Increased ΤGF-β3 in primary biliary cirrhosis: An abnormality related to pathogenesis?

AIM: To investigate the transforming growth factor-β (TGF-β) isoforms in the peripheral and hepatic venous blood of primary biliary cirrhosis (PBC) patients. METHODS: We examined TGF-β1, TGF-β2 and TGF-β3 (enzyme-linked immunosorbent assay), in 27 stage Ⅳ PBC patients (27 peripheral and 15 hepatic vein sera), 35 early (Ⅰ-Ⅱ) PBC and 60 healthy controls. As disease controls 28 hepatitis C virus (HCV) cirrhosis (28 peripheral and 17 hepatic vein serum), 44 chronic HCV hepatitis and 38 HCV-related hepatocellular carcinomas were included. We also tested liver tissue by immunohistochemistry to identify localization of TGF isoforms. RESULTS: TGF-β1 was significantly decreased in all cirrhotics (PBC Ⅲ-Ⅳ: median 13.4 ng/mL; range, 7.4-26.2, HCV cirrhosis: 11.6 ng/mL; range, 5.0-33.8), compared to controls (30.9 ng/mL; range, 20.9-37.8). TGF-β2 was increased in viral cirrhosis but not in PBC and chronic hepatitis. TGF-β3 (47.2 pg/mL; range, 27.0-79.7 in healthy controls) was increased in early and late PBC (Ⅰ-Ⅱ: 94.3 pg/mL; range, 41.5-358.6; Ⅲ-Ⅳ: 152.8 pg/mL; range, 60.4-361.2; P < 0.001) and decreased in viral cirrhosis (37.4 pg/mL; range, 13.3-84.0; P < 0.05). Hepatic vein TGF-β levels were analogous to those in peripheral blood. Immunohistochemistry identified all isoforms in portal tract lymphocytes, sinusoidal cells and cholangiocytes. TGF-β3 was additionally overexpressed in hepatocytes in PBC patients. CONCLUSION: The serum profile of TGF-β isoforms is different in cirrhotics. Increased TGF-β3 is characteristic of PBC. These findings may be related to the immunological abnormalities of PBC.

Clinical outcomes of compensated and decompensated cirrhosis: A long term study

AIM: To study these characteristics and prognostic patterns in a Greek patient population.METHODS: We analyzed a large cohort of cirrhotic patients referred to the department of Gastroenterology and Hepatology and the outpatient clinics of this tertiary hospital, between 1991 and 2008. We included patients with established cirrhosis, either compensated or decompensated, and further decompensation episodes were registered. A data base was maintained and updated prospectively throughout the study period.We analyzed differences in cirrhosis aetiology, time to and mode of decompensation, hepatocellular carcinoma(HCC) occurrence and ultimately patient survival.RESULTS: Five hundreds and twenty-two patients with median age 67(range, 29-91) years and average follow up 9 years-10 mo(range, 1-206 mo) were studied. Commonest aetiology was hepatitis C virus(HCV, 41%) followed by alcohol(31%). The median survival time in compensated cirrhotics was 115 mo(95%CI: 95-133), whereas in decompensated patients was 55 mo(95%CI: 36-75). HCV patients survived longer while HBV patients had over twice the risk of death of HCV patients. The median time to decompensation was 65 mo(95%CI: 51-79), with alcoholics having the highest risk(RR = 2.1 vs HCV patients). Hepatitis B virus(HBV) patients had the highest risk of HCC, alcoholics the lowest. Leading causes of death: liver failure, hepatorenal syndrome, sepsis and HCC progression. CONCLUSION: Cirrhosis aetiology and decompensation at presentation were predictors of survival. Alcoholics had the highest decompensation risk, HBV cirrhotics the highest risk of HCC and HCV cirrhotics the highest decompensation-free time.