Hepatology : official journal of the American Association for the Study of Liver Diseases
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Studies assessing morbidity and mortality in obese patients undergoing orthotopic liver transplantation (OLT) have produced conflicting results, mainly because of the small sample size. The objective of our study was to determine graft and patient survival in obese adults receiving OLT in the U. S. between 1988 through 1996 using the United Network for Organ Sharing (UNOS) database. ⋯ Kaplan-Meier survival was significantly lower in morbidly obese patients, and morbid obesity was an independent predictor of mortality. Obesity is associated with a significant increase in long-term mortality, mostly as a result of cardiovascular events. Weight loss should be recommended for all patients awaiting a liver transplantation, especially if their BMI is more than 35 kg/m(2).
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Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are immune-mediated chronic inflammatory diseases of the liver of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. 1,25-Dihydroxyvitamin D(3) has been implicated as an immunomodulator, which acts through its own receptor (VDR). Polymorphisms of the VDR have been linked to a variety of autoimmune diseases. ⋯ Furthermore we detected a significant association of the Fok polymorphims in AIH patients in comparison to controls (chi(2) = 9.71, P =.008) indicating a genetic link of VDR polymorphisms to autoimmune liver diseases such as PBC and AIH in German patients. These findings contribute to the knowledge of the complex events determining immunologic tolerance in the liver. Further studies are needed to elucidate the mechanisms by which the vitamin D receptor contributes to the development of autoimmune diseases.
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We observed that N-(4-hydroxyphenyl)retinamide (4HPR), a chemopreventive and chemotherapeutic agent, effectively induced apoptosis in hepatoma cells. Interestingly, Fas-negative (Hep 3B and PLC/PRF/5) hepatoma cells were shown to be more susceptible to apoptosis induced by 4HPR than were Fas-positive (Hep G2 and SK-HEP-1) hepatoma cells. Thus, we explored the mechanisms underlying 4HPR-induced apoptosis in Fas-defective hepatoma cells. ⋯ Activation of Bid or induction of proapoptotic Bax was not observed during apoptosis. In contrast, Bcl-xL expression was decreased during 4HPR-induced apoptosis. Taken together, these results indicate that 4HPR may be a potential chemotherapeutic drug, which is able to induce apoptosis in Fas-defective hepatoma cells through caspase-8 activation.
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Comparative Study
Short-term prognosis in critically ill patients with cirrhosis assessed by prognostic scoring systems.
The short-term prognosis of acutely ill patients with cirrhosis is influenced by the degree of hepatic insufficiency and by dysfunction of extrahepatic organ systems. The purpose of this study was to assess and compare the prognostic accuracy of the Child-Pugh classification, the Acute Physiology and Chronic Health Evaluation (APACHE) II system and the Sequential Organ Failure Assessment (SOFA) for predicting hospital mortality in patients with cirrhosis when used 24 hours after admission to a medical intensive care unit (ICU). Prospective data were recorded on 143 patients. ⋯ Hospital mortality rates below and above a cutoff of 8 SOFA points were 4% and 88%, respectively (P <.0005). The SOFA score also reflected resource use during the ICU treatment as measured by daily workload and length of stay. The SOFA is an easily applied tool with excellent prognostic abilities and can be used to enhance clinical judgment of prognosis as well as providing patients and families with objective information.
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Acute ethanol intoxication induces oxidative stress and apoptosis in primary cultured hepatocytes. Oxidative stress can trigger mitochondrial cytochrome c release initiating the mitochondrial pathway of apoptosis. Based on this information, we formulated the hypothesis that ethanol induced oxidative stress causes mitochondrial dysfunction resulting in apoptosis. ⋯ Ethanol-induced MPT was also attenuated by N'N'-dimethylthiourea (DMTU, a scavenger of hydrogen peroxide, 10 mmol/L) and N-acetyl-cysteine (NAC, an antioxidant, 5 mmol/L). Preventing hepatocyte MPT by DMTU or NAC attenuated cytochrome c release as well as caspase activation, suggesting that ethanol-induced oxidative stress mediates the MPT. Thus, acute ethanol induces MPT via oxidative stress, and the MPT mediates mitochondrial pathway of apoptosis in hepatocytes exposed to acute ethanol.