Direct-acting antivirals reverse insulin resistance in chronic HCV patients

Insulin resistance was improved or altogether eliminated in 76.5% of patients whose chronic hepatitis C virus (HCV) infections were cleared by direct-acting antiviral (DAA) treatment, Italian researchers reported in a study published in Hepatology.

This finding underscores the role that HCV plays in the development of insulin resistance. Thus, eradicating the virus can reverse insulin resistance and improve glycemic control, the investigators explained.

“It has been reported that the risk of developing type 2 diabetes mellitus is 11 times higher in patients with HCV infection and that insulin resistance is the link between HCV infection and diabetes,” wrote authors led by Luigi E. Adinolfi, MD, professor, Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.

Insulin resistance occurs in up to 70% of HCV-infected patients.

For this prospective case-control study, Dr. Adinolfi and colleagues enrolled 68 HCV–genotype-1 patients who were treated with oral DAAs and 65 HCV–genotype-1 patients who were not yet treated. At baseline, 52.3% of treated patients and 53.8% of control patients had insulin resistance.

DAA combinations used for treatment (with or without ribavirin) included simeprevir + sofosbuvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and ledipasvir/sofosbuvir.

At the end of the treatment period, all patients given DAAs were clear of HCV infection. At the 3-month follow-up, 95.6% of these patients had achieved a sustained virologic response (SVR). Notably, their measures of insulin resistance decreased significantly. They also showed increased insulin sensitivity, decreased insulin secretion, and reductions in serum glucose and insulin levels.

Patients in the control group had no significant changes in insulin resistance, serum fasting glucose, or insulin levels.

“Overall, 76.5% of SVR patients showed insulin resistance improvements, of which 41.2% [had] normalized insulin resistance. Improvement of insulin resistance was strictly associated with HCV clearance,” the authors wrote.

However, they found that patients with the highest levels of fibrosis continued to have some degree of insulin resistance.

“Considering that patients with very advanced hepatic fibrosis after HCV clearance have [a] lower rate of insulin resistance improvement, antiviral treatment should be made in earlier phases of liver disease to obtain the best therapeutic result on insulin resistance and insulin resistance-related clinical manifestations and complications,” Dr. Adinolfi and colleagues advised.

“In conclusion, the overall data of this study show that the HCV clearance by DAA treatments reverses or improves insulin resistance and reduces stress on ß-cell function,” they wrote. “This result can prevent insulin resistance-related pathological conditions such as worsening liver fibrosis, development of type 2 diabetes, metabolic syndrome, and cardiovascular disorders.”