17: 27.     CrossRef
  • Correspondence to editorial 1 on “Baveno VI-SSM stratifies the risk of portal hypertension-related events in patients with HBV-related cirrhosis”
    Haiyu Wang, Jinjun Chen
    Clinical and Molecular Hepatology.2025;[Epub]     CrossRef
  • Quantification of liver steatosis of metabolic dysfunction-associated steatotic liver disease based on body composition analysis
    Toshikazu Kohira, Satoshi Oeda, Erina Eto, Yoshihito Kubotsu, Misa Norita, Kaori Inoue, Nagisa Hara, Shotaro Noge, Kenichi Tanaka, Shigenobu Yoshimura, Noriko Oza, Keizo Anzai, Yuichiro Eguchi, Cheng Han Ng, Daniel Q. Huang, Mark D. Muthiah, Atsushi Kawag
    Scientific Reports.2025;[Epub]     CrossRef
  • Longitudinal Effects of Glecaprevir/Pibrentasvir on Liver Function, Fibrosis, and Hepatocellular Carcinoma Risk in Chronic Hepatitis C: A Prospective Multicenter Cohort Study
    Jung Hee Kim, Jae Hyun Yoon, Sung-Eun Kim, Ji-Won Park, Yewan Park, Gi-Ae Kim, Seong Kyun Na, Young-Sun Lee, Jeong Han Kim
    Medicina.2025; 61(9): 1601.     CrossRef
  • Comment on ‘Association Between Handgrip Strength and Cardiovascular Disease Risk in MASLD: A Prospective Study From UK Biobank’ by T. S. Lim et al.—Authors' Reply
    Tae Seop Lim, Sujin Kwon, Sung A Bae, Hye Yeon Chon, Seol A. Jang, Ja Kyung Kim, Chul Sik Kim, Seok Won Park, Kyoung Min Kim
    Journal of Cachexia, Sarcopenia and Muscle.2025;[Epub]     CrossRef
  • Aspirin Use and Risk of HCC and Gastrointestinal Bleeding in Patients With HBV‐Related Cirrhosis: A Landmark Analysis
    Mi Na Kim, Geun U. Park, Seng Chan You, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn
    Journal of Gastroenterology and Hepatology.2025; 40(11): 2750.     CrossRef
  • Prospects of late-stage development agents in the treatment of metabolic dysfunction-associated steatohepatitis
    Brian Lee, Ussama Ghumman, Lisa D. Pedicone, Andres Gomez Aldana, Eric Lawitz
    Clinical and Molecular Hepatology.2025; 31(4): 1167.     CrossRef
  • Discovery of ultrasound-derived fat fraction as a non-invasive tool for MASLD diagnosis
    Huiru Jin, Mengfan Jiao, Chengxiao Yu, Tingting Ren, Qingling Chen, Zixing Dai, Erfu Xie, Longfeng Jiang, Yuwen Li
    European Journal of Medical Research.2025;[Epub]     CrossRef
  • Mistakes in the utilization of vibration-controlled transient elastography in the evaluation of liver fibrosis: a narrative review
    Madunil Anuk Niriella, Uditha Bandara Dassanayake, Charith Priyanga Madurapperuma, Indeewari Prathibha Wijesingha, Arjuna Priyadarshin De Silva, Hithnadura Janaka de Silva
    Expert Review of Gastroenterology & Hepatology.2025; : 1.     CrossRef
  • Enhanced Prediction of Hepatitis B Virus-Related Hepatocellular Carcinoma Using Age-male-albumin-bilirubin-platelet (aMAP) and Liver Stiffness Assessed by Vibration-controlled Transient Elastography
    Hye Yeon Chon, Hyung Joon Yim, Seok-Jae Heo, Su Jong Yu, Ja Kyung Kim, Sang Hoon Ahn, Grace Lai-Hung Wong, Jimmy Che-To Lai, Terry Cheuk-Fung Yip, Sang Gyune Kim, Yeon Seok Seo, Seung Up Kim
    Clinical Gastroenterology and Hepatology.2025;[Epub]     CrossRef
  • Recent Trends in Noninvasive Tests for Assessing Hepatic Fibrosis in Patients with Chronic Liver Disease
    Jung Hwan Yu
    The Korean Journal of Medicine.2024; 99(5): 232.     CrossRef
  • Noninvasive Imaging Test to Assess Liver Fibrosis: Vibration-controlled Transient Elastography
    Mi Na Kim
    The Korean Journal of Gastroenterology.2024; 84(5): 201.     CrossRef
  • Non-Invasive Test for Assessment of Liver Fibrosis in Chronic Hepatitis B
    Ye Ji Jun, Minjong Lee, Ho Soo Chun, Tae Hun Kim
    The Korean Journal of Gastroenterology.2024; 84(5): 206.     CrossRef
  • Serological Markers to Assess Liver Fibrosis and Their Roles
    Beom Kyung Kim
    The Korean Journal of Gastroenterology.2024; 84(5): 195.     CrossRef
  • Liver Fibrosis Assessment in Chronic Liver Diseases Using Elastography: A Comprehensive Review of Vibration-Controlled Transient Elastography and Shear Wave Elastography
    Han Ah Lee
    Clinical Ultrasound.2024; 9(2): 70.     CrossRef
  • 12,786 View
  • 301 Download
  • 24 Web of Science
  • Crossref

Letter to the Editor

Viral hepatitis

Presence of liver fibrosis in chronic hepatitis B patients with varying serum hepatitis B virus DNA levels: Letter to the editor on “Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B”
Jian Wang, Shaoqiu Zhang, Chuanwu Zhu, Yuanwang Qiu, Chao Wu, Rui Huang
Clin Mol Hepatol 2025;31(1):e27-e30.
Published online August 7, 2024
DOI: https://doi.org/10.3350/cmh.2024.0602

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to letter to the editor on “Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B”
    Gi-Ae Kim, Seung Won Choi, Young-Suk Lim
    Clinical and Molecular Hepatology.2025; 31(1): e108.     CrossRef
  • 5,230 View
  • 62 Download
  • Crossref

Correspondence

Viral hepatitis

Correspondence to letter to the editor on “Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B”
Gi-Ae Kim, Seung Won Choi, Young-Suk Lim
Clin Mol Hepatol 2025;31(1):e108-e109.
Published online August 5, 2024
DOI: https://doi.org/10.3350/cmh.2024.0619
  • 4,244 View
  • 40 Download

Original Articles

Liver fibrosis, cirrhosis, and portal hypertension

Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis
Hee Yeon Kim, Jung Hwan Yu, Young Eun Chon, Seung Up Kim, Mi Na Kim, Ji Won Han, Han Ah Lee, Young-Joo Jin, Jihyun An, Miyoung Choi, Dae Won Jun
Clin Mol Hepatol 2024;30(Suppl):S199-S213.
Published online July 30, 2024
DOI: https://doi.org/10.3350/cmh.2024.0351
Background/Aims
Although important, clinically significant liver fibrosis is often overlooked in the general population. We aimed to examine the prevalence of clinically significant liver fibrosis using noninvasive tests (NITs) in the general population.
Methods
We collected data from four databases (MEDLINE, Embase, Cochrane Library, and KoreaMed) from inception to June 13, 2023. Original articles reporting the prevalence of clinically significant liver fibrosis in the general population were included. The Stata metaprop function was used to obtain the pooled prevalence of liver fibrosis with NITs in the general population.
Results
We screened 6,429 articles and included 45 eligible studies that reported the prevalence of clinically significant liver fibrosis in the general population. The prevalence of advanced liver fibrosis, using the high probability cutoff of the fibrosis-4 (FIB-4) index, was 2.3% (95% confidence interval [CI], 1.2–3.7%). The prevalence of significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis, assessed using vibration-controlled transient elastography (VCTE) among the general population, was 7.3% (95% CI, 5.9–8.8%), 3.5% (95% CI, 2.7–4.5), and 1.2% (95% CI, 0.8–1.8%), respectively. Region-based subgroup analysis revealed that the highest prevalence of advanced fibrosis using the high probability cutoff of the FIB-4 index was observed in the American region. Furthermore, the American region exhibited the highest prevalence of significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis, using VCTE.
Conclusions
Previously undiagnosed clinically significant liver fibrosis is found in the general population through NITs. Future research is necessary to stratify the risk in the general population.

Citations

Citations to this article as recorded by  Crossref logo
  • Spotting undiagnosed significant liver fibrosis in the general population: impact on subsequent clinical care: Editorial on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”
    Nana Peng, Mary Yue Wang, Sherlot Juan Song, Terry Cheuk-Fung Yip
    Clinical and Molecular Hepatology.2025; 31(1): 256.     CrossRef
  • Correspondence to editorial on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”
    Hee Yeon Kim, Miyoung Choi, Dae Won Jun
    Clinical and Molecular Hepatology.2025; 31(1): e48.     CrossRef
  • Letter regarding “Prevalence of clinically significant liver fibrosis in the general population”
    Wei Feng, Qile Wang, Qingwang Ye
    Clinical and Molecular Hepatology.2025; 31(1): e21.     CrossRef
  • Correspondence to letter to the editor on “Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis”
    Hee Yeon Kim, Miyoung Choi, Dae Won Jun
    Clinical and Molecular Hepatology.2025; 31(1): e105.     CrossRef
  • Hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor AMSP-30 m attenuates CCl4-induced liver fibrosis in mice by inhibiting the sonic hedgehog pathway
    Lili Lu, Yuchen Ma, Qing Tao, Jing Xie, Xiao Liu, Yongkang Wu, Yang Zhang, Xiuli Xie, Mingming Liu, Yong Jin
    Chemico-Biological Interactions.2025; 413: 111480.     CrossRef
  • Vibration-controlled transient elastography in shaping the epidemiology and management of steatotic liver disease: Editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023”
    Xiao-Dong Zhou, Terry Cheuk-Fung Yip, Daniel Q Huang, Mark Dhinesh Muthiah, Mazen Noureddin, Ming-Hua Zheng
    Clinical and Molecular Hepatology.2025; 31(2): 620.     CrossRef
  • Simple Clinical Prediction Rules for Identifying Significant Liver Fibrosis: Evaluation of Established Scores and Development of the Aspartate Aminotransferase-Thrombocytopenia-Albumin (ATA) Score
    Puwitch Charoenchue, Jiraporn Khorana, Apichat Tantraworasin, Suwalee Pojchamarnwiputh, Wittanee Na Chiangmai, Amonlaya Amantakul, Taned Chitapanarux, Nakarin Inmutto
    Diagnostics.2025; 15(9): 1119.     CrossRef
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Viral hepatitis

Vibration-controlled transient elastography for significant fibrosis in treatment-naïve chronic hepatitis B patients: A systematic review and meta-analysis
Mi Na Kim, Jihyun An, Eun Hwa Kim, Hee Yeon Kim, Han Ah Lee, Jung Hwan Yu, Young-Joo Jin, Young Eun Chon, Seung Up Kim, Dae Won Jun, Ji Won Han, Miyoung Choi
Clin Mol Hepatol 2024;30(Suppl):S106-S116.
Published online July 23, 2024
DOI: https://doi.org/10.3350/cmh.2024.0371
Backgrounds/Aims
Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of vibration-controlled transient elastography (VCTE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN).
Methods
The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of VCTE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of VCTE in the meta-analysis.
Results
Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 (95% confidence interval [CI], 0.66–0.86) and 0.72 (95% CI, 0.60–0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72–0.86). The optimal cutoff value of VCTE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50–0.76) and specificity of 0.83 (95% CI, 0.72–0.90).
Conclusions
Our study demonstrated that VCTE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Citations

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    Napoleon Bellua Sam, Saeed Folorunsho Majeed, Adams Dramani
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    Deniz Borcak, Zuhal Yesilbag, Yusuf Emre Ozdemir, Adile Sevde Demir, Esra Salim Dogdas, Aysegul Inci Sezen, Esra Canbolat Unlu, Sevtap Senoglu, Hayat Kumbasar Karaosmanoglu, Kadriye Kart Yasar
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    Jung Hwan Yu
    The Korean Journal of Medicine.2024; 99(5): 232.     CrossRef
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    Mi Na Kim
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    Han Ah Lee
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  • Crossref

Viral hepatitis

Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B
Gi-Ae Kim, Seung Won Choi, Seungbong Han, Young-Suk Lim
Clin Mol Hepatol 2024;30(4):793-806.
Published online July 19, 2024
DOI: https://doi.org/10.3350/cmh.2024.0252
Background/Aims
Serum hepatitis B virus (HBV) DNA levels and non-invasive liver fibrosis scores are significantly associated with hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. Nonetheless, the relationship between HBV DNA levels and liver fibrosis scores is unclear.
Methods
A historical cohort comprising 6,949 non-cirrhotic Korean CHB patients without significant alanine aminotransferase elevation was investigated. The association of HBV DNA levels with the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (FIB)-4 score at baseline was analyzed using general linear models.
Results
In HBeAg-negative patients (n=4,868), HBV DNA levels correlated linearly with both APRI and FIB-4 scores. In contrast, in HBeAg-positive patients (n=2,081), HBV DNA levels correlated inversely with both APRI and FIB-4 scores. Across the entire cohort, a significant non-linear parabolic relationship was identified between HBV DNA levels and fibrosis scores, independent of age and other covariates. Notably, moderate viral loads (6–7 log10 IU/mL) corresponded to the highest APRI and FIB-4 scores (p<0.001). Over a median 10-year follow-up, 435 patients (6.3%) developed HCC. Higher APRI scores ≥0.5 and FIB-4 scores ≥1.45 were significantly associated with elevated HCC risk (p<0.001 for both). HBV DNA level remained a significant predictive factor for HCC development, even after adjusting for APRI or FIB-4 scores.
Conclusions
HBV viral load is significantly correlated with APRI and FIB-4 scores, and is also associated with HCC risk independent of those scores in CHB patients. These findings suggest that HBV DNA level is associated with hepatocarcinogenesis through both direct and indirect pathways.

Citations

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Correspondence

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
  • 4,930 View
  • 63 Download

Review

Liver fibrosis, cirrhosis, and portal hypertension

Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis
Jiaorong Qu, Le Wang, Yufei Li, Xiaojiaoyang Li
Clin Mol Hepatol 2024;30(3):303-325.
Published online February 28, 2024
DOI: https://doi.org/10.3350/cmh.2024.0022
Liver sinusoidal endothelial cells (LSECs) are liver-specific endothelial cells with the highest permeability than other mammalian endothelial cells, characterized by the presence of fenestrae on their surface, the absence of diaphragms and the lack of basement membrane. Located at the interface between blood and other liver cell types, LSECs mediate the exchange of substances between the blood and the Disse space, playing a crucial role in maintaining substance circulation and homeostasis of multicellular communication. As the initial responders to chronic liver injury, the abnormal LSEC activation not only changes their own physicochemical properties but also interrupts their communication with hepatic stellate cells and hepatocytes, which collectively aggravates the process of liver fibrosis. In this review, we have comprehensively updated the various pathways by which LSECs were involved in the initiation and aggravation of liver fibrosis, including but not limited to cellular phenotypic change, the induction of capillarization, decreased permeability and regulation of intercellular communications. Additionally, the intervention effects and latest regulatory mechanisms of anti-fibrotic drugs involved in each aspect have been summarized and discussed systematically. As we studied deeper into unraveling the intricate role of LSECs in the pathophysiology of liver fibrosis, we unveil a promising horizon that pave the way for enhanced patient outcomes.

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Original Article

Cholestatic liver disease

Taurocholic acid promotes hepatic stellate cell activation via S1PR2/p38 MAPK/YAP signaling under cholestatic conditions
Jing Yang, Xujiao Tang, Zhu Liang, Mingzhu Chen, Lixin Sun
Clin Mol Hepatol 2023;29(2):465-481.
Published online February 20, 2023
DOI: https://doi.org/10.3350/cmh.2022.0327
Background/Aims
Disrupted bile acid regulation and accumulation in the liver can contribute to progressive liver damage and fibrosis. However, the effects of bile acids on the activation of hepatic stellate cells (HSCs) remain unclear. This study investigated the effects of bile acids on HSC activation during liver fibrosis, and examined the underlying mechanisms.
Methods
The immortalized HSCs, LX-2 and JS-1cells were used for the in vitro study. in vitro, the adeno-associated viruses adeno-associated virus-sh-S1PR2 and JTE-013 were used to pharmacologically inhibit the activity of S1PR2 in a murine model of fibrosis induced by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of S1PR2 in the regulation of fibrogenic factors as well as the activation properties of HSCs.
Results
S1PR2 was the predominant S1PR expressed in HSCs and was upregulated during taurocholic acid (TCA) stimulation and in cholestatic liver fibrosis mice. TCA-induced HSC proliferation, migration and contraction and extracellular matrix protein secretion were inhibited by JTE-013 and a specific shRNA targeting S1PR2 in LX-2 and JS-1 cells. Meanwhile, treatment with JTE-013 or S1PR2 deficiency significantly attenuated liver histopathological injury, collagen accumulation, and the expression of fibrogenesis-associated genes in mice fed a DDC diet. Furthermore, TCAmediated activation of HSCs through S1PR2 was closely related to the yes-associated protein (YAP) signaling pathway via p38 mitogen-activated protein kinase (p38 MAPK).
Conclusions
TCA-induced activation of the S1PR2/p38 MAPK/YAP signaling pathways plays a vital role in regulating HSC activation, which might be therapeutically relevant for targeting cholestatic liver fibrosis.

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Editorial

Steatotic liver disease

Non-invasive biomarkers of liver fibrosis in non-alcoholic fatty liver disease
Maamon Basheer, Mohamed Naffaa, Nimer Assy
Clin Mol Hepatol 2023;29(2):398-400.
Published online February 13, 2023
DOI: https://doi.org/10.3350/cmh.2023.0045

Citations

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  • New Biomarkers in Liver Fibrosis: A Pass through the Quicksand?
    Marzia Tagliaferro, Mariapaola Marino, Valerio Basile, Krizia Pocino, Gian Ludovico Rapaccini, Gabriele Ciasca, Umberto Basile, Valeria Carnazzo
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Reviews

Steatotic liver disease

Noninvasive imaging biomarkers for liver fibrosis in nonalcoholic fatty liver disease: current and future
Jung Hwan Yu, Han Ah Lee, Seung Up Kim
Clin Mol Hepatol 2023;29(Suppl):S136-S149.
Published online December 12, 2022
DOI: https://doi.org/10.3350/cmh.2022.0436
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide and becoming a major cause of liver disease-related morbidity and mortality. The presence of liver fibrosis in patients with NAFLD is closely related to prognosis, including the development of hepatocellular carcinoma and other complications of cirrhosis. Therefore, assessment of the presence of significant or advanced liver fibrosis is crucial. Although liver biopsy has been considered the “gold standard” method for evaluating the degree of liver fibrosis, it is not suitable for extensive use in all patients with NAFLD owing to its invasiveness and high cost. Therefore, noninvasive biochemical and imaging biomarkers have been developed to overcome the limitations of liver biopsy. Imaging biomarkers for the stratification of liver fibrosis have been evaluated in patients with NAFLD using different imaging techniques, such as transient elastography, shear wave elastography, and magnetic resonance elastography. Furthermore, artificial intelligence and deep learning methods are increasingly being applied to improve the diagnostic accuracy of imaging techniques and overcome the pitfalls of existing imaging biomarkers. In this review, we describe the usefulness and future prospects of noninvasive imaging biomarkers that have been studied and used to evaluate the degree of liver fibrosis in patients with NAFLD.

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Steatotic liver disease

Identification of high-risk subjects in nonalcoholic fatty liver disease
Christiane Stern, Laurent Castera
Clin Mol Hepatol 2023;29(Suppl):S196-S206.
Published online December 5, 2022
DOI: https://doi.org/10.3350/cmh.2022.0431
Non-alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease worldwide, and its burden is expected to increase due to the growing epidemic of obesity and diabetes. The key challenge among NAFLD patients is to identify those with advanced fibrosis (F3F4), who are at high risk of developing complications and will benefit from specialized management and treatment with new pharmacotherapies when they are approved. Liver biopsy appears unrealistic and unsuitable in practice, given the large number of high-risk patients and its well-known limitations. Non-invasive sequential algorithms using fibrosis-4 index as first-line test, followed by vibration-controlled transient elastography or patented blood test, are the best strategy for case finding of high-risk subjects. In fact, they are now recommended by several international guidelines, and should be used and disseminated to increase awareness among physicians beyond liver clinics where most NAFLD patients are seen.

Citations

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Steatotic liver disease

Noninvasive serum biomarkers for liver fibrosis in NAFLD: current and future
Tina Reinson, Ryan M. Buchanan, Christopher D. Byrne
Clin Mol Hepatol 2023;29(Suppl):S157-S170.
Published online November 22, 2022
DOI: https://doi.org/10.3350/cmh.2022.0348
In the last 20 years, noninvasive serum biomarkers to identify liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) have been developed, validated against liver biopsy (the gold standard for determining the presence of liver fibrosis) and made available for clinicians to use to identify ≥F3 liver fibrosis. The aim of this review is firstly to focus on the current use of widely available biomarkers and their performance for identifying ≥F3. Secondly, we discuss whether noninvasive biomarkers have a role in identifying F2, a stage of fibrosis that is now known to be a risk factor for cirrhosis and overall mortality. We also consider whether machine learning algorithms offer a better alternative for identifying individuals with ≥F2 fibrosis. Thirdly, we summarise the utility of noninvasive serum biomarkers for predicting liver related outcomes (e.g., ascites and hepatocellular carcinoma) and non-liver related outcomes (e.g., cardiovascular-related mortality and extra hepatic cancers). Finally, we examine whether serial measurement of biomarkers can be used to monitor liver disease, and whether the use of noninvasive biomarkers in drug trials for non-alcoholic steatohepatitis can accurately, compared to liver histology, monitor liver fibrosis progression/regression. We conclude by offering our perspective on the future of serum biomarkers for the detection and monitoring of liver fibrosis in NAFLD.

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Steatotic liver disease

Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis
Kuei-Chuan Lee, Pei-Shan Wu, Han-Chieh Lin
Clin Mol Hepatol 2023;29(1):77-98.
Published online October 13, 2022
DOI: https://doi.org/10.3350/cmh.2022.0237
The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. The dysfunction of lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes lipid accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress would further contribute to hepatocyte injury and death, leading to inflammation and immune dysfunction in the liver. During the healing process, the accumulation of an excessive amount of fibrosis might occur while healing. During the development of NASH and liver fibrosis, the gut-liver axis, adipose-liver axis, and renin-angiotensin system (RAS) may be dysregulated and impaired. Translocation of bacteria or its end-products entering the liver could activate hepatocytes, Kupffer cells, and hepatic stellate cells, exacerbating hepatic steatosis, inflammation, and fibrosis. Bile acids regulate glucose and lipid metabolism through Farnesoid X receptors in the liver and intestine. Increased adipose tissue-derived non-esterified fatty acids would aggravate hepatic steatosis. Increased leptin also plays a role in hepatic fibrogenesis, and decreased adiponectin may contribute to hepatic insulin resistance. Moreover, dysregulation of peroxisome proliferator-activated receptors in the liver, adipose, and muscle tissues may impair lipid metabolism. In addition, the RAS may contribute to hepatic fatty acid metabolism, inflammation, and fibrosis. The treatment includes lifestyle modification, pharmacological therapy, and non-pharmacological therapy. Currently, weight reduction by lifestyle modification or surgery is the most effective therapy. However, vitamin E, pioglitazone, and obeticholic acid have also been suggested. In this review, we will introduce some new clinical trials and experimental therapies for the treatment of NASH and related fibrosis.

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Letter to the Editor

Nutritional and Metabolic liver disease

Effects of interleukin-17 inhibitors on hepatic fibrosis index in patients with psoriasis and metabolic dysfunction-associated fatty liver disease: Directed acyclic graphs
Saori Takamura, Yuichi Teraki, Eri Katayama, Takumi Kawaguchi, Machiko Kawaguchi, Dan Nakano, Tsubasa Tsutsumi, Sumiko Nagoshi, Takekuni Nakama, Takuji Torimura
Clin Mol Hepatol 2022;28(2):269-272.
Published online February 15, 2022
DOI: https://doi.org/10.3350/cmh.2022.0040

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Editorial

Negligible risk of hepatocellular carcinoma in chronic hepatitis B patients in immune-tolerant phase: Myth or fact
Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, Vincent Wai-Sun Wong
Clin Mol Hepatol 2021;27(2):273-277.
Published online February 1, 2021
DOI: https://doi.org/10.3350/cmh.2021.0019

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Original Article

Hepatic neoplasm

Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein level predicts recurrence of hepatitis B virus-related hepatocellular carcinoma after curative resection
Hye Soo Kim, Seung Up Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Young Nyun Park, Dai Hoon Han, Kyung Sik Kim, Jin Sub Choi, Gi Hong Choi, Hyon-Suk Kim
Clin Mol Hepatol 2020;26(1):33-44.
Published online June 27, 2019
DOI: https://doi.org/10.3350/cmh.2018.0073
Background/Aims
To investigate whether serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) can predict the recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection.
Methods
Patients with chronic hepatitis B (CHB) who underwent curative resection for HCC between 2004 and 2015 were eligible for the study. Recurrence was sub-classified as early (<2 years) or late (≥2 years).
Results
A total of 170 patients with CHB were selected. During the follow-up period (median, 22.6 months), 64 (37.6%) patients developed recurrence. In multivariate analyses, WFA+-M2BP level was an independent predictor of overall (hazard ratio [HR]=1.490), early (HR=1.667), and late recurrence (HR=1.416), together with male sex, des-gamma carboxyprothrombin level, maximal tumor size, portal vein invasion, and satellite nodules (all P<0.05). However, WFA+- M2BP level was not predictive of grade B-C posthepatectomy liver failure. The cutoff value that maximized the sum of sensitivity (30.2%) and specificity (90.6%) was 2.14 (area under receiver operating characteristic curve=0.632, P=0.010). Patients with a WFA+-M2BP level >2.14 experienced recurrence more frequently than those with a WFA+-M2BP level ≤2.14 (P=0.011 by log-rank test), and had poorer postoperative outcomes than those with a WFA+-M2BP level ≤2.14 in terms of overall recurrence (56.0 vs. 34.5%, P=0.047) and early recurrence (52.0 vs. 20.7%, P=0.001).
Conclusions
WFA+-M2BP level is an independent predictive factor of HBV-related HCC recurrence after curative resection. Further studies should investigate incorporation of WFA+-M2BP level into tailored postoperative surveillance strategies for patients with CHB.

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Editorial

Viral hepatitis

Assessment of fibrotic burden among chronic hepatitis B virus-infected patients with normal transaminase level
Mi Young Jeon, Beom Kyung Kim, Seung Up Kim
Clin Mol Hepatol 2018;24(4):367-369.
Published online September 19, 2018
DOI: https://doi.org/10.3350/cmh.2018.1008

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Original Article

Viral hepatitis

Characterization and evaluation of liver fibrosis grade in patients with chronic hepatitis B virus infection and normal transaminases
San Juan López Cristina, Casado Martín Marta, González Sánchez Mercedes, Porcel Martín Almudena, Hernández Martínez Álvaro, Vega Sáenz Jose Luis, Parrón Carreño Tesifón
Clin Mol Hepatol 2018;24(4):384-391.
Published online July 4, 2018
DOI: https://doi.org/10.3350/cmh.2018.0004
Backgrounds/Aims
The
objective
of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis.
Methods
A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ≥7.9 kPa.
Results
A total of 214 patients were included in the analysis, and 62% of them had a BMI ≥25 kg/m2 . During follow-up, 4% of patients showed transaminase elevation (<1.5 times normal). Most patients had a viral DNA level <2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P<0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ≥25 kg/m2 versus 56% of patients without SF (P<0.05).
Conclusions
In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.

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Reviews

Viral hepatitis

Management of chronic hepatitis B patients in immunetolerant phase: what latest guidelines recommend
Grace Lai-Hung Wong
Clin Mol Hepatol 2018;24(2):108-113.
Published online January 22, 2018
DOI: https://doi.org/10.3350/cmh.2017.0068
The natural history of chronic hepatitis B (CHB) is complex and may run through different immune phases that may overlap. In particulars, the immune-tolerant phase is the most interesting and not as well understood as we thought. The concept of true immune tolerance have been under challenged from immunology points of view. The major international guidelines have not yet reached a consensus on the definition of the immune-tolerant phase. While positive hepatitis B e antigen (HBeAg), high serum hepatitis B virus (HBV) DNA and normal serum alanine aminotransferase (ALT) levels are the three key features of this phase, some guidelines also put age into consideration. A new nomenclature, Phase 1 or HBeAg-positive chronic HBV infection, is given by the latest European Association for the Study of the Liver (EASL) published in April 2017. While current guidelines advise against starting antiviral treatment for immune-tolerant CHB patients, some new data suggest treating such patients may reduce the risk of liver fibrosis progression and hepatocellular carcinoma.

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Liver fibrosis, cirrhosis, and portal hypertension

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Regina C. Lo, Haeryoung Kim
Clin Mol Hepatol 2017;23(4):302-307.
Published online December 20, 2017
DOI: https://doi.org/10.3350/cmh.2017.0078
The hepatic repair complex in the setting of cirrhosis has received increasing attention, as it implies the regression of cirrhosis, which was traditionally taken to be an irreversible state. In this brief review, the patterns of fibrosis, the existing staging systems for chronic liver disease and the histopathological features of cirrhosis regression are discussed.

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Liver Imaging

Liver fibrosis, cirrhosis, and portal hypertension

What we need to know when performing and interpreting US elastography
So Hyun Park, So Yeon Kim, Chong Hyun Suh, Seung Soo Lee, Kyoung Won Kim, So Jung Lee, Moon-Gyu Lee
Clin Mol Hepatol 2016;22(3):406-414.
Published online September 25, 2016
DOI: https://doi.org/10.3350/cmh.2016.0106
According to the increasing need for accurate staging of hepatic fibrosis, the ultrasound (US) elastography techniques have evolved significantly over the past two decades. Currently, US elastography is increasingly used in clinical practice. Previously published studies have demonstrated the excellent diagnostic performance of US elastography for the detection and staging of liver fibrosis. Although US elastography may seem easy to perform and interpret, there are many technical and clinical factors which can affect the results of US elastography. Therefore, clinicians who are involved with US elastography should be aware of these factors. The purpose of this article is to present a brief overview of US techniques with the relevant technology, the clinical indications, diagnostic performance, and technical and biological factors which should be considered in order to avoid misinterpretation of US elastography results.

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Original Articles

Liver fibrosis, cirrhosis, and portal hypertension

The usefulness of transient elastography, acoustic-radiation-force impulse elastography, and real-time elastography for the evaluation of liver fibrosis
Jong Ho Chung, Hyung Su Ahn, Sang Gyune Kim, Yun Nah Lee, Young Seok Kim, Soung Won Jeong, Jae Young Jang, Sae Hwan Lee, Hong Soo Kim, Boo Sung Kim
Clin Mol Hepatol 2013;19(2):156-164.
Published online June 27, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.2.156
Background/Aims

Several noninvasive methods have recently been developed for the evaluation of liver fibrosis. The accuracy of transient elastography (TE), acoustic-radiation-force impulse (ARFI) elastography, and real-time elastography (RTE) in predicting liver fibrosis were evaluated.

Methods

Seventy-four patients who had undergone a liver biopsy within the previous 6 months were submitted to evaluation with TE, ARFI, and RTE on the same day.

Results

There were significant correlations between fibrosis stage and liver stiffness measurement (LSM) using the three tested methods: TE, r2=0.272, P=0.0002; ARFI, r2=0.225, P=0.0017; and RTE, r2=0.228, P=0.0015. The areas under the receiver operating characteristic curves (AUROC) for the diagnosis of significant fibrosis (≥F2, Metavir stage) by TE, ARFI, RTE, TE/platelet count (PLT), velocity of shear wave (Vs)/PLT, and elasticity score (Es)/PLT were 0.727, 0.715, 0.507, 0.876, 0.874, and 0.811, respectively. The AUROC for the diagnosis of cirrhosis by TE, ARFI, RTE, TE/PLT, Vs/PLT, and Es/PLT were 0.786, 0.807, 0.767, 0.836, 0.819, and 0.838, respectively. Comparisons of AUROC between all LSMs for predicting significant fibrosis (≥F2) produced the following results: TE vs. RTE, P=0.0069; ARFI vs. RTE, P=0.0277; and TE vs. ARFI, P=0.8836. Applying PLT, the ability of each LSM to predict fibrosis stage significantly increased: TE/PLT vs. TE, P=0.0004; Vs/PLT vs. ARFI, P=0.0022; and Es/PLT vs. RTE, P<0.0001. However, the ability to predict cirrhosis was not enhanced, combining LSM and PLT.

Conclusions

TE and ARFI may be better methods for predicting significant liver fibrosis than RTE. This predictive ability increased significantly when accounting for platelet count. However, all of the measures had comparable efficacies for predicting cirrhosis.

Citations

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Comparison of various noninvasive serum markers of Liver fibrosis in chronic viral Liver disease
Sun Min Kim , Joo Hyun Sohn , Tae Yeob Kim , Young Wook Roh , Chang Soo Eun , Yong Cheol Jeon , Dong Soo Han , Young Ha Oh
Korean J Hepatol 2009;15(4):454-463.
Published online December 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.4.454
Background/Aims
The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. Methods: We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. Results: There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (≥F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (≥F3). Conclusions: Conclusions: All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis. (Korean J Hepatol 2009;15:454-463)

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The Relevance of Degree of Liver Fibrosis, Ito cell, and PKC Activity in Hepatic Fibrogenesis
Young Mi Jung, M.S., Kee Tack Jang, M.D., Yun Sil Lee1, Ph.D., In Kyoung Lim2, M.D., Mi Ran Kim, M.S., Min Jae Lee, Ph.D., Eui Keun Ham, M.D., Je G Chi, M.D., Jeong Wook Seo, M.D., In Ae Park, M.D., Chong Jai Kim, M.D., and Ja-June Jang, M.D.
Korean J Hepatol 1998;4(4):381-392.
Background
/ Aims : Hepatic fibrosis in rat induced by thioacet amide shares similar morphological and biochemical characteristics with human liver cirrhosis . Thioacetamide (T AA) initially induces accumulation of collagen in Disse space and event uallyleads to macro- and micronodular cirrhos is. Ito cell was believed to play a main role in hepatic fibrosis . And it s activity was known to be regulated by the expression of various genes . But little has been discovered about the upstream signal trans duction pathway of these genes in hepatic fibrosis. The expression of genesrelated to Ito cell activity was regulated by many transcription factors , the activity of which was regulated by protein kinase C( PKC) is oforms . So it is s upposed that PKC could be as s ociated with fibrosis in liver . Met hods : We investigated the correlation of PKC is oforms and It ocell activity in the course of hepatic fibrosis using TAA induced rat liver cirrhosis model. We used six week- old male rats , and administered 0.03% TAA in drinking water . The animals were sacrificed at 9, 20, and 30 weeks after TAA administration. The degree of hepatic fibrosis was evaluated by measuring the total amount of collagen. - SMA immunohist ochemical st aining of liver tissue was done to determine the Ito cell activity. The expression pattern of PKC isoforms was investigated by West ern blotting. Results : In TAA- treated group, collagen cont ent and Ito cell activity did not increase until 30 weeks and 20 weeks of treatment , respectively, while in control group collagen cont ent and Ito cell activity were not detected. Collagen content showed linear correlation with Ito cell activity. This implied that the proliferation of activated Ito cells was prior to the increase of collagen content . In view of expression pattern of PKC is oforms , PKC αshowed no difference in TAA- treated group and control group. In TAA-treated group, PKCβ1 exhibited increased level of expression in both particulate and cytosolic forms at 9 weeks , while PKCδand PKC εshowed striking shift to particulated form. After 20 weeks, all of the PKC β1, δ, and εdegenerated and showed remarkably decreased level of expression. This suggested PKC αhad no relation to hepatic fibrosis,while PKC β1, δ, and ε, showing activity at 9 weeks, were related to fibrosis og liver. In response to fibrogenic factors, molecules engaged in intracellular signal transduction pathway like PKC β1, δ, and ε, began to change prior to the increase of Ito cell activity, morphologic changes and alterations of collagen content. Conclusion : Our results strongly suggest that the activity of PKC isoforms play an important role in early step of hepatic fibrosis, while accompanying Ito cell activity do in later step.(Korean J Hepatol 1998;4:381 392)
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An Experimental Model of Hepatic Fibrosis Induced by Alcohol and CCl4 : Can the Lipopolysaccharide Prevent Liver Injury Induced by Alcohol and CCl4 ?
Hee Bok Chae, M.D., Lee Chan Jang, M.D.*, Seon Mee Park, M.D., Bo Ra Son, M.D.†, Rohyun Sung, M.D.‡, Jae Woon Choi, M.D.*
Korean J Hepatol 2002;8(2):173-178.
Background/Aims
It is well known that alcohol enhances the toxicity of CCL4. We tried to establish an alcoholic liver cirrhosis model by administration of alcohol and CCL4 to rats. We also wanted to know the hepatoprotective effect of low doses of lipopolysaccharide(LPS) in this animal model. Methods: Of 20 female adult rats, 8 were ingested with alcohol ad libitum(group 1) Another 6 were ingested with 10% alcohol and 50% 1mL/kg CCL4 intragastrically by Sonde twice a week(group 2) The remaining 6 were ingested with 10% alcohol, CCL4, and 0.1mg/kg LPS intraperitoneally twice a week(group 3) The fibrosis was evaluated semiquantitatively on a scale of 0(none) to 3(cirrhosis). Results: 1) After 10 weks, septal fibrosis or cirrhosis was produced in 9 out of 12 rats in groups 2 and 3 but there was no fibrotic change in group 1. 2) There was no significant difference in pathological grading between groups 2 and 3. Conclusions: Hepatic fibrosis or cirrhosis can be sufficiently induced by alcohol and repetitive CCL4 ingestion for 10 weeks. We can not prove the hepatoprotective effect of low dose LPS by semiquantitative evaluation of pathological grading.(Korean J Hepatol 2002;8:173-178)
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