Pro‐inflammatory signalling and gut‐liver axis in non‐alcoholic and alcoholic steatohepatitis: Differences and similarities along the path

Abstract Non‐alcoholic fatty liver disease (NAFLD) and alcohol‐associated liver disease (ALD) represent a spectrum of injury, ranging from simple steatosis to steatohepatitis and cirrhosis. In humans, in fact, fatty changes in the liver, possibly leading to end‐stage disease, were observed after chronic alcohol intake or in conditions of metabolic impairment. In this article, we examined the features and the pro‐inflammatory pathways leading to non‐alcoholic and alcoholic steatohepatitis. The involvement of several events (hits) and multiple inter‐related pathways in the pathogenesis of these diseases suggest that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination treatment towards multiple pro‐inflammatory targets would eventually be required. Gut‐liver crosstalk is involved not only in the impairment of lipid and glucose homoeostasis leading to steatogenesis, but also in the initiation of inflammation and fibrogenesis in both NAFLD and ALD. Modulation of the gut‐liver axis has been suggested as a possible therapeutic approach since gut‐derived components are likely to be involved in both the onset and the progression of liver damage. This review summarizes the translational mechanisms underlying pro‐inflammatory signalling and gut‐liver axis in non‐alcoholic and alcoholic steatohepatitis. With a multitude of people being affected by liver diseases, identification of possible treatments and the elucidation of pathogenic mechanisms are elements of paramount importance.