NAFLD/NASH progression to advanced liver disease tied to elevated mortality risk
Adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) who progress to advanced liver disease have an elevated risk of mortality compared with non-progressors, according to two separate studies conducted in Germany and France and presented at the International Liver Congress™ (ILC 2019).
In the first study, researchers led by Professor Ali Canbay from the University of Magdeburg Medical School in Magdeburg, Germany, identified 215,655 adult patients with NAFLD/NASH from the German InGef database between 2011 and 2016. Over the study period, 11.7 percent of patients progressed to advanced liver disease with 0.4 percent (n=411) developing compensated cirrhosis, 20.5 percent (n=20,614) developing decompensated cirrhosis, 0.4 percent (n=363) developing hepatocellular carcinoma (HCC), and 0.01 percent (n=11) undergoing liver transplant, while 78.7 percent (n=79,245) were non-progressors. About 21 percent of patients progressed from compensated to decompensated cirrhosis. [ILC 2019, abstract PS-060]
At 1 year, patients who had progressed to HCC had a mortality rate of 51.2 percent compared with non-progressors who had a mortality rate of 1.2 percent, while those with compensated and decompensated cirrhosis had mortality rates of 8.8 and 18.3 percent, respectively (p<0.0001 vs non-progressors).
At 5 years, the mortality rate remained elevated among those who had progressed to advanced liver disease compared with non-progressors (mortality rate of 14.8 percent among those with compensated cirrhosis, 25.6 percent with decompensated cirrhosis, and 64.5 percent with HCC compared with 2.8 percent among non-progressors; p<0.0001).
After adjusting for patient demographics and comorbidities, the risk of mortality was highest among patients who had developed HCC compared with non-progressors with a 13.69-fold risk, while mortality risk among those who developed compensated cirrhosis and decompensated cirrhosis and those who underwent liver transplant was 2.71, 4.21, and 2.23 times that of non-progressors.
In the second study, researchers from France identified 125,052 adults (mean age, 55.9 years) with NAFLD/NASH from the French National Database on hospital care (PMSI) between 2009 and 2015. Of these, 1.2 percent (n=1,491; mean age, 62.2 years) were diagnosed with compensated cirrhosis, 6.3 percent (n=7,846; mean age, 65 years) with decompensated cirrhosis, and 0.9 percent (n=1,144; mean age, 70.1 years) with HCC. About 6 percent progressed to advanced liver disease, while 27.5 percent of patients progressed from compensated to decompensated cirrhosis over the 7-year study period. [ILC 2019, abstract THU-299]
Patients who developed compensated cirrhosis had twice the mortality rate of non-progressors at 1 year (4.6 percent vs 2.1 percent) and 7 years (16.3 percent vs 7.9 percent). At 1 year, mortality rate was four times higher among patients who progressed to decompensated cirrhosis compared with compensated cirrhosis (19.1 percent vs 4.6 percent), with the mortality rate still higher at 7 years (34.6 percent vs 16.3 percent).
“Those with advanced liver disease in Germany had a high mortality rate that significantly increased with disease progression,” said Canbay and co-authors.
“[In France], the overall NAFLD/NASH mortality rate of 7.9 percent was higher than the expected rate for the general similarly aged population of 4.6 percent, and increased with liver disease progression,” said study lead author Professor Jerome Boursier from Angers University Hospital in Angers, France.
Of particular note was the likely underdiagnosis of compensated cirrhosis in patients with NAFLD and NASH in both studies.
“We were surprised by the … apparent rate of underdiagnosis of cirrhotic patients, the majority only being identified following a decompensation event,” said Boursier.
“This shows us we must direct greater effort into finding and treating NAFLD/NASH patients as early as possible, so we can stop or even reverse disease progression,” he added.