Liver disease in pregnancy

J. Eileen Hay – 26 February 2008 – Abnormal liver tests occur in 3%–5% of pregnancies, with many potential causes, including coincidental liver disease (most commonly viral hepatitis or gallstones) and underlying chronic liver disease. However, most liver dysfunction in pregnancy is pregnancy‐related and caused by 1 of the 5 liver diseases unique to the pregnant state: these fall into 2 main categories depending on their association with or without preeclampsia.

The cyclophilin inhibitor Debio‐025 shows potent anti–hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus

Robert Flisiak, Andrzej Horban, Philippe Gallay, Michael Bobardt, Suganya Selvarajah, Alicja Wiercinska‐Drapalo, Ewa Siwak, Iwona Cielniak, Jozef Higersberger, Jarek Kierkus, Christian Aeschlimann, Pierre Grosgurin, Valérie Nicolas‐Métral, Jean‐Maurice Dumont, Hervé Porchet, Raf Crabbé, Pietro Scalfaro – 26 February 2008 – Debio‐025 is an oral cyclophilin (Cyp) inhibitor with potent anti–hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double‐blind, placebo‐controlled study.

S‐adenosylmethionine inhibits lipopolysaccharide‐induced gene expression via modulation of histone methylation

Ainhoa Iglesias Ara, Meng Xia, Komal Ramani, José M. Mato, Shelly C. Lu – 21 February 2008 – We previously showed that S‐adenosylmethionine (SAMe) and its metabolite methylthioadenosine (MTA) blocked lipopolysaccharide (LPS)‐induced tumor necrosis factor α (TNFα) expression in RAW (murine macrophage cell line) and Kupffer cells at the transcriptional level without affecting nuclear factor κ B nuclear binding. However, the exact molecular mechanism or mechanisms of the inhibitory effect were unclear. While SAMe is a methyl donor, MTA is an inhibitor of methylation.

Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease

Winston Dunn, Ronghui Xu, Jeffrey B. Schwimmer – 21 February 2008 – People at risk for coronary heart disease are often at risk for nonalcoholic fatty liver disease (NAFLD). The association of modest wine consumption with NAFLD has not been studied and the recommendation of wine for patients at risk for both diseases is controversial. The aim is to test the hypothesis that modest wine consumption is associated with decreased prevalence of NAFLD.

Autophagy activation by rapamycin eliminates mouse Mallory‐Denk bodies and blocks their proteasome inhibitor‐mediated formation

Masaru Harada, Shinichiro Hanada, Diana M. Toivola, Nafisa Ghori, M. Bishr Omary – 21 February 2008 – The proteasomal and lysosomal/autophagy pathways in the liver and other tissues are involved in several biological processes including the degradation of misfolded proteins. Exposure of hepatocyte cell lines to proteasome inhibitors (PIs) results in the formation of inclusions that resemble Mallory‐Denk bodies (MDBs). Keratins are essential for MDB formation and keratin 8 (K8)‐overexpressing transgenic mice are predisposed to MDB formation.

Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration

Ghazaleh Aram, James J. Potter, Xiaopu Liu, Michael S. Torbenson, Esteban Mezey – 19 February 2008 – The role of nitric oxide (NO) in liver injury and fibrosis is unclear. The purpose of this study was to determine whether inducible NO synthase deficiency (iNOS−/−) affects liver injury and fibrosis produced in mice by chronic carbon tetrachloride (CCl4) administration. Wild‐type (WT) or iNOS−/− mice were subjected to biweekly CCl4 injections over 8 weeks, whereas controls were given isovolumetric injections of olive oil.

Transforming growth factor‐β gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer

Cédric Coulouarn, Valentina M. Factor, Snorri S. Thorgeirsson – 19 February 2008 – Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The clinical heterogeneity of HCC, and the lack of good diagnostic markers and treatment strategies, has rendered the disease a major challenge. Patients with HCC have a highly variable clinical course, indicating that HCC comprises several biologically distinctive subgroups reflecting a molecular heterogeneity of the tumors.

Fractional allelic imbalance could allow for the development of an equitable transplant selection policy for patients with hepatocellular carcinoma

Igor Dvorchik, Myron Schwartz, M. Isabel Fiel, Sydney D. Finkelstein, J. Wallis Marsh – 11 February 2008 – Liver transplantation (LT) in the presence of hepatocellular carcinoma (HCC) remains a controversial issue because the current staging systems are not sufficiently predictive of outcomes. Paraffin blocks from 183 patients that underwent LT in the presence of HCC were collected. Molecular analysis was carried out blindly on the native liver specimens in all cases with respect to recurrence outcomes.

Health‐related fitness and physical activity in patients with nonalcoholic fatty liver disease

Joanne B. Krasnoff, Patricia L. Painter, Janet P. Wallace, Nathan M. Bass, Raphael B. Merriman – 11 February 2008 – Nonalcoholic fatty liver disease (NAFLD) has been referred to as the hepatic manifestation of the metabolic syndrome. There is a lower prevalence of metabolic syndrome in individuals with higher health‐related fitness (HRF) and physical activity (PA) participation. The relationship between NAFLD severity and HRF or PA is unknown. Our aim was to compare measures of HRF and PA in patients with a histological spectrum of NAFLD severity.

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