Clinical and biochemical expression of the histopathological lesions of primary biliary cirrhosis

Background/Aims: This study aimed to assess the relationships which may lin k elementary histological lesions with symptoms and biochemistries in prima ry biliary cirrhosis. Methods: We studied 103 patients with primary biliary cirrhosis who partici pated in a double-blind, placebo-controlled trial of UDCA treatment and in whom liver biopsy specimens obtained at entry were reassessed. Relationship s between histological features, fatigue, pruritus and biochemistries were calculated by using exact tests for 2 ordinal variables. Results: The degrees of severity of fatigue and pruritus were significantly and exclusively related to the presence of florid interlobular bile duct l esions (p<0.01 and p<0.02, respectively). The only laboratory parameter ass ociated with the presence of interlobular bile duct florid lesion was IgM l evel. The most discriminant biochemical test for interlobular bile duct pau city was gamma glutamyltranspeptidase activity. The degree of severity of b oth lymphocytic hepatocellular piecemeal necrosis and lobular inflammation and necrosis was mainly associated with increased gammaglobulin and IgG lev els and to a lesser extent with increased IgM and aspartate aminotransferas e levels. The extent of fibrosis was mainly associated with gammaglobulin l evels and to a lesser degree with serum albumin, bilirubin and IgG levels. Conclusions: Symptoms and biochemistries classically used to assess primary biliary cirrhosis reflect in part the degree of severity of the main eleme ntary histological lesions. We propose that the picture of primary biliary cirrhosis results from the clinical and biochemical expression of three dis tinct processes, e.g., bile duct inflammation and destruction, parenchymal inflammation and necrosis, and fibrosis. The various combinations of these processes may explain why the spectrum of primary biliary cirrhosis varies from typical primary biliary cirrhosis to mixed type of primary biliary cir rhosis and autoimmune hepatitis and suggests that the response to therapies may depend on the predominance of each process in a given patient.