Revista de medicina y complicaciones diabéticas

Diabetes 2018: Interferon-Based Antiviral Treatment of Chronic Hepatitis C in Combination with Metformin in Patients with HCV-1 Genotype and Insulin Resistance : Olga Tarasova - University of Russia (RUDN University)

Abstract

Olga Tarasova

The efficacy of the antiviral therapy in patients with HCV genotype 1 infection rarely exceeds 40%.The main pre-treatment predictors of a sustained virological response (SVR) are: host genotype (in particular the CC genotype at the locus rs12979860 of the IL28B gene), viral genotype and pre-treatment viral load Other baseline factors providing a sustained response are: the right doses of Peginterferon (1.5 mcg/kg/week) and RBV (>10.6 mg/kg/ day), female gender, age less than 40 years, body weight (≤ 75 kg), elevated ALT (three-fold higher than upper limit of normal), the absence of bridging fibrosis or cirrhosis and the absence of insulin resistance (IR) [1-3]. Insulin resistance is the basic pathogenetic part of the metabolic syndrome. Obesity which is observed worldwide increases the number of patients with metabolic syndrome and hepatitis C. Also, it is assumed that HCV infection contributes to insulin resistance.IR caused by HCV together with insulin resistance as a result of metabolic syndrome, can accelerate the progression of disorders of carbohydrate metabolism leading to diabetes type II. Insulin resistance in hepatitis C, regardless of the pathogenesis leads to the development of steatohepatitis, promotes the progression of hepatic fibrosis, cirrhosis, and also reduces SVR rate during antiviral therapy for chronic hepatitis C. The most discussed drug, which can reduce IR, and may increase the SVR rate in patients with chronic hepatitis C- is metformin . Better insulin sensitivity may increase the response to antiviral treatment. The results of several clinical trials that have used insulin sensitizers (metformin and PPAR-γagonists) have proved the efficacy of these drugs in patients with HCV [8]. Since November 2009 we have conducted a prospective study aimed to estimate the frequency of the SVR in 133 Russian patients with chronic hepatitis C (HCV-1), receiving standard therapy (PegIFNα-2b+ribavirin) in combination with metformin (in IR patients only). We studied IR using the method of "Homeostatic model» (Homeostasis Model Assessment). HOMA-index (HOMA-IR) is calculated based on the indices of insulin and glucose in one portion of serum: HOMA-IR = fasting insulin level (MkME/mL) x fasting glucose (mmol/L)/22.5. The criterion for the presence of IR value was decided to be HOMA-IR ≥ 2. All patients were assigned to the standard combination therapy PegIFN-α-2b (1.5 mcg/kg/ week) and ribavirin (15 mg/kg/day). 28 of 70 patients with chronic hepatitis C (HCV-1) and IR were given metformin (20 mg/kg/day). Liver fibrosis was measured with FibroScan®502 (Table 1).

Results

133 patients were tested: 63 patients without IR and 70 patients with IR. 28 of 70 patients with IR received metformin. Metformin was prescribed at the start of antiviral treatment, or 3-6 months before the start of treatment and continued throughout the whole course of therapy. Patients in the second (control) group with IR did not receive metformin (n=42) (Table 2).

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