Browsing by Author "Adams, Leon A."

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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
    (Elsevier, 2018-08) Vilar-Gomez, Eduardo; Calzadilla-Bertot, Luis; Wong, Vincent Wai-Sun; 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; Chan, Anthony Wing Hung; Chalasani, Naga; George, Jacob; Adams, Leon A.; Romero-Gomez, Manuel; Medicine, School of Medicine
    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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    Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Non-alcoholic Steatohepatitis-related, Child-Pugh A Cirrhosis
    (Elsevier, 2020) Vilar-Gomez, Eduardo; Calzadilla-Bertot, Luis; Wong, Vincent Wai-Sun; Castellanos, Marlen; Aller-de la Fuente, Rocio; Eslam, Mohammed; Wong, Grace Lai-Hung; George, Jacob; Romero-Gomez, Manuel; Adams, Leon A.; Medicine, School of Medicine
    Background & Aims Factors that affect outcomes of patients with non-alcoholic steatohepatitis (NASH) related cirrhosis are unclear. We studied associations of type 2 diabetes, levels of hemoglobin A1c (HbA1c), and use antidiabetic medications with survival and liver-related events in patients with NASH and compensated cirrhosis. Methods We collected data from 299 patients with biopsy-proven NASH with Child-Pugh A cirrhosis from tertiary hospitals in Spain, Australia, Hong Kong, and Cuba, from April 1995 through December 2016. We obtained information on presence of type 2 diabetes, level of HbA1c, and use of antidiabetic medications. Cox proportional and competing risk models were used to estimate and compare rates of transplant-free survival, hepatic decompensation, and hepatocellular carcinoma (HCC). Results Two-hundred and twelve patients had type 2 diabetes at baseline and 8/87 patients developed diabetes during a median follow-up time of 5.1 y (range, 0.5–10.0 y). A lower proportion of patients with diabetes survived the entire follow-up period (38%) than of patients with no diabetes (81%) (adjusted hazard ratio [aHR], 4.23; 95% CI, 1.93–9.29). Higher proportions of patients with diabetes also had hepatic decompensation (51% vs 26% of patients with no diabetes; aHR, 2.03; 95% CI 1.005–4.11) and HCC (25% vs 7% of patients with no diabetes; aHR, 5.42; 95% CI 1.74–16.80). Averaged annual HbA1c levels over time were not associated with outcomes. Metformin use over time was associated with a significant reduction in risk of death or liver transplantation (aHR, 0.41; 95% CI, 0.26–0.45), hepatic decompensation (aHR, 0.80; 95% CI, 0.74–0.97), and HCC (aHR, 0.78; 95% CI, 0.69–0.96). Metformin significantly reduced risk of hepatic decompensation and HCC only in subjects with HbA1c levels above 7.0% (aHR, 0.97; 95% CI, 0.95–0.99 and aHR, 0.67; 95% CI, 0.43–0.94, respectively). Conclusions In an international cohort of patients with biopsy-proven NASH and Child-Pugh A cirrhosis, type 2 diabetes increased risk of death and liver-related outcomes, including HCC. Patients who took metformin had higher rates of survival and lower rates of decompensation and HCC.