Hepatitis C Virus Eradication With Direct-acting Antiviral Improves Insulin Resistance

Francesco Paolo Russo; Alberto Zanetto; Martina Gambato; Ilaria Bortoluzzi; Ramona Al Zoairy; Enrica Franceschet; Federica De Marchi; Luca Marzi; Erica Nicola Lynch; Annarosa Floreani; Fabio Farinati; Benedikt Schaefer; Patrizia Burra; Heinz Zoller; Andrea Mega


J Viral Hepat. 2020;27(2):188-194. 

In This Article

Materials and Methods

Study Cohort

All consecutive HCV-infected patients who were referred to the Gastroenterology Unit of Padua University Hospital, to the Division of Gastroenterology of Bolzano Hospital and to the Department of Medicine I of Medical University of Innsbruck for antiviral treatment with DAAs from May 2015 to December 2016 were considered eligible for the study and were prospectively enrolled. Exclusion criteria were as follows: co-infection with hepatitis B virus or human immunodeficiency virus, significant alcohol consumption, presence of T2DM, therapy with biguanides or thiazolidinediones.

Antiviral therapy was administered according to the European Association for The Study of the Liver guidelines for HCV treatment 2015 and 2016.[31,32] SVR after the end of therapy (EOT) was defined as serum HCV-RNA levels below the lower limit of quantification (LLOQ, 15 IU/mL).

Liver stiffness was evaluated by noninvasive liver transient elastography (TE) (Fibroscan® 402 [Echosens] equipped with probe M according to the manufacturer's guidelines). Transient elastography has been performed in fasting patients for at least 6 hours; the stiffness value was calculated by averaging at least 10 valid measurements, a success rate of at least 80% and an interquartile range of less than 30% of the mean value. The definition of fibrosis stages was based on international cut-offs for patients with chronic hepatitis C.[33] More particularly, patients with liver stiffness between 2.5 and 7 kPa were classified as F0-F1, patients with liver stiffness between 7 and 9.5 kPa were classified as F2, patients with liver stiffness between 9.5 and 12.5 kPa were classified as F3, patients with liver stiffness higher than 12.5 kPa were classified as F4.

The study was conducted according to the Declaration of Helsinki, and all patients gave written consent at recruitment. The Padua University Hospital Ethical Committee approved the study (number: 3103/A0/14).

Biochemical and Virological Parameters, Insulin Resistance and Liver Stiffness Measurements During Follow-up

Baseline clinical, biochemical and virological data were collected as follows: age, sex, body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), serum albumin, serum bilirubin, serum creatinine, fasting blood glucose, insulin, serum total cholesterol, serum low density lipoprotein cholesterol, triglycerides, glycated haemoglobin (HBa1C), HCV-RNA value, HCV genotype, IL-28 polymorphism, previous history of antiviral treatment, previous history of HCC and previous history of decompensation.

Blood samples for virological, biochemical and metabolic assessments were collected at baseline, 12 weeks (12W) after EOT, 24 weeks (24W) after EOT and 48 weeks (48W) after EOT. HCV-RNA was collected at the EOT as well.

Liver stiffness was evaluated at baseline, at 24W after EOT and 48W after EOT.

Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated according to the following formulas: HOMA-IR = ([glycaemia (mg/dL) × insulinemia (μU/mL)]/405), at the following time points: baseline, 12W, 24W and 48 W after EOT. Patients with HOMA-IR score ≥2.5 were defined as being insulin resistant.

Statistical Analysis

Qualitative data were described as frequencies and percentages. Quantitative data were described by mean ± standard deviation (SD). Categorical variables were compared by using McNemar's test and Bowman's test for symmetry, Chi-square and Fisher's exact test. Statistical significance was considered with P equal to or less than .05. All calculations were done with SPSS version 22.0.0 software.