Abstract
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. To determine the efficacy of oral anti-viral agents in reducing HCC risk in relationship with other known factors. Published studies of at least 20 CHB patients treated with an oral anti-viral agent and followed for >2 years were analysed for incidence of HCC per 100 person years follow-up. 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 10 025 treated patients showed HCC incidence of 1.3 per 100 person years, independent of the agent used. Patient age >50 years 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. 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.
Highlights
Worldwide chronic hepatitis B virus (HBV) infection is the most frequently identified cause of liver disease that predisposes patients to the development of hepatocellular carcinoma (HCC).[1, 2] Established risk factors for the development of HCC in untreated chronic HBV patients include subject age, male gender, the presence of cirrhosis, hepatitis B e antigen (HBeAg) + serostatus and higher levels of serum HBV-DNA.[2]
Patient age >50 years 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
HCC still develops at a rate of 1.3 per 100 patient years in chronic hepatitis B (CHB) patients receiving an oral anti-viral agent
Summary
Worldwide chronic hepatitis B virus (HBV) infection is the most frequently identified cause of liver disease that predisposes patients to the development of hepatocellular carcinoma (HCC).[1, 2] Established risk factors for the development of HCC in untreated chronic HBV patients include subject age, male gender, the presence of cirrhosis, hepatitis B e antigen (HBeAg) + serostatus and higher levels of serum HBV-DNA.[2] In a large cohort of untreated Taiwanese patients with chronic HBV followed up for a mean of 11.4 years, high levels of HBV replication as manifest by high levels of HBV-DNA at enrolment and during follow-up were independent and strong predictors of developing HCC.[3] Over the past 20 years, five oral nucleos(t)ide analogues have been approved for the treatment of chronic HBV with improved short- and intermediate-term outcomes.[4, 5] The newer oral anti-viral agents, entecavir (ETV), tenofovir (TDF) and telbivudine (TBV) have been shown to be more potent suppressors of HBV replication compared with lamivudine (LAM) and adefovir (ADV) with a lower likelihood of leading to the emergence of drug-resistant HBV during prolonged therapy.[6] the impact of these newer agents on the incidence of HCC is not clear due to the limited number of treated patients and relatively short duration of follow-up. Analyses were undertaken to identify the role of other clinical features on the risk of developing HCC in chronic HBV patients receiving an oral anti-viral agent
Sign-in/Register to view highlights & summary 
Submitted Version (
Free)
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call