STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection.

BACKGROUND & AIMS: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.

Chronic hepatitis C treated with peginterferon alfa plus ribavirin in clinical practice.

BACKGROUND/AIMS: The role of genotype and viremia were retrospectively evaluated on sustained virological response (SVR) rates in routine clinical practice. METHODOLOGY: From 1907 patients with chronic hepatitis C proposed for treatment, we analysed 1380 (1124 naive and 256 treatment-experienced) with complete follow-up. Genotype and HCV RNA quantification were assayed by commercial tests. Viremia was considered high if >800,000IU/mL, and low if <400,000IU/mL. Liver fibrosis was staged in 614 patients. RESULTS: Genotype 1 was the most frequent (60%), followed by 3 (25%), 4 (9%) and 2 (2%); 3.2% had other or unclassified genotype. Genotype 1 was more prevalent in central Portugal and genotype 4 in the south. Viremia was =800,000IU/mL in 54.6% and <400,000IU/mL in 34.6% of the patients, particularly in genotype 2 (p<0.03) and 4 (p<0.001). Genotype non-1 had a significantly lower viral load (p=0.004). Mild or moderate fibrosis was present in 71.7% and bridging fibrosis or cirrhosis in 28.3%, with no differences among genotypes. Treatment was discontinued in 19.8%. SVR was achieved in 55.3% of naive and 36.3% of re-treated patients. CONCLUSIONS: Standard treatment of chronic hepatitis C in real-life achieves similar results obtained in clinical trials, despite differences of demographic and viral parameters.

[Treatment of HBV HCV co-infection: exceeded response]. / Tratamento da co-infecção do virus da hepatite B e C: resposta excedida.

Hepatitis B (HBV) and hepatitis C (HCV) are the most common causes of chronic liver disease. Due to shared routes of transmission, co-infection with HBV and HCV is not uncommon. Higher rates of cirrhosis and hepatocelular carcinoma have been demonstrated in HBV/HCV co-infected patients. No treatment standard has been established for HBV/HCV co-infected patients. Treatment decisions must be made based upon identification of the dominant virus, usually HCV, thus patients should receive pegylated interferon alpha with ribavirin as for HCV monoinfection. Sustained virological response rates for HCV are broadly comparable with HCV monoinfected patients. There is limited information regarding the benefit of combination with nucleos(t)ide analogues. Treatment decisions may modify the complex interaction between HBV and HCV, as flares of the untreated virus may occur, namely with reactivation of HBV. The authors report a case of HBV/HCV co-infection, without a dominant profile, in which the treatment response exceeded expectations regarding the available evidence.