• NAFLD/NASH (MAFLD)
• hepatitis C virus
• hepatocellular carcinoma
• interferon-based therapy
• interferon-free direct-acting antivirals
• metabolic syndrome
• steatosis

• 108-2314-B-037-079-MY3 Ministry of Science and Technology, Taiwan
• 110-2314-B-037-102, 110-2314-B-037-119 Ministry of Science and Technology, Taiwan
• KMU-KI110002 Kaohsiung Medical University
• KMUH-DK(C)110011 Kaohsiung Medical University Hospital

Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin resistance (IR), measured as a reduction of homeostasis model assessment (HOMA) scores after 24 weeks of therapy, and reduced fasting serum insulin and serum glucose levels. The present meta-analysis aimed to evaluate the effect of HCV treatment response on IR in HCV patients who achieved SVR and those who did not (non-SVR) after receiving interferon (IFN)-based therapy. The PubMed, Cochrane and Embase databases were searched using combinations of the following search terms: ‘HCV’, ‘hepatitis C’, ‘interferon’, ‘antiviral’, ‘treatment response’ and ‘insulin resistance’. The incidence of IR, HOMA-IR and HOMA-β, as well as fasting glucose and fasting insulin levels, were summarized in terms of basal values and values after the end of treatment for each study. A total of 8 studies were included in the final analysis. There was no significant difference in the reduction in IR between the SVR and non-SVR groups (odds ratio, 0.995; 95% CI=0.613–1.616; P=0.984). However, the SVR group had a significantly higher mean reduction in HOMA-IR (difference in means=−0.485; 95%CI=−0.713 to −0.256; P<0.001) and HOMA-β (difference in means=−15.448; 95%CI=−23.326 to −7.570; P<0.001) compared to the non-SVR group. In conclusion, HCV patients who achieved SVR after IFN-based therapy exhibited improvement in HOMA-IR and HOMA-β. The present results suggest that clinical management of IR and serum glucose levels may be an important way to impact the therapeutic response in HCV patients.

• HOMA-IR
• HOMA-β
• hepatitis C virus
• insulin resistance
• meta-analysis
• sustained viral response

• Hepatitis C virus
• direct acting antivirals
• homeostatic model assessment for insulin resistance
• homeostatic model assessment-S
• homeostatic model assessment-β

• Adult
• Aged
• Antiviral Agents/administration & dosage
• Antiviral Agents/pharmacology
• Female
• Hepatitis C, Chronic/drug therapy
• Humans
• Insulin Resistance
• Male
• Middle Aged
• Sustained Virologic Response
• Treatment Outcome
• Young Adult

We conducted a pilot study assessing the feasibility, efficacy, and safety of a simplified combination HIV antiretroviral and hepatitis C virus (HCV) antiviral regimen in HIV–HCV coinfection.

Participants on suppressive antiretrovirals and HCV genotype 1 infection were switched to single-tablet daily-dosed elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) and 1 month later initiated single-tablet-regimen daily-dosed ledipasvir-sofosbuvir for 12 weeks. E/C/F/TAF was continued during HCV treatment and for 12 weeks after.

Twenty-six individuals were screened, 25 enrolled, and 23 completed all HIV and HCV treatment. Participants were predominantly male, with a mean age (SD) of 55 (7.5) years. The median transient elastography score (interquartile range [IQR]) was 5.9 (5.3 to 7.6) kPa, and the mean CD4 count (SD) was 579 (223) cells/µL. The median adherence to HCV medications, assessed by pill count, was 100% (95% confidence interval [CI], 100%–100%), and HIV ranged from 99% to 100% (100%; 95% CI, 90%–100%) over the 7-month study duration. HIV undetectability was maintained in all but 1 participant enrolled with unsuspected multiclass resistance. Treatment was well tolerated, with no study medication modification due to adverse events and no serious adverse event related to the study drug. All participants achieved sustained virological response. The mean CD4 count (SD) increased to 673 (361) cells/µL, and the fibrosis score (IQR) declined to 5.2 (4.4 to 7.4) kPa by week 12 after HCV treatment. There was no treatment effect on glucose metabolism. Cholesterol increased during and after treatment.

Provision of this 2-tablet daily HIV–HCV regimen is feasible, well tolerated, and safe, avoids drug–drug interactions between HIV and HCV medications, maintains HIV suppression in the absence of drug resistance, and is highly curative of HCV.

• antiviral therapy
• cirrhosis
• insulin resistance
• lipid metabolism
• viral hepatitis

• Chronic viral hepatitis C
• pegylated interferon and ribavirin
• predictors of virological response
• sustained virological response

Chronic hepatitis C (HCV) infection perturbs lipid and glucose metabolism. The influence of direct acting antiviral (DAA) treatment and ribavirin on these measures was evaluated. Furthermore, the effect of HCV cure on these parameters was assessed. Participants were allocated to one of three 12-week treatment groups: non-cirrhotic genotype 1a-paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) plus ribavirin; non-cirrhotic 1b-PrOD; compensated cirrhotic 1a or 1b-PrOD plus ribavirin. Fasting insulin, glucose, lipid and apolipoprotein measures were assessed at baseline, Treatment Weeks 4 and 12, and 12 and 24 weeks post-dosing. Twenty-three of 24 participants achieved SVR (PP= 23/24, 96% SVR). Overall, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels all increased in treatment and post-dosing. However, LDL-C levels decreased during treatment in ribavirin recipients. Fasting glucose, insulin, and HOMA-IR were unchanged during treatment and 12 weeks post-treatment. By 12 weeks post-treatment, controlled attenuation parameter (CAP) scores, a measure of steatosis, increased from baseline (mean 30.3 ± 63.5, p = 0.05). This regimen was safe and highly effective and did not influence glucose metabolism. Ribavirin exposure may mitigate some on-treatment lipid changes. Further mechanistic studies are needed to understand how ribavirin impacts lipid pathways, as there could be therapeutic implications. The metabolic pathophysiology of increased CAP score with HCV treatment requires explanation.

• antiviral therapy
• cirrhosis
• insulin resistance
• lipid metabolism
• viral hepatitis

• Antiviral therapy
• Cholesterol
• Daclatasvir
• Hepatitis C
• Quality of life
• Sofosbuvir

• Adult
• Antiviral Agents/therapeutic use
• Female
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/mortality
• Humans
• Interferon-alpha/therapeutic use
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/mortality
• Male
• Middle Aged
• Ribavirin/therapeutic use
• Risk Factors
• Sustained Virologic Response

• Kaoshiung Chang Gung Memorial Hospital

• Adult
• Antiviral Agents/therapeutic use
• Biomarkers/blood
• Blood Glucose/drug effects
• Blood Glucose/metabolism
• Drug Therapy, Combination
• Female
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/diagnosis
• Hepatitis C, Chronic/drug therapy
• Humans
• Insulin/blood
• Insulin Resistance
• Male
• Middle Aged
• Sustained Virologic Response
• Time Factors
• Treatment Outcome

We comprehensively analyzed how hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting-antiviral-agents (DAAs) affects liver steatosis and atherogenic risk.

Patients treated with IFN-free-DAAs who underwent transient elastography before and at 24-weeks post-treatment, including controlled attenuation parameter (CAP), and achieved sustained viral response (SVR) were enrolled. The association between changes in liver steatosis, lipid-metabolism, and genetic and clinical factors was analyzed.

A total of 117 patients were included. The mean CAP and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated at SVR24. However, baseline LDL-C and CAP values were significantly negatively correlated with changes in these values after HCV eradication, indicating that in patients with high baseline values, the values generally decreased after HCV eradication. Mean small-dense LDL-C (sdLDL-C), which has greater atherogenic potential, was significantly elevated only in patients with both dyslipidemia (LDL-C >140 mg/dL) and liver steatosis (CAP >248 dB/m) at SVR24. Those patients had significant higher baseline BMI, LDL-C, and total-cholesterol levels.

Generally, successful HCV eradication by IFN-free-DAAs decreases CAP and LDL-C in patients with high baseline values. However, elevated LDL-C was accompanied with elevated sdLDL-C only in patients with liver steatosis and dyslipidemia at SVR24; therefore, those patients may require closer monitoring.

Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated.

Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV).

Total, LDL−, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL− and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels.

Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.

• Apolipoproteins
• Disturbed lipid metabolism
• Hepatitis C virus infection

• Apolipoprotein
• Chronic hepatitis C
• Direct-acting antiviral
• Lipid
• Therapy

• FIB4
• HCV
• antiviral treatment
• lipid profiles
• triglycerides

• add-on
• fluvastatin
• hepatitis C virus
• simeprevir

To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.

We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].

HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.

Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.

• Hepatitis C virus
• Diabetes mellitus
• Insulin resistance
• Liver fibrosis
• Treatment

• Antiviral Agents/therapeutic use
• Blood Glucose/analysis
• Carcinoma, Hepatocellular/complications
• Diabetes Complications/therapy
• Healthy Volunteers
• Hepatitis C/complications
• Hepatitis C/therapy
• Homeostasis
• Humans
• Hypoglycemic Agents/therapeutic use
• Insulin Resistance
• Liver Cirrhosis/complications
• Liver Neoplasms/complications
• Prevalence
• Severity of Illness Index

To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype.

Mono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol (TCHOL), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component (direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene’s test and student’s t test. Mean differences in lipid profiles were compared between genotypes using ANOVA, post hoc analysis via the Bonferroni correction or Dunnett T3.

Three hundred and seventy five patients enrolled with 321 (85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1 (GT1), 18.1% genotype 2 (GT2), 9.7% genotype 3 (GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3 (ΔGT1, p and ΔGT3, p), with TCHOL increasing (+5.3, P = 0.005 and +16.1, P < 0.001), HDL increasing (+12.5, P < 0.001 and +7.9, P = 0.038), LDL increasing (+7.4, P = 0.058 and +12.5, P < 0.001), and TG decreasing (-5.9, P = 0.044 and -9.80 P = 0.067). Among genotypes (ΔGT1 v. ΔGT2 v. ΔGT3, ANOVA), significant mean differences were seen with TCHOL (+5.3 v. +0.1 v. +16.1, P = 0.017) and HDL (+12.3 v. +2 v. +7.9, P = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2 (P = 0.028 and P = 0.019).

Successful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/GT3. Changes are most pronounced in GT3.

• Hepatitis C genotypes
• Lipids
• Metabolic syndrome

• Aged
• Alanine Transaminase/blood
• Antiviral Agents/therapeutic use
• Benzimidazoles/therapeutic use
• Cholesterol/blood
• Cohort Studies
• Drug Therapy, Combination
• Female
• Fluorenes/therapeutic use
• Genotype
• Hepacivirus/genetics
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/virology
• Humans
• Interferon-alpha/therapeutic use
• Lipoproteins, HDL/blood
• Lipoproteins, LDL/blood
• Male
• Middle Aged
• Polyethylene Glycols/therapeutic use
• Prospective Studies
• Recombinant Proteins/therapeutic use
• Ribavirin/therapeutic use
• Simeprevir/therapeutic use
• Sofosbuvir/therapeutic use
• Sustained Virologic Response
• Treatment Outcome
• Triglycerides/blood

• chronic hepatitis C
• insulin resistance
• metabolic syndrome
• overweight

• ELF
• FibroScan
• Liver fibrosis
• Liver stiffness measurement
• Non-invasive serum markers

There is controversy regarding some aspects of hepatitis C virus (HCV) infection-associated liver steatosis, and their relationship with body fat stores. It has classically been found that HCV, especially genotype 3, exerts direct metabolic effects which lead to liver steatosis. This supports the existence of a so called viral steatosis and a metabolic steatosis, which would affect HCV patients who are also obese or diabetics. In fact, several genotypes exert metabolic effects which overlap with some of those observed in the metabolic syndrome. In this review we will analyse the pathogenic pathways involved in the development of steatosis in HCV patients. Several cytokines and adipokines also become activated and are involved in “pure” steatosic effects, in addition to inflammation. They are probably responsible for the evolution of simple steatosis to steatohepatitis, making it difficult to explain why such alterations only affect a proportion of steatosic patients.

• Hepatitis C virus steatosis adiponectin
• Leptin
• Insulin resistance
• Proinflammatory cytokines
• Triglyceride synthesis
• Fatty acid oxidation