Direct-acting antiviral hepatitis C virus treatment perturbation of the metabolic milieu

Abstract

Objective Hepatitis C virus (HCV), cirrhosis, and HCV medications including direct-acting antivirals (DAAs) ±ribavirin may all influence the metabolic milieu. While interferon-based regimens improve glucose tolerance, evidence is limited on DAAs. Cases of elevated lactate have recently been reported in patients treated with DAAs, and lactic acidosis is a known complication of antivirals used to treat hepatitis B virus and HIV. Patients and methods Measures were evaluated at baseline, week 4, end of treatment, and 12–24 weeks after treatment. Mixed-effects modeling was used to determine factors influencing glucose and lactate over time. Results In total, 442 patients were treated (mean age 56, 65% male, 72% genotype 1, 48% cirrhotic). Glucose did not change on or after DAA treatment from baseline (P=0.51) aside from those with untreated diabetes, which declined (P=0.02). Overall, there was a decline in lactate following HCV treatment (mean 2.4–2.1 mmol/l; P<0.001). Lactate initially increased on treatment and then decreased after treatment completion in male patients treated with ribavirin. This pattern was not observed in other groups. There was no evidence of lactic acidosis with HCV nucleotide use. Conclusion Distinct glucose and lactate trajectories were identified without evidence of DAA metabolic toxicity. HCV treatment does not improve random glucose levels aside from perhaps in untreated diabetic patients.

Direct-acting Antiviral in the Treatment of Chronic Hepatitis C: Bonuses and Challenges

“…Overall, a numerical increase was observed from baseline in both total cholesterol (P=0.06) and triglyceride levels (P=0.40). And patients with diabetes were noted to have an elevation in cholesterol after treatment (P=0.05 by Wilcoxon test; n=10), but no significant change in triglycerides (P=0.50 by Wilcoxon test; n=7) [48].In line with these results, several clinical studies provided strong evidence that lipoprotein levels and liver lipid accumulation were inclined to normalize after the initiation of combination therapy including sofosbuvir/ribavirin, sofosbuvir/ledipasvir, asunaprevir/daclatasvir and grazoprevir/elbasvir. These modifications appear to be associated with significant improvement of steatosis and atherogenesis [49][50][51][52][53].…”

Association between hepatitis C antiviral treatment and diabetes mellitus: A case series

“…In the majority of cases, liver function, fibrosis, and stiffness improve after SVR through both interferon and DAA treatments (44)(45)(46)(47). Though the majority of patients do not experience changes in glucose homeostasis (48), some patients experience improvement of diabetic control after achieving SVR (15,47,49). However, we describe three cases in which the treatment of HCV appears to have induced the development of insulin resistance or islet cell destruction.…”

Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact

“…Lacerda et al found that 1-year post-treatment levels of total cholesterol, LDL, VLDL and triglycerides were significantly elevated in patients who had achieved SVR [77]. Similarly, a study by Driedger et al, carried out on 442 HCV patients who were treated with DAA, found that the level of serum cholesterol and triglycerides were also elevated after achieving SVR [78]. The role of HCV genotype on post-SVR hypercholes-terolemia has been also investigated.…”