WASHINGTON (FRONTLINE MEDICAL NEWS) – The true impact of advanced fibrosis and cirrhosis advancing to serious hepatic and nonhepatic complications in nonalcoholic fatty liver disease remains somewhat a mystery, but a multinational prospective cohort study has found that patients with bridging fibrosis are at risk of nonhepatic malignancies and vascular problems while patients with cirrhosis are prone to predominantly liver-related complications that result in higher rates of death and liver transplant, according to a report presented at the annual meeting of the American Association for the Study of Liver Diseases.

“NAFLD patients with biopsy-proven cirrhosis have a higher mortality and liver-related complications than those with bridging fibrosis, whereas vascular events and nonhepatic malignancies are the commonest complications in those with bridging fibrosis,” said Eduardo Vilar-Gomez, MD, PhD, of Indiana University, Indianapolis. “Among compensated cirrhotic patients, those with Child-Pugh (CP) A6 are at highest risk of liver-related outcomes and mortality.”

Dr. Vilar-Gomez reported on a multicenter, international prospective cohort study of 458 NAFLD patients, 159 with biopsy-proven bridging fibrosis and 299 with compensated cirrhosis (222 with CP A5 and 77 with CP A6) who were followed at six academic centers in four different countries between April 1995 and December 2016.

During a mean follow-up of 5.7 years, 41 patients died, 43 had liver transplants, 90 had initial hepatic decompensation events, 42 were diagnosed with hepatocellular carcinoma (HCC), 14 had major vascular events, and 30 were diagnosed with nonhepatic cancers. The overall death or transplant rates were 3% (four) in the bridging fibrosis group, 14% (32) in the cirrhosis and CP A5 group, and 62% (48) in the cirrhosis and CP A6 group.

Liver-related death rates were also highest among patients with cirrhosis, Dr. Vilar-Gomez said. While the four deaths in the fibrosis patients were evenly split between liver- and non–liver-related causes, 79% of deaths (15) in the cirrhosis and CP A5 patients were liver related, as were all 18 deaths in the cirrhosis and CP A6 group.

“Cirrhotic patients displayed the highest rates of hepatic outcomes overall as compared to those with bridging fibrosis,” Dr. Vilar-Gomez said. Rates of hepatic decompensation were 3% (5) for bridging fibrosis, 18% (40) for cirrhosis and CP A5, and 58% (48) for cirrhosis and CP A6. Likewise, HCC rates were also highest in cirrhotic patients: 9% (21) and 25% (19) for those with CP A5 and CP A6 disease, respectively, vs. 1% (2) for those with bridging fibrosis.

But nonhepatic outcomes were highest among the bridging fibrosis patients, Dr. Vilar-Gomez noted. “These include higher rates of major vascular events – 5% (eight) for those with bridging fibrosis vs. 2% (five) and 1% (one) for those with cirrhosis and CP A5 or CP A6 disease, respectively,” he said. “Rates of nonhepatic malignancies were comparable: 8% (13) for those with bridging fibrosis, 5% (10) for those with cirrhosis and CP5 disease and 9% (7) for those with cirrhosis and CP6 disease.

“Cirrhosis increased the risk of death/transplant, decompensation, and hepatocellular carcinoma by 4.3-, 4.5-, and 3.9-fold, respectively,” Dr. Vilar-Gomez said, “but was associated with a lower risk of vascular events.”

He noted that the study identified a number of risk factors associated with overall mortality and severity of liver disease in cirrhosis compared with bridging fibrosis. Cirrhosis patients tended to be 2-3 years older, had lower body mass index and blood pressure, had higher rates of type 2 diabetes, had lower lipid levels, and had worse liver and renal function.

“Type 2 diabetes and steatosis severity on liver histology, among other factors, were independent predictors for liver-related outcomes,” Dr. Vilar-Gomez said. The findings have implications in assessing patients with advanced NAFLD and for the design and interpretation of clinical trials, he added.

Dr. Vilar-Gomez had no financial relationships to disclose.


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