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Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study

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Vilar-Gomez, Eduardo, Calzadilla-Bertot, Luis, Wai-Sun Wong, Vincent, Castellanos, Marlen, Aller-de la Fuente, Rocio, Metwally, Mayada, Eslam, Mohammed, Gonzalez-Fabian, Licet +9 more·2018·Gastroenterology
DOI 10.1053/j.gastro.2018.04.034
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Abstract

Background & aims Little is known about the natural course of nonalcoholic fatty liver disease (NAFLD) with advanced fibrosis. We describe long-term outcomes and evaluate the effects of clinical and histologic parameters on disease progression in patients with advanced NAFLD.Methods We conducted a multi-national study of 458 patients with biopsy-confirmed NAFLD with bridging fibrosis (F3, n = 159) or compensated cirrhosis (222 patients with Child-Turcotte-Pugh scores of A5 and 77 patients with scores of A6), evaluated from April 1995 through November 2013 and followed until December 2016, death, or liver transplantation at hepatology centers in Spain, Australia, Hong Kong, and Cuba. Biopsies were re-evaluated and scored; demographic, clinical, laboratory, and pathology data for each patient were collected from the time of liver biopsy collection. Cox proportional and competing risk models were used to estimate rates of transplantation-free survival and major clinical events and to identify factors associated with outcomes.Results During a mean follow-up time of 5.5 years (range, 2.7-8.2 years), 37 patients died, 37 received liver transplants, 88 had initial hepatic decompensation events, 41 developed hepatocellular carcinoma, 14 had vascular events, and 30 developed nonhepatic cancers. A higher proportion of patients with F3 fibrosis survived transplantation-free for 10 years (94%; 95% confidence interval [CI], 86%-99%) than of patients with cirrhosis and Child-Turcotte-Pugh A5 (74%; 95% CI, 61%-89%) or Child-Turcotte-Pugh A6 (17%; 95% CI, 6%-29%). Patients with cirrhosis were more likely than patients with F3 fibrosis to have hepatic decompensation (44%; 95% CI, 32%-60% vs 6%, 95% CI, 2%-13%) or hepatocellular carcinoma (17%; 95% CI, 8%-31% vs 2.3%, 95% CI, 1%-12%). The cumulative incidence of vascular events was higher in patients with F3 fibrosis (7%; 95% CI, 3%-18%) than cirrhosis (2%; 95% CI, 0%-6%). The cumulative incidence of nonhepatic malignancies was higher in patients with F3 fibrosis (14%; 95% CI, 7%-23%) than cirrhosis (6%; 95% CI, 2%-15%). Death or transplantation, decompensation, and hepatocellular carcinoma were independently associated with baseline cirrhosis and mild (<33%) steatosis, whereas moderate alcohol consumption was associated with these outcomes only in patients with cirrhosis.Conclusions Patients with NAFLD cirrhosis have predominantly liver-related events, whereas those with bridging fibrosis have predominantly nonhepatic cancers and vascular events.

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  • People with NASH and fibrosis may develop end-stage complications such as cirrhosis, portal hypertension, or hepatocellular carcinoma, which carry a much worse prognosis.

    “Ultimately, those with NASH and fibrosis may develop end-stage complications such as cirrhosis, portal hypertension or hepatocellular carcinoma (HCC), which portend a much worse prognosis.6–10”

    From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [8]

  • Fibrosis stage is predictive of liver-specific morbidity and mortality.

    “fibrosis stage is predictive of liver-specific morbidity and mortality.”

    From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [8]

  • Approximately 25%-30% of individuals with NAFLD can progress to NASH, whereas the same proportion of individuals with NASH can progress to cirrhosis and hepatocellular carcinoma, especially those with liver fibrosis.

    “Approximately 25%–30% of individuals with NAFLD can progress to NASH [65], whereas the same proportion of individuals with NASH can progress to cirrhosis and hepatocellular carcinoma, especially those with liver fibrosis [66,67].”

    From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [66]

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Research works printed but not linked: 2

  1. Bruix J, Sherman M. American Association for the Study of Liver Diseases. Management of hepatocellular carci- noma: an update. Hepatology 2011;53:1020-1022.
  2. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/ AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2935-2959. 457.e3 Vilar-Gomez et al Gastroenterology Vol. 155, No. 2

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Authors
Vilar-Gomez, E., Calzadilla-Bertot, L., Wai-Sun Wong, V., Castellanos, M., Aller-de la Fuente, R., Metwally, M., Eslam, M., Gonzalez-Fabian, L., Alvarez-Quiñones Sanz, M., Conde-Martin, A. F., De Boer, B., McLeod, D., Hung Chan, A. W., Chalasani, N., George, J., Adams, L. A., & Romero-Gomez, M.
Affiliations
  • The University of Sydney (AU)
  • Westmead Hospital (AU)
  • Indiana University Hospital (US)
  • The University of Western Australia (AU)
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2018-08
Volume
155
Issue
2
Pages
443-457.e17
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2018.04.034
OpenAlex
W2800368679
Cited by
806
References
64
Citations by year
2026: 65 · 2025: 90 · 2024: 104 · 2023: 110 · 2022: 115 · 2021: 132 · 2020: 107 · 2019: 67 · 2018: 13
FWCI
62.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion, other-oa)
  • Purdue University Indianapolis (Indiana University) (submittedVersion, other-oa)
Funders
  • Australian Government
  • School of Medicine, Indiana University
  • Instituto de Salud Carlos III (PI16/01842)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
non-alcoholic fatty liver disease, advanced liver fibrosis, bridging fibrosis, compensated cirrhosis, cause-specific mortality, liver transplantation, Child-Pugh score, hepatic decompensation, hepatocellular carcinoma, vascular events, disease progression, transplant-free survival, competing risk analysis, liver biopsy
MeSH terms
Aged, Biopsy, Cardiovascular Diseases, Female, Follow-Up Studies, Carcinoma, Hepatocellular, Humans, Liver, Liver Cirrhosis, Liver Neoplasms, Male, Middle Aged, Severity of Illness Index, Incidence, Liver Transplantation, Disease Progression, Non-alcoholic Fatty Liver Disease

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