Large variations in risk of hepatocellular carcinoma and mortality in treatment naïve hepatitis B patients: systematic review with meta-analyses

PLoS One. 2014 Sep 16;9(9):e107177. doi: 10.1371/journal.pone.0107177. eCollection 2014.

Abstract

Background: The complications to chronic hepatitis B (HBV) include incidence of hepatocellular carcinoma (HCC) and mortality. The risk of these complications may vary in different patient groups.

Aim: To estimate the incidence and predictors of HCC and in untreated HBV patients.

Methods: Systematic review with random effects meta-analyses of randomized controlled trials and observational studies. Results are expressed as annual incidence (events per 100 person-years) with 95% confidence intervals. Subgroup and sensitivity analyses of patient and study characteristics were performed to identify common risk factors.

Results: We included 68 trials and studies with a total of 27,584 patients (264,919 person-years). In total, 1,285 of 26,687 (5%) patients developed HCC and 730 of 12,511 (6%) patients died. The annual incidence was 0.88 (95% CI, 0.76-0.99) for HCC and 1.26 (95% CI, 1.01-1.51) for mortality. Patients with cirrhosis had a higher risk of HCC (incidence 3.16; 95% CI, 2.58-3.74) than patients without cirrhosis (0.10; 95% CI, 0.02-0.18). The risk of dying was also higher for patients with than patients without cirrhosis (4.89; 95% CI, 3.16-6.63; and 0.11; 95% CI, 0.09-0.14). The risk of developing HCC increased with HCV coinfection, older age and inflammatory activity. The country of origin did not clearly predict HCC or mortality estimates.

Conclusions: Cirrhosis was the strongest predictor of HCC incidence and mortality. Patients with HBV cirrhosis have a 31-fold increased risk of HCC and a 44-fold increased mortality compared to non-cirrhotic patients. The low incidence rates should be taken into account when considering HCC screening in non-cirrhotic patients.

Trial registration: Prospero CRD42013004764.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Asian People
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / mortality*
  • Coinfection
  • Hepatitis B, Chronic / complications*
  • Hepatitis C
  • Humans
  • Incidence
  • Liver Cirrhosis / etiology
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / mortality*
  • Risk
  • White People

Grants and funding

MT has received a working grant from University of Southern Denmark (www.sdu.dk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No other authors received specific funding for this work.