Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study

Eduardo Vilar-Gomez, Luis Calzadilla-Bertot, Vincent Wai-Sun Wong, Marlen Castellanos, Rocio Aller-de la Fuente, Mayada Metwally, Mohammed Eslam, Licet Gonzalez-Fabian, María Alvarez-Quiñones Sanz, Antonio Felix Conde-Martin, Bastiaan De Boer, Duncan McLeod, Anthony Wing Hung Chan, Naga Chalasani, Jacob George, Leon A. Adams, Manuel Romero-Gomez

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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.

Original languageEnglish
Pages (from-to)443-457.e17
JournalGastroenterology
Volume155
Issue number2
DOIs
Publication statusPublished - 1 Aug 2018

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Fibrosis
Cohort Studies
Mortality
Confidence Intervals
Liver
Blood Vessels
Hepatocellular Carcinoma
Transplantation
Non-alcoholic Fatty Liver Disease
Biopsy
Neoplasms
Cuba
Clinical Pathology
Incidence
Hong Kong
Gastroenterology
Alcohol Drinking
Liver Cirrhosis
Liver Transplantation
Spain

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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 ; Alvarez-Quiñones Sanz, María ; Conde-Martin, Antonio Felix ; De Boer, Bastiaan ; McLeod, Duncan ; Hung Chan, Anthony Wing ; Chalasani, Naga ; George, Jacob ; Adams, Leon A. ; Romero-Gomez, Manuel. / Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease : A Multi-National Cohort Study. In: Gastroenterology. 2018 ; Vol. 155, No. 2. pp. 443-457.e17.
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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.",
keywords = "Competing Risk Analysis, Cryptogenic Cirrhosis, Gastroesophageal Varices, Nonalcoholic Steatohepatitis",
author = "Eduardo Vilar-Gomez and Luis Calzadilla-Bertot and {Wai-Sun Wong}, Vincent and Marlen Castellanos and {Aller-de la Fuente}, Rocio and Mayada Metwally and Mohammed Eslam and Licet Gonzalez-Fabian and {Alvarez-Qui{\~n}ones Sanz}, Mar{\'i}a and Conde-Martin, {Antonio Felix} and {De Boer}, Bastiaan and Duncan McLeod and {Hung Chan}, {Anthony Wing} and Naga Chalasani and Jacob George and Adams, {Leon A.} and Manuel Romero-Gomez",
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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, AF, De Boer, B, McLeod, D, Hung Chan, AW, Chalasani, N, George, J, Adams, LA & Romero-Gomez, M 2018, 'Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study' Gastroenterology, vol. 155, no. 2, pp. 443-457.e17. https://doi.org/10.1053/j.gastro.2018.04.034

Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease : A Multi-National Cohort Study. / Vilar-Gomez, Eduardo; Calzadilla-Bertot, Luis; Wai-Sun Wong, Vincent; Castellanos, Marlen; Aller-de la Fuente, Rocio; Metwally, Mayada; Eslam, Mohammed; Gonzalez-Fabian, Licet; Alvarez-Quiñones Sanz, María; Conde-Martin, Antonio Felix; De Boer, Bastiaan; McLeod, Duncan; Hung Chan, Anthony Wing; Chalasani, Naga; George, Jacob; Adams, Leon A.; Romero-Gomez, Manuel.

In: Gastroenterology, Vol. 155, No. 2, 01.08.2018, p. 443-457.e17.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease

T2 - A Multi-National Cohort Study

AU - Vilar-Gomez, Eduardo

AU - Calzadilla-Bertot, Luis

AU - Wai-Sun Wong, Vincent

AU - Castellanos, Marlen

AU - Aller-de la Fuente, Rocio

AU - Metwally, Mayada

AU - Eslam, Mohammed

AU - Gonzalez-Fabian, Licet

AU - Alvarez-Quiñones Sanz, María

AU - Conde-Martin, Antonio Felix

AU - De Boer, Bastiaan

AU - McLeod, Duncan

AU - Hung Chan, Anthony Wing

AU - Chalasani, Naga

AU - George, Jacob

AU - Adams, Leon A.

AU - Romero-Gomez, Manuel

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - Competing Risk Analysis

KW - Cryptogenic Cirrhosis

KW - Gastroesophageal Varices

KW - Nonalcoholic Steatohepatitis

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U2 - 10.1053/j.gastro.2018.04.034

DO - 10.1053/j.gastro.2018.04.034

M3 - Article

VL - 155

SP - 443-457.e17

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

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