Therapy of hepatitis C: Alpha interferon and ribavirin

O Reichard, R Schvarcz, O Weiland – 30 December 2003 – Ribavirin is a nucleoside analogue that has been evaluated as a therapy of chronic hepatitis C alone and in combination with α interferon. Ribavirin is well absorbed orally and is typically given in doses of 1,000 to 1,200 mg/d. Three randomized, placebo‐controlled studies comprising more than 150 patients have shown that therapy with ribavirin alone for 24 to 48 weeks resulted in a significant reduction in serum alanine aminotransferase (ALT) levels during therapy.

Therapy of hepatitis C: Interferon alfa‐n1 trials

G C Farrell – 30 December 2003 – Interferon alfa‐n1 is produced from a lymphoid cell line and consists of multiple α interferon subtypes. Early studies indicated that interferon alfa‐n1 was effective against hepatitis C, and a meta‐ analysis of published trials indicated that it was equally likely as recombinant α interferons to produce an end‐of‐treatment biochemical and histological response.

Hepatic growth hormone receptor, insulin‐like growth factor I, and insulin‐like growth factor‐binding protein messenger RNA expression in pediatric liver disease

R I Holt, P A Crossey, J S Jones, A J Baker, B Portmann, J P Miell – 30 December 2003 – Major changes in serum levels of insulin‐like growth factor I (IGF‐I) and IGF‐binding proteins (IGFBPs) occur in children with end‐stage liver disease in association with changes in body composition. We hypothesized that these changes would be associated with changes in hepatic messenger RNA (mRNA) expression. Eleven children with end‐stage extrahepatic biliary atresia and 11 controls (liver donors) were studied.

Modulation of circadian expression of D‐site binding protein by the schedule of parenteral nutrition in rat liver

A Ogawa, M Yano, T Tsujinaka, T Morimoto, S Morita, M Taniguchi, H Shiozaki, K Okamoto, S Sato, M Monden – 30 December 2003 – The aim of this study was to investigate the changes in the circadian rhythm of the expression of liver‐specific genes caused by different schedules of parenteral nutrition (PN). Rats received PN continuously throughout the day or intermittently during the night or day for 7 days. They were examined for gene expression of D‐site binding protein (DBP), albumin, and cytochrome P450 cholesterol 7α‐hydroxylase (CYP7) in the liver.

Enhanced expression of cytokine‐induced neutrophil chemoattractant in rat hepatic allografts during acute rejection

Y Yamaguchi, O Ichiguchi, F Matsumura, E Akizuki, T Matsuda, K Okabe, S Yamada, J Liang, K Mori, M Ogawa – 30 December 2003 – The kinetics of messenger RNA (mRNA) and protein levels of cytokine‐induced neutrophil chemoattractant (CINC) in rat hepatic allografts during acute rejection were investigated. Infiltrating cells were identified by double immunostaining with anti‐CINC and anti‐macrophage monoclonal antibodies, ED1 and ED2. The serum CINC concentration in untreated hepatic allograft recipients increased significantly at a constant rate over time after transplantation.

Dual expression of matrix metalloproteinase‐2 and membrane‐type 1‐matrix metalloproteinase in fibrotic human livers

T Takahara, K Furui, Y Yata, B Jin, L P Zhang, S Nambu, H Sato, M Seiki, A Watanabe – 30 December 2003 – We have previously reported increased expression of matrix metalloproteinase‐2 (MMP‐2) using a rat model of liver fibrosis. However we did not clarify how the precursor of MMP‐2 (proMMP‐2) was activated. Therefore, we used human liver specimens with chronic hepatitis (CH) and liver cirrhosis (LC) to examine expression of membrane‐type‐1‐MMP (MT1‐MMP), which has recently been determined to activate proMMP‐2.

Chromosomal aberrations in hepatocellular carcinomas: Relationship with pathological features

U Zimmermann, D Feneux, G Mathey, F Gayral, D Franco, P Bedossa – 30 December 2003 – Fluorescence in situ hybridization performed on tissue sections can reveal chromosomal abnormalities related to histopathological features. This technique was performed on serial frozen sections from seven normal livers and 29 hepatocellular carcinomas (HCCs) using pericentromeric repeat‐specific probes for chromosomes 1, 4, 6, 7, 8, 16, and 17. For each HCC and each probe, the percentage of cells showing one, two, or more than two signals was counted and compared with the distribution in the normal liver.

Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels

C Puoti, A Magrini, T Stati, P Rigato, F Montagnese, P Rossi, L Aldegheri, S Resta – 30 December 2003 – This study was aimed to evaluate demographic, clinical, histological, and virological characteristics of 46 hepatitis C virus (HCV) carriers with persistently normal alanine transaminase (ALT) levels and to compare the results with those obtained in a group of 52 HCV‐RNA‐positive patients with elevated ALT levels.

The effects of low dietary levels of polyunsaturates on alcohol‐induced liver disease in Rhesus monkeys

R J Pawlosky, B M Flynn, N Salem – 30 December 2003 – Rhesus monkeys that were maintained on a diet containing low, yet adequate, amounts of vitamins C and E and in which linoleate and linolenate represented 1.4% and 0.08% of the total caloric intake, respectively, developed liver fibrosis after consuming alcohol (mean, 2.6 g kg‐1 d‐1) over a period of 3 years. In the liver, several polyunsaturated fatty acids including 18:2n6, 20:4n6, and 22:6n3 decreased compared with dietary controls, and similar findings were also observed in plasma lipoproteins and erythrocytes.

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