Pathomorphology of liver fibrosis in trepanobioptates of patients with steatohepatitis: main types, sources of development, features of progression
DOI:
https://doi.org/10.14739/2310-1237.2017.3.118299Keywords:
steatohepatitis, hepatic stellate cells, fibroblasts, liver cirrhosis, biopsyAbstract
Until recently, among the pathologists, hepatologists and gastroenterologists, a discussion continues on the morphogenesis and gradation of liver fibrosis in non-alcoholic patients (NASH) and alcoholic steatohepatitis (ASH).
Purpose of the study. Studying the main types and sources of liver fibrosis in patients with nonalcoholic and alcoholic steatohepatitis, justifying the gradation of its severity, taking into account the quantitative dynamics of fibrogenic producer cells, the relative area of fibrosis and the deposition of type I, III and IV collagen in the liver.
Material and methods. Histological and histochemical examination of liver fibrosis was performed in 198 patients with NASH of 18-79 years and in 79 patients with ASH of 47-63 years. Immunohistochemical study with measurement of the area of expression of activated αSMA + perisinusoidal stellate cells and αSMA + portal myofibroblasts with F1 (mild), F2 (moderate), F3 (severe) fibrosis and F4 fibrosis / cirrhosis was performed in 80 trepanobioptates of patients with NASH (20 cases in each group), electron microscopic examination of the liver – in 10 deceased patients suffering from NASH.
Results. In patients with NASH and ASH, there are two major types of liver fibrosis progress: the perisinusoidal pericellular and portal-Z3 perisinusoidal fibrosis, the development of which is the new generation of αSMA + star cells and αSMA + portal myofibroblasts of the fibrogenic immunophenotype, with co-expression of fascin and vimentin and absence of desmine expression. As the perisinusoidal pericellular fibrosis progresses from the mild F1 degree, to the severe F3 fibrosis and to the extremely severe F4 fibrosis / cirrhosis of the pericellular type, the area of the Masson-positive extracellular molecular-fibrous matrix (H = 88,70 р = 0,05 ) and the area of αSMA + collagen-producing stellate cells of perisinusoidal-pericellular localization (H = 45,12, p = 0,05). According to the data of photometric morphometry, with increasing severity of portal-Z3 perisinusoidal hepatic fibrosis from F1 to F4, the area of the Masson-positive extracellular molecular-fibrous matrix (N = 76,56 p = 0,05) in areas fibrofacitiously increases, as well as the area of activated αSMA + collagen-producing portal myofibroblasts and perisinusoid stellate cells of Z3 zones of hepatic lobules (H = 43,18, p = 0,05). Activation and increase in the number of CD-68+ macrophages in the centers of intensive hepatocyte steatosis, as well as the appearance of S100 (A4)+ macrophages that activate stellate cells, suggests that the phenomenon of pericellularity of liver fibrosis in NASH and ASH is due to exosomal macrophage involvement in zone of balloon steatonecrosis and necroptosis of hepatocytes, as well as local exosomal-cytokine activation of perisinusoid stellate cells of fibrogenic type.
Conclusion: As the progression of fibrosis from F1 to F4 degree in the liver the area of activated αSMA + fibroblasts, and the area of deposition of collagen I, III and IV type perisinusoidal pericellular or portal-Z3 perisinusoidal localization significantly increase.
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