This study demonstrates that in cases of chronic hepatitis C, the significant association of HPC expression with the severity of disease and more specifically with the response to treatment implies that HPC development and proliferation may provide additional prognostic information and predict prognosis in such cases.

Bcl-2 oncoprotein regulates programmed cell death by providing a survival advantage to rapidly proliferating cells, and bax protein promotes apoptosis by enchanting cell susceptibility to apoptotic stimuli. In this study, we assessed the expression of bcl-2 and bax in liver biopsies from patients with chronic hepatitis (CH) Type B (HBV) and C (HCV). The study comprised 65 liver biopsies from 65 patients with HBV (n = 37) and HCV (n = 28) and 10 normal liver biopsies as controls. The HAI score ranged from 3/18-13/18, and the fibrosis Stage, from 1-6 (7 HBV/10 HCV). Pathologic examination included the following: (1) immunohistochemical stains in paraffin sections for bcl-2 and bax protein expression, (2) Western blot analysis (bcl-2 and bax protein levels evaluation), (3) ISH (detection of bcl-2 and bax mRNA), and (4) ISH (TUNEL-ABI [apoptotic body index]). In CH cases, both bcl-2 and bax protein and mRNA were detected in portal and intralobular lymphocytes and in cholangiolar epithelial cells in interface areas and fibrous bands. Bax protein and mRNA was expressed within hepatocytes and epithelial cells of interlobular ducts in portal tracts. Bcl-2 mRNA was present in periportal hepatocytes only in cases with Stage 5-6 fibrosis. Western blot analysis showed a decreased bcl-2 and an increased bax expression toward advanced fibrotic stages. In CH cases, ABI was reverse correlated with the percentage of bcl-2 expression and was correlated directly with the percentage of bax expression (P <.001). The results of this study suggest that in cases of chronic HBV or HCV infection, bax may be involved in the hepatocyte cycle regulation during infection, whereas its expression in intraportal bile duct epithelium implies that this protein enhances susceptibility of these particular cells to apoptosis. The increased bax expression and ABI in fibrosis Stages 1-5, imply that they are responsible for hepatocytes depletion through apoptosis, during progress of liver fibrosis and fibrous tissue accumulation, until cirrhosis is established. Bcl-2 mRNA expression in periportal hepatocytes only in Stages 5 and 6 suggests that this oncogene is involved in the late stages of progressive liver fibrosis and failure and furthermore that periportal hepatocytes are resistant to apoptosis. Bcl-2 expression, in cholangioles of interface area, suggests that this oncoprotein may be involved in growth regulation of these epithelial cells. Further research is warranted to specify the exact role of apoptosis and apoptotic genes involved in liver fibrosis process in cases of chronic HBV and HCV infection. This may lead to new strategies in the management of human liver disease to prevent the progression to chronic liver failure.

minate CVH from CIR. The alternative Doppler indexes can accurately differentiate chronic virus hepatitis from cirrhosis. These indexes can be used in monitoring chronic virus hepatitis and avoiding unnecessary biopsies. INTRODUCTIONChronic viral hepatitis, mainly caused by hepatitis virus B or C, results in liver parenchyma damage and inflammation and may lead to fibrosis, cirrhosis and/or hepatocellular carcinoma [1][2][3] . Cirrhosis often occurs as an indolent disease and a lot of patients remain asymptomatic [4,5] until the occurrence of decompensation, and are characterised by portal hypertension, variceal bleeding, ascites and hepatic encephalopathy.Liver biopsy is the gold standard for diagnosis and determination of the fibrosis and necroinflammatory changes in chronic viral hepatitis and cirrhosis. However, the use of biopsy in clinical practice has some limitations related to sample errors with an estimated false negative percentage of 24% morbidity and mortality in series of blind biopsies [6] and complications [7] . The non-invasive assessment of chronic liver disease has been attempted by various research groups using either clinical signs [8,9] , gray scale [10][11][12][13][14][15] and colour Doppler ultrasound (CDU) signs and indexes [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] , or biochemical parameters in the blood [9] . The use of CDU in diagnosis and staging of chronic viral liver disease has been based on the hypothesis that alteration in liver haemodynamics due to chronic inflammatory changes may indirectly reflect histological alterations. Therefore, positive correlation studies have usually referred to the velocity ratio of hepatic RESULTS: ROC analysis showed that PV congestion index, PV D/VTAM and HA/PV VTAM indices had the best sensitivity and specificity in discriminating CVH from CIR.Stepwise discriminant analysis showed that 88.9% of the originally grouped cases could be correctly classified by the three qualitative and four quantitative variables selected as statistically significant predictors. Among the CVH patients who underwent to biopsy, statistically significant changes were found in those at fibrosis stage 5 compared to fibrosis stages 1-4.

The case of a 38-year-old white female, with a long history of myasthenia gravis, who developed sarcoidosis is presented. The diagnosis of myasthenia gravis had been established on the basis of typical clinical symptoms with severe myastenic crises necessitating respiratory support, characteristic electromyographic findings, positive anti-acetylcholine receptor antibodies and response to appropriate medications. After 9 years of disease and while in apparent remission, she presented with ankle arthritis and bilateral hilar adenopathy. A transbronchial lung biopsy showed noncaseating granuloma, typical of sarcoidosis. To our knowledge, the combination of myasthenia gravis and sarcoidosis is extremely rare and emphasizes the intriguing tendency of some immunologic disorders to appear together in certain individuals.

The bcl-2 gene is involved in the regulation of programmed cell death by providing a survival advantage to rapidly proliferating cells. This study investigates bcl-2 protein expression in liver biopsies with acute or chronic viral hepatitis B (HBV) or C(HCV). The study comprised 60 liver biopsies with hepatitis B or C. These included 10 biopsies from cases with acute lobular hepatitis (ALH), and 50 with chronic hepatitis (CH). In addition, 10 liver biopsies were used as controls. In CH cases, HAI grade ranged from 3/18 to 15/18, and stage from 1 to 6 (6HBV/8HCV). Immunohistochemical bcl-2 expression was assessed using the streptavidin-biotin method and the presence of apoptotic cells was evaluated by TUNEL method. Immunohistochemical and in situ hybridization (TUNEL) results were expressed following morphometric analysis. In CH cases, bcl-2 was detected in portal and intralobular lymphocytes, and in cholangiolar epithelial cells of the interface area. In ALH and control cases, bcl-2 was expressed only in lymphocytes. Lymphocytic bcl-2 expression was correlated directly with categories A, C and D of HAI (P < 0.001), whereas the degree of fibrosis was reversibly correlated to bcl-2 expression. In conclusion, in cases of chronic hepatitis, bcl-2 expression in cholangioles of interface area suggests that this oncoprotein may be involved in regulation of growth of these epithelial cells.