Quality of life before and after liver transplantation for cholestatic liver disease

Cynthia R. Gross, Michael Malinchoc, W. Ray Kim, Roger W. Evans, Russell H. Wiesner, Janice L. Petz, Jeffrey S. Crippin, Goran B. Klintmalm, Marlon F. Levy, Paola Ricci, Terry M. Therneau, E. Rolland Dickson – 30 December 2003 – Liver transplantation (LT) is an established therapy for patients with end‐stage primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). In this report, we describe the health status and quality of life (QOL) in patients with these cholestatic liver diseases before and after LT.

Natural history of untreated nonsurgical hepatocellular carcinoma: Rationale for the design and evaluation of therapeutic trials

Josep M. Llovet, Javier Bustamante, Antoni Castells, Ramon Vilana, Maria Del Carmen Ayuso, Margarita Sala, Concepció Brú, Joan Rodés, Jordi Bruix – 30 December 2003 – This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni‐ and multivariate analyses.

Clinical significance of serum bilirubin levels under ursodeoxycholic acid therapy in patients with primary biliary cirrhosis

Anne‐Marie Bonnand, E. Jenny Heathcote, Keith D. Lindor, Renée Eugénie Poupon – 30 December 2003 – We determined whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). We estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). We used a database of 548 patients with PBC followed in three trials of UDCA.

Transient selection of a hepatitis B virus polymerase gene mutant associated with a decreased replication capacity and famciclovir resistance

Christian Pichoud, Béatrice Seignères, Zhirui Wang, Christian Trépo, Fabien Zoulim – 30 December 2003 – Prolonged therapy for chronic hepatitis B (HBV) with nucleoside analogs may result in the emergence of HBV mutants resistant to antivirals. Here, we describe the transient selection of an HBV polymerase gene mutant that was associated with viral persistence in an immune competent patient treated with famciclovir. Viral polymerase gene sequence was analyzed directly on polymerase chain reaction (PCR) products and also after cloning.

Presence of distinct AP‐1 dimers in normal and transformed rat hepatocytes under basal conditions and after epidermal growth factor stimulation

F Nadori, B Lardeux, M Rahmani, A Bringuier, A Durand‐Schneider, D Bernuau – 30 December 2003 – Activation of the transcriptional regulator AP‐1, a dimeric complex formed of various combinations of Fos and Jun proteins, is a key step in the cellular response to mitogens. Because different dimers are believed to display different regulatory functions, we hypothesized that transformed cells that lack normal growth constraints might display AP‐1 dimers that are different from those of normal cells.

Human hepatic myofibroblasts increase invasiveness of hepatocellular carcinoma cells: Evidence for a role of hepatocyte growth factor

V Neaud, S Faouzi, J Guirouilh, B Le Bail, C Balabaud, P Bioulac‐Sage, J Rosenbaum – 30 December 2003 – The stroma of hepatocellular carcinomas (HCC) is infiltrated with myofibroblasts (MFs). Preliminary in vivo data have suggested that liver MF express hepatocyte growth factor (HGF), a cytokine that has been implicated in several tumor models. Our aim was to investigate the role of MF and HGF in HCC. Cultured liver MF expressed HGF messenger RNA (mRNA) and secreted HGF in their medium, as shown by Western blot, immunoprecipitation, and enzyme‐linked immunosorbent assay (ELISA).

Exposure of primary rat hepatocytes in long‐term DMSO culture to selected transition metals induces hepatocyte proliferation and formation of duct‐like structures

E E Cable, H C Isom – 30 December 2003 – We previously showed that primary rat hepatocytes plated on a rat‐tail collagen coated dish and fed a chemically‐defined medium supplemented with 2% dimethylsulfoxide (DMSO) can be maintained in a well‐differentiated, non‐replicating state for periods of several months. In this study, we show that the addition of copper, iron, and zinc to the DMSO‐containing chemically defined medium induced DNA synthesis and cell replication during the first two months in culture without loss of hepatic differentiation.

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