Hepatic stellate cell activation in nonalcoholic steatohepatitis and fattyliver

Factors associated with the development of fibrosis in nonalcoholic steatoh epatitis (NASH) are largely unknown, although an association with increased hepatic iron has been suggested. Hepatic stellate cells are the principal collagen-producing cells in many liver diseases and when activated express alpha-smooth muscle actin (alpha-SMA). Hepatic stellate cell activation and association with fibrosis, necroinflammatory activity steatosis, and stain able iron in 60 cases of NASH and 16 cases of steatosis were evaluated. All 76 patients were obese or had other risk factors for NASH. All biopsy spec imens were stained for alpha-smooth muscle actin to evaluate the pattern of hepatic stellate cell activation and were evaluated for inflammatory activ ity (0 to 3), fibrosis (0 to 4), and stainable iron stores (0 to 4). The zo nal location of activated stellate cells was recorded, and the degree of ac tivation was graded as high-grade or low-grade based on the percentage of l obular alpha-SMA+ cells. Activated stellate cells were identified in the he patic lobule in 74 of 76 biopsy specimens and graded as low-grade in 26 and high-grade in 48. Zone 3 was involved in 72 of 74 positive cases, and in 3 3 cases, the activated stellate cells were preferentially located in zone 3 , The degree of stellate cell activation correlated with fibrosis but not w ith inflammatory activity, severity of steatosis, or stainable iron. In mos t cases, the degree of stellate cell activation paralleled the degree of he patic fibrosis, but in 25 cases, the degree of hepatic stellate cell activa tion was greater than expected, raising the question of whether such patien ts are at risk for disease progression. Copyright (C) 2000 by W.B. Saunders Company.