Flaherty, John F.

Chronic hepatitis B (CHB) is the most common cause of hepatocellular carcinoma (HCC) worldwide. Antiviral treatment reduces the risk of HCC and mortality; nonetheless, globally in 2019, only 2.2% of CHB patients received treatment. Current international CHB guidelines recommend antiviral treatment only in subsets of patients with clear evidence of liver damage. This contrasts with hepatitis C or HIV where early treatment is recommended in all infected patients, regardless of end-organ damage. This narrative review aims to provide an overview of data on the early initiation of antiviral treatment and its related potential economic impact. Literature searches were performed using PubMed and abstracts from international liver congresses (2019–2021). Data on risk of disease progression and HCC and the impact of antiviral treatment in currently ineligible patients were summarized. Cost-effectiveness data on early antiviral treatment initiation were also collated. Accumulating molecular, clinical, and economic data suggest that early initiation of antiviral treatment could save many lives through HCC prevention in a highly cost-effective manner. In light of these data, we consider several alternative expanded treatment strategies that might further a simplified ‘treatment as prevention’ approach.

BACKGROUNDEfficacy trials have shown that antiviral therapy improves the outcomes of patients with chronic hepatitis B virus (HBV) infection. However, prospective data regarding the effect of antiviral therapy on the incidence of hepatocellular carcinoma (HCC), especially among patients without cirrhosis, are limited. The authors examined the impact of tenofovir disoproxil fumarate (TDF) on the incidence of HCC using a validated prediction model.METHODSThe incidence of HCC in patients treated with TDF was obtained in the pivotal TDF registration studies after 384 weeks of follow‐up. The predicted risk of HCC in individual patients was calculated using the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH‐B) model, which estimates HCC incidence for up to 10 years based on age, sex, alanine aminotransferase level, hepatitis B e antigen status, and HBV‐DNA. Standardized incidence ratios (SIRs) were calculated comparing the observed and predicted numbers of HCC cases in the study cohort.RESULTSAmong 634 patients with evaluable baseline biopsies, 152 had cirrhosis (Ishak fibrosis score of 5 or 6) and 482 did not. During the 384 weeks of study, 14 cases of HCC were reported, with 4 occurring within the first year. The incidence of HCC was 0.37% per year in the study as a whole (0.28% among patients without cirrhosis and 0.65% among patients with cirrhosis). Among patients without cirrhosis, the observed incidence of HCC was significantly lower than predicted (SIR, 0.40; 95% confidence interval, 0.199‐0.795). The last HCC case in a patient with cirrhosis occurred around week 192 with an SIR of 0.51 (95% confidence interval, 0.231‐1.144) reported at week 384.CONCLUSIONSBased on the REACH‐B risk calculator, long‐term therapy with TDF was associated with a reduced incidence of HCC among patients without cirrhosis who met treatment criteria. Cancer 2015;121:3631–3638. © 2015 American Cancer Society.