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Steatotic liver disease

Correspondence on Letter regarding “Prognosis of biopsy-confirmed MASLD: A sub-analysis of the CLIONE study”
Hideki Fujii, Michihiro Iwaki, Yoshihiro Kamada
Clin Mol Hepatol 2024;30(2):281-283.
Published online April 1, 2024
DOI: https://doi.org/10.3350/cmh.2024.0214

Citations

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  • Reply to correspondence on “Prognosis of biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: A sub-analysis of the CLIONE study”
    Eileen Laurel Yoon, Dae Won Jun
    Clinical and Molecular Hepatology.2024; 30(4): 1033.     CrossRef
  • 5,148 View
  • 49 Download
  • Crossref

Original Articles

Steatotic liver disease

Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study
Michihiro Iwaki, Hideki Fujii, Hideki Hayashi, Hidenori Toyoda, Satoshi Oeda, Hideyuki Hyogo, Miwa Kawanaka, Asahiro Morishita, Kensuke Munekage, Kazuhito Kawata, Tsubasa Tsutsumi, Koji Sawada, Tatsuji Maeshiro, Hiroshi Tobita, Yuichi Yoshida, Masafumi Naito, Asuka Araki, Shingo Arakaki, Takumi Kawaguchi, Hidenao Noritake, Masafumi Ono, Tsutomu Masaki, Satoshi Yasuda, Eiichi Tomita, Masato Yoneda, Akihiro Tokushige, Yoshihiro Kamada, Hirokazu Takahashi, Shinichiro Ueda, Shinichi Aishima, Yoshio Sumida, Atsushi Nakajima, Takeshi Okanoue, Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)
Clin Mol Hepatol 2024;30(2):225-234.
Published online January 24, 2024
DOI: https://doi.org/10.3350/cmh.2023.0515
Background/Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study.
Methods
This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD.
Results
Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4).
Conclusions
Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.

Citations

Citations to this article as recorded by  Crossref logo
  • Metabolic dysfunction-associated steatotic liver disease and risk of four intrahepatic and extrahepatic diseases
    Yiyuan Xiao, Sihua Xu, Wenyan Hu, Jiapeng Huang, Deke Jiang, Rong Na, Zhaoqing Yin, Jingjing Zhang, Haitao Chen
    Annals of Hepatology.2025; 30(1): 101750.     CrossRef
  • Alcohol Intake and Cardiometabolic Risk Factors Are Independently Associated With a Higher AST/Platelet Ratio Index in Obese Males
    Hideki Fujii, Yoshihiro Kamada, Yuichiro Suzuki, Koji Sawada, Miwa Tatsuta, Tatsuji Maeshiro, Hiroshi Tobita, Tsubasa Tsutsumi, Takemi Akahane, Chitomi Hasebe, Miwa Kawanaka, Takaomi Kessoku, Yuichiro Eguchi, Hayashi Syokita, Atsushi Nakajima, Tomoari Kam
    Liver International Communications.2025;[Epub]     CrossRef
  • Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma
    Toru Nakamura, Atsutaka Masuda, Dan Nakano, Keisuke Amano, Tomoya Sano, Masahito Nakano, Takumi Kawaguchi
    Cells.2025; 14(6): 428.     CrossRef
  • Reducing complications of metabolic dysfunction–associated steatotic liver disease
    Naohiro Wada, Michihiro Iwaki, Takashi Kobayashi, Atsushi Nakajima, Masato Yoneda
    Expert Review of Gastroenterology & Hepatology.2025; 19(5): 577.     CrossRef
  • Cardiometabolic dysfunction burden and mortality outcomes in metabolic dysfunction-associated steatotic liver disease
    Ying Wen, Yu Min, Yi Lei, Zhigong Wei, Sophia Eugenia Martínez-Vázquez
    PLOS One.2025; 20(7): e0327772.     CrossRef
  • The PNPLA3 I148M variant is associated with immune cell infiltration and advanced fibrosis in MASLD: a prospective genotype–phenotype study
    Jaejun Lee, Jung Hoon Cha, Hee Sun Cho, Keungmo Yang, Hyun Yang, Heechul Nam, Mi Young Byun, Seok Keun Cho, Jinsung Park, Hyuk Wan Ko, Seong Wook Yang, Pil Soo Sung, Si Hyun Bae
    Journal of Gastroenterology.2025; 60(10): 1284.     CrossRef
  • Effects of laser acupuncture (stress-free therapy) on blood liver function indicators
    Yoshihiro Kamada, Takunori Sato, Takaomi Kessoku, Yoshio Sumida, Masafumi Ono, Kenji Ryotokuji
    Laser Therapy.2025;[Epub]     CrossRef
  • Clinical impact of five cardiometabolic risk factors in metabolic dysfunction-associated steatotic liver disease (MASLD): Insights into regional and ethnic differences
    Joo Hyun Oh, Dae Won Jun
    Clinical and Molecular Hepatology.2024; 30(2): 168.     CrossRef
  • Correspondence on Letter regarding “Prognosis of biopsy-confirmed MASLD: A sub-analysis of the CLIONE study”
    Hideki Fujii, Michihiro Iwaki, Yoshihiro Kamada
    Clinical and Molecular Hepatology.2024; 30(2): 281.     CrossRef
  • Usefulness of health checkup‐based indices in identifying metabolic dysfunction‐associated steatotic liver disease
    Takao Miwa, Satoko Tajirika, Nanako Imamura, Miho Adachi, Ryo Horita, Tatsunori Hanai, Cheng Han Ng, Mohammad Shadab Siddiqui, Taku Fukao, Masahito Shimizu, Mayumi Yamamoto
    JGH Open.2024;[Epub]     CrossRef
  • Association between nonalcholic fatty liver disease and pancreatic cancer: Epidemiology, mechanisms, and antidiabetic medication
    Takahiko Sakaue, Hiroya Terabe, Hidetoshi Takedatsu, Takumi Kawaguchi
    Hepatology Research.2024; 54(8): 729.     CrossRef
  • Reply to correspondence on “Prognosis of biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: A sub-analysis of the CLIONE study”
    Eileen Laurel Yoon, Dae Won Jun
    Clinical and Molecular Hepatology.2024; 30(4): 1033.     CrossRef
  • Metabolic-associated fatty liver disease is less effective in predicting mortality than non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease: Letter to the editor on “Prognosis of biopsy-confirmed metabolic dysfun
    Yixuan Zhu, Xiaoyan Ma, Wenjing Ni, Yee Hui Yeo, Junping Shi, Jie Li
    Clinical and Molecular Hepatology.2024; 30(4): 974.     CrossRef
  • Sequential Diagnostic Approach Using FIB-4 and ELF for Predicting Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease
    Yeo-Wool Kang, Yang-Hyun Baek, Sang-Yi Moon
    Diagnostics.2024; 14(22): 2517.     CrossRef
  • Combi-Elastography versus Transient Elastography for Assessing the Histological Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease
    Yun Kyu Lee, Dong Hyeon Lee, Sae Kyung Joo, Heejoon Jang, Young Ho So, Siwon Jang, Dong Ho Lee, Jeong Hwan Park, Mee Soo Chang, Won Kim
    Gut and Liver.2024; 18(6): 1048.     CrossRef
  • 9,734 View
  • 277 Download
  • 18 Web of Science
  • Crossref

Hepatic neoplasm

Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment
Miguel Sogbe, Idoia Bilbao, Francesco P. Marchese, Jon Zazpe, Annarosaria De Vito, Marta Pozuelo, Delia D’Avola, Mercedes Iñarrairaegui, Carmen Berasain, Maria Arechederra, Josepmaria Argemi, Bruno Sangro
Clin Mol Hepatol 2024;30(2):177-190.
Published online December 29, 2023
DOI: https://doi.org/10.3350/cmh.2023.0426
Background/Aims
New prognostic markers are needed to identify patients with hepatocellular carcinoma (HCC) who carry a worse prognosis. Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess both circulating tumor DNA (ctDNA) fraction and large structural genomic alterations. Here, we studied the performance of ULP-WGS of plasma cfDNA to infer prognosis in patients with HCC.
Methods
Plasma samples were obtained from patients with HCC prior to surgery, locoregional or systemic therapy, and were analyzed by ULP-WGS of cfDNA to an average genome-wide fold coverage of 0.3x. ctDNA and copy number alterations (CNA) were estimated using the software package ichorCNA.
Results
Samples were obtained from 73 HCC patients at different BCLC stages (BCLC 0/A: n=37, 50.7%; BCLC B/C: n=36, 49.3%). ctDNA was detected in 18 out of 31 patients who received systemic treatment. Patients with detectable ctDNA showed significantly worse overall survival (median, 13.96 months vs not reached). ctDNA remained an independent predictor of prognosis after adjustment by clinical-pathologic features and type of systemic treatment (hazard ratio 7.69; 95%, CI 2.09–28.27). Among ctDNA-positive patients under systemic treatments, the loss of large genomic regions in 5q and 16q arms was associated with worse prognosis after multivariate analysis.
Conclusions
ULP-WGS of cfDNA provides clinically relevant information about the tumor biology. The presence of ctDNA and the loss of 5q and 16q arms in ctDNA-positive patients are independent predictors of worse prognosis in patients with advanced HCC receiving systemic therapy.

Citations

Citations to this article as recorded by  Crossref logo
  • Prognostic value of circulating tumor DNA in different cancer types detected by ultra-low-pass whole-genome sequencing: a systematic review and patient-level survival data meta-analysis
    Miguel Sogbe, Daniel Aliseda, Paloma Sangro, Manuel de la Torre-Aláez, Bruno Sangro, Josepmaria Argemi
    Carcinogenesis.2025;[Epub]     CrossRef
  • Liquid biopsy in hepatocellular carcinoma: Challenges, advances, and clinical implications
    Jaeho Park, Yi-Te Lee, Vatche G. Agopian, Jessica S Liu, Ekaterina K. Koltsova, Sungyong You, Yazhen Zhu, Hsian-Rong Tseng, Ju Dong Yang
    Clinical and Molecular Hepatology.2025; 31(Suppl): S255.     CrossRef
  • Somatic Copy Number Alterations in Circulating Cell-Free DNA as a Prognostic Biomarker for Hepatocellular Carcinoma: Insights from a Proof-of-Concept Study
    Elisa Pinto, Elisabetta Lazzarini, Filippo Pelizzaro, Martina Gambato, Laura Santarelli, Sara Potente, Paola Zanaga, Teresa Zappitelli, Romilda Cardin, Patrizia Burra, Fabio Farinati, Chiara Romualdi, Diego Boscarino, Valeria Tosello, Stefano Indraccolo,
    Cancers.2025; 17(7): 1115.     CrossRef
  • Genome-Wide Methylation Sequencing to Identify DNA Methylation Markers for Early-stage Hepatocellular Carcinoma in Liver and Blood
    Siyu Fu, Ruben G. Boers, Joachim B. Boers, Pam E. van der Meeren, Jean Helmijr, Vanja de Weerd, Michail Doukas, Maurice Jansen, Bettina E. Hansen, Roeland F. de Wilde, Dave Sprengers, Joost Gribnau, Saskia M. Wilting, José D. Debes, Andre Boonstra
    Journal of Experimental & Clinical Cancer Research.2025;[Epub]     CrossRef
  • Redefining precision medicine in hepatocellular carcinoma through omics, translational, and AI-based innovations
    Rashi Jain, Sathish Kumar Mungamuri, Prabha Garg
    The Journal of Precision Medicine: Health and Disease.2025; 1: 100003.     CrossRef
  • Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer
    Carolyn Hruban, Daniel C. Bruhm, Inna M. Chen, Shashikant Koul, Akshaya V. Annapragada, Nicholas A. Vulpescu, Sarah Short, Susann Theile, Kavya Boyapati, Bahar Alipanahi, Zachary L. Skidmore, Alessandro Leal, Stephen Cristiano, Vilmos Adleff, Julia S. Joh
    Science Advances.2025;[Epub]     CrossRef
  • Shallow whole-genome sequencing of circulating tumour DNA predicts clinical outcomes to systemic therapy in advanced hepatocellular carcinoma
    Venkata Ramana Mallela, Sultan N. Alharbi, Mathew Vithayathil, Caroline Ward, Rishi Patel, Rohini Sharma
    European Journal of Cancer.2025; 227: 115633.     CrossRef
  • Hepatic Metabolic Signature and Its Association with the Response to Immunotherapy in Hepatocellular Carcinoma
    Hyewon Park, Sowon Park, Kena Park, Sun Young Yim, Ju-Seog Lee, Sung Hwan Lee
    ImmunoTargets and Therapy.2025; Volume 14: 787.     CrossRef
  • Dual tissue mRNA and serum protein signatures improve risk stratification in hepatocellular carcinoma
    Ding-Fan Guo, Lin-Wei Fan, Qi Wen, Jin-Ke Wang, Yun-Hui Liang, Qi Feng, Ting Wang, Kun-He Zhang
    npj Precision Oncology.2025;[Epub]     CrossRef
  • Genomics and Epigenomics Approaches for the Quantification of Circulating Tumor DNA in Liquid Biopsy: Relevance of a Multimodal Strategy
    Elisa De Paolis, Alessia Perrucci, Gabriele Albertini Petroni, Alessandra Conca, Matteo Corsi, Andrea Urbani, Angelo Minucci
    International Journal of Molecular Sciences.2025; 26(22): 10982.     CrossRef
  • Advances in the Diagnosis, Treatment, and Management of Liver Nodules: A Comprehensive Review
    Chang Gao, Dongyang Chen, Youpeng Chen
    Portal Hypertension & Cirrhosis.2025;[Epub]     CrossRef
  • Research progress and frontier trends in liver cancer immunotherapy in the post-COVID-19 era (2020–2024): a visualization analysis based on bibliometric methods
    Shicai Liang, Xusheng Zhang, Xuebo Wang, Yannan Xie, Jialong Wang, Jiawei Wang, Bendong Chen
    Discover Oncology.2025;[Epub]     CrossRef
  • Exploring the prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma
    Ji Eun Han, Hyo Jung Cho
    Clinical and Molecular Hepatology.2024; 30(2): 160.     CrossRef
  • Clinical significance of circulating biomarkers of immune-checkpoint molecules with atezolizumab plus bevacizumab therapy in unresectable hepatocellular carcinoma
    Makoto Chuma, Haruki Uojima, Hidenori Toyoda, Atsushi Hiraoka, Yoshitake Arase, Masanori Atsukawa, Norio Itokawa, Tomomi Okubo, Toshifumi Tada, Kazushi Numata, Manabu Morimoto, Makoto Sugimori, Akito Nozaki, Shuichiro Iwasaki, Satoshi Yasuda, Yuichi Koshi
    Hepatology International.2024; 18(5): 1472.     CrossRef
  • Clinical Parameters Work Well as Predictive Factors for Atezolizumab and Bevacizumab Treatment in Hepatocellular Carcinoma
    Ji Yeon Lee, Pil Soo Sung
    Gut and Liver.2024; 18(4): 558.     CrossRef
  • From haystack to high precision: advanced sequencing methods to unraveling circulating tumor DNA mutations
    Tamires Ferreira da Silva, Juscelino Carvalho de Azevedo, Eliel Barbosa Teixeira, Samir Mansour Moraes Casseb, Fabiano Cordeiro Moreira, Paulo Pimentel de Assumpção, Sidney Emanuel Batista dos Santos, Danielle Queiroz Calcagno
    Frontiers in Molecular Biosciences.2024;[Epub]     CrossRef
  • Correspondence to editorial on “Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma”
    Su Bin Lim, Hyo Jung Cho
    Clinical and Molecular Hepatology.2024; 30(4): 1009.     CrossRef
  • Genomic biomarkers to predict response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma: Insights from the IMbrave150 trial
    Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S. Lee, Ahmed O. Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A. Curran, Ji Hoon Kim, Ju-Seog Lee
    Clinical and Molecular Hepatology.2024; 30(4): 807.     CrossRef
  • Blood biomarkers of hepatocellular carcinoma: a critical review
    Junsheng Zhao, Zekai Hu, Xiaoping Zheng, Yajie Lin, Xiao Liu, Junjie Zhang, Jing Peng, Hainv Gao
    Frontiers in Cell and Developmental Biology.2024;[Epub]     CrossRef
  • 12,504 View
  • 368 Download
  • 16 Web of Science
  • Crossref

Letter to the Editor

Viral hepatitis

Dear Editor, I read with great interest the editorial paper by Oh and Sinn [1] entitled “Is liver biopsy mandatory to identify immunetolerant phase of chronic hepatitis B?” published online ahead of print. In their paper, Oh and Sinn [1] suggested that the status of patients presumed to be in the immune-tolerant phase without histological information should be carefully evaluated. I would like to draw attention to the following printing error related to the normal serum alanine aminotransferase (ALT) levels according to the American Association for the Study of Liver Disease (AASLD) guidelines. The recommended normal serum ALT level for males was incorrectly written as “<33 U/L” in both the text and Table 1. However, according to the AASLD 2018 hepatitis B guidance [2], the upper limit of normal for ALT in males is 35 U/L. I believe that correcting this printing error will prevent any possible confusion in daily practice guiding management decisions.
  • 4,913 View
  • 33 Download

Editorials

Viral hepatitis

Citations

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  • 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
    Clinical and Molecular Hepatology.2024; 30(Suppl): S106.     CrossRef
  • Letter regarding “Is liver biopsy essential to identifying the immune tolerant phase of chronic hepatitis B?”
    Halil Haldun Emiroglu
    Clinical and Molecular Hepatology.2023; 29(3): 812.     CrossRef
  • The Relationship between Mean Platelet Volume and Neutrophil–Lymphocyte Ratio and Liver Fibrosis in Patients with Chronic Hepatitis B
    Mehmet Onder Ekmen, Metin Uzman
    Medicina.2023; 59(7): 1287.     CrossRef
  • 7,143 View
  • 77 Download
  • 4 Web of Science
  • Crossref

Viral hepatitis

The imitator of immune-tolerant chronic hepatitis B: A killer in disguise
Moon Haeng Hur, Jeong-Hoon Lee
Clin Mol Hepatol 2023;29(2):363-366.
Published online March 9, 2023
DOI: https://doi.org/10.3350/cmh.2023.0079

Citations

Citations to this article as recorded by  Crossref logo
  • Extrahepatic malignancies and antiviral drugs for chronic hepatitis B: A nationwide cohort study
    Moon Haeng Hur, Dong Hyeon Lee, Jeong-Hoon Lee, Mi-Sook Kim, Jeayeon Park, Hyunjae Shin, Sung Won Chung, Hee Jin Cho, Min Kyung Park, Heejoon Jang, Yun Bin Lee, Su Jong Yu, Sang Hyub Lee, Yong Jin Jung, Yoon Jun Kim, Jung-Hwan Yoon
    Clinical and Molecular Hepatology.2024; 30(3): 500.     CrossRef
  • Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma
    Jeayeon Park, Sung Won Chung, Yun Bin Lee, Hyunjae Shin, Moon Haeng Hur, Heejin Cho, Min Kyung Park, Jeonghwan Youk, Ji Yun Lee, Jeong-Ok Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Tae Min Kim, Jeong-Hoon Lee
    Clinical and Molecular Hepatology.2023; 29(3): 794.     CrossRef
  • 6,448 View
  • 107 Download
  • 2 Web of Science
  • Crossref

Original Article

Viral hepatitis

Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune-tolerant phase
Jeong-Ju Yoo, Soo Young Park, Ji Eun Moon, Yu Rim Lee, Han Ah Lee, Jieun Lee, Young Seok Kim, Yeon Seok Seo, Sang Gyune Kim
Clin Mol Hepatol 2023;29(2):482-495.
Published online January 5, 2023
DOI: https://doi.org/10.3350/cmh.2022.0322
Background/Aims
The histologic status of the immune-tolerant (IT) phase of chronic hepatitis B relative to long-term outcomes is unclear. This study aimed to discover how the serological criteria currently in use correspond to histologic criteria in determining the IT phase and indication for liver biopsy.
Methods
Patients in the serological IT phase determined by positive hepatitis B e antigen, hepatitis B virus (HBV) DNA ≥106 IU/mL, and normal or minimally elevated alanine aminotransferase (ALT) ≤60 IU/L, who underwent liver biopsy at three different hospitals were included. The distribution of the histologic IT phase, defined as fibrosis of stage 1 or less and inflammation of grade 1 or less, was compared with that of the serological IT phase. The risk factors for the incidence of liver-related events, such as hepatocellular carcinoma, liver cirrhosis, liver transplantation, and death, were also analyzed.
Results
Eighty-two (31.7%) out of 259 clinically suspected IT phase patients belonged to the histologic IT phase. Age over 35, high AST, and low albumin were useful for ruling out the histologic IT phase. Risk factors predicting liver-related events were age and significant fibrosis stage. There was no significant difference in the proportion of histologic IT phase and clinical prognosis between normal ALT and mildly elevated ALT groups. However, even in patients with normal ALT, age was an important factor in predicting the presence of the histologic IT phase.
Conclusions
A significant number of patients who belonged to the serological IT phase were not in the histologic IT phase. Patients over 35 years and those with high AST, low albumin, and low HBV DNA levels were more likely to experience poor long-term clinical outcomes. Therefore, additional histologic assessment should be considered.

Citations

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  • Risk of Hepatocellular Carcinoma Decreases After Antiviral Therapy–Induced HBsAg Seroclearance
    Han Ah. Lee, Hyun Woong Lee, Yeon Seok Seo, Dong Hyun Sinn, Sang Hoon Ahn, Beom Kyung Kim, Seung Up Kim
    Journal of Gastroenterology and Hepatology.2025; 40(7): 1675.     CrossRef
  • Unraveling Demographic Patterns in Hepatitis B Clinical and Laboratory Profiles: Insights From a Ghanaian Cohort: A Retrospective Study
    Napoleon Bellua Sam, Saeed Folorunsho Majeed, Adams Dramani
    Health Science Reports.2025;[Epub]     CrossRef
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    Tai-Chung Tseng, Tetsuya Hosaka, Mei-Hung Pan, Chun-Jen Liu, Fumitaka Suzuki, Chien-Jen Chen, Tung-Hung Su, Hiromitsu Kumada, Wan-Ting Yang, Hung-Chih Yang, Chen-Hua Liu, Pei-Jer Chen, Hwai-I. Yang, Jia-Horng Kao
    Hepatology.2025;[Epub]     CrossRef
  • Cost‐Effectiveness of Antiviral Therapy in Patients With High Viremic Indeterminate Phase Chronic Hepatitis B
    Suk‐Chan Jang, Won‐Mook Choi, Gi‐Ae Kim, Gwang Hyeon Choi, Yun Bin Lee, Dong Hyun Sinn, Hye‐Lin Kim, Young‐Suk Lim
    Liver International.2025;[Epub]     CrossRef
  • Comparison of the efficacy and action mechanism of Chinese patent medicines for liver fibrosis and cirrhosis
    Lingping Fu, Jin Xie, ZeXin Wang, Tao Jiang, Yi Zeng, Jing Yan, Rong Sun, Mengshuang Huang, Shengyi Du, Xiaobao Wang, Yuyang Liu, Kailai Xi, Ailin Chen, Xiao Ma, Jinhao Zeng, Thomas Efferth
    Phytomedicine.2025; 148: 157246.     CrossRef
  • Longitudinal observation of chronic domestic cat hepadnavirus infection in cats with evidence of extrahepatic involvement
    Sabrina Wahyu Wardhani, Sitthichok Lacharoje, Tanit Kasantikul, Chutchai Piewbang, Somporn Techangamsuwan
    Journal of Feline Medicine and Surgery.2025;[Epub]     CrossRef
  • Should Indications for Antiviral Therapy for Hepatitis B Be Broadened to Include Immune-Tolerant Patients, Inactive Carriers, or Patients in the “Gray Zone”?
    Yen-Chun Liu, Wen-Juei Jeng
    Current Hepatology Reports.2024; 23(1): 11.     CrossRef
  • Stat3 activation-triggered transcriptional networks govern the early stage of HBV-induced hepatic inflammation
    Jinglin Tang, Jiaxuan Zhang, Gaoli Zhang, Wenhui Peng, Ning Ling, Yingzhi Zhou, Hongmei Xu, Hong Ren, Min Chen, Marthandan Mahalingam, Swati Jain
    mBio.2024;[Epub]     CrossRef
  • Noninvasive Models to Assess Liver Inflammation and Fibrosis in Chronic HBV Infected Patients with Normal or Mildly Elevated Alanine Transaminase Levels: Which One Is Most Suitable?
    Shasha Ma, Lian Zhou, Shutao Lin, Mingna Li, Jing Luo, Lubiao Chen
    Diagnostics.2024; 14(5): 456.     CrossRef
  • Lack of association between early on-treatment HBeAg seroclearance and development of hepatocellular carcinoma or decompensated cirrhosis
    Hyunjae Shin, Won-Mook Choi, Seung Up Kim, Yunmi Ko, Youngsu Park, Jeayeon Park, Moon Haeng Hur, Min Kyung Park, Yun Bin Lee, Yoon Jun Kim, Jung-Hwan Yoon, Jeong-Hoon Lee, Fabien Zoulim
    JHEP Reports.2024; 6(7): 101089.     CrossRef
  • Inverse relationship between HBV DNA levels and liver histopathological changes in immune‐tolerant CHB patients
    Deliang Huang, Huiyi Lai, Zhibin Zhu, Hong Yu, Jinghan Peng, Yuanyuan Chen, Xuejiao Liao, Jun Chen
    Journal of Viral Hepatitis.2024; 31(7): 363.     CrossRef
  • Editorial: High qHBsAg—is it a good or bad signal?
    Beom Kyung Kim
    Alimentary Pharmacology & Therapeutics.2024; 59(12): 1616.     CrossRef
  • Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase
    Jian Wang, Li Zhu, Zhiyi Zhang, Shaoqiu Zhang, Yifan Pan, Yuanyuan Li, Fei Cao, Chao Jiang, Tao Fan, Ye Xiong, Jiacheng Liu, Yuxin Chen, Shengxia Yin, Xin Tong, Chuanwu Zhu, Xingxiang Liu, Jie Li, Chao Wu, Rui Huang
    Virology Journal.2024;[Epub]     CrossRef
  • Estimating the key outcomes and hepatocellular carcinoma risk in patients in immune‐tolerant phase of chronic hepatitis B virus infection: A systematic review and meta‐analysis
    Min Liu, Taixue Zhao, Jinyang Zhang, Bing Bu, Ruyi Zhang, Xueshan Xia, Jiawei Geng
    Reviews in Medical Virology.2024;[Epub]     CrossRef
  • Significant liver histological change is common in HBeAg-positive chronic hepatitis B with normal ALT
    Menghui Duan, Huanming Xiao, Meijie Shi, Yubao Xie, Pengtao Zhao, Sheng Li, Xiaoling Chi, Xueen Liu, Hui Zhuang
    BMC Infectious Diseases.2024;[Epub]     CrossRef
  • Preface
    Seung Up Kim
    Clinical and Molecular Hepatology.2024; 30(Suppl): S3.     CrossRef
  • 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
    Clinical and Molecular Hepatology.2024; 30(Suppl): S106.     CrossRef
  • HBeAg-positive CHB patients with indeterminate phase associated with a high risk of significant fibrosis
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Review

Steatotic liver disease

Non-alcoholic fatty liver disease: the pathologist’s perspective
Wei-Qiang Leow, Anthony Wing-Hung Chan, Paulo Giovanni L. Mendoza, Regina Lo, Kihan Yap, Haeryoung Kim
Clin Mol Hepatol 2023;29(Suppl):S302-S318.
Published online November 15, 2022
DOI: https://doi.org/10.3350/cmh.2022.0329
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases characterized by fatty accumulation in hepatocytes, ranging from steatosis, non-alcoholic steatohepatitis, to cirrhosis. While histopathological evaluation of liver biopsies plays a central role in the diagnosis of NAFLD, limitations such as the problem of interobserver variability still exist and active research is underway to improve the diagnostic utility of liver biopsies. In this article, we provide a comprehensive overview of the histopathological features of NAFLD, the current grading and staging systems, and discuss the present and future roles of liver biopsies in the diagnosis and prognostication of NAFLD.

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Original Article

Discovery of dipeptidyl peptidase-4 inhibitor specific biomarker in non-alcoholic fatty liver disease mouse models using modified basket trial
Ju Hee Oh, Dae Won Jun, Hye Young Kim, Seung Min Lee, Eileen L. Yoon, Jungwook Hwang, Jung Hwan Park, Hanbi Lee, Wankyu Kim, Hyunsung Kim
Clin Mol Hepatol 2022;28(3):497-509.
Published online April 28, 2022
DOI: https://doi.org/10.3350/cmh.2022.0019
Background/Aims
We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD).
Methods
An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy.
Results
DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels.
Conclusions
The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.

Citations

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    Nutrients.2024; 16(7): 920.     CrossRef
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Editorial

Hepatic neoplasm

Biopsy or cytology for diagnosing hepatic focal lesions?
Haeryoung Kim
Clin Mol Hepatol 2021;27(2):278-280.
Published online March 4, 2021
DOI: https://doi.org/10.3350/cmh.2021.0031

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Original Article

Hepatic neoplasm

Direct comparison of biopsy techniques for hepatic malignancies
Shang-Chin Huang, Ja-Der Liang, Shih-Jer Hsu, Tzu-Chan Hong, Hung-Chih Yang, Jia-Horng Kao
Clin Mol Hepatol 2021;27(2):305-312.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0301
Background/Aims
The core needle biopsy (CNB), fine needle aspiration cytology (FNAC) and touch imprint cytology (TIC) are commonly used tools for the diagnosis of hepatic malignancies. However, little is known about the benefits and criteria for selecting appropriate technique among them in clinical practice. We aimed to compare the sensitivity of ultrasound-guided CNB, FNAC, TIC as well as combinations for the diagnosis of hepatic malignancies, and to determine the factors associated with better sensitivity in each technique.
Methods
From January 2018 to December 2019, a total of 634 consecutive patients who received ultrasound-guided liver biopsies at the National Taiwan University Hospital was collected, of whom 235 with confirmed malignant hepatic lesions receiving CNB, FNAC and TIC simultaneously were enrolled for analysis. The clinical and procedural data were compared.
Results
The sensitivity of CNB, FNAC and TIC for the diagnosis of malignant hepatic lesions were 93.6%, 71.9%, and 85.1%, respectively. Add-on use of FNAC or TIC to CNB provided additional sensitivity of 2.1% and 0.4%, respectively. FNAC exhibited a significantly higher diagnostic rate in the metastatic cancers (P=0.011), hyperechoic lesions on ultrasound (P=0.028), and those with depth less than 4.5 cm from the site of needle insertion (P=0.036).
Conclusions
The sensitivity of CNB is superior to that of FNAC and TIC for the diagnosis of hepatic malignancies. Nevertheless, for shallow (depth <4.5 cm) and hyperechoic lesions not typical for primary liver cancers, FNAC alone provides excellent sensitivity.

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Review

Steatotic liver disease

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a major cause of liver fibrosis and cirrhosis. Accurate assessment of liver fibrosis is important for predicting disease outcomes and assessing therapeutic response in clinical practice and clinical trials. Although noninvasive tests such as transient elastography and magnetic resonance elastography are preferred where possible, histological assessment of liver fibrosis via semiquantitative scoring systems remains the current gold standard. Collagen proportionate area provides more granularity by measuring the percentage of fibrosis on a continuous scale, but is limited by the absence of architectural input. Although not yet used in routine clinical practice, advances in second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy imaging show great promise in characterising architectural features of fibrosis at the individual collagen fiber level. Quantification and calculation of different detailed variables of collagen fibers can be used to establish algorithm-based quantitative fibrosis scores (e.g., qFibrosis, q-FPs), which have been validated against fibrosis stage in NAFLD. Artificial intelligence is being explored to further refine and develop quantitative fibrosis scoring methods. SHG-microscopy shows promise as the new gold standard for the quantitative measurement of liver fibrosis. This has reaffirmed the pivotal role of the liver biopsy in fibrosis assessment in NAFLD, at least for the near-future. The ability of SHG-derived algorithms to intuitively detect subtle nuances in liver fibrosis changes over a continuous scale should be employed to redress the efficacy endpoint for fibrosis in NASH clinical trials; this approach may improve the outcomes of the trials evaluating therapeutic response to antifibrotic drugs.

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Editorial

Artificial intelligence, epidemiology, methodology, or others

Is liver biopsy still useful in the era of non-invasive tests?
Tae Seop Lim, Ja Kyung Kim
Clin Mol Hepatol 2020;26(3):302-304.
Published online July 1, 2020
DOI: https://doi.org/10.3350/cmh.2020.0081

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Original Article

Cholestatic liver disease

Clinical application of ultrasonography-guided percutaneous liver biopsy and its safety over 18 years
Young Chang, Jun Il Kim, Bora Lee, Sang Gyune Kim, Min Jung Jung, Young Seok Kim, Soung Won Jeong, Jae Young Jang, Jeong-Ju Yoo
Clin Mol Hepatol 2020;26(3):318-327.
Published online May 25, 2020
DOI: https://doi.org/10.3350/cmh.2019.0019n
Background/Aims
Liver biopsy (LB) remains the gold standard for the evaluation of liver disease. However, over the past two decades, many noninvasive tests have been developed and utilized in clinical practice as alternatives to LB. The aim of this study was to evaluate the clinical use and safety of LB in the era of noninvasive assessment of liver fibrosis.
Methods
This retrospective study included 1,944 consecutive cases of LB performed between 2001 and 2018 in a tertiary hospital. All of the LBs were conducted under ultrasonography guidance with 18-gauge cutting needles.
Results
LBs were performed an average of approximately 108 times per year during the study period. Chronic hepatitis B (25.3%) and suspected malignancy (20.5%) were the two most common indications for LB. The use of LB for nonalcoholic fatty liver disease increased from 8.1% to 17.2% in the past 5 years compared to the last 10 years, while that for viral hepatitis decreased from 40.3% to 18.9%. Discordance rate between the suspected diagnosis and the final diagnosis was 2.6% (51 cases). The overall rate of major adverse events was 0.05% (one case), which involved delayed bleeding at the biopsy site. Liver cirrhosis was observed in 563 cases (28.9%), and the presence of cirrhosis did not affect the frequency of complications (P=0.289).
Conclusions
LB is widely used in clinical practice as an irreplaceable diagnostic tool, even in the era of noninvasiveness. Ultrasonography-guided LB can be performed safely in patients with liver cirrhosis.

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Review

Benign liver tumors and cystic disease of liver

Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma
Massimo Roncalli, Amedeo Sciarra, Luca Di Tommaso
Clin Mol Hepatol 2016;22(2):199-211.
Published online May 18, 2016
DOI: https://doi.org/10.3350/cmh.2016.0101
Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.

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Original Articles

Liver fibrosis, cirrhosis, and portal hypertension

Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis
Kyoung Min Moon, Gaeun Kim, Soon Koo Baik, Eunhee Choi, Moon Young Kim, Hyoun A Kim, Mee Yon Cho, Seung Yong Shin, Jung Min Kim, Hong Jun Park, Sang Ok Kwon, Young Woo Eom
Clin Mol Hepatol 2013;19(4):389-398.
Published online December 28, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.4.389
Background/Aims

We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis.

Methods

Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated.

Results

The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4.

Conclusions

The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.

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Prediction of compensated liver cirrhosis by ultrasonography and routine blood tests in patients with chronic viral hepatitis
Hong Sub Lee, Jai Keun Kim, Jae Youn Cheong, Eun Jin Han, So-Yeon An, Jun Ha Song, Yun Jung Jung, Sung Chan Jeon, Min Wook Jung, Eun-Jung Jang, Sung Won Cho
Korean J Hepatol 2010;16(4):369-375.
Published online December 31, 2010
DOI: https://doi.org/10.3350/kjhep.2010.16.4.369
Background/Aims

Liver biopsy is a standard method for diagnosis of liver cirrhosis in patients with chronic hepatitis. Because liver biopsy is an invasive method, non-invasive methods have been used for diagnosis of compensated liver cirrhosis in patients with chronic hepatitis. The current study was designed to evaluate the usefulness of ultrasonography and routine blood tests for diagnosis of compensated liver cirrhosis in patients with chronic viral hepatitis.

Methods

Two hundred three patients with chronic viral hepatitis who underwent liver biopsy were included in this study and ultrasonography and routine blood tests were analyzed retrospectively. Ultrasonographic findings, including surface nodularity, parenchyma echogenecity, and spleen size, were evaluated. The diagnostic accuracy of ultrasonography and routine blood tests were examined.

Results

Discriminant analysis with forward stepwise selection of variables showed that liver surface nodularity, platelet count, and albumin level were independently associated with compensated liver cirrhosis (p<0.05). Cross-tabulation revealed that the following 4 variables had >95% specificity: platelet count <100,000 /uL; albumin level <3.5 g/dL; INR >1.3; and surface nodularity. If at least one of the four variables exists in a patient with chronic viral hepatitis, we can predict liver cirrhosis with 90% specificity and 61% sensitivity.

Conclusions

These results suggest that four variables (platelet count <100,000 /uL, albumin level <3.5 g/dL, INR >1.3, and surface nodularity) can be used for identification of liver cirrhosis in patients with chronic viral hepatitis with high specificity.

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Case Report

A case of acute cholestatic hepatitis induced by Corydalis speciosa Max.
Hyun Seok Kang , Hyuk Soon Choi , Tae Jung Yun , Kwang Gyun Lee , Yeon Seok Seo , Jong Eun Yeon , Kwan Soo Byun , Soon Ho Um , Chang Duck Kim , Ho Sang Ryu
Korean J Hepatol 2009;15(4):517-523.
Published online December 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.4.517
Herbs are widely used as treatments for various symptoms. However, several herbs have been reported to be inducers of liver injury. We report herein a case of hepatotoxicity induced by Corydalis speciosa Max. A 37-year-old male complained of jaundice and mild abdominal discomfort. A thorough history was taken, and laboratory investigation, diagnostic imaging studies, and percutaneous liver biopsy sampling were conducted to determine the cause of liver injury. An accurate cause was not revealed. We administered supportive management for acute cholestatic hepatitis of unknown origin, after which his symptoms disappeared and serum aminotransferase levels decreased gradually to near normal levels. However, at 2 months after discharge, the symptoms and the elevation of aminotransferase levels recurred. At that time he told us that he had repeatedly but unintentionally eaten a herb called “Hwang-geun cho”(Corydalis speciosa Max.). Thus, we diagnosed his case as herbal hepatotoxicity. (Korean J Hepatol 2009;15:517-523)

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Review

Pathology of nonalcoholic steatohepatitis
Yoon Mi Jeen , So Young Jin
Korean J Hepatol 2009;15(2):122-130.
Published online June 30, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.2.122
Nonalcoholic steatohepatitis (NASH), one of the NAFLDs (nonalcoholic fatty liver diseases), is regarded as a hepatic manifestation of metabolic syndrome. NASH can progress to cirrhosis, and possibly to hepatic malignancy. Currently, liver biopsy is the only reliable method of assessing the presence or absence of NASH and the stage of fibrosis. The finding of steatosis with evidence of hepatocyte injury such as inflammation, ballooning, degeneration, and/or fibrosis, is generally essential for making a diagnosis of NASH. However, its diagnostic criteria have not yet been established. The pathologic findings of NASH and related diseases, and the grading system currently in use are reviewed herein. (Korean J Hepatol 2009;15:122-130)

Citations

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Liver Pathology

Well differentiated hepatocellular carcinoma: Pathological diagnosis of needle biopsied Liver tissue
Jae Yeon Seok , Young Nyun Park
Korean J Hepatol 2009;15(1):96-100.
Published online March 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.1.96
  • 4,663 View
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Original Articles

Hepatitis B core antigen expression pattern predicts response to Lamivudine therapy in patients with chronic hepatitis B
Kyeh Dong Shi, M.D., Seong Gyu Hwang, M.D., Ju Hyun Choi, M.D., Il Joon Hwang, M.D., Jai Ho Yoon, M.D., Kwang Il Kim, M.D.1, Chang-Il Kwon, M.D., Sung Pyo Hong, M.D., Pil Won Park, M.D., Kyu Sung Rim, M.D.
Korean J Hepatol 2008;14(2):197-205.
Published online June 20, 2008
DOI: https://doi.org/10.3350/kjhep.2008.14.2.197
Backgrounds/Aims
Negative hepatitis B core antigen (HBcAg) staining in hepatocytes is indicative of viral replication by an active immune response. HBcAg is expressed mainly in the cytoplasm in patients with active hepatitis and hepatocyte regeneration, and mainly in the nuclei of hepatocytes in patients with minimal liver injury in the absence of hepatocyte regeneration. The aim of this study was to elucidate whether the existence and expression pattern of HBcAg predicts the response to antiviral treatment. Methods: The study involved 58 patients with biopsy-proven chronic hepatitis B who were treated with lamivudine. Hepatitis B e antigen (HBeAg), antibody to HBeAg, hepatitis B virus DNA, and alanine aminotransferase in serum were recorded every 3 months. The inflammation grade and the fibrosis stage of chronic hepatitis were scored from 0 to 4 according to lobular inflammation, portal inflammation, periportal inflammation, and fibrosis. Results: The 58 patients included 49(84%) HBcAg-positive patients, with HBcAg staining confined to the cytoplasm in 15(31%) and in both cytoplasm and nuclei in 34(69%). The grade of lobular inflammation and the total histology score were significantly higher in patients with cytoplasmic expression of HBcAg than in HBcAgnegative patients (lobular inflammation: 2.9 vs 2.1, P=0.02; total histology score: 12.2 vs 10.3, P=0.04). The virologic responses at 3, 6, 9, and 12 months differed significantly between the cytoplasmic and mixed expression groups (P<0.01). Conclusions: The expression pattern of HBcAg (including its possible absence) before initial therapy appears to predict the response to antiviral treatment. (Korean J Hepatol 2008;14:197- 205)

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  • Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study
    Anil Alpsoy, Haydar Adanir, Zeynep Bayramoglu, Gulsum Ozlem Elpek
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    Sun Young Yim, Tae Hyung Kim, Suh Sang Jun, Eun Sun Kim, Bora Keum, Yeon Seok Seo, Hyung Joon Yim, Yoon Tae Jeen, Hoon Jai Chun, Hong Sik Lee, Soon Ho Um, Chang Duck Kim, Nam Hee Won, Ho Sang Ryu
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Diagnostic Accuracy of Ultrasonography - Huided Needle Bopsy of the Liver as determined by Postsurgical Sampling
Young Doo Lee, M.D., Seong Woo Jeon, M.D., Seung Yup Lee, M.D., Jae Hong Park, M.D., Seung Soo Ha, M.D., Dae Hyun Kim, M.D., Won Young Tak, M.D., Young Oh Kwon, M.D., Sung Kuk Kim, M.D., Yong Hwan Choi, M.D., Joon Mo Chung, M.D., Dong Ja Kim, M.D.1 and Han Ik Bae, M.D.1
Korean J Hepatol 2000;6(3):321-327.
Background/Aims
It is questionable whether the needle biopsy of the liver can represent the whole pathology of the liver. This study evaluates the diagnostic accuracy of ultrasonography-guided needle biopsy of the liver as determined by surgically resected liver. Method: The histopathologic findings of preoperative ultrasonography-guided needle biopsy for confirming the background liver disease and surgically resected liver were compared in the 40 patients with primary hepatocellular carcinoma. Results: 1) Of the 40 cases, 30 (75.0%) cases showed the same histopathological diagnosis between the two methods. Their histopathological results were: 20 cases of cirhosis, 6 cases of chronic hepatitis and 4 cases of normal tissue.2) There was a direct proportion between histologic concordance, the number of portal areas, and the size of the needle biopsy specimen. The histologic concordance rate was 79.2% in the cases with 4 portal areas in their biopsy sample and 100% in the cases with more than 5 areas. 3) Of the 10 cases in which diagnostic discrepancy was found between the two methods, 8 cases of chronic hepatitis and 1 case of normal tissue, all diagnosed by needle biopsy, proved to be cirrhosis by surgically resected liver. One case of normal tissue proved to be chronic hepatitis. The causes of diagnostic error were fragmentations of tissue and inadequate specimens. Conclusion: The diagnostic accuracy of the ultrasonography-guided needle biopsy of the liver was 75.0% in our study. To lessen the diagnostic error, at least 4 or more portal areas should be contained in the biopsy sample and the fragmentation of tissue should be minimized.
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Histopathologic Correlation between Chronic Hepatitis B and Nephropathy
Hyun Woong Lee, M.D., Chae Yoon Chon, M.D., Young Nyun Park, M.D.*, Kwan Sik Lee, M.D., Sang Hoon Ahn, M.D., Chang Hwan Choi, M.D., Young Soo Park, M.D., June-Won Cheong, M.D., Joo Hyuk Sohn, M.D., Jae Youn Cheong, M.D., Kun Hoon Song, M.D., Kwang-hyub Han, M.D., and Young Myoung Moon, M.D.
Korean J Hepatol 2001;7(4):413-422.
Background
/ Aims : The relationship between HBV infection and nephropathy has been reported with some differences according to the investigators and regions studied. Liver biopsis were not performed in most of the reports. In this study both liver and kidney biopsis were performed. The histologic correlation was analyzed between chronic B viral hepatitis and nephropathy. Methods : From January 1985 ro june and hebaturia. Also, a new histopathologic calssification of chronic hepatitis was applied in the assessment of liver disease. Results : Light microscopy of kidneys showed IgA nephropathy in 7 cases(27%) ; minimal change nephrotic syndrome(MCNS) in 1 case (3.8%); and membranous glomerulonephritis(MGN) in 9 cases(34.6%), membranoproliferative glomerulonephritis (MPGN) in 9 cases (34.6%). Among the cases with a higher hepatitis activity index and fibrosis score, the frequency of MGN and MPGN was higher. The hepatitis activity index of cases with MGN was significantly higher than IgA nephropathy and MPGN (p=0.011, p=0.039). The fibrosis score of cases with MGN and MPGN was significantly higher than IgA nephropathy (p=0.011, p=0.003). The positivity of HBeAg was highest in cases with MGN.Serum C3 level was low in all cases but the serum C4 level was within normal range. Immunofluorescence studies showed granular deposition of Ig G and C3 in the capillary loops in MGN. Conclusion : The frequency of MGN and MPGN was higher when the liver disease was more severe. It was suggested that HBeAg, IgG AND C3 might ciontribute to the pathogenesis of MGN in HBsAg positive patients. (Korean J Hepatol 2001;7 : 413 - 422)
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Case Reports

A Case of Intraluminal Gallbladder Hematoma after Percutaneous Liver Biopsy
Taek Kun Kwon, M.D., Sang Hoon Jeon, M.D., Hae Won Park, M.D., Woo Jin Jung, M.D., Jun Young Hwang, M.D., Kyung Sik Park, M.D., Kwang Bum Cho, M.D., Jae Seok Hwang, M.D., Sung Hoon Ahn, M.D., and Soong Kook Park, M.D.
Korean J Hepatol 2002;8(4):486-489.
Percutaneous liver biopsy is valued in the diagnosis of diffuse or localized liver disease. Serious complications after ultrasonography-guided liver biopsy are rare. We report a case of a 69-year-old man who underwent a percutaneous liver biopsy for the evaluation of his underlying liver disease with subsequent late complication of intraluminal gallbladder hematoma.(Korean J Hepatol 2002;8:486-489)
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A Case of Nodular Regenerative Hyperplasia of Liver that mimicked Primary Biliary Cirrhosis
Sung Gon Shim , Joo Hyun Sohn , Jae Woong Lee , Chang Hee Paik , Young Woo Chung , Jong Pyo Kim , Dong Soo Han , Yong Chul Jeon , Joon Soo Hahm , Dong Hoo Lee , Choon Su
Korean J Hepatol 2004;10(4):313-318.
Nodular regenerative hyperplasia (NRH) of the liver is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma without fibrosis. The exact pathogenesis of NRH has not been established, but it`s been suggested that o
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Needle tract implantation of hepatocellular carcinoma (HCC) is a rare complication of percutaneous biopsy, and it is largely associated with end-cutting needles or aspiration biopsy. The CT findings that have been reported include oval or round soft tissue nodules with persistent contrast enhancement along the needle tract, mostly in the subcutaneous tissue or the intercostal muscle layers. In this report, we describe a case of needle tract implantation of HCC after US-guided percutaneous biopsy with an 18G tru-cut needle. (Korean J Hepatol 2006;12:439-443)
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Review
Hepatic fibrosis and cirrhosis are the consequences of many types of chronic liver disease. The precise quantification of fibrosis is important to predict the prognosis and monitor the response of treatment modality. The liver biopsy has a role to estimate the stage of fibrosis. However, its sensitivity is below 80%. Its use is limited by sampling errors, inter- and intraobserver variability and possible morbidity and mortality. There is increasing attention to developing clinical algorithms and new noninvasive alternative techniques to predict the stage of fibrosis. However none of these can replace the utility of liver biopsy in the intermediate stage of hepatic fibrosis. Therefore, the liver biopsy is still the “gold standard” to assess the precise stage of hepatic fibrosis. (Korean J Hepatol 2007;13:138-145)
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