Clinical and Molecular Hepatology

"Pil Soo Sung"

Letter to the Editor

Plasma Exchange and Abrogation of Monocyte Activation in Wilson’s Disease: Kwon Yong Tak, Min Seo Park, Pil Soo Sung; Received September 12, 2025 Accepted October 1, 2025 Published online October 13, 2025; DOI: https://doi.org/10.3350/cmh.2025.1039 [Accepted]

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Reply to Correspondence

Reply to correspondence on “Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway”: Eun Ji Jang, Pil Soo Sung; Clin Mol Hepatol 2026;32(1):e115-e116.
Published online May 13, 2025; DOI: https://doi.org/10.3350/cmh.2025.0498

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Editorial

A novel link between tumor cell metabolism and patient prognosis: Editorial on “Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway”: Eun Ji Jang, Pil Soo Sung; Clin Mol Hepatol 2026;32(1):420-422.
Published online April 16, 2025; DOI: https://doi.org/10.3350/cmh.2025.0395

Citations

Citations to this article as recorded by

Correspondence to editorial on “Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway”
Tomoko Aoki, Naoshi Nishida, Masatoshi Kudo
Clinical and Molecular Hepatology.2026; 32(1): e79. CrossRef
Reply to correspondence on “Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway”
Eun Ji Jang, Pil Soo Sung
Clinical and Molecular Hepatology.2026; 32(1): e115. CrossRef
Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography: A Potential Imaging Biomarker for Predicting Response to Combination Immunotherapy in Hepatocellular Carcinoma
Masatoshi Kudo
Liver Cancer.2025; 14(5): 511. CrossRef

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31 Download
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Special Issue

Steatotic liver disease

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, on behalf of The Korean Association for the Study of the Liver (KASL); Clin Mol Hepatol 2025;31(Suppl):S1-S31.
Published online February 19, 2025; DOI: https://doi.org/10.3350/cmh.2025.0045

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Eun Ji Jang, Ho Joong Choi, Young Kyoung You, Deok Hwa Seo, Mi Hyun Kwon, Keungmo Yang, Jaejun Lee, Jeong Won Jang, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
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The Korean Journal of Gastroenterology.2025; 85(2): 126. CrossRef
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Rui-Qi Ye, Yi-Fan Chen, Chang Ma, Xi Cheng, Wei Guo, Sha Li
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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
Food Nutrients and Bioactive Compounds for Managing Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review
Erdenetsogt Dungubat, Kohei Fujikura, Masahiko Kuroda, Toshio Fukusato, Yoshihisa Takahashi
Nutrients.2025; 17(13): 2211. CrossRef
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Jeayeon Park, Goh Eun Chung, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Eun Ju Cho
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Extrahepatic manifestation of metabolic dysfunction-associated steatotic liver disease
Anoushka Shenoy, Aijaz Ahmed, Donghee Kim
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Young Mi Jung, Taesu Kim, Min-Jeong Oh, Dong Hyeon Lee, Geum Joon Cho, Won Kim
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Time-updated FIB-4 index predicts coronary artery calcification progression in individuals with metabolic dysfunction–associated steatotic liver disease
Yesung Lee, Woncheol Lee
Scientific Reports.2025;[Epub] CrossRef

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Original Articles

Viral hepatitis

Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity: Jin Seoub Kim, Hye Seon Kim, Kwon Yong Tak, Ji Won Han, Heechul Nam, Pil Soo Sung, Sung Won Lee, Jung Hyun Kwon, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jeong Won Jang; Clin Mol Hepatol 2025;31(2):509-524.
Published online January 2, 2025; DOI: https://doi.org/10.3350/cmh.2024.0545

Background/Aims
Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods
We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
Result
s: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.
Conclusions
Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

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C. Gerdes, S. Rengarajan, K. Murugesan, J.S. Ross, S. Bartels, A. Vogel, A. Saborowski
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Shelterin Component TPP1 Drives Tumor Progression and Predicts Poor Prognosis in Hepatocellular Carcinoma
Jung Eun Jang, Hye Seon Kim, Jin Seoub Kim, Jae Mo Han, Hee Sun Cho, Kwon Yong Tak, Ji Won Han, Pil Soo Sung, Si Hyun Bae, Jeong Won Jang
Biomedicines.2026; 14(2): 364. CrossRef
Transcriptional regulation of tumor suppressor gene RASSF1A by HBx
Yanhong Kang, Wei Li, Junfeng Wei, Lin Yang, Yi Kang
Molecular and Cellular Probes.2025; 82: 102034. CrossRef
Optimized digital polymerase chain reaction enables detection of telomerase reverse transcriptase C228T mutation for prognostic assessment in hepatocellular carcinoma
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World Journal of Gastrointestinal Oncology.2025;[Epub] CrossRef

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Liver Transplantation

Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation: Soon Kyu Lee, Ho Joong Choi, Young Kyoung You, Pil Soo Sung, Seung Kew Yoon, Jeong Won Jang, Jong Young Choi; Clin Mol Hepatol 2025;31(1):131-146.
Published online October 2, 2024; DOI: https://doi.org/10.3350/cmh.2024.0451

Background/Aims
This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV).
Methods
Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified.
Result
s: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05).
Conclusions
This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

Citations

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Intrapatient variability of tacrolimus trough level may be not the cause, but an indirect parameter of comorbidities: Editorial on “Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development foll
Jongman Kim
Clinical and Molecular Hepatology.2025; 31(2): 589. CrossRef
Correspondence to letter to the editor on “Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation”
Soon Kyu Lee, Jong Young Choi
Clinical and Molecular Hepatology.2025; 31(2): e212. CrossRef
Clinical significance and gene prediction of a novel classification system based on tacrolimus concentration-to-dose ratio in the early post-liver transplant period
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Frontiers in Pharmacology.2025;[Epub] CrossRef
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World Journal of Transplantation.2025;[Epub] CrossRef

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Letter to the Editor

Autoimmune liver disease represented as primary biliary cholangitis after SARS-CoV-2 infection: A need for population-based cohort study: Soon Kyu Lee, Jung Hyun Kwon, Nara Yoon, Soon Woo Nam, Pil Soo Sung; Clin Mol Hepatol 2022;28(4):926-928.
Published online September 5, 2022; DOI: https://doi.org/10.3350/cmh.2022.0233

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Ka Shing Cheung, Chiu Hang Mok, Wai Kay Seto, Man Fung Yuen
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Mazen Abdalla Rasheed, Vinícius Remus Ballotin, Lucas Goldmann Bigarella, Jonathan Soldera
World Journal of Methodology.2023; 13(4): 296. CrossRef
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Ju-Yeon Cho, Young-Sun Lee, Soon Sun Kim, Do Seon Song, Jeong-Hoon Lee, Ji Hoon Kim
Clinical and Molecular Hepatology.2022; 28(4): 929. CrossRef

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Reviews

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases: Han Ah Lee, Young Chang, Pil Soo Sung, Eileen L. Yoon, Hye Won Lee, Jeong-Ju Yoo, Young-Sun Lee, Jihyun An, Do Seon Song, Young Youn Cho, Seung Up Kim, Yoon Jun Kim; Clin Mol Hepatol 2022;28(3):425-472.
Published online July 1, 2022; DOI: https://doi.org/10.3350/cmh.2022.0186

Abstract
PDF

The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

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Case 9: A 62-Year-Old Woman With Jaundice and General Weakness
Hee Sun Cho, Ji Won Han, Ji Hoon Kim, Heechul Nam, Pil Soo Sung, Si Hyun Bae
Journal of Korean Medical Science.2023;[Epub] CrossRef
Visión actual sobre el diagnóstico y los cuidados integrales en la encefalopatía hepática
F. Higuera-de-la-Tijera, J.A. Velarde-Ruiz Velasco, R.H. Raña-Garibay, G.E. Castro-Narro, J.M. Abdo-Francis, R. Moreno-Alcántar, J.L. Pérez-Hernández, A. Torre, R. Contreras-Omaña, A. Cano-Contreras, M. Castillo-Barradas, J. Pérez-Escobar, J.M. Aldana-Led
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Current vision on diagnosis and comprehensive care in hepatic encephalopathy
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Revista de Gastroenterología de México (English Edition).2023; 88(2): 155. CrossRef
Multiple Hepatic Artery Pseudoaneurysms With Eosinophilia
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International Journal of Molecular Sciences.2022; 23(24): 15931. CrossRef
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International Journal of Molecular Sciences.2022; 23(24): 16168. CrossRef

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Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma: Pil Soo Sung; Clin Mol Hepatol 2022;28(3):333-350.
Published online October 19, 2021; DOI: https://doi.org/10.3350/cmh.2021.0308

Abstract
PDF

The tumor microenvironment generally shows a substantial immunosuppressive activity in hepatocellular carcinoma (HCC), accounting for the suboptimal efficacy of immune-based treatments for this difficult-to-treat cancer. The crosstalk between tumor cells and various cell types in the tumor microenvironment is strongly related to HCC progression and treatment resistance. Monocytes are recruited to the HCC tumor microenvironment by various factors and become tumor-associated macrophages (TAMs) with distinct phenotypes. TAMs often contribute to weakened tumor-specific immune responses and a more aggressive phenotype of malignancy. Recent single-cell RNA-sequencing data have demonstrated the central roles of specific TAMs in tumorigenesis and treatment resistance by their interactions with various cell populations in the HCC tumor microenvironment. This review focuses on the roles of TAMs and the crosstalk between TAMs and neighboring cell types in the HCC tumor microenvironment.

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Original Article

Persistence of intrahepatic hepatitis B virus DNA integration in patients developing hepatocellular carcinoma after hepatitis B surface antigen seroclearance: Jeong Won Jang, Jin Seoub Kim, Hye Seon Kim, Kwon Yong Tak, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Lewis R. Roberts; Clin Mol Hepatol 2021;27(1):207-218.
Published online December 3, 2020; DOI: https://doi.org/10.3350/cmh.2020.0115

Background/Aims
The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.

Methods
Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.

Result
s: HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.

Conclusions
The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

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Letter to the Editor

Liver fibrosis, cirrhosis, and portal hypertension

Clinical characteristics of portal hypertension complicated by gastroesophageal varices in patients with myeloproliferative neoplasms: Jaejun Lee, Pil Soo Sung, Ki-Seong Eom, Hyun Yang, Soon Kyu Lee, Aung Hlaing Bwa, Angelo Lozada, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; Clin Mol Hepatol 2020;26(1):78-82.
Published online November 26, 2019; DOI: https://doi.org/10.3350/cmh.2019.0078

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Original Articles

Viral hepatitis

Effect of antiviral therapy in reducing perinatal transmission of hepatitis B virus and maternal outcomes after discontinuing them: Kwang Il Seo, Si Hyun Bae, Pil Soo Sung, Chung-Hwa Park, Hae Lim Lee, Hee Yeon Kim, Hye Ji Kim, Bo Hyun Jang, Jeong Won Jang, Seung Kew Yoon, Jong Young Choi, In-Yang Park, Juyoung Lee, Hyun Seung Lee, Sa-Jin Kim, Jung Hyun Kwon, U Im Chang, Chang Wook Kim, Se Hyun Jo, Young Lee, Fisseha Tekle, Jong-Hyun Kim; Clin Mol Hepatol 2018;24(4):374-383.
Published online June 26, 2018; DOI: https://doi.org/10.3350/cmh.2017.0082

Abstract
PDF

Background/Aims
There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes.
Methods
The HBV-infected pregnant women treated with antiviral agents to prevent MTCT were retrospectively reviewed. Forty-one pregnant women who received telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed. Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants after 7 months of birth. Eleven mothers were followed >1 year after delivery.
Result
s: The mean HBV DNA titer before antiviral therapy was 8.67 (6.60–9.49) log copies/mL, and the median age at delivery was 32 years (range, 22–40). Eleven patients were treated with tenofovir and 30 with telbivudine. The median duration was 57 days (range, 23–100), and the median HBV DNA titer at birth was 5.06 log copies/mL (range, 2.06–6.50). Antiviral treatments were associated with significant HBV DNA reduction (P<0.001). Among 43 infants (two cases of twins), HBsAb was not detected in two, subsequently confirmed to have HBV infection. Biochemical flare was observed in two of 11 mothers followed >12 months, and an antiviral agent was administered.
Conclusions
Antiviral treatment during late pregnancy effectively reduced MTCT. Long-term follow-up should be required in such cases. In addition, given that maternal biochemical flare occurred in 18% of mothers, re-administration of antiviral agents might be required.

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Viral hepatitis

Interferon-free treatment for hepatitis C virus infection induces normalization of extrahepatic type I interferon signaling: Pil Soo Sung, Eun Byul Lee, Dong Jun Park, Angelo Lozada, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; Clin Mol Hepatol 2018;24(3):302-310.
Published online March 12, 2018; DOI: https://doi.org/10.3350/cmh.2017.0074

Abstract
PDF

Background/Aims
Hepatitis C virus (HCV) replicates in the peripheral blood mononuclear cells (PBMCs), leading to the production of type I interferons (IFNs). It is well known that the gene expression profile of PBMC is similar to that of the liver. The present study explored the dynamic gene expression profile of PBMCs collected from HCV-infected patients undergoing direct-acting antiviral (DAA) therapy.
Methods
A prospective cohort comprising 27 patients under DAA therapy was formed. Expression level of IFN-β and its downstream interferon-stimulated genes (ISGs) was measured in PBMCs before and after DAA treatment. Furthermore, immunoblotting was performed to identify the signaling molecules involved in the expression of ISGs.
Result
s: The pretreatment expression level of interferon-induced protein 44 (IFI44) and C-X-C motif chemokine ligand 10 (CXCL10) correlated with the pretreatment expression level of IFN-β. After DAA treatment, a significant decrease in the expression levels of IFN-β, IFI44, and CXCL10 was observed in the PBMCs. Furthermore, the pretreatment expression level of IFN-β and ISGs correlated with the level of signal transducer and activator of transcription 1 (STAT1) phosphorylation, and DAA treatment abrogated STAT1 phosphorylation.
Conclusions
Pretreatment activation of IFN-β response is rapidly normalized after DAA treatment. The present study suggests that the decreased type I IFN response by the clearance of HCV might contribute to DAA-induced alleviation of extrahepatic manifestation of chronic HCV infection.

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Differences in the patterns and outcomes of enhanced viral replication between hepatitis C virus and hepatitis B virus in patients with hepatocellular carcinoma during transarterial chemolipiodolization: Pil Soo Sung, Si Hyun Bae, Jeong Won Jang, Do Seon Song, Hee Yeon Kim, Sun Hong Yoo, Chung-Hwa Park, Jung Hyun Kwon, Myeong Jun Song, Chan Ran You, Jong Young Choi, Seung Kew Yoon; Korean J Hepatol 2011;17(4):299-306.
Published online December 26, 2011; DOI: https://doi.org/10.3350/kjhep.2011.17.4.299

Abstract
PDF

Background/Aims

Enhanced replication of hepatitis C virus (HCV) is well described in the setting of moderate to severe immunosuppression. The aims of this retrospective study were to determine the incidence of enhanced HCV replication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemolipiodolization (TACL) and to identify the factors associated with enhanced replication of HCV. The clinical pattern of enhanced HCV replication was compared with hepatitis B virus (HBV) reactivation during TACL.

Methods

This study enrolled 49 anti-HCV-seropositive patients who were diagnosed with HCC between January 2005 and December 2010 and who underwent TACL using epirubicin and/or cisplatin with consecutive HCV RNA copies checked. For comparison, 46 hepatitis B surface antigen¹-positive patients with HCC who were treated with TACL were also enrolled. The frequency, associated factors, and clinical outcomes of enhanced HCV replication were analyzed and compared with those of HBV reactivation during TACL.

Results

Enhanced replication of HCV occurred in 13 (26.5%) of the 49 anti-HCV-seropositive patients during TACL. Of these 13 patients, 4 developed hepatitis, but none of the subjects developed decompensation due to the hepatitis. No significant clinical factors for enhanced HCV replication during TACL were found. Compared with HBV reactivation, the frequency of hepatitis attributed to enhanced HCV replication was significantly lower than that for HBV reactivation (8.2% vs. 23.9%, P=0.036).

Conclusions

TACL can enhance HCV replication; however, the likelihood of hepatitis and decompensation stemming from enhanced HCV replication was lower than that for HBV reactivation in patients undergoing TACL.

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