Abstract

This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second-generation generic direct-acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment. A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%), and sofosbuvir with ribavirin (1%). There were 96% cases of chronic hepatitis, 3% cases compensated cirrhosis, and 1% cases of decompensated cirrhosis. Genotype 3 (99.6%) was the most common genotype. Overall SVR after 12 weeks was 98% for all treatment regimens. High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), then sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%). SVR rates were high in chronic hepatitis C patients (98.2%) as compared with cirrhotic patients (92.1%) and it was high in treatment-naive (98.8%) then interferon experienced patients (90.1%). In multivariate binary logistic regression analysis, patients' education status, treatment strategy, viral load, and alanine aminotransferase had a statistically significant association with SVR at 12 weeks. No major adverse events occurred which required treatment discontinuation. Generic oral direct acting antiviralss (sofosbuvir with daclatasvir) achieved higher SVR12 rates and were well tolerated in this large real-world cohort of genotype 3 infected patients.

Highlights

  • Chronic hepatitis C virus (HCV) infection is the main cause of liver pathologies and hepatocellular carcinoma (HCC) worldwide [1]

  • A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%) and sofosbuvir with ribavirin (1%)

  • High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%)

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Summary

Introduction

Chronic hepatitis C virus (HCV) infection is the main cause of liver pathologies and hepatocellular carcinoma (HCC) worldwide [1]. According to recent estimates Pakistan has the secondlargest HCV burden in the world, with of 4.5–8.2% HCV sero-prevalence [3, 4]. In Pakistan, HCV is transmitted by many risk factors, such as health care practices i.e. injections and blood transfusion in health care professionals (27- 42.3%) and in the general population (7.8–68%), community-based activities i.e. ear and nose piercing, barbering, and injecting drug use [4, 7, 8]. Before the introduction of DAAs, the HCV treatment was interferon (IFN)-based that had many side effects i.e. poorly tolerated and low SVR rate (50%) [9]. Inspite of “Chief Minister’s Program for Hepatitis B and C Control in Pakistan”, the IFN-based treatment was only effective in 67%–74% of the infected population [10, 11]. This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second generation generic direct-acting antivirals in Pakistani chronic Hepatitis C patients

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