Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: Real-world study of 18 million patients in four European cohorts

Research output: Contribution to journalArticlepeer-review


  • Myriam Alexander
  • A. Katrina Loomis
  • Johan Van Der Lei
  • Talita Duarte-Salles
  • Daniel Prieto-Alhambra
  • And 9 others
  • David Ansell
  • Alessandro Pasqua
  • Francesco Lapi
  • Peter Rijnbeek
  • Mees Mosseveld
  • Dawn M. Waterworth
  • Stuart Kendrick
  • Naveed Sattar
  • William Alazawi

Colleges, School and Institutes

External organisations

  • GlaxoSmithKline
  • Pfizer Inc.
  • Erasmus University Medical Center
  • Fundacio Institut Universitari per A la Recerca A l'Atencio Primaria de Salut Jordi Gol i Gurina
  • Department of Experimental Psychology
  • Quintile IMS
  • Health Search
  • GlaxoSmithKline, USA
  • University of Glasgow
  • Barts and The London Queen Mary's School of Medicine and Dentistry


Background: Non-alcoholic fatty liver disease (NAFLD) is a common condition that progresses in some patients to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Here we used healthcare records of 18 million adults to estimate risk of acquiring advanced liver disease diagnoses in patients with NAFLD or NASH compared to individually matched controls. Methods: Data were extracted from four European primary care databases representing the UK, Netherlands, Italy and Spain. Patients with a recorded diagnosis of NAFLD or NASH (NAFLD/NASH) were followed up for incident cirrhosis and HCC diagnoses. Each coded NAFLD/NASH patient was matched to up to 100 "non-NAFLD" patients by practice site, gender, age ± 5 years and visit recorded within ± 6 months. Hazard ratios (HR) were estimated using Cox models adjusted for age and smoking status and pooled across databases by random effects meta-analyses. Results: Out of 18,782,281 adults, we identified 136,703 patients with coded NAFLD/NASH. Coded NAFLD/NASH patients were more likely to have diabetes, hypertension and obesity than matched controls. HR for cirrhosis in patients compared to controls was 4.73 (95% CI 2.43-9.19) and for HCC, 3.51 (95% CI 1.72-7.16). HR for either outcome was higher in patients with NASH and those with high-risk Fib-4 scores. The strongest independent predictor of a diagnosis of HCC or cirrhosis was baseline diagnosis of diabetes. Conclusions: Real-world population data show that recorded diagnosis of NAFLD/NASH increases risk of life-threatening liver outcomes. Diabetes is an independent predictor of advanced liver disease diagnosis, emphasising the need to identify specific groups of patients at highest risk.


Original languageEnglish
Article number95
JournalBMC Medicine
Issue number1
Publication statusPublished - 20 May 2019


  • Cirrhosis, Hepatocellular cancer, NAFLD, NASH, Population

ASJC Scopus subject areas