NAFLD-related mortality: simple hepatic steatosis is not as 'benign' as thought

“Is life worth living? It all depends on the liver” (American philosopher William James [1842— 1910]) Nonalcoholic fatty liver disease (NAFLD) is currently the most frequent global liver disease [1]. Disease presentation includes various clinical phenotypes ranging from simple steatosis (nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), fibrosis without inflammation, cirrhosis and hepatocellular carcinoma. In the majority of NAFLD patients, liver histology is characterized by simple steatosis, whereas up to 30% of patients exhibits liver inflammation + fibrosis. Several cohort studies have suggested that NAFLDrelated mortality is mainly due to cardiovascular diseases, extrahepatic cancers and liver-related complications. Furthermore, whereas prognosis of simple steatosis is generally considered rather “benign”, various studies from the past years have supported the notion that not necro-inflammation but stage of fibrosis drives long-term prognosis and mortality [2] [3]. A recent meta-analysis of 13 studies (including a total of 4428 patients) reported that NAFLD-related fibrosis correlated with risk of mortality and liver-related morbidity [4]. Stage of fibrosis was highly predictive for all-cause mortality, whereas NASH and simple steatosis were not prognostically relevant [4]. Bridging fibrosis as suggested from another multicentre study was associated predominantly with extrahepatic cancers [5]. ....