Cytochromes P450 and uridine triphosphate‐glucuronosyltransferases: Model autoantigens to study drug‐induced, virus‐induced, and autoimmune liver disease

M P Manns, P Obermayer‐Straub – 30 December 2003 – Enzymes of phase I (cytochromes P450) and phase II (UDP [uridine diphosphate]‐glucuronosyltransferases) of drug metabolism are targets of autoimmunity in the following chronic liver diseases of different etiology: 1)autoimmune hepatitis (AIH); 2) hepatitis associated with the autoimmune polyendocrine syndrome type 1 (APS‐1); 3) virus‐induced autoimmunity; and 4) drug‐induced hepatitis.

Partial cloning of rat CD34 cDNA and expression during stem cell‐ dependent liver regeneration in the adult rat

N Omori, M Omori, R P Evarts, T Teramoto, M J Miller, T N Hoang, S S Thorgeirsson – 30 December 2003 – The sialomucin CD34 is expressed on human and mouse hematopoietic stem cells and is used as an important marker for isolating the hematopoietic stem/progenitor cells. The involvement of hepatic stem cells in liver regeneration under certain conditions in adult rats is now well supported. The objective of the present research was to explore the idea that CD34 might also be expressed on hepatic stem cell progeny.

Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats

G Boigk, L Stroedter, H Herbst, J Waldschmidt, E O Riecken, D Schuppan – 30 December 2003 – Silymarin (SIL), a standardized plant extract containing about 60% polyphenole silibinin, is used as a hepatoprotective agent. Its antifibrotic potential in chronic liver diseases has not been explored. Therefore, we applied SIL to adult Wistar rats that were subjected to complete bile duct occlusion (BDO) by injection of sodium amidotrizoate (Ethibloc). This treatment induces progressive portal fibrosis without significant inflammation.

Up‐regulation of type I procollagen C‐proteinase enhancer protein messenger RNA in rats with CCl4‐induced liver fibrosis

I Ogata, A S Auster, A Matsui, P Greenwel, A Geerts, T D'Amico, K Fujiwara, E Kessler, M Rojkind – 30 December 2003 – Using a polyclonal antibody raised against a liver stellate cell (LSC) line derived from a rat CCl4‐cirrhotic liver, we isolated 14 clones from a complementary DNA library prepared with total RNA extracted from the same cell line, with nucleotide sequences homologous to that of the type I procollagen C‐proteinase enhancer protein (PCPE) gene. The longest PCPE insert of 1,530 base pairs contained an open reading frame coding for 468 amino acids.

Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: A case‐control study in Italy

F Donato, A Tagger, R Chiesa, M L Ribero, V Tomasoni, M Fasola, U Gelatti, G Portera, P Boffetta, G Nardi – 30 December 2003 – We performed a case‐control study to assess the association of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol drinking.

Pilot study of the combination of interferon alfa and ribavirin as therapy of recurrent hepatitis C after liver transplantation

T Bizollon, U Palazzo, C Ducerf, M Chevallier, M Elliott, J Baulieux, M Pouyet, C Trepo – 30 December 2003 – Recurrent hepatitis C virus (HCV) in liver transplant patients is a major cause of graft loss, liver failure, and need for retransplantation. The results available to date with the use of interferon alfa (IFN‐α) in the treatment of recurrent HCV in liver transplant patients have been disappointing.

Assessment of hepatic vitamin E status in adult patients with liver disease

A Nagita, M Ando – 30 December 2003 – No published reports compare hepatic α‐tocopherol (adjusted for hepatic lipid content) with indicators of blood α‐tocopherol in adult patients with various liver diseases. α‐Tocopherol was simultaneously measured in liver biopsy tissues and blood from 66 subjects (9 comparison patients hospitalized for biliary tract surgery, 13 with chronic persistent hepatitis, 9 with chronic aggressive hepatitis, 10 with acute hepatitis, 10 with cirrhosis, 7 with both cirrhosis and hepatic cell carcinoma, and 8 with fatty liver).

Co‐expression and regulation of Met and Ron proto‐oncogenes in human hepatocellular carcinoma tissues and cell lines

Q Chen, D Seol, B Carr, R Zarnegar – 30 December 2003 – Met and ron proto‐oncogenes encode the cell surface receptors for hepatocyte growth factor (HGF) and hepatocyte growth factor‐like (HLP) protein, respectively, and induce mitogenesis, motogenesis, morphogenesis, and metastatic activity in various cell types. Overexpression of met in human carcinoma has been reported by several groups including ours; however, the mechanisms that control met gene expression are thus far unclear.

Does antimitochondrial antibody status affect response to treatment in patients with primary biliary cirrhosis? Outcomes of ursodeoxycholic acid therapy and liver transplantation

W R Kim, J J Poterucha, R A Jorgensen, K P Batts, H A Homburger, E R Dickson, R A Krom, R H Wiesner, K D Lindor – 30 December 2003 – Approximately 5% to 10% of patients with features otherwise consistent with primary biliary cirrhosis (PBC) lack antimitochondrial antibodies (AMA). Most of these patients have other autoantibodies, a syndrome recently named “autoimmune cholangitis.” We report our experience in patients with AMA‐negative PBC treated with ursodeoxycholic acid (UDCA) and/or liver transplantation (OLT). The study of response to UDCA was performed as follows.

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