Liver inflammatory cells, apoptosis, regeneration and stellate cell activation in non-alcohol steatohepatitis

Background, The pathogenesis of non-alcoholic steatohepatitis remains unclear from several points of view. Minimal diagnostic criteria are still not defined. Aim. To gather information useful for diagnosis and to improve the understanding of pathogenic mechanisms.

Patients. A series of 14 patients with non-alcoholic steatohepatitis, identified among liver outpatients, were paired for age, sex and alanine amino transferase values with 14 patients with hepatitis C virus infection without steatosis.

Methods. Clinical, biochemical and immunohistological examination, including characterisation of inflammatory cell population, evaluation of type 111 collagen and tenascin deposition, activation of stellate cells, hepatocellular apoptosis and proliferation.

Results. Patients with non-alcoholic steatohepatitis were more frequently obese, had higher triglyceride concentrations and lower gamma-globulins. T lymphocytes outnumbered polymorphonuclear cells, both in hepatitis C and in steatohepatitis, with a larger number of CD8 lymphocytes in patients with viral hepatitis but a comparable number of granulocytes. This resulted in a higher granulocytes to T cells ratio in steatohepatitis, possibly making these cells more easily detectable in spite of similar absolute numbers. Portal fibrosis and piecemeal necrosis were prevalent in hepatitis C virus infection, pericentral fibrosis was similar. Hepatocellular, apoptosis and proliferation as well as stellate cell activation were less relevant in steatohepatitis than in hepatitis C virus infection in spite of similar alanine amino transferase levels.

Conclusions. These data provide a possible explanation for the relatively low tendency to progression of non-alcoholic steatohepatitis in most patients despite increased alanine amino transferase and suggest that non-death-related release of alanine amino transferase might occur in non-alcoholic steatohepatitis. This makes liver biopsy an essential part of the clinical setting supporting diagnosis, evaluation of severity and possibly definition of the evolutionary trend.