Cytotoxic effect of 7α‐hydroxy‐4‐cholesten‐3‐one on HepG2 cells: Hypothetical role of acetaldehyde‐modified Δ4‐3‐ketosteroid‐5β‐reductase (the 37‐kd‐liver protein) in the pathogenesis of alcoholic liver injury in the rat

Renee C. Lin, Michael J. Fillenwarth, Xiangnan Du – 30 December 2003 – We recently identified ▵4‐3‐ketosteroid‐5β‐reductase as the 37 kd liver protein which is highly susceptible to acetaldehyde modification in rats continuously fed alcohol. The 5β‐reductase is a key enzyme involved in bile acid synthesis. We report here that the ability to degrade 7α‐hydroxy‐4‐cholesten‐3‐one (HCO) was lower in the liver cytosol of alcohol‐fed rats than in control animals, suggesting an inhibition of the 5β‐reductase enzyme activity by acetaldehyde modification.

Therapy of hepatitis C: Other options

H L Bonkovsky – 30 December 2003 – Because current standard therapy of chronic hepatitis C with α interferon is less than ideal, numerous other approaches have been studied. Iron in the liver, particularly that found in vascular endothelial cells of portal tracts, has been associated with decreased responsiveness to α interferon therapy. Iron reduction alone, generally achieved by therapeutic phlebotomy, regularly has been associated with biochemical improvement (decrease in serum alanine aminotransferase), but not with virological improvement.

Factors predictive of a beneficial response to therapy of hepatitis C

G L Davis, J Y Lau – 30 December 2003 – Alpha interferon is the only drug that has been shown to be effective in the treatment of chronic hepatitis C, but only half of patients respond, either transiently or permanently. Pretreatment features that are associated with a greater likelihood of response to short courses of interferon include low hepatitis C virus (HCV) RNA levels, viral genotypes 2 or 3, and the absence of fibrosis or cirrhosis on liver biopsy. Each of these features is more predictive of sustained response (SR) than the end‐of‐treatment response (ETR).

Natural history of hepatitis C

L B Seeff – 30 December 2003 – Approximately 85% of persons with acute hepatitis C develop chronic hepatitis as determined by persistently abnormal serum enzymes and/or viremia (hepatitis C virus [HCV] RNA). Both the acute and chronic illnesses are predominantly asymptomatic. For this reason and because the chronic illness runs an extremely protracted course, it has been difficult to accurately define the frequency and rate of progression to symptomatic or end‐stage liver disease, specifically cirrhosis and hepatocellular carcinoma (HCC). Three evaluation strategies have been used.

Histological and clinical outcome after liver transplantation for hepatitis C

M C Shuhart, M P Bronner, D R Gretch, L V Thomassen, C F Wartelle, H Tateyama, S S Emerson, J D Perkins, R L Carithers – 30 December 2003 – Hepatitis frequently recurs after liver transplantation for hepatitis C. However, the histological progression of disease, predictors of recurrence and disease severity, and patient survival remain uncertain. Fifty‐five patients with cirrhosis caused by chronic hepatitis C underwent liver transplantation between January 1990 and December 1993.

An improved digitonin‐collagenase perfusion technique for the isolation of periportal and perivenous hepatocytes from a single rat liver: Physiological implications for lobular heterogeneity

T Tordjmann, B Berthon, B Lardeux, A Moreau, E Jacquemin, L Combettes, G Feldmann, M Claret – 30 December 2003 – Morphological and functional heterogeneity of hepatocytes according to their position in the liver lobule has been known for many years. The digitonin‐collagenase perfusion technique is widely used to study hepatocyte heterogeneity and has yielded reliable data. However, with this procedure, periportal (PP) or perivenous (PV) hepatocytes are isolated from different livers, allowing only comparison between cell populations issued from two separate animals.

Progesterone metabolites and bile acids in serum of patients with intrahepatic cholestasis of pregnancy: Effect of ursodeoxycholic acid therapy

L Meng, H Reyes, M Axelson, J Palma, I Hernandez, J Ribalta, J Sjovall – 30 December 2003 – The concentrations in serum of sulfated metabolites of progesterone are known to be elevated in patients with intrahepatic cholestasis of pregnancy (ICP). The profiles of these metabolites and conjugated bile acids were analyzed in serum from 11 patients with ICP before and during administration of ursodeoxycholic acid (UDCA) (8 patients) or placebo (3 patients).

Interleukin‐6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent

C A Camargo, J F Madden, W Gao, R S Selvan, P Clavien – 30 December 2003 – Interleukin‐6 (IL‐6) is an acute reactant cytokine with anti‐inflammatory properties, which has been found to prevent injury in a model of acute hepatitis in mice through downregulation of tumor necrosis factor α (TNF‐α); to correlate inversely with markers of hepatocellular injury in patients with liver ischemia; and to initiate liver regeneration in mice. In this study, we investigated the role of IL‐6 in rodent models of hepatic warm ischemia/reperfusion (WI/Rp) injury.

Infection complicating percutaneous liver biopsy in liver transplant recipients

A M Larson, G C Chan, C F Wartelle, J P McVicar, R L Carithers, G M Hamill, K V Kowdley – 30 December 2003 – There is controversy about the frequency of and risk factors for infectious complications of percutaneous liver biopsy in liver transplant recipients. The aim of this study was to identify the incidence and nature of complications associated with liver biopsy after orthotopic liver transplantation (OLT), with particular emphasis on infection.

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