**7.11 With or without small amount of alcohol, so-called 'NASH + ASH'**

NAFLD and alcohol-related fatty liver disease (AFLD) [165] are already undoubtedly, and will continue to be, leading drivers of progressive liver disease and hepatocellular carcinoma (HCC) worldwide. Severe alcohol abuse leads to accelerated disease progression with higher rates of HCC, liver-related deaths and poor prognosis. In contrast, NAFLD is most frequently related to metabolic dysfunction (MAFLD: metabolic dysfunction-associated fatty liver disease) and is associated with an increased risk of cardiometabolic disease and cancer.

Although the main environmental triggers of fat accumulation differ between AFLD and NAFLD, they are frequently superimposed, and the pathogenesis of inflammation and progressive liver damage share numerous mechanisms [166].

The progression of liver damage is accelerated when, especially at times of acute insults during the natural history of the disease, excess fat and lipotoxicity lead to inflammation, hepatocellular damage and fibrogenesis, in a condition referred to as 'steatohepatitis' (NASH and acute alcohol-related steatohepatitis (ASH)) [167].

Just as all heavy drinkers do not progress to cirrhosis and HCC, nor do all patients with non-alcoholic steatosis progress. However, if NASH patients drink small amounts (EtOH: male <210 g/w, female <140 g/w) of alcohol, in my clinical experience of following more than 200 biopsy-proven NASH patients, the progression of liver fibrosis and deposition of iron at the hepatocytes seem to be more conspicuous compared to those who do not drink any alcohol.

A small amount of alcohol seems to modify and accelerate clinical manifestation and the progression of NASH.
