Su-Wei Chang1, Mei-Ling Cheng2, Ming-Shi Shiao3, Chau-Ting Yeh4, Chao-Hung Wang5, Chun-Ming Fan3, Cheng-Tang Chiu4, Ming-Ling Chang6. 1. Liver Research Centre, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Paediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Clinical Informatics and Medical Statistics Research Centre, Chang Gung University, Taoyuan, Taiwan. 2. Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan; Metabolomics Core Laboratory, Healthy Aging Research Centre, Chang Gung University, Taoyuan, Taiwan; Clinical Phenome Centre, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 3. Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan. 4. Liver Research Centre, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 5. Department of Internal Medicine, Division of Cardiology, Heart Failure Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 6. Liver Research Centre, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: mlchang8210@gmail.com.
Abstract
BACKGROUND: How hepatitis C virus (HCV)-associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. OBJECTIVE: The aforementioned recovery pattern was investigated. METHODS: In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). RESULTS: CHC patients had lower baseline lipid levels than controls. Among CHC patients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHC patients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-β-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and β-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHC patients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. CONCLUSIONS: At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHC patients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR.
BACKGROUND: How hepatitis C virus (HCV)-associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. OBJECTIVE: The aforementioned recovery pattern was investigated. METHODS: In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). RESULTS:CHCpatients had lower baseline lipid levels than controls. Among CHCpatients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHCpatients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-β-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and β-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHCpatients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. CONCLUSIONS: At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHCpatients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR.