GIFT‐I is a phase 3 trial evaluating the efficacy and safety of a 12‐week regimen of coformulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) for treatment of Japanese hepatitis C virus genotype 1b–infected patients. It consists of a double‐blind, placebo‐controlled substudy of patients without cirrhosis and an open‐label substudy of patients with compensated cirrhosis. Patients without cirrhosis were randomized 2:1 to once‐daily OBV/PTV/r (25 mg/150 mg/100 mg; group A) or placebo (group B). Patients with cirrhosis received open‐label OBV/PTV/r (group C). The primary efficacy endpoint was the rate of sustained virological response 12 weeks posttreatment in interferon‐eligible, treatment‐naive patients without cirrhosis and hepatitis C virus RNA ≥100,000 IU/mL in group A. A total of 321 patients without cirrhosis were randomized and dosed with double‐blind study drug (106 received double‐blind placebo and later received open‐label OBV/PTV/r), and 42 patients with cirrhosis were enrolled and dosed with open‐label OBV/PTV/r. In the primary efficacy population, the rate of sustained virological response 12 weeks posttreatment was 94.6% (106/112, 95% confidence interval 90.5‐98.8). Sustained virological response 12 weeks posttreatment rates were 94.9% (204/215) in group A, 98.1% (104/106) in group B (open‐label), and 90.5% (38/42) in group C. Overall, virological failure occurred in 3.0% (11/363) of patients who received OBV/PTV/r. The rate of discontinuation due to adverse events was 0%‐2.4% in the three patient groups receiving OBV/PTV/r. The most frequent adverse event in patients in any group was nasopharyngitis. Conclusion: In this broad hepatitis C virus genotype 1b–infected Japanese patient population with or without cirrhosis, treatment with OBV/PTV/r for 12 weeks was highly effective and demonstrated a favorable safety profile. (Hepatology 2015;62:1037‐1046)

SVR patients with CH-C who are elderly, male, or have an advanced histologic stage are at a high risk for the development of HCC after IFN therapy. We recommend that SVR patients should be observed carefully for more than 10 years after the completion of IFN therapy, even if they only have early fibrosis.

A spontaneous regression of hepatocellular carcinoma is an extremely rare phenomenon. A 69-year-old Japanese man with hepatitis C virus-related chronic hepatitis presented with a liver tumor. We diagnosed the tumor to be hepatocellular carcinoma in the course of spontaneous regression, by imaging studies and changes in the tumor markers. Because the possible presence of viable cancer cells could not be ruled out, we recommended surgery. He refused all treatments at first, but finally agreed to undergo surgery about 10 months after presentation. A hepatectomy was performed. Histologically, no viable tumor cells were found. In our case, the vascularity of the tumor according to the imaging findings was followed up during the clinical course. The patient is now doing well and without any evidence of recurrence at 37 months after surgery.

The cEVR results in this study suggest that high rates of sustained virological response can be achieved in retreated and treatment-naïve patients using DFPP in combination with PEG-IFN/RBV therapy. Results indicate that this therapy could be safely conducted, even in elderly patients.

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved HBV infection during and after treatment with direct-acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti-HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)-positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti-HBs titres at baseline with those at post-DAA therapy in 123 patients without HBsAg. There was no significant difference in anti-HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV-reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy.