Curing Hepatitis C Lowers but Does Not Eliminate Risk of Liver Cancer
Attaining sustained virologic response (SVR) with an interferon-based hepatitis C (HCV) regimen lowered risk of hepatocellular carcinoma (HCC) 80% in a large Canadian cohort. But HCC did develop after SVR, especially in patients with cirrhosis before SVR.
The impact of HCV cure (indicated by SVR) on HCC risk is not well established in North America. Low uptake and efficacy of interferon-based HCV therapy were expected to have a low population-level impact on HCC risk. Treatment with direct-acting antivirals (DAAs) could have a larger impact on HCC risk, but data on long-term DAA outcomes will take years to accrue. Therefore, researchers working with the British Columbia Hepatitis Testers Cohort (BCHTC) conducted this SVR and HCC analysis in interferon-treated patients.
The BCHTC includes approximately 1.5 million people tested for HCV in 1992-2013, about 67,000 of whom tested positive. Cohort members are linked to data on medical visits, hospitalizations, cancers, prescription drugs and mortality. This analysis included people who filled at least one interferon prescription for HCV infection and had HCV RNA monitoring. The researchers defined SVR as undetectable HCV RNA at least 12 weeks after treatment ended. The primary outcome was new diagnosis of HCC in the BC Cancer Registry after treatment ended.
The analysis focused on 4663 cohort members who achieved SVR and 3484 who did not. The SVR group included a lower proportion of men (65.6% versus 70.3%), a lower proportion with cirrhosis (3.1% versus 7.5%) or decompensated cirrhosis (1.7% versus 3.6%), and a lower proportion with diabetes (8.2% versus 13.7%) or HIV infection (3.9% versus 5.3%).
Through a median follow-up of 5.6 years, HCC developed in 29 people with SVR to yield an incidence of 1.1 per 1000 person-years. In the no-SVR group, HCC developed in 145 people for an incidence of 7.2 per 1000 person-years. Proportional hazards modeling using competing risk regression determined that SVR lowered the risk of HCC more than 80% (adjusted hazard ratio [aHR] 0.18, 95% confidence interval [CI] 0.12 to 0.27). The impact of SVR on HCC risk was greater in people without cirrhosis (aHR 0.16, 95% CI 0.10 to 0.26) than in those with cirrhosis (aHR 0.31, 95% CI 0.12 to 0.79).
Cirrhosis almost tripled HCC risk (aHR 2.74, 95% CI 1.78 to 4.22), while male sex doubled the risk (aHR 2.03, 95% CI 1.38 to 2.97). Age 50 to 59 (versus 49 or younger) more than quadrupled HCC risk (aHR 4.60, 95% CI 3.09 to 6.83), while age 60 or older raised the risk more than seven-fold (aHR 7.08, 95% CI 4.33 to 11.59). Diabetes or problem alcohol use did not affect HCC risk in this analysis.
HCC incidence measured 7.0 per 1000 person-years with SVR and cirrhosis versus 0.9 per 1000 with SVR and no cirrhosis. HCC incidence was 20.1 per 1000 person-years with no SVR and cirrhosis and 6.3 per 1000 with no SVR and no cirrhosis.
Among cohort members with SVR, cirrhosis tripled HCC risk (aHR 3.23, 95% CI 1.17 to 8.98), male sex tripled HCC risk (aHR 3.32, 95% CI 1.14 to 9.61), age 50 to 59 versus 49 or younger more than quadrupled HCC risk (aHR 4.40, 95% CI 1.69 to 11.47), as did age 60 or older (aHR 4.39, 95% CI 1.26 to 15.31).
The researchers proposed that HCC prevention requires early treatment of HCV. They suggested that patients with advanced HCV liver disease and older age need continued HCC surveillance to allow early detection.
Mark Mascolini writes about HIV and hepatitis virus infection.