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

<jats:title>SUMMARY</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Five oral nucleos(t)ide analogues are available to treat chronic hepatitis B (<jats:styled-content style="fixed-case">CHB</jats:styled-content>). With the availability of newer agents, their efficacy on incidence of hepatocellular carcinoma (<jats:styled-content style="fixed-case">HCC</jats:styled-content>) is not well described.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>To determine the efficacy of oral anti‐viral agents in reducing <jats:styled-content style="fixed-case">HCC</jats:styled-content> risk in relationship with other known factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Published studies of at least 20 <jats:styled-content style="fixed-case">CHB</jats:styled-content> patients treated with an oral anti‐viral agent and followed for >2 years were analysed for incidence of <jats:styled-content style="fixed-case">HCC</jats:styled-content> per 100 person years follow‐up.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Pooled homogeneous data from six studies showed lamivudine (<jats:styled-content style="fixed-case">LAM</jats:styled-content>) treatment (<jats:italic>n</jats:italic> = 3306) to reduce <jats:styled-content style="fixed-case">HCC</jats:styled-content> risk by 51% compared with no treatment (<jats:italic>n</jats:italic> = 3585) (3.3 vs. 9.7 per 100 person years, <jats:italic>P</jats:italic> < 0.0001). Pooled data from 49 studies (23 with <jats:styled-content style="fixed-case">LAM</jats:styled-content>; 16 with adefovir; and 10 with entecavir, tenofovir or telbivudine) of 10 025 treated patients showed <jats:styled-content style="fixed-case">HCC</jats:styled-content> incidence of 1.3 per 100 person years, independent of the agent used. Patient age >50 years and hepatitis B virus‐<jats:styled-content style="fixed-case">DNA</jats:styled-content> detectability at <jats:styled-content style="fixed-case">HCC</jats:styled-content> diagnosis increased risk of <jats:styled-content style="fixed-case">HCC</jats:styled-content> 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Lamivudine treatment significantly reduces the incidence of <jats:styled-content style="fixed-case">HCC</jats:styled-content> compared with no treatment. However, <jats:styled-content style="fixed-case">HCC</jats:styled-content> still develops at a rate of 1.3 per 100 patient years in <jats:styled-content style="fixed-case">CHB</jats:styled-content> patients receiving an oral anti‐viral agent. This finding highlights the need for continued <jats:styled-content style="fixed-case">HCC</jats:styled-content> surveillance, particularly in <jats:styled-content style="fixed-case">CHB</jats:styled-content> patients with inadequate viral suppression, older age and cirrhosis.</jats:p></jats:sec>