Background To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to direct-acting antivirals (DAAs), especially among people who inject drugs (PWID). We aimed to determine the effectiveness of providing DAAs in primary care, compared with hospital-based specialist care. Methods We randomized PWID with HCV attending primary care sites in Australia or New Zealand to receive DAAs at their primary care site or local hospital (standard of care [SOC]). The primary outcome was to determine whether people treated in primary care had a noninferior rate of sustained virologic response at Week 12 (SVR12), compared to historical controls (consistent with DAA trials at the time of the study design); secondary outcomes included comparisons of treatment initiation, SVR12 rates, and the care cascade by study arm. Results We recruited 140 participants and randomized 136: 70 to the primary care arm and 66 to the SOC arm. The SVR12 rate (100%, 95% confidence interval [CI] 87.7–100) of people treated in primary care was noninferior when compared to historical controls (85% assumed). An intention-to-treat analysis revealed that the proportion of participants commencing treatment in the primary care arm (75%, 43/57) was significantly higher than in the SOC arm (34%, 18/53; P < .001; relative risk [RR] 2.48, 95% CI 1.54–3.95), and the proportion of participants with SVR12 was significantly higher in the primary care arm, compared to in the SOC arm (49% [28/57] and 30% [16/53], respectively; P = .043; RR 1.63, 95% CI 1.0–2.65). Conclusions Providing HCV treatment in primary care increases treatment uptake and cure rates. Approaches that increase treatment uptake among PWID will accelerate elimination strategies. Clinical Trials Registration NCT02555475.

Hepatocellular carcinoma (HCC) incidence is rising rapidly in many developed countries. Primary epidemiological data have invariably been derived from cancer registries that are heterogeneous in data quality and registration methodology; many registries have not adopted current clinical diagnostic criteria for HCC and still rely on histology for classification. We performed the first population-based study in Australia using current diagnostic criteria, hypothesizing that HCC incidence may be higher than reported. Incident cases of HCC (defined by American Association for the Study of Liver Diseases diagnostic criteria or histology) were prospectively identified over a 12-month period (2012)(2013)) from the population of Melbourne, Australia. Cases were captured from multiple sources: admissions to any of Melbourne's seven tertiary hospitals; attendances at outpatients; and radiology, pathology, and pharmacy services. Our cohort was compared to the Victorian Cancer Registry (VCR) cohort (mandatory notified cases) for the same population and period, and incidence rates were compared for both cohorts. There were 272 incident cases (79% male; median age: 65 years) identified. Cirrhosis was present in 83% of patients, with hepatitis C virus infection (41%), alcohol (39%), and hepatitis B virus infection (22%) the commonest etiologies present. Agestandardized HCC incidence (per 100,000, Australian Standard Population) was 10.3 (95% confidence interval [CI]: 9.0-11.7) for males and 2.3 (95% CI: 1.8 to 3.0) for females. The VCR reported significantly lower rates of HCC: 5.3 (95% CI: 4.4 to 6.4) and 1.0 (95% CI: 0.7 to 1.5) per 100,000 males and females respectively (P < 0.0001). Conclusions: HCC incidence in Melbourne is 2-fold higher than reported by cancer registry data owing to under-reporting of clinical diagnoses. Adoption of current diagnostic criteria and additional capture sources will improve registry completeness. Chronic viral hepatitis and alcohol remain leading causes of cirrhosis and HCC. (HEPATOLOGY 2016;63:1205-1212 SEE EDITORIAL ON PAGE 1078 P rimary liver cancer (PLC) has become the second leading cause of cancer mortality worldwide and is also the fifth-most common cancer. (1) Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, mostly arises in the setting of cirrhosis, with the most common etiologies being chronic viral hepatitis B and C, alcohol, and nonalcoholic fatty liver disease.

Background and Aims: As the merits of screening at-risk populations for hepatocellular carcinoma (HCC) remain unclear, we compared the clinico-pathologic features and survival of patients with cirrhosis and HCC detected by screening (Group A) to that in non-screened cases (Group B). Methods: We studied cirrhotics who developed HCC between 1994 and 2002. During this period, cirrhotics managed by the Gastroenterology Unit were regularly screened at 6-12 monthly intervals while those managed by other hospital units were not. Demographic data, tumor details, treatment received and survival were recorded and compared according to screening status. Results: There were 96 cases identified; 41 by screening (group A) and 55 by non-screening methods (Group B). HCC in Group A were smaller (P < 0.01), more likely unilobar (P < 0.01), at an early stage (P < 0.0005) and before vascular invasion (P < 0.005) than Group B cases. The frequency of hepatic surgery and/or local ablation was higher in Group A than Group B (P = 0.001). Overall median survival of Group A was 882 days versus 99 days in Group B (P < 0.0001). One-and 3-year probabilities of survival in Group A were 89% and 38%, versus 33% and 19% in Group B (P < 0.001). Independent predictors of survival included screening, Child-Pugh score, creatinine, tumor stage and absence of alcohol as the etiology. Conclusions: Screening for HCC in cirrhosis identifies tumors at an earlier stage, results in a higher chance of receiving curative treatment and possibly improves patient survival. The absence of alcoholic liver disease impacts favorably on survival.