Impact of long‐term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B

• Published in: Cancer Vol. 121; no. 20; pp. 3631 - 3638
• Main Authors: Kim, W. Ray, Loomba, Rohit, Berg, Thomas, Aguilar Schall, Raul E., Yee, Leland J., Dinh, Phillip V., Flaherty, John F., Martins, Eduardo B., Therneau, Terry M., Jacobson, Ira, Fung, Scott, Gurel, Selim, Buti, Maria, Marcellin, Patrick
• Format: Journal Article
• Language: English
• Published: United States 15.10.2015
• Subjects: Adult; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; antiviral therapy; Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - virology; chronic hepatitis B; Double-Blind Method; Drug Administration Schedule; Female; fumarate; Hepatitis B virus; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - drug therapy; hepatocellular carcinoma; Humans; Incidence; Liver Cirrhosis - complications; Liver Cirrhosis - epidemiology; Liver Cirrhosis - virology; Liver Neoplasms - epidemiology; Liver Neoplasms - virology; Male; Middle Aged; REACH‐B; Risk Assessment; Tenofovir - administration & dosage; Tenofovir - therapeutic use; tenofovir disoproxil; chronic hepatitis B; REACH-B; tenofovir disoproxil; antiviral therapy; fumarate; hepatocellular carcinoma
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.29537

BACKGROUND Efficacy 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. METHODS The 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. RESULTS Among 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. CONCLUSIONS Based 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. Efficacy trials have shown that antiviral therapy improves the outcomes of patients with chronic hepatitis B virus infection. Based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH‐B) risk calculator, long‐term therapy with tenofovir disoproxil fumarate appears to be associated with a reduced incidence of hepatocellular carcinoma among patients without cirrhosis who meet treatment criteria.