ObjectiveThe treatment outcome of direct-acting antivirals (DAAs) in chronic hepatitis C patients with hepatocellular carcinoma (HCC) is controversial. The current study aimed to address the treatment efficacy and safety of DAAs in patients with curative or active HCC, compared with those of patients without HCC.DesignA prospective cohort studySettingA medical centre and two regional hospitals in TaiwanParticipantsA total of 713 Taiwanese patients (601 non-HCC, 74 curative HCC and 38 active HCC patients) who received standard-of-care DAAs were consecutively enrolled in the study.Main outcome measurementThe primary objective was to determine treatment efficacy, defined as undetectable hepatitis C virus RNA throughout 12 weeks of the post-treatment follow-up period (sustained virological response 12 [SVR12]).ResultsThe overall SVR12 rate was 96.9%. The SVR12 rate was similar between the patients with HCC and those without HCC (95.5% vs 97.2%, p=0.37). The HCC patients were divided into two groups, those with curative HCC and those with viable HCC; a substantially but not significantly lower SVR rate, 92.1% (35/38), was observed in the patients with viable HCC compared with the SVR rate, 97.3% (72/74), in those with curative HCC (p=0.33). Compared with the patients with curative HCC, the patients with viable HCC had a significantly higher proportion of serious adverse events (10.5% vs 1.0%, p=0.002), early treatment discontinuation (10.5% vs 2.8%, p=0.03) and mortality (5.3% vs 0.1%, p=0.008).ConclusionsAn equivalently high SVR rate was observed in patients with either past or active HCC compared with those without HCC. The safety concerns in the HCC patients did not compromise treatment efficacy.

ObjectiveHCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme.DesignThe ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and ‘No-C HD’ (no HCV-viremic subjects at the end of follow-up).ResultsAt the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and ‘No-C HD’ were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively.ConclusionOutreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population.ClinicalTrials.gov identifierNCT03803410 and NCT03891550

Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11–19.46, P < 0.001), followed by HDV RNA positivity (HR/ CI 5.73/1.35–24.29, P = 0.02), age > 50 years old (HR/CI 3.64/2.03–6.54, P < 0.001), male gender (HR/CI 2.69/1.29–5.60, P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03–1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04–19.09, P = 0.04) and BMI (HR/CI 1.11/1.03–1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.