The Effects of Direct Acting Antiviral-based Therapy on Insulin Resistance Index and Metabolic Parameters in Patients with Chronic Hepatitis C

Abstract

Background: Insulin resistance (IR) is a condition associated with chronic hepatitis C (CHC). The change in IR after direct antivirals (DAA)-based therapy has been interesting. Objective: To assess the impact of DAA-based therapy on the homeostatic model assessment for insulin resistance (HOMA-IR) index and other metabolic parameters in CHC patients. Materials and Methods: A total of 54 CHC patients with stage 2 liver fibrosis or more were enrolled. Patients with diabetes, obesity, decompensated liver disease, and HIV were excluded. HOMA-IR was calculated before onset and at end of treatment (EOT), as well as 3 months and 6 months after treatment. IR was defined as HOMA-IR greater than 2. Patients were treated according to genotype from the government policy and Thailand Practice Guideline. Results: The mean age of patients was 53 years. Most of the patients, 40 (73.1%), were in advanced stage liver fibrosis. More than half (55.6%) had cirrhosis. More than one-third (38.8%) were overweight. Median HOMA-IR was 4.05 (0.26 to 26.22) and onethird of the patients had quantitative hepatic fat of more than 33%. There were no changes in fasting plasma glucose, insulin levels, body weight or HOMA-IR after DAA treatment in all three follow-up periods (p = 0.47, 0.48, 0.15, 0.53) respectively. Whereas a decline in the mean percentage of HOMA-IR index was seen in patients who had baseline IR, the opposite results had occurred in patients without IR at EOT and 6 months after DAA-based therapy (-25.4% vs. 356.4%, p = 0.003; -17.7% vs. 139.3%, p = 0.018). Improvement of inflammation (ALT 113 to 58 IU/L, p<0.001) and fibrosis regression were achieved at EOT (21.3 to 15.9 kPa, p<0.0001). Conclusion: DAA-based therapy ameliorates IR in non-diabetic CHC patients with high baseline of HOMA-IR index independent of weight reduction. Keywords: Alanine aminotransferase, Chronic hepatitis C, HOMA-IR, Insulin resistance