Systematic review with meta-analysis: risk of hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis compared to other liver diseases

Aliment Pharmacol Ther. 2018 Oct;48(7):696-703. doi: 10.1111/apt.14937. Epub 2018 Aug 22.


Background: Given the lack of long-term prospective studies, it is challenging for clinicians to make informed decisions about screening and treatment decisions regarding the risk of hepatocellular carcinoma (HCC) in patients with non-alcoholic steatohepatitis (NASH) who do not have cirrhosis.

Aim: To characterise the pooled risk of HCC in the non-cirrhosis population.

Methods: Published studies were identified through April 2016 in MEDLINE, Scopus, Science Citation Index, AMED and the Cochrane Library. Two independent reviewers screened citations and extracted data. Random effect odds ratios (OR) were calculated to obtain aggregate estimates of effect size between NASH and non-NASH groups. Between-study variability and heterogeneity were assessed.

Results: Nineteen studies with 168 571 participants were included. Eighty-six per cent of included subjects had cirrhosis. The prevalence of HCC in non-cirrhotic NASH was 38.0%; among other aetiologies in non-cirrhotics, it was 14.2% (P < 0.001). Non-cirrhotic NASH subjects were at greater odds of developing HCC than non-cirrhotic subjects of other aetiologies (OR 2.61, 95% CI 1.27-5.35, P = 0.009). When examining all NASH subjects either with or without cirrhosis, those with NASH as the underlying liver disease did not have a significantly increased risk of HCC (OR 1.43, 95% CI 0.77-2.65, P = 0.250).

Conclusions: In non-cirrhotic subjects, those with NASH have a higher risk of HCC compared to other aetiologies of liver disease. Further study investigating the risk factors of HCC among non-cirrhotic NASH patients is needed.

Publication types

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

MeSH terms

  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / pathology
  • Case-Control Studies
  • Cohort Studies
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / pathology
  • Liver Diseases / classification
  • Liver Diseases / complications
  • Liver Diseases / epidemiology*
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / pathology
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / epidemiology*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Observational Studies as Topic / statistics & numerical data
  • Prospective Studies
  • Risk Factors