Histological features of cerebellar neuropathology in patients with alcoholic and nonalcoholic steatohepatitis

Abstract

Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) affect 29 million people in the European Union. Patients with ASH and NASH may exhibit cognitive impairment, reducing their quality of life. Steatohepatitis induces cerebral alterations. It is not known if histological analysis could allow distinguishing ASH, NASH, and/or cirrhosis neuropathology and other entities. The aim of this work was to analyze a set of histopathological features characterizing the brain lesions due to ASH, NASH, and cirrhosis. We performed a histological study using hematoxylin and eosin staining and immunohistochemical techniques in cerebellum of 31 subjects who died with healthy liver (n=6), NASH (n=14), ASH (n=3), nonalcoholic cirrhosis (n=4), and alcoholic cirrhosis (n=4). We analyzed in cerebellum, as an early marker for brain injury: 1) vascular damage; 2) cerebellar atrophy and neurodegeneration in Purkinje layer; and 3) microglia and astrocytes activation in white matter and molecular layer. Patients with steatohepatitis have increased number of microtrombi in cerebellar parenchyma, neuronal loss in Purkinje layer and microglial and astrocyte activation in white matter and molecular layer. These alterations are stronger in patients with ASH than in those with NASH. These results provide a set of histopathological features in brain that may allow differentiation of steatohepatitis from other conditions.