Clinical and Molecular Hepatology

"Kyun-Hwan Kim"

Editorial

Viral manipulation of host cell glutamine metabolism and glutamine rewiring in hepatic diseases: Editorial on “Glutamate dehydrogenase 1-dependent α-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalently closed circular DNA minichromosome”: Mehrangiz Dezhbord, Kyun-Hwan Kim; Clin Mol Hepatol 2026;32(1):385-389.
Published online April 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0366

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Erratum

Viral hepatitis

Erratum to ‘Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction’ [Clin Mol Hepatol 2024;30:539-560]: Mehrangiz Dezhbord, Seong Ho Kim, Soree Park, Da Rae Lee, Nayeon Kim, Juhee Won, Ah Ram Lee, Dong-Sik Kim, Kyun-Hwan Kim; Clin Mol Hepatol 2024;30(4):1060-1065.
Published online July 24, 2024; DOI: https://doi.org/10.3350/cmh.2024.0060e; Corrects: Clin Mol Hepatol 2024;30(3):539

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Hepatocyte‐Derived FGF1 Alleviates Isoniazid and Rifampicin‐Induced Liver Injury by Regulating HNF4α‐Mediated Bile Acids Synthesis
Qian Lin, Jiaren Zhang, Jie Qi, Jialin Tong, Shenghuan Chen, Sudan Zhang, Xingru Liu, Huatong Lou, Jiaxuan Lv, Ruoyu Lin, Junjun Xie, Yi Jin, Yang Wang, Lei Ying, Jiamin Wu, Jianlou Niu
Advanced Science.2025;[Epub] CrossRef

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Correspondence

Viral hepatitis

Correspondence on editorial regarding “Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction”: Mehrangiz Dezhbord, Kyun-Hwan Kim; Clin Mol Hepatol 2024;30(4):1028-1030.
Published online July 9, 2024; DOI: https://doi.org/10.3350/cmh.2024.0515

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Reply to correspondence on “Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction”
Cho-Rong Lee, Sung-Gyoo Park
Clinical and Molecular Hepatology.2024; 30(4): 1053. CrossRef

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Original Articles

Viral hepatitis

Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction: Mehrangiz Dezhbord, Seong Ho Kim, Soree Park, Da Rae Lee, Nayeon Kim, Juhee Won, Ah Ram Lee, Dong-Sik Kim, Kyun-Hwan Kim; Clin Mol Hepatol 2024;30(3):539-560.
Published online May 14, 2024; DOI: https://doi.org/10.3350/cmh.2024.0060

Background/Aims
The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells.
Methods
Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively.
Results
We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function.
Conclusions
Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.

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The Role of CD4+ T Helper Cell Subsets in Hepatocellular Carcinoma: Implications for Tumour Progression and Immunotherapy
Jijie Shao, Jintong Na, Honghua Huang, Lei Xiao, Fengqiu Dang, Rongshun Zheng, Liping Zhong, Yongxiang Zhao
Cells.2026; 15(4): 350. CrossRef
DPP4 inhibition affects metabolism and inflammation associated pathways in hiPSC-derived steatotic HLCs
Christiane Loerch, Wasco Wruck, Annika Wittich, Rabea Hokamp, Julian Reiss, Ole Pless, James Adjaye, Nina Graffmann
Frontiers in Cell and Developmental Biology.2026;[Epub] CrossRef
Cytotoxic CD4+ T cells: origin, biological functions, diseases and therapeutic targets
Longyong Lai, Shuan Ran, Yuan Li, Jikai Cui, Xi Zhang, Jizhang Yu, Yanqiang Zou, Cheng Zhou, Jiahong Xia, Jie Wu
Signal Transduction and Targeted Therapy.2026;[Epub] CrossRef
IFI35 suppresses the transcription of hepatitis B virus cccDNA minichromosome via promoting HNF4α proteasomal degradation
Nayeon Kim, Jae Jin Shin, Jae Won Oh, Juhee Won, Ah Ram Lee, Mehrangiz Dezhbord, Jeongwoo Park, Ki-Young Lee, Dong-Sik Kim, Kwang Pyo Kim, Kyun-Hwan Kim
Journal of Biomedical Science.2026;[Epub] CrossRef
Impact of VHSV on CIITA-mediated MHCII expression and antigen presentation in largemouth bass
Xiaobing Lu, Ziling Qin, Zhe Hu, Hao Huang, Jie Su, Xiaoru Zhang, Meisheng Yi, Kuntong Jia
Fish & Shellfish Immunology.2025; 162: 110336. CrossRef
Viral oncogenesis in cancer: from mechanisms to therapeutics
Qing Xiao, Yi Liu, Tingting Li, Chaoyu Wang, Sanxiu He, Liuyue Zhai, Zailin Yang, Xiaomei Zhang, Yongzhong Wu, Yao Liu
Signal Transduction and Targeted Therapy.2025;[Epub] CrossRef
Bioinformatics and system biology approach to discover the common pathogenetic processes between COVID-19 and chronic hepatitis B
Xiao Ma, Tengda Huang, Yujia Song, Hongyuan Pan, Ao Du, Xinyi Zhou, Yong Zeng, Kefei Yuan, Xiaosheng Tan
PLOS One.2025; 20(5): e0323708. CrossRef
Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells
Enis Kostallari, Robert F. Schwabe, Adrien Guillot
Cellular & Molecular Immunology.2025; 22(10): 1205. CrossRef
Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection
Eun-Sook Park, Juhee Won, Sung Hyun Ahn, Ah Ram Lee, Donghyo Lee, Ju-Yeon Moon, Man Ho Choi, Kyun-Hwan Kim
Animal Cells and Systems.2024; 28(1): 466. CrossRef
Class II transactivator restricts viral replication, extending its effect to HBV: Editorial on “Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction”
Cho-Rong Lee, Sung-Gyoo Park
Clinical and Molecular Hepatology.2024; 30(4): 724. CrossRef
Chronic Hepatitis B Genotype C Mouse Model with Persistent Covalently Closed Circular DNA
Deok-Hwa Seo, Wonhee Hur, Juhee Won, Ji-Won Han, Seung-Kew Yoon, Songmee Bae, Kyun-Hwan Kim, Pil-Soo Sung
Viruses.2024; 16(12): 1890. CrossRef

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Viral hepatitis

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial: Do Seon Song, Won Kim, Sang Hoon Ahn, Hyung Joon Yim, Jae Young Jang, Young Oh Kweon, Yong Kyun Cho, Yoon Jun Kim, Gun Young Hong, Dong Joon Kim, Young Kul Jung, Joo Hyun Sohn, Jin-Woo Lee, Sung Jae Park, Byung Seok Lee, Ju Hyun Kim, Hong Soo Kim, Seung Kew Yoon, Moon Young Kim, Kwan Sik Lee, Young Suk Lim, Wan Sik Lee, Jin Mo Yang, Kyun-Hwan Kim, Kwang-Hyub Han, Soon Ho Um; Clin Mol Hepatol 2021;27(2):346-359.
Published online January 25, 2021; DOI: https://doi.org/10.3350/cmh.2020.0307

Background/Aims
Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients.
Methods
Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV).
Results
Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group.
Conclusions
BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Citations

Citations to this article as recorded by

Correspondence to editorial on “Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial”
Hyung Joon Yim, Seong Hee Kang, Young Kul Jung, Jin Mo Yang
Clinical and Molecular Hepatology.2026; 32(1): e55. CrossRef
Prodrug strategies in developing antiviral nucleoside analogs
R. Rama Suresh, Tuniyazi Abuduani, Mahesh Kasthuri, Zhe Chen, Zahira Tber, Mohammed Loubidi, HongWang Zhang, Longhu Zhou, Shaoman Zhou, Chenwei Li, Amita Kumari, Sijia Tao, John M. Wiseman, Selwyn J. Hurwitz, Franck Amblard, Raymond F. Schinazi
RSC Medicinal Chemistry.2026; 17(1): 105. CrossRef
Comparison of hepatocellular carcinoma incidence after long-term treatment with besifovir vs. tenofovir AF
Hyuk Kim, Jae-Young Kim, Yoon E. Shin, Hye-Jin Yoo, Jeong-Ju Yoo, Sang Gyune Kim, Young-Seok Kim
Scientific Reports.2025;[Epub] CrossRef
Switching to besifovir in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate: A randomized trial
Hyung Joon Yim, Yeon Seok Seo, Ji Hoon Kim, Won Kim, Young Kul Jung, Jae Young Jang, Sae Hwan Lee, Yun Soo Kim, Chang Wook Kim, Hyoung Su Kim, Jae-Jun Shim, Eun-Young Cho, In Hee Kim, Byung Seok Lee, Jeong-Hoon Lee, Byung Seok Kim, Jeong Won Jang, Hyun Wo
Clinical and Molecular Hepatology.2025; 31(3): 810. CrossRef
Besifovir dipivoxil maleate versus other antivirals in reducing hepatocellular carcinoma in chronic hepatitis B
Jae Seung Lee, Sung Won Lee, Hae Lim Lee, Jeong-Ju Yoo, Yeon Seok Seo, Su Jong Yu, Hyung Joon Yim, Young Kul Jung, Jisu Moon, Hye Won Lee, Mi Na Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Sang Gyune Kim, Seung Up Kim
Scientific Reports.2025;[Epub] CrossRef
Comparative Renal Safety of Besifovir Dipivoxil Maleate and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients: Insights From a Nationwide Cohort Study
Hyun Bin Choi, Jae Young Kim, Jeong-Ju Yoo, Sang Gyune Kim, Young-Seok Kim
Journal of Korean Medical Science.2025;[Epub] CrossRef
Statin use is associated with better post‐operative prognosis among patients with hepatitis B virus‐related hepatocellular carcinoma
Byungyoon Yun, Sang Hoon Ahn, Juyeon Oh, Jin‐Ha Yoon, Beom Kyung Kim
European Journal of Clinical Investigation.2023;[Epub] CrossRef
Comparison of decline in renal function between patients with chronic hepatitis B with or without antiviral therapy
Jae Seung Lee, Chan‐Young Jung, Jung Il Lee, Sang Hoon Ahn, Beom Seok Kim, Seung Up Kim
Alimentary Pharmacology & Therapeutics.2023; 58(1): 99. CrossRef
Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: a systematic review and meta-analysis
Hui Liu, Cheng-Long Han, Bao-Wen Tian, Zi-Niu Ding, Ya-Fei Yang, Yun-Long Ma, Chun-Cheng Yang, Guang-Xiao Meng, Jun-Shuai Xue, Dong-Xu Wang, Zhao-Ru Dong, Zhi-Qiang Chen, Jian-Guo Hong, Tao Li
Expert Review of Gastroenterology & Hepatology.2023; 17(6): 623. CrossRef
Prediction model of hepatitis B virus-related hepatocellular carcinoma in patients receiving antiviral therapy
Beom Kyung Kim, Sang Hoon Ahn
Journal of the Formosan Medical Association.2023; 122(12): 1238. CrossRef
Identification and Characterization of Besifovir-Resistant Hepatitis B Virus Isolated from a Chronic Hepatitis B Patient
Jong Chul Kim, Hye Young Lee, Ah Ram Lee, Mehrangiz Dezhbord, Da Rae Lee, Seong Ho Kim, Juhee Won, Soree Park, Na Yeon Kim, Jae Jin Shin, Sang Gyune Kim, Young Seok Kim, Jeong-Ju Yoo, Kyun-Hwan Kim
Biomedicines.2022; 10(2): 282. CrossRef
KASL clinical practice guidelines for management of chronic hepatitis B

Clinical and Molecular Hepatology.2022; 28(2): 276. CrossRef
Susceptibility of Drug Resistant Hepatitis B Virus Mutants to Besifovir
Juhee Won, Ah Ram Lee, Mehrangiz Dezhbord, Da Rae Lee, Seong Ho Kim, Jong Chul Kim, Soree Park, Nayeon Kim, Byengjune Jae, Kyun-Hwan Kim
Biomedicines.2022; 10(7): 1637. CrossRef
Besifovir dipivoxil maleate: a novel antiviral agent with low toxicity and high genetic barriers for chronic hepatitis B
Jeong Eun Song, Jun Yong Park
Expert Opinion on Pharmacotherapy.2021; 22(18): 2427. CrossRef
Entecavir versus tenofovir in patients with chronic hepatitis B: Enemies or partners in the prevention of hepatocellular carcinoma
Sung Won Lee, Jonggi Choi, Seung Up Kim, Young-Suk Lim
Clinical and Molecular Hepatology.2021; 27(3): 402. CrossRef

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Viral hepatitis

The efficacy of tenofovir-based therapy in patients showing suboptimal response to entecavir-adefovir combination therapy: Jeong Han Kim, Sung Hyun Ahn, Soon Young Ko, Won Hyeok Choe, Kyun-Hwan Kim, So Young Kwon; Clin Mol Hepatol 2016;22(2):241-249.
Published online June 15, 2016; DOI: https://doi.org/10.3350/cmh.2015.0053

Abstract
PDF

Background/Aims
Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. Methods: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. Results: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. Conclusions: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.

Citations

Citations to this article as recorded by

Switching from Tenofovir-Based Combination Therapy to Tenofovir Monotherapy in Multidrug-Experienced Chronic Hepatitis B Patients: a 5-Year Experience at Two Centers
Jung Hun Kim, Jeong Han Kim, Won Hyeok Choe, So Young Kwon, Byung-chul Yoo, Eileen L. Yoon, Seong Hee Kang
Antimicrobial Agents and Chemotherapy.2022;[Epub] CrossRef
Delayed viral suppression during antiviral therapy is associated with increased hepatocellular carcinoma rates in HBeAg‐positive high viral load chronic hepatitis B
J. Y. Nam, Y. Chang, H. Cho, S. H. Kang, Y. Y. Cho, E. J. Cho, J.‐H. Lee, S. J. Yu, J.‐H. Yoon, Y. J. Kim
Journal of Viral Hepatitis.2018; 25(5): 552. CrossRef
Adherence, virological outcome, and drug resistance in Chinese HIV patients receiving first-line antiretroviral therapy from 2011 to 2015
Pengtao Liu, Lingjie Liao, Wei Xu, Jing Yan, Zhongbao Zuo, Xuebing Leng, Jing Wang, Wei Kan, Yinghui You, Hui Xing, Yuhua Ruan, Yiming Shao
Medicine.2018; 97(50): e13555. CrossRef
Is the tenofovir based therapy almighty for previous treatment failure in chronic hepatitis B?
Hyung Joon Yim
Clinical and Molecular Hepatology.2016; 22(2): 238. CrossRef

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Viral hepatitis

Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers: Kyun-Hwan Kim, Hye-Young Chang, Jun Yong Park, Eun-Sook Park, Yong Kwang Park, Kwang-Hyub Han, Sang Hoon Ahn; Clin Mol Hepatol 2014;20(3):251-260.
Published online September 25, 2014; DOI: https://doi.org/10.3350/cmh.2014.20.3.251

Abstract
PDF

Background/Aims

Occult HBV infection can persist following HBsAg loss and be transmitted, but the virological features are not well defined.

Methods

Here we investigated 25 Korean patients who lost HBsAg during follow up, either spontaneously or subsequent to therapy.

Results

Whereas subtype adr (genotype C) was found in 96% of HBsAg positive patients, 75 % of patients who lost HBsAg spontaneously were seemed to be infected with the ayw subtype with sequence similar to genotype D. Mutations in the major hydrophilic region (MHR) of HBsAg were found in 7 patients who lost HBsAg spontaneously. The mutations include T123S, M125I/N, C139R, D144E, V177A, L192F, and W196L, some of which have not been reported before. Functional analysis via transfection experiments indicate that the C139R and D144E mutations drastically reduced HBsAg antigenicity, while the Y225del mutation found in one interferon-treated patient impaired HBsAg secretion.

Conclusions

Lack of detectable HBsAg in patient serum could be explained by low level of ccc DNA in liver tissue, low antigenicity of the surface protein, or its secretion defect.

Citations

Citations to this article as recorded by

Editorial: Predicting Hepatocellular Cancer in Clinical Practice. Authors' Reply
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Ultra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population
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Yu. V. Ostankova, A. V. Semenov, Kh. N. Faizullaev, E. I. Kazakova, A. V. Kozlov, E. I. Musabaev, A. A. Totolyan
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Occult hepatitis B virus infection: clearance or disguise?
Jin-Wook Kim
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