Clinical and Molecular Hepatology

"Sang Hyub Lee"

Original Articles

Autoimmune liver disease

Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial: Woo Hyun Paik, Joo Kyung Park, Moon Jae Chung, Gunn Huh, Ce Hwan Park, Sang Hyub Lee, Heon Se Jeong, Hee Jin Kim, Do Hyun Park; Clin Mol Hepatol 2025;31(1):119-130.
Published online September 24, 2024; DOI: https://doi.org/10.3350/cmh.2024.0629

Background/Aims
A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC.
Methods
In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events.
Results
The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated.
Conclusions
HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Citations

Citations to this article as recorded by

Pruritus in Chronic Cholestatic Liver Diseases, Especially in Primary Biliary Cholangitis: A Narrative Review
Tatsuo Kanda, Reina Sasaki-Tanaka, Naruhiro Kimura, Hiroyuki Abe, Tomoaki Yoshida, Kazunao Hayashi, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai
International Journal of Molecular Sciences.2025; 26(5): 1883. CrossRef
Future Treatment Options for Managing Primary Sclerosing Cholangitis and Cholestatic Pruritus
Taranika Sarkar Das, Raj Vuppalanchi
Clinics in Liver Disease.2025; 29(4): 781. CrossRef

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5 Web of Science
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Viral hepatitis

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; Clin Mol Hepatol 2024;30(3):500-514.
Published online May 10, 2024; DOI: https://doi.org/10.3350/cmh.2024.0055

Background/Aims
Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment.
Methods
Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders.
Results
The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.01, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88–1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60–0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81–0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62–0.75, P<0.01; E-value for SHR=2.30).
Conclusions
TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.

Citations

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Chronic hepatitis B, extrahepatic malignancies and the use of antiviral drugs
Meng-Che Wu, Shih-Chi Yang, Shuo-Yan Gau
Clinical and Molecular Hepatology.2025; 31(1): e19. CrossRef
The critical role of ferroptosis in virus-associated hematologic malignancies and its potential value in antiviral-antitumor therapy
Miao Miao, Yuelei Chen, Xuehan Wang, Shengyang Li, Rong Hu
Virulence.2025;[Epub] CrossRef
Antiviral Therapy Reduces Dyslipidemia and Cardiovascular Risk in Chronic Hepatitis B: TDF as the Most Effective Agent
Hyuk Kim, Jae‐Young Kim, Hyun Bin Choi, Ji‐Soo Lee, Yoon E. Shin, Jeong‐Ju Yoo, Sang Gyune Kim, Young‐Seok Kim
Journal of Medical Virology.2025;[Epub] CrossRef
Characteristics and outcomes in atorvastatin therapy for chronic subdural hematoma: a national, observational real-world study in China, 2019–2024
Tao Liu, Zhihao Zhao, Jiao Wang, Xiaoying Chen, Jinhao Huang, Weiwei Jiang, Yunhu Yu, Xide Zhu, Kaijie Wang, Kun Lin, Hu Qin, Baixiang Peng, Guohe Zhang, Zhiyong Liu, Weiliang Chen, Jun Shen, Baozhi Chen, Shengjie Li, Mingqi Liu, Wanqiang Su, Wanhai Ding,
The Lancet Regional Health - Western Pacific.2025; 63: 101688. CrossRef
Association between atherogenic index of plasma and incident aortic disease: a population-based prospective analysis
Cuihong Tian, Xiao Wang, Liang Tao, Wanyi Wei, Xuan Zhang, Haoxian Tang, Yequn Chen, Xuerui Tan
Open Heart.2025; 12(2): e003511. CrossRef
Nucleos(t)ide analog therapy of chronic hepatitis B and extrahepatic cancer risk: Is tenofovir better than entecavir?: Editorial on “Extrahepatic malignancies and antiviral drugs for chronic hepatitis B: A nationwide cohort study”
Yewan Park, Dong Hyun Sinn
Clinical and Molecular Hepatology.2024; 30(4): 718. CrossRef
Effect of SARS-CoV-2 infection on liver function in patients with hepatitis B
Tong Sun, Hongbo Chi, Jing Wang, Yufen Zheng, Hongguo Zhu, Jingxian Zhao, Kai Zhou, Mengyuan Chen, Donglian Wang, Tao-Hsin Tung, Jiaqin Xu, Bo Shen
BMC Infectious Diseases.2024;[Epub] CrossRef

6,699 View
220 Download
6 Web of Science
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Pretreatment serum HBsAg-to-HBV DNA ratio predicts a virologic response to entecavir in chronic hepatitis B: Joon Chang Song, Bo Young Min, Jin-Wook Kim, Jong Yeop Kim, Yeo Myeong Kim, Cheol Min Shin, Sang Hyub Lee, Jin-Hyeok Hwang, Sook-Hyang Jeong, Nayoung Kim, Dong Ho Lee; Korean J Hepatol 2011;17(4):268-273.
Published online December 26, 2011; DOI: https://doi.org/10.3350/kjhep.2011.17.4.268

Abstract
PDF

Background/Aims

Decay of hepatitis B surface antigen (HBsAg) titers has previously been shown to be predictive of a virologic response (VR), especially during peginterferon-alpha therapy. However, the role of HBsAg levels in predicting a VR to nucleos(t)ide analog therapy has not yet been established. In this study we sought to determine whether the VR can be predicted from HBsAg titers in nucleos(t)ide-naïve chronic hepatitis B (CHB) patients treated with entecavir.

Methods

CHB patients who started entecavir as an initial antiviral therapy were enrolled in this study. Serum hepatitis B virus (HBV) DNA, HBsAg, and alanine aminotransferase levels were measured every 3 months during treatment. A VR was defined as undetectable serum HBV DNA titer by real-time PCR assay (<60 IU/mL).

Results

Fifty-two patients were enrolled, and the median duration of treatment was 26 months (range 7-35 months). Forty-five patients achieved a VR; the cumulative VR rates at 3, 6, 12, and 24 months were 40%, 71.2%, 81.5%, and 88%, respectively. Baseline HBV DNA levels were significantly lower in patients with VR, whereas the HBsAg levels did not differ significantly between patients with or without VR. In a univariate analysis the cumulative VR rate was significantly higher in HBeAg negative patients and patients with an HBsAg/HBV DNA ratio above 0.56. However, in a multivariate analysis only an HBsAg/HBV DNA ratio above 0.56 was an independent predictor of VR (P=0.003). The area under the receiver operating characteristic curve was larger for the HBsAg/HBV DNA ratio than for either HBV DNA or HBsAg.

Conclusions

Pretreatment HBsAg/HBV DNA ratio can predict a long-term VR to entecavir therapy in nucleos(t)ide-naïve CHB patients.

Citations

Citations to this article as recorded by

Naif Kronik Hepatit B Tedavisinde Tenofovir Alafenamid: Tek Merkezli Retrospektif Çalışma
Cihan Semet
ANKEM Dergisi.2024; 38(1): 1. CrossRef
Risk factors related to low-level viraemia in chronic hepatitis B patients receiving entecavir treatment
Zhong-Bin Li, Dan-Dan Chen, Yun-Fei Jia, Qing-Juan He, Li Cui, Feng-Xia Du, Yao-Jie Kang, Xin Feng, Mengwen He, Xue-Yuan Jin, Jing Chen, Yudong Wang, Dong Ji, George Lau, Shu-Gao Wu
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
Association between the Expression Patterns of Hepatitis B Surface Antigen and Hepatitis B Core Antigen with Clinicopathological Parameters and Antiviral Therapy in Liver Biopsies Obtained from Chronically Infected Hepatitis B Positive Omani Patients
Asma Mohammed Salim ALshuili, Shadia Al-Sinawi, Radiya Al-Ajmi, Asem Shalaby, Mohamed Mabruk
Biomedical and Pharmacology Journal.2023; 16(2): 1019. CrossRef
A novel baseline hepatitis B virus sequencing-based strategy for predicting adefovir antiviral response
Yu-Wei Wang, Xuefeng Shan, Yao Huang, Haijun Deng, Wen-Xiang Huang, Da-Zhi Zhang, Juan Chen, Ni Tang, You-Lan Shan, Jin-Jun Guo, Ailong Huang
Infection, Genetics and Evolution.2015; 33: 269. CrossRef
Short-term spontaneous fluctuations of HBV DNA levels in a Senegalese population with chronic hepatitis B
Sarah Maylin, Jean-Marie Sire, Papa Saliou Mbaye, François Simon, Anna Sarr, Marie-Louise Evra, Fatou Fall, Jean Daveiga, Aboubakry Diallo, Jean-Marc Debonne, Loic Chartier, Muriel Vray
BMC Infectious Diseases.2015;[Epub] CrossRef
Correlation of hepatitis B surface antigen level with response to telbivudine in naive patients with chronic hepatitis B
Xuefen Li, Yiyin Wang, Dongsheng Han, Wen Zhang, Zike Zhang, Xianfei Ye, Li Tian, Yuejiao Dong, Qiaoyun Zhu, Yu Chen
Hepatology Research.2014; 44(2): 187. CrossRef
Polymorphism of estrogen receptor alpha (ESR1) is associated with virological response to entecavir (ETV) in nucleoside-naïve adult patients with chronic hepatitis B
T.-T. Zhang, J. Ye, S.-L. Xia, Y.-F. Zhang, Q. Su, Z.-H. Zhang, X. Li
Infection.2013; 41(2): 371. CrossRef
Hepatitis B surface antigen seroclearance in patients with chronic hepatitis B infection: A clinical study
Peng Ruan, Shao-Yong Xu, Bo-Ping Zhou, Jian Huang, Zuo-Jiong Gong
Journal of International Medical Research.2013; 41(5): 1732. CrossRef
Quantitative Hepatitis B Surface Antigen Analysis in Hepatitis B E Antigen-Positive Nucleoside-Naive Patients Treated with Entecavir
Robert G Gish, Ting-Tsung Chang, Ching-Lung Lai, Robert A De Man, Adrian Gadano, Cyril Llamoso, Hong Tang
Antiviral Therapy.2013; 18(5): 691. CrossRef

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Serum prohepcidin levels in chronic hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease: Sang Hyub Lee, Sook-Hyang Jeong, Young Soo Park, Jin-Hyeok Hwang, Jin-Wook Kim, Nayoung Kim, Dong Ho Lee; Korean J Hepatol 2010;16(3):288-294.
Published online September 30, 2010; DOI: https://doi.org/10.3350/kjhep.2010.16.3.288

Abstract
PDF

Background/Aims

Patients with various chronic liver diseases frequently have increased body iron stores. Prohepcidin is an easily measurable precursor of hepcidin, which is a key regulator of iron homeostasis. This study investigated the serum prohepcidin levels in patients with various chronic liver diseases with various etiologies.

Methods

Serum prohepcidin levels were measured in patients with chronic hepatitis C (CH-C) (n=28), nonalcoholic fatty liver disease (NAFLD) (n=24), and alcoholic liver disease (ALD) (n=22), and in healthy controls (n=25) using commercial ELISA. Serum interleukin 6 (IL-6) levels and blood iron indices were also measured.

Results

The serum levels of both prohepcidin and IL-6 were significantly higher in CH-C patients than in healthy controls, and there was a positive correlation between the IL-6 and prohepcidin levels (r=0.505, p=0.020). The prohepcidin levels in ALD patients did not differ from those in controls, despite their significantly elevated IL-6 levels. There was a tendency for a negative correlation between serum prohepcidin levels and transferrin saturation in ALD patients (r=-0.420, p=0.051). Neither prohepcidin nor IL-6 was significantly elevated in the NAFLD group, despite the presence of elevated serum iron and ferritin levels.

Conclusions

The role of prohepcidin may differ in different human liver diseases. In the setting of CH-C, both the serum prohepcidin and IL-6 levels were significantly elevated and were positively correlated with each other.

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