Interferon-Free Therapy for Hepatits C in Brazil and Sustained Virological Response

Introduction: Hepatitis C has been treated with interferon and ribavirin for over a decade with described global sustained virological response rates of 33% to 56%. Direct acting antiviral drugs available since 2013 in USA and 2015 in Brazil are changing this reality. Purpose: Analyze the real-life efficacy and safety of interferon-free therapy. Methods: Repot six cases of different treatments guided by north-american and european guildelines. Results: Every reported patient achieved sustained virological response. The only adverse event was anemia in one patient. Conclusion: Direct-acting antiviral drugs will dramatically change the population which can be treated and increase sustained virological response rates.


Introduction
Chronic hepatitis C (HCV) is one of the most common liver diseases, affecting around 185 million people worldwide [1] and it can evolve into cirrhosis and hepatocellular carcinoma. In Brazil, it is estimated a prevalence of 1.23%, found among blood donors with positive serology [2], and that 3.9 to 7.6 million people are chronically infected [3].
For about two decades, the treatment of HCV was based in interferon and ribavirin regimens. Although it has been used until recently, only 33% to 43% achieved sustained virological response [4]. With the introduction of pegylated interferon, SVR increased to a peak of 54% to 56% [5].
The introduction since 2013 in USA and since 2015 in Brazil of direct-acting antiviral drugs (DAAD) sofosbuvir, daclastasvir, simeprevir and ledipasvir has increased SVR rates and reduced adverse events associated with treatment dramatically [6].
This paper aims to report six cases of patients treated with DAAD between 2015 and 2016 based in guidelines from American Association for Study of the Liver (AASLD) and European Association for Study of the Liver (EASL) and review the literature regarding this topic.

Discussion
The goal for HCV treatment has always been one: achievement of sustained virological response, which increases quality of life and reduces morbidity and mortality. Among cirrhotic patients, it has been associated to lower MELD score and better liver function. The better understanding of the viral genome and its proteins has allowed the development of DAAD, which are close to the ideal drug -high SVR rates, taken once daily, lower side-effects and shorter period of treatment [6].
Sofosbuvir (SOF) is a nucleotide analog inhibitor of the NS5B polymerase of pangenotipic action and is highly tolerated with few side-effects [7]. Simeprevir (SIM) is a NS3/4 protease inhibitor of second generation used only for genotype 1 [8]. Daclatasvir (DCL) is a NS5A polymerase inhibitor of pangenotipic action [9].
Patients with genotype 1 naïve treated with SOF and SIM have achieved SVR of 93 to 95% [8,10] and treated with SOF and DCL reached SVR around 98% in 12-week-treatment in naïve patients and 100% [9] in 24-week-treatments in experimented patients. In genotype 3, it has been achieved a SVR of 90% and 86% for naïve and experimented patients, respectively, with a 12 week regimen [11]. It has been described a prevalence of 1.8 to 8% of HCV infection in kidney transplantation recipients, most of them infected pre-transplantation. Hence, it's important to test these patients for HCV before and after kidney transplantation [12].
Patient D had her treatment chosen based on SOLAR-2 study, which accessed efficacy of SOF and ledipasvir association for decompensated cirrhosis for genotypes 1 and 4, with high SVRs and improvement in liver function [13].
Patient F was treated with SOF plus DCL plus RBV for 12 weeks according to study ALLY-1, which showed a 100% SVR rate on patients with genotype 1b and decompensated cirrhosis [14]. Data from a Brazilian cohort of 219 patients has been published recently, achieving high SVR [15]. These treatments were prescribed in 2015, before there was a Brazilian clinical protocol for treatment of HCV. Later, such was published, and recommended treatments were different than those who were used based on north-american and European guidelines available in that period of time.

Conclusion
Therapeutic regimens for HCV treatment with DAA are bound to change the natural history of HCV infection, since it is allowing treatment for patients who would otherwise be referred for liver transplantation: decompensated cirrhosis and post-kidney transplantation.