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"Drug therapy"

Original Article

Evaluating treatment response thresholds for cost-effective treatment in metabolic dysfunction-associated steatotic liver disease
Eileen L. Yoon, Jeong-Yeon Cho, Huiyul Park, Mimi Kim, Ji-Hyeon Park, Hye-Lin Kim, Dae Won Jun
Clin Mol Hepatol 2026;32(1):276-288.
Published online November 3, 2025
DOI: https://doi.org/10.3350/cmh.2025.0796
Background/Aims
The first metabolic dysfunction-associated steatotic liver disease (MASLD) drug was approved with an unsatisfactorily small effect size. This study aimed to determine key factors impacting the cost-effectiveness of a new hypothetical MASLD drug as well as its treatment efficacy.
Methods
A Markov model reflecting the natural history of MASLD was developed, incorporating fibrosis progression, cardiovascular disease risk, and mortality. Treatment effect of drug X (with $20,000 of annual cost) was assumed to achieve a ≥1 stage fibrosis regression, with a 25% gap of effect size in regression rate over non-treatment in the first year. The incremental cost-effectiveness ratio (ICER) over a 20-year horizon was estimated. And sensitivity analyses were conducted to explore uncertainty and identify influential factors.
Results
In the base case analysis, drug X provided an incremental gain of 1.32 quality-adjusted life years (QALYs) and 1.20 life years compared to the non-treatment, with an ICER of $68,010/QALY–below the $100,000/QALY willingnessto- pay threshold, indicating that drug X treatment is cost-effective. Two-way sensitivity analysis further highlighted that the drug should achieve at least a 15% initial regression gap and maintain a minimum 3% sustained durability gap to remain cost-effective. In addition baseline fibrosis stage distribution also acted as an influencing factor.
Conclusions
Long-term sustained durability of the hypothetical drug, patient distribution based on baseline fibrosis stage, as well as initial treatment response rate are key factors that influence the cost-effectiveness of new MASLD drugs.

Citations

Citations to this article as recorded by  Crossref logo
  • The MASLD Journey in the General Population: Linkage‐to‐Care and Patient‐Reported Uptake of Fibrosis Risk Assessment
    Joo Hyun Oh, Jun‐Hyuk Lee, Sang Bong Ahn, Eunjoo Kwon, Eileen L. Yoon, Hyo Young Lee, Seon Cho, Dae Won Jun
    Liver International.2026;[Epub]     CrossRef
  • 3,654 View
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  • 6 Web of Science
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Review

Liver fibrosis, cirrhosis, and portal hypertension

Anti-fibrotic treatments for chronic liver diseases: The present and the future
Naoshi Odagiri, Tsutomu Matsubara, Misako Sato-Matsubara, Hideki Fujii, Masaru Enomoto, Norifumi Kawada
Clin Mol Hepatol 2021;27(3):413-424.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0187
Liver fibrosis reflects tissue scarring in the liver due to the accumulation of excessive extracellular matrix in response to chronically persistent liver injury. Hepatocyte cell death can trigger capillarization of liver sinusoidal endothelial cells, stimulation of immune cells including macrophages and Kupffer cells, and activation of hepatic stellate cells (HSCs), resulting in progression of liver fibrosis. Liver cirrhosis is the terminal state of liver fibrosis and is associated with severe complications, such as liver failure, portal hypertension, and liver cancer. Nevertheless, effective therapy for cirrhosis has not yet been established, and liver transplantation is the only radical treatment for severe cases. Studies investigating HSC activation and regulation of collagen production in the liver have made breakthroughs in recent decades that have advanced the knowledge regarding liver fibrosis pathophysiology. In this review, we summarize molecular mechanisms of liver fibrosis and discuss the development of novel anti-fibrotic therapies.

Citations

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    American Journal of Gastroenterology.2026; 121(5): 1132.     CrossRef
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    Journal of Ethnopharmacology.2026; 356: 120862.     CrossRef
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    International Journal of Pharmaceutics.2026; 688: 126437.     CrossRef
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    Life Sciences.2026; 386: 124166.     CrossRef
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  • 22,212 View
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  • 60 Web of Science
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Original Articles

Hepatic neoplasm

Bi-monthly hepatic arterial infusion chemotherapy as a novel strategy for advanced hepatocellular carcinoma in decompensated cirrhotic patients
Kei Moriya, Tadashi Namisaki, Shinya Sato, Masanori Furukawa, Akitoshi Douhara, Hideto Kawaratani, Kosuke Kaji, Naotaka Shimozato, Yasuhiko Sawada, Soichiro Saikawa, Hiroaki Takaya, Koh Kitagawa, Takemi Akahane, Akira Mitoro, Junichi Yamao, Hitoshi Yoshiji
Clin Mol Hepatol 2019;25(4):381-389.
Published online August 13, 2019
DOI: https://doi.org/10.3350/cmh.2019.0037
Background and Aim
We previously reported the comparable efficacy of bi-monthly hepatic arterial infusion chemotherapy (B-HAIC) to that of sorafenib chemotherapy for the treatment of advanced hepatocellular carcinoma (aHCC) in patients with compensated cirrhosis. In this study, we demonstrate the efficacy of B-HAIC in patients with decompensated cirrhosis.
Methods
Forty-five patients with aHCC refractory to transcatheter arterial chemo-embolization (TACE) were treated with B-HAIC and were divided into two groups according to hepatic functional reserve (Child-Pugh grade). Overall survival period, treatment response, and adverse events in each group were analyzed.
Results
Efficacy and disease control rates in the Child-Pugh B group (n=24; 21% and 71%, respectively) were not significantly impaired compared the Child-Pugh A group (n=21; 38% and 67%, respectively). Median survival time and survival rate at 12 months in the Child-Pugh B group were 422 days and 58.3%, respectively, whereas those in the ChildPugh A group were 567 days and 70.8%, respectively. Importantly, the hepatic functional reserve of patients did not worsen in either group during the treatment period. Furthermore, the occurrence rate of adverse events leading to discontinuation of anti-tumor treatment was not significantly increased in the Child-Pugh B group.
Conclusions
Given the preservation of hepatic functional reserve afforded by B-HAIC chemotherapy in patients with decompensated cirrhosis, B-HAIC might be an acceptable alternative strategy for aHCC patients who do not respond to TACE.

Citations

Citations to this article as recorded by  Crossref logo
  • Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in the Era of Systemic Therapies (2020–2025)
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    Jaejun Lee, Ji-Won Han, Pil-Soo Sung, Soon-Kyu Lee, Hyun Yang, Hee-Chul Nam, Sun-Hong Yoo, Hae-Lim Lee, Hee-Yeon Kim, Sung-Won Lee, Jung-Hyun Kwon, Jeong-Won Jang, Chang-Wook Kim, Soon-Woo Nam, Jung-Suk Oh, Ho-Jong Chun, Si-Hyun Bae, Jong-Young Choi, Seun
    Journal of Clinical Medicine.2021; 10(18): 4045.     CrossRef
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    Yuki Zaizen, Masahito Nakano, Kazuta Fukumori, Yoichi Yano, Kota Takaki, Takashi Niizeki, Kotaro Kuwaki, Masaru Fukahori, Takahiko Sakaue, Sohei Yoshimura, Mika Nakazaki, Ryoko Kuromatsu, Shusuke Okamura, Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono,
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    Beom Kyung Kim, Do Young Kim, Hwa Kyung Byun, Hye Jin Choi, Seung-Hoon Beom, Hye Won Lee, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Jinsil Seong, Kwang-Hyub Han
    International Journal of Radiation Oncology*Biology*Physics.2020; 107(1): 106.     CrossRef
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    Cancers.2020; 12(9): 2527.     CrossRef
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  • Appraisal of Long-Term Outcomes of Liver-Directed Concurrent Chemoradiotherapy for Hepatocellular Carcinoma with Major Portal Vein Invasion


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Viral hepatitis

Efficacy of L-carnitine on ribavirin-induced hemolytic anemia in patients with hepatitis C virus infection
Shinya Sato, Kei Moriya, Masanori Furukawa, Soichiro Saikawa, Tadashi Namisaki, Mitsuteru Kitade, Hideto Kawaratani, Kosuke Kaji, Hiroaki Takaya, Naotaka Shimozato, Yasuhiko Sawada, Kenichiro Seki, Koh Kitagawa, Takemi Akahane, Akira Mitoro, Yasushi Okura, Junichi Yamao, Hitoshi Yoshiji
Clin Mol Hepatol 2019;25(1):65-73.
Published online February 25, 2019
DOI: https://doi.org/10.3350/cmh.2018.0070
Background/Aims
L-carnitine not only alleviates hyperammonemia and reduces muscle cramps in patients with liver cirrhosis, but also improves anemia in patients with chronic hepatitis and renal dysfunction. This study prospectively evaluated the preventative efficacy of L-carnitine supplementation against hemolytic anemia during antiviral treatment using ribavirin in patients with hepatitis C virus (HCV)-related chronic liver disease.
Methods
A total of 41 patients with chronic hepatitis were consecutively enrolled in this study. Group A (n=22) received sofosbuvir plus ribavirin for 3 months, whereas group B (n=19) was treated with sofosbuvir, ribavirin, and L-carnitine. Hemoglobin concentration changes, the effects of antiviral treatment, and the health status of patients were analyzed using short form-8 questionnaires.
Results
A significantly smaller decrease in hemoglobin concentration was observed in group B compared to group A at every time point. Moreover, the prescribed dose intensity of ribavirin in group B was higher than that of group A, resulting in a higher ratio of sustained virological response (SVR) 24 in group B compared with group A. The physical function of patients in group B was also significantly improved compared to group A at the end of antiviral treatment.
Conclusions
L-carnitine supplementation alleviates ribavirin-induced hemolytic anemia in patients with HCV and helps relieve the physical burden of treatment with ribavirin-containing regimens. These advantages significantly increase the likelihood of achieving SVR.

Citations

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  • Altered branched chain ketoacids underlie shared metabolic phenotypes in type 1 diabetes and maple syrup urine disease
    Domenico Roberti, Abby L. Grier, Julie A. Reisz, Fara Vallefuoco, Alicia Key, Shaun Bevers, Monika Dzieciatkowska, Travis Nemkov, Marcella Contieri, Angela Zanfardino, Philip J. Norris, Michael P. Busch, Vienna Kauffman, Holmes D. Morton, Eric J. Earley,
    Communications Medicine.2025;[Epub]     CrossRef
  • Shining light on liquid–liquid phase separation in chronic liver disease
    Ming-Hui Li, Yang Yang, Qi-Qi Dong, Wen-Jie Sun, Hui Tao, Jing-Jing Yang
    Drug Discovery Today.2025; 30(10): 104464.     CrossRef
  • Advances in clinical application on nursing intervention for ribavirin-associated adverse events
    Li-Li Jiang, Qing Wang, Jia-Xin Zhang, Jing-Hui Fan, Jing Li
    Frontiers in Pharmacology.2025;[Epub]     CrossRef
  • LC–MS/MS separation and quantitation of ribavirin in chicken and comparison of different mass spectrometric platforms
    Daokun Xu, Haolun Huang, Wenyan Hu, Xinmei Liu, Jun Yang
    BMC Chemistry.2023;[Epub]     CrossRef
  • Can l-carnitine reduce post-COVID-19 fatigue?
    Roya Vaziri-harami, Parisa Delkash
    Annals of Medicine and Surgery.2022; 73: 103145.     CrossRef
  • Artemisinin and l‐carnitine combination therapy alters the erythrocytes redox status
    Mehdi Basaki, Akbar Hashemvand, Hossein Tayefi‐Nasrabadi, Yousef Panahi, Mahdi Dolatyarieslami
    Cell Biology International.2022; 46(7): 1137.     CrossRef
  • Hemolytic anemia in COVID-19
    Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Ajeet Kaushik, Małgorzata Kujawska, Gaber El-Saber Batiha
    Annals of Hematology.2022; 101(9): 1887.     CrossRef
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  • 8 Web of Science
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High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B
Hee Bok Chae, Mee Jin Kim, Eui Geun Seo, Yong Hyeok Choi, Hee Seung Lee, Joung Ho Han, Soon Man Yoon, Seon Mee Park, Sei Jin Youn
Korean J Hepatol 2012;18(1):75-83.
Published online March 22, 2012
DOI: https://doi.org/10.3350/kjhep.2012.18.1.75
Background/Aims

Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance.

Methods

Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log10 copies/mL after 6 months of combination therapy.

Results

The IVR rate was 76%. The proportion of patients with a high viral load (≥5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%).

Conclusions

ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.

Citations

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  • Entecavir Interacts with Influx Transporters hOAT1, hCNT2, hCNT3, but Not with hOCT2: The Potential for Renal Transporter-Mediated Cytotoxicity and Drug–Drug Interactions
    Jana Mandíková, Marie Volková, Petr Pávek, Lucie Navrátilová, Lucie Hyršová, Zlatko Janeba, Jan Pavlík, Pavel Bárta, František Trejtnar
    Frontiers in Pharmacology.2016;[Epub]     CrossRef
  • Tenofovir rescue regimen following prior suboptimal response to entecavir and adefovir combination therapy in chronic hepatitis B patients exposed to multiple treatment failures
    Qian Zhang, Tao Han, Cai‐Yun Nie, Fu‐Shuang Ha, Lei Liu, Hua Liu
    Journal of Medical Virology.2015; 87(6): 1013.     CrossRef
  • Impact of Nucleos(t)ide Analogue Combination Therapy on the Estimated Glomerular Filtration Rate in Patients With Chronic Hepatitis B
    Xun Qi, Jinyu Wang, Liang Chen, Yuxian Huang, Yanli Qin, Richeng Mao, Jiming Zhang
    Medicine.2015; 94(15): e646.     CrossRef
  • Entecavir plus adefovir versus adefovir plus lamivudine in hepatitis B virus e antigen‐positive, lamivudine‐resistant chronic hepatitis B
    Jeong Heo, Sang Hoon Ahn, Young‐Oh Kweon, Byung‐Ho Kim, Henry L Y Chan, Andrzej Horban, Suchat Wongcharatrawee, Cyril Llamoso, Kwan Sik Lee
    Journal of Gastroenterology and Hepatology.2014; 29(7): 1485.     CrossRef
  • Efficacy of 2years of entecavir plus adefovir therapy in patients with chronic hepatitis B who had failed on prior nucleos(t)ide analog treatment
    Xiaohong Wang, Changjiang Zhang, Yan Zhu, Yulin Xiong, Yuming Wang
    Antiviral Research.2014; 103: 71.     CrossRef
  • Comparison of Lamivudine Plus Adefovir Therapy Versus Entecavir With or Without Adefovir Therapy for Adefovir-resistant Chronic Hepatitis B
    Seong Hee Kang, Hyung Joon Yim, Hae Rim Kim, Keunhee Kang, Sang Jun Suh, Hyun Jung Lee, Eileen L. Yoon, Ji Hoon Kim, Yeon Seok Seo, Jong Eun Yeon, Kwan Soo Byun
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    Ki Bae Bang
    World Journal of Gastroenterology.2014; 20(33): 11641.     CrossRef
  • Adefovir and Lamivudine Combination Therapy in Patients with Entecavir-Resistant Chronic Hepatitis B: Antiviral Responses and Evolution of Mutations
    Hyung Joon Yim, Hyun Jung Lee, Sang Jun Suh, Yeon Seok Seo, Chang Wook Kim, Chang Don Lee, Sang Hoon Park, Myung Seok Lee, Choong Kee Park, Hee Bok Chae, Moon Young Kim, Soon Koo Baik, Yun Soo Kim, Ju Hyun Kim, Jung Il Lee, Jin Woo Lee, Sun Pyo Hong, Soon
    Intervirology.2014; 57(5): 239.     CrossRef
  • Predictive Factors for Delayed Virologic Response of Adefovir Add-on Therapy in Lamivudine-resistant Chronic Hepatitis B
    Ae Rin Baek, Dae Yong Kim, Young Seok Kim, Sang Gyune Kim, Jung Hyun Kim, Min Suk Kim, Tae Jin Kim, Yun Nah Lee, Sae Hwan Lee, Soung Won Jeong, Jae Young Jang, Hong Soo Kim, Boo Sung Kim
    Soonchunhyang Medical Science.2013; 19(1): 10.     CrossRef
  • OAT1 and OAT3: Targets of drug–drug interaction between entecavir and JBP485
    Qinghan Xu, Changyuan Wang, Qiang Meng, Qi Liu, Huijun Sun, Jinyong Peng, Xiaochi Ma, Taiichi Kaku, Kexin Liu
    European Journal of Pharmaceutical Sciences.2013; 48(4-5): 650.     CrossRef
  • Options for the management of antiviral resistance during hepatitis B therapy: reflections on battles over a decade
    Hyung Joon Yim, Seong Gyu Hwang
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  • Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice
    Xian-Hua Xu, Gai-Li Li, Yang Qin, Qiang Li, Fa-Qun He, Jin-Ye Li, Quan-Rong Pan, Jie-Yin Deng
    Virology Journal.2013;[Epub]     CrossRef
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