Clinical and Molecular Hepatology

"Liver biopsy"

Correspondence

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

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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

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Original Article

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.
Result
s: 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

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The Bubble-Destruction Curve Obtained Using Contrast-Enhanced Ultrasound is Useful for Assessing Liver Fibrosis and Identifying At-risk MASH in Patients With MASLD
Noritaka Wakui, Yu Ogino, Naohisa Kamiyama, Takuma Oguri, Tomoya Uchimura, Takahide Kudo, Kenichi Maruyama, Hideki Nagumo, Naoyuki Yoshimine, Kunihide Mouri, Kojiro Kobayashi, Takanori Mukozu, Teppei Matsui, Hidenari Nagai, Yoshinori Igarashi, Takahisa Ma
Ultrasound in Medicine & Biology.2026; 52(1): 237. CrossRef
Ethnic disparities in metabolic dysfunction-associated steatotic liver disease and clinical outcomes
Yusuke Miyatani, Aoi Ogawa, Tomoki Sempokuya, Chuong Tran, Davis James, Todd Seto, Cecilia Shikuma, Scott K. Kuwada
Frontiers in Endocrinology.2026;[Epub] CrossRef
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Annals of Hepatology.2025; 30(1): 101750. CrossRef
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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
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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
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
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Editorials

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

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Clinical and Molecular Hepatology.2024; 30(3): 500. CrossRef
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Clinical and Molecular Hepatology.2023; 29(3): 794. CrossRef

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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

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

Abstract
PDF

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.
Result
s: 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

Abstract
PDF

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

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

Abstract
PDF

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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Crossref

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

Abstract
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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)

Citations

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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
World Journal of Hepatology.2022; 14(1): 260. CrossRef
Expression of Hepatocyte Hepatitis B Core Antigen and Hepatitis B Surface Antigen as a Marker in the Management of Chronic Hepatitis B Patients
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
Gut and Liver.2017; 11(3): 417. CrossRef
Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients
Jeong Guil Lee, Seong Gyu Hwang, Harry Yoon, Myung Su Son, Dae Young Kim, Jeong Hwan Yoo, Kwang Il Kim, Kyu Sung Rim
Gut and Liver.2013; 7(4): 462. CrossRef

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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.

Abstract
PDF

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 Report

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.

Abstract
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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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Review

Role of Liver Biopsy in the Assessment of Hepatic Fibrosis -Its Utility and Limitations: So Young Jin; Korean J Hepatol 2007;13(2):138-145.

Abstract
PDF

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)