All stages of nonalcoholic fatty liver disease (NAFLD) are associated with significantly increased overall mortality, and this risk increases progressively with worsening disease, Swedish researchers have found. Deaths from extrahepatic cancer and cirrhosis accounted for most of this excess mortality, they report in Gut. "Our findings underscore the importance of reversing all stages of NAFLD, while also highlighting the need for effective public health strategies designed to prevent cancer and cirrhosis, in this high-risk and growing population," Dr. Jonas F. Ludvigsson of Karolinska Institutet, in Stockholm, and colleagues write. NAFLD is the most common cause of chronic liver disease in the Western world and affects almost 25% of U.S. and European adults, the researchers note. Nearly a third of these patients go on to develop progressive/non-fibrotic steatohepatitis and fibrosis, which can lead to cirrhosis, decompensated liver disease and death. Although it's widely believed that liver fibrosis is the only significant histological predictor of survival among patients with NAFLD, "the risk of overall and cause-specific mortality across the full histological spectrum of NAFLD has yet to be established," according to Dr. Ludvigsson and his colleagues. The team examined prospectively recorded liver-histopathology data collected from all 28 pathology departments in Sweden from 1966 to 2017. The 10,568 adults with histologically confirmed NAFLD were matched for age, sex and county with nearly 50,000 contemporaneous population comparators. None of the former had another etiology of liver disease, a history of alcohol abuse, or liver transplant. Among the liver patients, 67% had simple steatosis, 16% had non-cirrhotic fibrosis, 12% had steatohepatitis without fibrosis and 6% had cirrhosis. Their average age at index biopsy was 52, and 44.8% were female. The patients were more likely than the population comparators to have cardiovascular disease, diabetes, hypertension and dyslipidemia. There were 4,338 deaths among NAFLD patients (28.6/1,000 person-years) and 13,911 among comparators (16.9/1,000 PY). On multivariable analysis, NAFLD patients had a 1.93-fold higher risk of overall mortality (95% confidence interval, 1.86 to 2.00). The significant association between NAFLD and increased mortality held true for both women and men and in patients with and without cardiovascular disease, diabetes, dyslipidemia, hypertension or metabolic syndrome. Hazard estimates for overall mortality were higher among patients diagnosed at less than 60 years of age. Mortality risk increased significantly with greater NAFLD severity. Compared with population controls, all four NAFLD subtypes (simple steatosis, non-cirrhotic fibrosis, steatohepatitis without fibrosis, and cirrhosis) saw significantly elevated overall mortality. Again, this was true of both men and women and of people with and without cardiovascular disease, diabetes, hypertension, dyslipidemia and metabolic syndrome. NAFLD patients had significantly higher rates of mortality due to extrahepatic cancer (9.3 vs. 4.8/1,000 PY), followed by cardiovascular disease (8.3 vs. 6.9/1,000 PY), cirrhosis (2.8 vs. 0.2/1,000 PY) and hepatocellular carcinoma (1.3 vs. 0.1/1,000 PY). Dr. Zobair M. Younossi, a hepatologist at Inova Fairfax Medical Campus, in Falls Church, Virginia, who was not involved in the new work, told Reuters Health by email, "This study clearly shows that the entire spectrum of NAFLD is associated with adverse clinical outcomes, including liver mortality and extrahepatic mortality." "The study is the largest group of NAFLD patients with liver biopsy and longitudinal follow-up," he added, calling it "a very important study which should inform clinicians, patients and policy makers about the burden of NAFLD." Dr. Eduardo Vilar Gomez of Indiana University School of Medicine, who also studies liver disease, said, "As expected, overall mortality rates were highest among patients with non-cirrhotic fibrosis and cirrhosis, which might support previous studies reporting that fibrosis severity may be a major determinant on the clinical course of patients with NAFLD." "The study findings shed light on the importance of fibrosis severity as a major driver of the natural history of NAFLD, and reinforce the significance of carefully assessing risk of fibrosis in patients with NAFLD to detect patients at highest risk of mortality," Dr. Vilar Gomez, who was not part of the new research, told Reuters Health by email. Dr. Ludvigsson could not be reached for comment. —Scott Baltic Source
