Hepatitis C virus (HCV) is a worldwide health problem, because infection often leads to chronic hepatitis, eventually progressing to liver cirrhosis and hepatocellular carcinoma. Improved insight into HCV replication cycle and the role of non-structural HCV proteins has recently enabled the identification of drugs directly acting on specific HCV target structures. Combinations of two or more of these drugs from different classes achieve high (> 90%) HCV clearance rates and are well tolerated [6].
In our study, all patients received the regimen (sofosbuvir 400 mg once daily plus daclatasvir 60 mg once daily) for 24 weeks. More than 96% of patients achieved sustained virological response (SVR) after treatment. Regarding the primary outcome of the present study, we found that serum level of ALT had returned to the normal range in concordance with the rapid viral clearance. This course of treatment indicates that hepatic inflammation due to HCV replication might induce substantial stress on the liver. Hence, eradication of HCV infection could reverse the hepatic function abnormalities, even in patients with advanced cirrhosis. Surprisingly, serum AFP levels decreased significantly during and after treatment. Previously, an elevated AFP level was associated with an increased risk of HCC [7]. Post-interferon treatment, elevated ALT, and AFP levels were associated with a risk of hepatocarcinogenesis in patients with HCV-related liver cirrhosis [8]. It remains unclear whether the further development of HCC will be inhibited by HCV eradication with DAA therapy. It is important to monitor patients for HCC development after treatment [9]. Our study follow-up lasted for 12 weeks after treatment, and none of our patients developed HCC. Therefore, further studies with long-term follow-up are recommended to give more impressions about the occurrence of HCC after treatment.
In agreement with these findings, Yek and colleagues conducted a retrospective observational study involving all patients receiving DAA-based HCV therapy. The authors reported an SVR of 95% of patients who had been followed up [10].
Similarly, Del Rio-Valencia and colleagues performed an observational study to evaluate the efficacy of DAA’s regimens for patients with chronic HCV genotype 1–4 infections. Different DAA’s regimens achieved SVR more than 95% [11]. Ahmed and colleagues conducted a systematic review of six randomized trials (n = 1427 patients) to investigate the safety and efficacy of velpatasvir plus sofosbuvir in treatment of chronic HCV infection. The authors reported that the regimen achieved 99% SVR in patients with chronic genotype 4 infection [12]. Similarly, daclatasvir containing regimen achieved 95% SVR in patients with genotype 4 infection [13].
In return, laboratory data in our study as serum albumin, total bilirubin, INR, and Child-Pugh score were significantly improved after treatment. Our study has shown that liver cirrhosis is not a “point of no return.” HCV eradication with DAA regimen (sofosbuvir 400 mg plus daclatasvir 60 mg) does not result in an improvement of liver function tests only but can also lead to a significant improvement in platelet count post-treatment. The adverse effects of this regimen (sofosbuvir 400 mg plus daclatasvir 60 mg) were generally minimal and tolerable; there was no premature treatment discontinuation.
In agreement to these findings, Sharma et al. [14] studied the efficacy and tolerability of direct antiviral agents by assessing liver function parameters (ALT, AST, and albumin) in HCV patients awaiting renal transplantation. The results showed that serum AST/ALT levels decreased significantly (P < 0.0001) after DAA therapy.
In concordance with our findings, Morii et al. [15] intended to estimate whether patients with HCV-related cirrhosis and clinically significant portal hypertension could demonstrate reasonable virological and safety outcomes for DAA therapy. A total of 113 patients were included in this study; 26 with clinically significant portal hypertension and 87 without clinically significant portal hypertension. SVR rates were equally good in patients with clinically significant portal hypertension (96%) and in those without (93%). Proper improvement in hepatic function has been detected in patients who have achieved SVR. The main limitations of this study were single-center experience and short-term follow-up.