Clinical and Molecular Hepatology

"Carnitine"

Correspondences

Correspondence to the editorial “ASB3 degrades the gateway to β-oxidation: on Hepatocytic ASB3 deficiency alleviates MASLD by decreasing ubiquitin-mediated CPT1A”: Dongqin Yang, Yuli Lin, Chunhua Song, Ming Guan; Received September 25, 2025 Accepted September 27, 2025 Published online September 29, 2025; DOI: https://doi.org/10.3350/cmh.2025.1100 [Accepted]

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Correspondence to the editorial on “Targeting the ASB3-CPT1A axis—a new player in combating metabolic dysfunction-associated steatotic liver disease (CHM-2025-1013)”: Yuli Lin, Dongqin Yang, Zhihao Wu, Ming Guan, Chunhua Song; Received September 23, 2025 Accepted September 27, 2025 Published online September 29, 2025; DOI: https://doi.org/10.3350/cmh.2025.1086 [Accepted]

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Editorial

Targeting the ASB3-CPT1A axis—a new player in combating metabolic dysfunction-associated steatotic liver disease: Yueying Yang, Ying Yang, Yan Lu; Received September 8, 2025 Accepted September 8, 2025 Published online September 15, 2025; DOI: https://doi.org/10.3350/cmh.2025.1013 [Accepted]

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Original Articles

Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver disease by decreasing ubiquitin-mediated carnitine palmitoyl transferase 1A: Yuli Lin, Wulei Hou, Mengxiao Ge, Zhihao Wu, Linlin Huang, Haoye Liu, Wenli Zhang, Xiyu Deng, Lanxin Wang, Ming Guan, Chunhua Song, Zuoyun Wang, Dongqin Yang; Clin Mol Hepatol 2025;31(4):1333-1354.
Published online August 8, 2025; DOI: https://doi.org/10.3350/cmh.2024.1041

Background/Aims
Excessive lipid accumulation in hepatocytes is a critical cause of metabolic dysfunction-associated steatotic liver disease (MASLD) progression. Ankyrin repeat and SOCS box protein 3 (ASB3) is an E3 ubiquitin ligase that mediates diverse disease processes; however, the direct substrates of ASB3 in lipid metabolism and its role in MASLD remain unexplored.
Methods
We generated ASB3 knockout mice fed a high-fat diet to induce MASLD. Oxygen consumption and fatty acid oxidation (FAO) were used to assess lipid metabolism. LC-MS/MS and IP were used to verify the ASB3 target protein. Correlation analysis was conducted on the cohort of MASLD patients vs. the control group.
Results
Loss of the ASB3 E3 ubiquitin ligase in hepatocytes strengthens mitochondrial FAO, thereby influencing energy consumption to decrease triglyceride storage and lipid accumulation. Quantitative lysine ubiquitination proteomics revealed that ASB3 directly mediated the ubiquitin levels at two sites (K180 and K639) in carnitine palmitoyl transferase 1A (CPT1A), a rate-limiting enzyme of FAO, to induce CPT1A degradation. Moreover, both constitutive and hepatocyte-specific ASB3 knockout enhance FAO and delay lipid accumulation, liver steatosis, and MASLD progression in a CPT1A-dependent manner. Hepatic ASB3 deficiency also delays fibrosis in MASLD. Analysis of public databases and liver tissue samples from MASLD patients revealed that ASB3 was highly expressed in MASLD patients and was negatively correlated with CPT1A.
Conclusions
Our study reveals the key roles of ASB3 in the development of MASLD and suggests a novel therapeutic potential for MASLD.

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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

Abstract
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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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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
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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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