Advances in Treatment of Hepatitis C Advances in Treatment of Hepatitis C Advances in Treatment of Hepatitis C

Hepatitis C infection (HCV) is a major cause of chronic hepatitis and cirrhosis world- wide. Interferon-based regimen has been the sole therapy to eradicate HCV infection for decades. However, this interferon and ribavirin combination is associated with several serious adverse events and the sustained virologic response rate was suboptimal. The recent discovery of oral direct-acting antiviral agents (DAAs) heralded a revolution in the treatment of chronic HCV. This breakthrough in HCV resulted in high rates of HCV eradication with sustained virologic response rates ranging between 90 and 100% across different genotypes. New therapies were administered orally for 12 or 24 months and this resulted in better compliance and few adverse events . DAAs are categorized into four major groups namely: NS5B nucleotide inhibitors, NS5B nonnucleoside inhibitors, NS5A replication complex inhibitors, and NS3/4A protease inhibitors (PI). Several interferon- free regimens have been approved and adequately assessed and several new regimens with high potencies, less cross-resistance, and better safety profile are in the process of approval. Thus, the era of HCV eradication and cure has begun. Pegylation of the interferon molecule resulted in modification of the pharmacokinetic profile of IFN-α-2. Both PEG-IFN-α-2a and PEG-IFN-α-2b have slower absorption, more reduced distribution and lower elimination rate than the nonpegylated IFN-α. The maintained concentrations of PEG-IFNα allowed longer periods of viral inhi bition with once a week dosing. Pegylated interferon and ribavirin therapy resulted in improved sustained virologic response (SVR), defined as undetectable HCV RNA 24 weeks after completion of treatment. With pegylated interferon alpha-2 and ribavirin (RBV) com -bination, response rates in genotypes 2 and 3 range between 70 and 80%. However, SVR rates in chronic HCV genotypes 1 and 4 infection are suboptimal. Adverse events are com mon with interferon-based regimen and include fatigue, flu-like symptoms, anxiety, skin rash, and gastrointestinal symptoms such as nausea and diarrhea. Hemolytic anemia is frequent due to the use of ribavirin. Some patients treated with PEG-IFN and RBV may develop cardiac arrhythmias or severe neuropsychiatric adverse events depression and suicidal tendency. The various adverse effects, the long duration of therapy and the need to inject interferon reduce compliance and treatment adherence. These factors have driven the urgent need to develop new treatments that are safer and more effective ( Figure 1 ). The discovery of direct-acting antiviral agents (DAAs) heralded the dawn of a new era of HCV cure which was a dream. and dasabuvir plus RBV in HCV/HIV-1 coinfected patients for 12 or 24 weeks. The study enrolled HCV treatment-naïve or PEG-IFN/RBV-experienced patients, with or without Child-Pugh A cirrhosis. Patients with CD4+ count ≥200 cells/mm3 or CD4+ % ≥14%, and plasma HIV-1 RNA suppressed on a stable atazanavir- or raltegravir-inclusive antiretro viral (ART) regimen were included. Among patients treated with 3D+RBV for 12 weeks, 93.5% achieved SVR12. Among patients receiving 24 weeks of treatment, 96.9% achieved EOTR; the most common AEs were fatigue, insomnia, and nausea. Elevation in total bilirubin was the most common laboratory abnormality, occurring predominantly in patients receiving atazanavir.