Effect Of DAAs For Treatment Of HCV On Normal Kidney

Antiviral Drug Adverse Reaction

Direct Acting Antiviral Agents (DAAs)

The aim of the study is to determine the effect of different direct acting antiviral drugs used for treatment of chronic HCV infected patients on normal kidney.

Hepatitis C virus (HCV) infection is a major health problem. The World Health Organization (WHO) estimated that at least 150-170 million people, approximately 3% of the world's population, are chronically infected. These patients are known to be at risk of developing liver complications, i.e., cirrhosis and liver cancer, with an estimated liver-related mortality of 350,000 people/year. However, the risks of morbidity and mortality are underestimated because they do not take into account the extra-hepatic consequences of HCV infection. Numerous extra-hepatic manifestations (HCV-EHMs) have been reported. In some large cohort studies, up to 74% of patients experienced HCV-EHMs of different severity, from perceived to disabling conditions. Treatment of HCV infection has a long history. It began with interferon (IFN) mono-therapy, with less than 20% sustained virological response (SVR). Milestones include the addition of ribavirin (RBV) to the treatment protocol and providing pegylated-IFN (PegIFN) as an alternative treatment. Treatment with PegIFN/RBV was the standard of care for about 10 years. The success rate of treatment with this regimen is very dependent on patient characteristics, including age, body mass index, ethnicity, and genetic factors. Viral factors, especially HCV genotype, also affect the response to HCV treatment, and there are always additional factors that should be taken into account in each treatment approach, including treatment success rate, duration, cost, and side effects. In light of these concerns, attempts have continued to introduce better therapeutic regimens. Treatment of chronic HCV infection has been revolutionized in recent years. The FDA has approved different IFN-free direct acting antiviral regimens (DAAs) including: Sofosbuvir (SOF) in combination with Ledipasvir (LDV), combination of Ombitasvir/Paritaprevir/ Dasabuvir (a three direct acting antiviral, or 3D), combination therapy with Grazoprevir/Elbasvir (GZR/EBR), Simeprevir (SMV) and Daclatasvir (DCV) also in combination with SOF. More than 95% of patients have a sustained viral response (SVR) using DAA. The recent Cohort studies have demonstrated that the new regimens of DAAs may be associated with renal side effects, especially when using SOF combinations. So, to aid in the correct use of DAAs in treatment of HCV patients, their potential renal toxicity must be known. The close monitoring of renal function is required. Although, new DAAs were well tolerated, recent real-life studies have demonstrated some nephrotoxic effect in Frail populations treated with SOF based regimens. The use of direct acting antiviral agents (DAAs) in HCV patients might be expected to result in improved outcomes in hepatic functions even in end stage liver disease. But, the effect of DAAs on the kidney still needing a specific study.

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