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Gastroenterology. 2015 Aug;149(2):389-97.e10. doi: 10.1053/j.gastro.2015.04.043. Epub 2015 Apr 29.

Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease.

Author information

1
Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, Lexington, Kentucky.
2
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland. Electronic address: kleinerd@mail.nih.gov.
3
Department of Medicine, Koege University Hospital, Koege, Denmark.
4
School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
5
Faculty of Medicine, University of Iceland, Section of Gastroenterology and Hepatology, National University Hospital, Reykjavik, Iceland.
6
Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
7
Gartnavel General Hospital, Glasgow, United Kingdom.
8
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
9
Department of Pediatrics, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
10
Department of Gastroenterology, Hvidovre Hospital and Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.

Abstract

BACKGROUND & AIMS:

Histologic analysis of liver biopsy specimens allows for grading and staging of nonalcoholic fatty liver disease (NAFLD). We performed a longitudinal study to investigate the long-term prognostic relevance of histologic features for patients with NAFLD.

METHODS:

We performed a retrospective analysis of 619 patients diagnosed with NAFLD from 1975 through 2005 at medical centers in the United States, Europe, and Thailand. Patients underwent laboratory and biopsy analyses, and were examined every 3-12 months after their diagnosis. Outcomes analyzed were overall mortality, liver transplantation, and liver-related events. Cumulative outcomes were compared by log-rank analysis. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (HRs). Time at risk was determined from the date of liver biopsy to the date of outcome or last follow-up examination.

RESULTS:

Over a median follow-up period of 12.6 years (range, 0.3-35.1 y), 193 of the patients (33.2%) died or underwent liver transplantation. Features of liver biopsies significantly associated with death or liver transplantation included fibrosis stage 1 (HR, 1.88; 95% confidence interval [CI], 1.28-2.77), stage 2 (HR, 2.89; 95% CI, 1.93-4.33), stage 3 (HR, 3.76; 95% CI, 2.40-5.89), and stage 4 (HR, 10.9; 95% CI, 6.06-19.62) compared with stage 0, as well as age (HR, 1.07; 95% CI, 1.05-1.08), diabetes (HR, 1.61; 95% CI, 1.13-2.30), current smoking (HR, 2.62; 95% CI, 1.67-4.10), and statin use (HR, 0.32; 95% CI, 0.14-0.70). Twenty-six patients (4.2%) developed liver-related events; fibrosis stage 3 (HR, 14.2; 95% CI, 3.38-59.68) and stage 4 (HR, 51.5; 95% CI, 9.87-269.2) compared with stage 0, were associated significantly with the events. Patients with fibrosis, regardless of steatohepatitis or NAFLD activity score, had shorter survival times than patients without fibrosis.

CONCLUSIONS:

In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.

KEYWORDS:

NASH; PRELHIN Study; Prediction; Prognosis

PMID:
25935633
PMCID:
PMC4516664
DOI:
10.1053/j.gastro.2015.04.043
[Indexed for MEDLINE]
Free PMC Article

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