Modulation of glucose metabolism and insulin resistance following hepatitis C virus clearance via direct-acting antivirals

The positive sense RNA virus, hepatitis C virus (HCV), is affiliated with the Flaviviridae family. Approximately 1% of people around the globe experience the impact of the HCV, which can coax them into potentially fatal conditions, including cirrhosis and carcinoma. The second-highest hepatitis C infection burden lies in Pakistan. The case of a HCV-infected patient who additionally has obesity or concurrent medical conditions like diabetes, HBV infection, or HIV infection is susceptible to becoming direr. Direct-acting antiviral medications replaced interferons as a staple of the treatment plan since they have fewer, milder side effects and a higher SVR rate in patients. The present study sought to assess the modifications to glucose homeostasis in non-diabetic chronic HCV-infected patients getting DAA treatment and the factors that independently pertain to insulin resistance. The study enrolled 250 patients, with 190 individuals having HCV-positive PCR results. The analysis included CBC, LFTs, glycaemic and insulin measurements, and the insulin resistance index calculation. Key cardiometabolic risk factors crucial for defining MASLD were assessed, including BMI measurement, evaluation of type 2 diabetes, and lipid profile analysis. The same tests were repeated following DAA therapy, and HOMA-IR was computed to compare pre-and post-treatment results. Among the 250 recruited patients, 190 were detected as HCV positive by the PCR assay, 57% (110 patients) were women, 43% (80 patients) were men, and patients were 47 years old on average. The patients showed high BMI (average 26.28 kg/m²) and signs of severe insulin resistance (HOMA-IR > 2.5). Multivariable logistic regression analysis pointed out that elevated baseline levels of triglycerides, ALT, ALP, cholesterol, and total bilirubin were independently associated with high insulin resistance. A notable improvement in HOMA-IR from 13.63 ± 2.63 to 3.16 ± 1.52 (p < 0.005) was spotted after administering interferon-free antiviral therapy for 3 months. The presence of high BMI, hyperlipidemia, and elevated levels of ALP, ALT, and AST in non-diabetic HCV-infected patients were independently associated with IR. In patients who previously had a higher IR index, there was a decrease in the HOMA-IR index after infection clearance by direct-acting antivirals.