Eduardo Vilar-Gomez1, Luis Calzadilla-Bertot2, Vincent Wai-Sun Wong3, Marlen Castellanos4, Rocio Aller-de la Fuente5, Mayada Metwally6, Mohammed Eslam6, Licet Gonzalez-Fabian7, María Alvarez-Quiñones Sanz8, Antonio Felix Conde-Martin9, Bastiaan De Boer10, Duncan McLeod11, Anthony Wing Hung Chan12, Naga Chalasani13, Jacob George6, Leon A Adams2, Manuel Romero-Gomez14. 1. Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indiana; Unit for the Clinical Management of Digestive Diseases. Centro para la Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, Virgen del Rocio University Hospital, University of Seville, Seville, Spain. Electronic address: evilar@iu.edu. 2. Medical School, Faculty of Health and Medical Sciences, the University of Western Australia, Nedlands, Australia. 3. Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China. 4. Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba. 5. Department of Digestive Disease, Institute of Endocrinology and Nutrition, University of Valladolid, Valladolid, Spain. 6. Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, New South Wales, Australia. 7. Department of Pathology, National Institute of Gastroenterology, Havana, Cuba. 8. Department of Pathology, Hospital Clinico Universitario, Valladolid, Spain. 9. Department of Pathology, Valme University Hospital, Seville, Spain. 10. Department of Pathology, Sir Charles Gairdner Hospital, Perth, Australia. 11. Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sidney, New South Wales, Australia. 12. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong. 13. Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indiana. 14. Unit for the Clinical Management of Digestive Diseases. Centro para la Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, Virgen del Rocio University Hospital, University of Seville, Seville, Spain.
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.
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.
Authors: Donghee Kim; Won Kim; Adeyinka C Adejumo; George Cholankeril; Sean P Tighe; Robert J Wong; Stevan A Gonzalez; Stephen A Harrison; Zobair M Younossi; Aijaz Ahmed Journal: Hepatol Int Date: 2019-01-29 Impact factor: 6.047