The occurrence of hepatocellular carcinoma in different risk stratifications of clinically noncirrhotic nonalcoholic fatty liver disease

Int J Cancer. 2017 Oct 1;141(7):1307-1314. doi: 10.1002/ijc.30784. Epub 2017 Jun 30.

Abstract

Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular carcinoma (HCC), but its high prevalence challenges current surveillance strategies. We aimed to evaluate HCC incidences in different risk stratifications for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research Database, we located 31,571 patients with NAFLD between the years 1998 and 2012. After excluding other causes of hepatitis, underlying cirrhosis or malignancy, 18,080 patients were recruited for final analysis. Cumulative incidences of HCC were analyzed after adjusting for competing mortality. With a median follow-up duration of 6.32 years in the study cohort, the 10-year cumulative incidence of HCC was 2.73% [95% confidence interval (CI): 1.69-3.76%]. Hepatoprotectant was used as a surrogate marker for elevated serum alanine transaminase (ALT). After adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, gout, statin use, metformin use and aspirin use, elevated ALT was independently associated with an increased HCC risk [hazard ratio (HR) 6.80, 95% CI: 3.00-15.42; p < 0.001]. Multivariate stratified analysis verified this association in all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05-1.11) and statin use (HR 0.29, 95% CI: 0.12-0.68) were also identified as independent risk factors. The 10-year cumulative HCC incidence was highest in older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99-18.83%), but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0-1.08%). The incidence of HCC was relatively low in patients with clinically noncirrhotic NAFLD, however, HCC risk was significantly increased in older patients experiencing an elevated serum ALT.

Keywords: fatty liver; hepatoma; incidence; transaminase.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alanine Transaminase / blood*
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / mortality
  • Cohort Studies
  • Confidence Intervals
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Incidence
  • Liver Cirrhosis / epidemiology
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / epidemiology*
  • Outcome Assessment, Health Care
  • Risk Assessment
  • Risk Factors
  • Taiwan / epidemiology
  • Time Factors

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Alanine Transaminase