Steatohepatitis/Metabolic Liver Disease

The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: An international collaborative study†‡§

  1. Neeraj Bhala1,2,3,¶,*,
  2. Paul Angulo4,5,
  3. David van der Poorten3,
  4. Eric Lee3,
  5. Jason M. Hui3,
  6. Giorgio Saracco6,
  7. Leon A. Adams5,7,
  8. Phunchai Charatcharoenwitthaya5,8,
  9. Joanne H. Topping10,
  10. Elisabetta Bugianesi9,
  11. Christopher P. Day10,
  12. Jacob George3

Article first published online: 9 AUG 2011

DOI: 10.1002/hep.24491

Issue

Hepatology

Hepatology

Volume 54, Issue 4, pages 1208–1216, October 2011

Additional Information

How to Cite

Bhala, N., Angulo, P., van der Poorten, D., Lee, E., Hui, J. M., Saracco, G., Adams, L. A., Charatcharoenwitthaya, P., Topping, J. H., Bugianesi, E., Day, C. P. and George, J. (2011), The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: An international collaborative study. Hepatology, 54: 1208–1216. doi: 10.1002/hep.24491

Author Information

  1. 1

    Clinical Trial Service Unit & Epidemiological Studies Unit, Richard Doll Building, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

  2. 2

    Department of Gastroenterology, John Radcliffe Hospital, Oxford, United Kingdom

  3. 3

    Storr Liver Unit, Westmead Millenium Institute, University of Sydney, Westmead, New South Wales, Australia

  4. 4

    Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, Lexington, Kentucky, USA

  5. 5

    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA

  6. 6

    Division of Gastroenterology, Osperdale S. Giovanni Battista, University of Turin, Turin, Italy

  7. 7

    School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia

  8. 8

    Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

  9. 9

    Department of Medicine, Alma Mater Studiorum University, Bologna, Italy

  10. 10

    Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne, United Kingdom

  1. fax: +44 1865 743 985

*Clinical Trial Service Unit & Epidemiological Studies Unit, Richard Doll Building, Nuffield Department of Medicine, University of Oxford, OX3 7LF, United Kingdom

  1. †

    Potential conflict of interest: Nothing to report.

  2. ‡

    N.B. is funded by the UK Medical Research Council and by Dame Sheila Sherlock (Royal College of Physicians) and Berkeley Trust (University College London and Gonville and Caius College, Cambridge) Travelling Fellowships for his period of study in Sydney. L.A.A. was supported by research scholarships from the Australian National Health and Medical Research Council (no. 353710) and the University of Western Australia (Athelstan and Amy Saw Scholarship). This study was supported by a National Institute of Health R01 DK82426 grant (to P.A.). These sponsors played no role in the study design or the collection, analysis, and interpretation of data.

  3. §

    See Editorial on Page 1118.

Publication History

  1. Issue published online: 27 SEP 2011
  2. Article first published online: 9 AUG 2011
  3. Accepted manuscript online: 17 JUN 2011 02:13PM EST
  4. Manuscript Accepted: 3 JUN 2011
  5. Manuscript Received: 18 MAR 2011

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Abstract

Information on the long-term prognosis of nonalcoholic fatty liver disease (NAFLD) is limited. We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis by prospectively studying 247 such patients from four international centers (in Australia, USA, UK and Italy). Their natural history was then compared with 264 patients with HCV infection who were either naïve or non-responders to treatment. Both cohorts were Child-Pugh class A and had advanced fibrosis (stage 3) or cirrhosis (stage 4) confirmed by liver biopsy at enrollment. In the NAFLD cohort, followed up for a mean of 85.6 months (range, 6-297), there were 48 (19.4%) liver-related complications and 33 (13.4%) deaths or liver transplants. In the HCV cohort, followed up for 74.9 months (mean; range, 6-238), there were 47 (16.7%) liver-related complications and 25 (9.4%) deaths or liver transplants. When adjusting for baseline differences in age and gender, the cumulative incidence of liver-related complications was lower in the NAFLD than the HCV cohort (P = 0.03), including incident hepatocellular cancer (6 versus 18; P = 0.03), but that of cardiovascular events (P = 0.17) and overall mortality (P = 0.6) were similar in both groups. In the NAFLD cohort, platelet count, stage 4 fibrosis, lowered platelet count, and lowered serum cholesterol and alanine aminotrasferase (ALT) levels were associated with liver-related complications; an aspartate aminotransferase/ALT ratio >1 and older age were associated with overall mortality, and higher serum bilirubin levels and stage 4 fibrosis were associated with liver-related mortality. Conclusions: Patients with NAFLD with advanced fibrosis or cirrhosis have lower rates of liver-related complications and hepatocellular cancer than corresponding patients with HCV infection, but similar overall mortality. Some clinical and laboratory features predict liver-related complications and other outcomes in patients with NAFLD. (HEPATOLOGY 2011;54:1208–1216)

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