Meta-analysis: the impact of oral anti-viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B

Background Five oral nucleos(t)ide analogues are available to treat chronic hepatitis B (CHB). With the availability of newer agents, their efficacy on incidence of hepatocellular carcinoma (HCC) is not well described. Aim To determine the efficacy of oral anti-viral agents in reducing HCC risk in relationship with other known factors. Methods Published studies of at least 20 CHB patients treated with an oral anti-viral agent and followed for >2years were analysed for incidence of HCC per 100 person years follow-up. Results Pooled homogeneous data from six studies showed lamivudine (LAM) treatment (n=3306) to reduce HCC risk by 51% compared with no treatment (n=3585) (3.3 vs. 9.7 per 100 person years, P<0.0001). Pooled data from 49 studies (23 with LAM; 16 with adefovir; and 10 with entecavir, tenofovir or telbivudine) of 10025 treated patients showed HCC incidence of 1.3 per 100 person years, independent of the agent used. Patient age >50years and hepatitis B virus-DNA detectability at HCC diagnosis increased risk of HCC by twofold with a 10-fold higher risk among patients with cirrhosis compared with chronic hepatitis. Meta-regression showed patient age, study location (Eastern vs. Western) and type of study (randomised or not) contributed to heterogeneity. Conclusions Lamivudine treatment significantly reduces the incidence of HCC compared with no treatment. However, HCC still develops at a rate of 1.3 per 100 patient years in CHB patients receiving an oral anti-viral agent. This finding highlights the need for continued HCC surveillance, particularly in CHB patients with inadequate viral suppression, older age and cirrhosis.