Clinical and Molecular Hepatology

"Kwan Sik Lee"

Original Articles

Hepatic neoplasm

Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study: Young Eun Chon, Dong Yun Kim, Mi Na Kim, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Yeonjung Ha, Joo Ho Lee, Kwan Sik Lee, Beodeul Kang, Jung Sun Kim, Hong Jae Chon, Do Young Kim; Clin Mol Hepatol 2024;30(3):345-359.
Published online March 12, 2024; DOI: https://doi.org/10.3350/cmh.2023.0553

Background/Aims
Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV.
Methods
This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching.
Results
This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the
objective
response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups.
Conclusions
In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.

Citations

Citations to this article as recorded by

Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma
Kazuki Maesaka, Hayato Hikita, Yuki Tahata, Chinatsu Nishioka, Machiko Kai, Kumiko Shirai, Kazuhiro Murai, Yuki Makino, Yoshinobu Saito, Takahiro Kodama, Kazuyoshi Ohkawa, Masanori Miyazaki, Yasutoshi Nozaki, Takayuki Yakushijin, Ryotaro Sakamori, Nobuyuk
Journal of Gastroenterology.2026; 61(1): 68. CrossRef
EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma
Bruno Sangro, Josepmaria Argemi, Maxime Ronot, Valerie Paradis, Tim Meyer, Vincenzo Mazzaferro, Peter Jepsen, Rita Golfieri, Peter Galle, Laura Dawson, Maria Reig
Journal of Hepatology.2025; 82(2): 315. CrossRef
Lenvatinib versus sorafenib as second-line therapy following progression on atezolizumab–bevacizumab in patients with unresectable hepatocellular carcinoma: a multicenter retrospective study from Korea and Japan
Jaekyung Cheon, Shigeo Shimose, Hyung-Don Kim, Takashi Niizeki, Min-Hee Ryu, Tomotake Shirono, Baek-Yeol Ryoo, Hideki Iwamoto, Changhoon Yoo
Journal of Cancer Research and Clinical Oncology.2025;[Epub] CrossRef
Treatment for hepatocellular carcinoma after immunotherapy
Landon L. Chan, Tsz Tung Kwong, Johnny C.W. Yau, Stephen L. Chan
Annals of Hepatology.2025; 30(2): 101781. CrossRef
Evaluating Sorafenib (SORA-2) as Second-Line Treatment for Unresectable Hepatocellular Carcinoma: A European Retrospective Multicenter Study
Christian Möhring, Moritz Berger, Farsaneh Sadeghlar, Xin Zhou, Taotao Zhou, Malte Benedikt Monin, Kateryna Shmanko, Sabrina Welland, Friedrich Sinner, Birgit Schwacha-Eipper, Ulrike Bauer, Christoph Roderburg, Angelo Pirozzi, Najib Ben Khaled, Peter Schr
Cancers.2025; 17(6): 972. CrossRef
Therapeutic Sequences of Systemic Therapy After Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma: Real‐World Analysis of the IMMUreal Cohort
Najib Ben Khaled, Valentina Zarka, Bernard Hobeika, Julia Schneider, Monika Rau, Alexander Weich, Hans Benno Leicht, Liangtao Ye, Ignazio Piseddu, Michael T. Dill, Arne Kandulski, Matthias Pinter, Ursula Ehmer, Peter Schirmacher, Jens U. Marquardt, Julia
Alimentary Pharmacology & Therapeutics.2025; 61(11): 1755. CrossRef
Application of the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique in conversion therapy for hepatocellular carcinoma
Jingyun Ning, Cao Dai, Qin Liu, Haoming Lin, Rui Zhang
British Journal of Surgery.2025;[Epub] CrossRef
Recent advances in polydopamine-coated metal–organic frameworks for cancer therapy
Jingchao He, Guangtian Wang, Yongfang Zhou, Bin Li, Pan Shang
Frontiers in Bioengineering and Biotechnology.2025;[Epub] CrossRef
Targeting STAT3 by erianin to overcome sorafenib resistance in hepatocellular carcinoma: Integrated network pharmacology with molecular docking, dynamics simulations, and in vitro validation
Zixian Liu, Ruoning Qian, Yuanchao Feng, Ruogu Qi, Zhengguang Zhang, Fuqiong Zhou
Biochemical and Biophysical Research Communications.2025; 778: 152348. CrossRef
PEGylated liposomal metformin overcomes pharmacokinetic barriers to trigger potent mitochondrial disruption and cell cycle arrest in hepatocellular carcinoma
Zeinab A. Elzanaty, Medhat W. Shafaa, Seifeldin Elabed, Mohamed M. Omran
Scientific Reports.2025;[Epub] CrossRef
Multicenter Phase 2 Trial of Second-Line Regorafenib in Patients with Unresectable Hepatocellular Carcinoma after Progression on Atezolizumab plus Bevacizumab
Jaekyung Cheon, Baek-Yeol Ryoo, Hong Jae Chon, Hyung-Don Kim, Min-Hee Ryu, Kyu-Pyo Kim, Beodeul Kang, Richard S. Finn, Stephen Lam Chan, Changhoon Yoo
Liver Cancer.2025; 14(4): 446. CrossRef
Development and validation of a risk prediction model for patients with hepatocellular carcinoma receiving atezolizumab–bevacizumab
Heechul Nam, Dong Yun Kim, Do Young Kim, Ji Hoon Kim, Chang Wook Kim, Jaejun Lee, Keungmo Yang, Ji Won Han, Pil Soo Sung, Seung Kew Yoon, Hee Sun Cho, Hyun Yang, Si Hyun Bae, Soon Kyu Lee, Jung Hyun Kwon, Soon Woo Nam, Ahlim Lee, Do Seon Song, U Im Chang,
Hepatology.2025;[Epub] CrossRef
Multicenter single-arm phase II trial of lenvatinib in patients with advanced hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab
Hyung-Don Kim, Sun Jin Sym, Hong Jae Chon, Moonho Kim, Jung Hun Kang, Baek-Yeol Ryoo, Choong-kun Lee, Joohyun Hong, Hyewon Ryu, Woo Kyun Bae, Hyeyeong Kim, Hyunho Kim, Jin Won Kim, Tae-Yong Kim, Changhoon Yoo
Journal of Hepatology.2025;[Epub] CrossRef
Lenvatinib vs. sorafenib as second-line treatment post atezolizumab plus bevacizumab for hepatocellular carcinoma: The LEVIATHAN study
Pasquale Lombardi, Jung Sun Kim, Giulia F. Manfredi, Ciro Celsa, Claudia A.M. Fulgenzi, Antonio D’Alessio, Bernardo Stefanini, Niraj C. Doshi, Emily Warmington, Thomas U. Marron, Matthias Pinter, Bernhard Scheiner, Beodeul Kang, Ho Yeong Lim, Wei-Fan Hsu,
JHEP Reports.2025; 7(12): 101595. CrossRef
Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions
Yang Gao, Jian-Ping Wang, De-Fei Hong, Chang Yang, Hua Naranmandura
Bioengineering.2025; 12(11): 1206. CrossRef
The potential of lenvatinib in breast cancer therapy
Yuefeng Shang, Tong Liu, Wenjing Wang
Medical Oncology.2024;[Epub] CrossRef
Sorafenib and SIAIS361034, a novel PROTAC degrader of BCL-xL, display synergistic antitumor effects on hepatocellular carcinoma with minimal hepatotoxicity
Xiaoyi Zhang, Yachuan Tao, Zhongli Xu, Biao Jiang, Xiaobao Yang, Taomin Huang, Wenfu Tan
Biochemical Pharmacology.2024; 230: 116542. CrossRef
Second-line systemic therapy after atezolizumab plus bevacizumab: Is it time to boldly go beyond the known?
Edoardo G. Giannini
Digestive and Liver Disease.2024; 56(12): 2077. CrossRef
Correspondence to editorial on “Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study”
Young Eun Chon, Dong Yun Kim, Hong Jae Chon, Do Young Kim
Clinical and Molecular Hepatology.2024; 30(4): 1005. CrossRef
Improved survival with second-line hepatic arterial infusion chemotherapy after atezolizumab-bevacizumab failure in hepatocellular carcinoma
Ji Yeon Lee, Jaejun Lee, Suho Kim, Jae-sung Yoo, Ji Hoon Kim, Keungmo Yang, Ji Won Han, Jeong Won Jang, Jong Yong Choi, Seung Kew Yoon, Ho Jong Chun, Jung Suk Oh, Pil Soo Sung
Frontiers in Oncology.2024;[Epub] CrossRef

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21 Web of Science
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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

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
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.2025;[Epub] 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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16 Web of Science
Crossref

Viral hepatitis

Efficacy and safety of entecavir versus lamivudine over 5 years of treatment: A randomized controlled trial in Korean patients with hepatitis B e antigen-negative chronic hepatitis B: Kwan Sik Lee, Young-Oh Kweon, Soon-Ho Um, Byung-Ho Kim, Young Suk Lim, Seung Woon Paik, Jeong Heo, Heon-Ju Lee, Dong Joon Kim, Tae Hun Kim, Young-Sok Lee, Kwan Soo Byun, Daeghon Kim, Myung Seok Lee, Kyungha Yu, Dong Jin Suh; Clin Mol Hepatol 2017;23(4):331-339.
Published online September 26, 2017; DOI: https://doi.org/10.3350/cmh.2016.0040

Abstract
PDF

Background/Aims
Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks.
Methods
Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA<300 copies/mL) at week 24. Secondary
objective
s included alanine aminotransferase (ALT) normalization and emergence of ETV resistance (week 96), VR and log reduction in HBV DNA levels (week 240), and safety evaluation.
Results
In total, 120 patients (>16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P<0.0001), and week 240 (95.0% vs. 47.6%, P<0.0001). At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P<0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P<0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications.
Conclusions
Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.

Citations

Citations to this article as recorded by

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
Cost–effectiveness of switching from tenofovir disoproxil fumarate to tenofovir alafenamide versus entecavir for chronic hepatitis B patients in Greece
Emmanouil Sinakos, Nandita Kachru, Christos Tsoulas, Sushanth Jeyakumar, Nathaniel J Smith, Alon Yehoshua, Evangelos Cholongitas
Journal of Comparative Effectiveness Research.2024;[Epub] CrossRef
Entecavir: A Review and Considerations for Its Application in Oncology
Tânia Lourenço, Nuno Vale
Pharmaceuticals.2023; 16(11): 1603. CrossRef
No Difference in Incidence of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection Treated With Entecavir vs Tenofovir
Hyunwoo Oh, Eileen L. Yoon, Dae Won Jun, Sang Bong Ahn, Hyo-Young Lee, Jae Yoon Jeong, Hyoung Su Kim, Soung Won Jeong, Sung Eun Kim, Jae-Jun Shim, Joo Hyun Sohn, Yong Kyun Cho
Clinical Gastroenterology and Hepatology.2020; 18(12): 2793. CrossRef
Adverse events of nucleos(t)ide analogues for chronic hepatitis B: a systematic review
Raquel Scherer de Fraga, Victor Van Vaisberg, Luiz Cláudio Alfaia Mendes, Flair José Carrilho, Suzane Kioko Ono
Journal of Gastroenterology.2020; 55(5): 496. CrossRef
Entecavir and tenofovir on renal function in patients with hepatitis B virus‐related hepatocellular carcinoma
Mi Young Jeon, Jae Seung Lee, Hye Won Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Kwang‐Hyub Han, Sang Hoon Ahn, Seung Up Kim
Journal of Viral Hepatitis.2020; 27(9): 932. CrossRef
Low-level viremia and cirrhotic complications in patients with chronic hepatitis B according to adherence to entecavir
Seung Bum Lee, Joonho Jeong, Jae Ho Park, Seok Won Jung, In Du Jeong, Sung-Jo Bang, Jung Woo Shin, Bo Ryung Park, Eun Ji Park, Neung Hwa Park
Clinical and Molecular Hepatology.2020; 26(3): 364. CrossRef
A comparative network meta-analysis of standard of care treatments in treatment-naïve chronic hepatitis B patients
Urbano Sbarigia, Talitha Vincken, Peter Wigfield, Mahmoud Hashim, Bart Heeg, Maarten Postma
Journal of Comparative Effectiveness Research.2020; 9(15): 1051. CrossRef
Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults
Roger Chou, Ian Blazina, Christina Bougatsos, Rebecca Holmes, Shelley Selph, Sara Grusing, Janice Jou
JAMA.2020; 324(23): 2423. CrossRef
External validation of the modified PAGE‐B score in Asian chronic hepatitis B patients receiving antiviral therapy
Hye Won Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang‐Hyub Han, Beom Kyung Kim
Liver International.2019; 39(9): 1624. CrossRef
Antiviral treatment for treatment-naïve chronic hepatitis B: systematic review and network meta-analysis of randomized controlled trials
William W. L. Wong, Petros Pechivanoglou, Josephine Wong, Joanna M. Bielecki, Alex Haines, Aysegul Erman, Yasmin Saeed, Arcturus Phoon, Mina Tadrous, Mona Younis, Noha Z. Rayad, Valeria Rac, Harry L. A. Janssen, Murray D. Krahn
Systematic Reviews.2019;[Epub] CrossRef

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Crossref

Viral hepatitis

Efficacy and safety of entecavir plus carnitine complex (GODEX®) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study: Dae Won Jun, Byung Ik Kim, Yong Kyun Cho, Hong Ju Kim, Young Oh Kwon, Soo Young Park, Sang Young Han, Yang Hyun Baek, Yong Jin Jung, Hwi Young Kim, Won Kim, Jeong Heo, Hyun Young Woo, Seong Gyu Hwang, Kyu Sung Rim, Jong Young Choi, Si Hyun Bae, Young Sang Lee, Young Suck Lim, Jae Youn Cheong, Sung Won Cho, Byung Seok Lee, Seok Hyun Kim, Joo Hyun Sohn, Tae Yeob Kim, Yong Han Paik, Ja Kyung Kim, Kwan Sik Lee; Clin Mol Hepatol 2013;19(2):165-172.
Published online June 27, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.2.165

Abstract
PDF

Background/Aims

Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients.

Methods

130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months.

Results

Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment.

Conclusions

ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.

Citations

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Developments in small molecule antiviral drugs against hepatitis B and C viruses: FDA approved therapies and new drugs in clinical trials
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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
Clinical and Molecular Hepatology.2022; 28(3): 425. CrossRef
Prolonged Use of Carnitine-Orotate Complex (Godex®) Is Associated with Improved Mortality: A Nationwide Cohort Study
Kye-Yeung Park, Sangmo Hong, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
Journal of Personalized Medicine.2022; 12(12): 1970. CrossRef
Role of Carnitine in Non-alcoholic Fatty Liver Disease and Other Related Diseases: An Update
Na Li, Hui Zhao
Frontiers in Medicine.2021;[Epub] CrossRef
High L-Carnitine Levels Impede Viral Control in Chronic Hepatitis B Virus Infection
Shuqin Gu, Xin Fu, Guofu Ye, Chengcong Chen, Xiaoyi Li, Shihong Zhong, Libo Tang, Haitao Chen, Deke Jiang, Jinlin Hou, Yongyin Li
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Besifovir dipivoxil maleate: a novel antiviral agent with low toxicity and high genetic barriers for chronic hepatitis B
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Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway
Jung-Hee Hong, Moon-Kyu Lee
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Farzaneh Pirmadah, Nahid Ramezani-Jolfaie, Mohammad Mohammadi, Nasir Talenezhad, Cain C. T. Clark, Amin Salehi-Abargouei
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Influence of Besifovir Dipivoxil Maleate Combined with L-Carnitine on Hepatic Steatosis in Patients with Chronic Hepatitis B
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Viral hepatitis

High effectiveness of peginterferon alfa-2a plus ribavirin therapy in Korean patients with chronic hepatitis C in clinical practice: Nae-Yun Heo, Young-Suk Lim, Han Chu Lee, Yung Sang Lee, Kang Mo Kim, Kwan Soo Byun, Kwang-Hyub Han, Kwan Sik Lee, Seung Woon Paik, Seung Kew Yoon, Dong Jin Suh; Korean J Hepatol 2013;19(1):60-69.
Published online March 25, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.1.60

Abstract
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Background/Aims

Identifying the impact of a patient's ethnicity on treatment responses in clinical practice may assist in providing individualized treatment regimens for chronic hepatitis C (CHC). The effectiveness of standard peginterferon plus ribavirin therapy and the need for triple combination therapy with protease inhibitors in Koreans remain matters of debate. These issues were investigated in the present study.

Methods

The clinical data of 272 treatment-naïve Korean CHC patients who were treated in a community-based clinical trial (Clinical Trial group; n=51) and in clinical practice (Cohort group; n=221), were analyzed and compared. All were treated with standard protocols of peginterferon alfa-2a plus ribavirin therapy.

Results

For patients with hepatitis C virus (HCV) genotype 1, the sustained virological response (SVR) rates in the Clinical Trial and Cohort groups were 81% (21/26) and 55% (58/106), respectively, by intention-to-treat (ITT) analysis (P=0.02), and 100% (13/13) and 80% (32/40), respectively, in treatment-adherent patients (P=0.18). For patients with HCV genotype 2, the SVR rates in these two groups were 96% (24/25) and 88% (101/115), respectively, by ITT analysis (P=0.31). Adherence and treatment duration were independent predictors of SVR for genotypes 1 and 2, respectively (P<0.01 for each). Korean patients with CHC achieved high SVR rates with peginterferon alfa-2a plus ribavirin in both the clinical trial and clinical practice settings.

Conclusions

Measures to raise adherence to standard therapy in clinical practice may improve the SVR rates in these patients as effectively as adding protease inhibitors, thus obviating the need for the latter.

Citations

Citations to this article as recorded by

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