Oncogenic and tumor suppressive roles of polo‐like kinases in human hepatocellular carcinoma

Rossella Pellegrino, Diego F. Calvisi, Sara Ladu, Volker Ehemann, Tommaso Staniscia, Matthias Evert, Frank Dombrowski, Peter Schirmacher, Thomas Longerich – 30 November 2009 – Polo‐like kinase (PLK) proteins play critical roles in the control of cell cycle progression, either favoring or inhibiting cell proliferation, and in DNA damage response. Although either overexpression or down‐regulation of PLK proteins occurs frequently in various cancer types, no comprehensive analysis on their function in human hepatocellular carcinoma (HCC) has been performed to date.

Expression of pituitary tumor–transforming gene 1 (PTTG1)/securin in hepatitis B virus (HBV)‐associated liver diseases: Evidence for an HBV X protein–mediated inhibition of PTTG1 ubiquitination and degradation

Francisca Molina‐Jiménez, Ignacio Benedicto, Miki Murata, Samuel Martín‐Vílchez, Toshihito Seki, José Antonio Pintor‐Toro, María Tortolero, Ricardo Moreno‐Otero, Kazuichi Okazaki, Kazuhiko Koike, José Luchi Barbero, Koichi Matsuzaki, Pedro L. Majano, Manuel López‐Cabrera – 30 November 2009 – Chronic infection with hepatitis B virus (HBV) is strongly associated with hepatocellular carcinoma (HCC), and the viral HBx protein plays a crucial role in the pathogenesis of liver tumors.

5‐lipoxygenase deficiency reduces hepatic inflammation and tumor necrosis factor α–induced hepatocyte damage in hyperlipidemia‐prone ApoE‐null mice

Marcos Martínez‐Clemente, Natàlia Ferré, Ana González‐Périz, Marta López‐Parra, Raquel Horrillo, Esther Titos, Eva Morán‐Salvador, Rosa Miquel, Vicente Arroyo, Colin D. Funk, Joan Clària – 30 November 2009 – The actual risk factors that drive hepatic inflammation during the transition from steatosis to steatohepatitis are unknown. We recently demonstrated that hyperlipidemia‐prone apolipoprotein E–deficient (ApoE−/−) mice exhibit hepatic steatosis and increased susceptibility to hepatic inflammation and advanced fibrosis.

Hepatitis B virus infection among American patients with chronic hepatitis C virus infection: Prevalence, racial/ethnic differences, and viral interactions

Edmund J. Bini, Ponni V. Perumalswami – 30 November 2009 – Little is known about hepatitis B virus (HBV) infection among patients with chronic hepatitis C virus (HCV) infection in the United States. We prospectively enrolled 1,257 patients with chronic HCV infection from two medical centers in New York City. A total of 61.5% (95% confidence interval, 58.8%–64.2%) had evidence of prior exposure to HBV (hepatitis B core antibody–positive), whereas 5.8% (95% confidence interval, 4.5%–7.1%) had dual infection with HBV (hepatitis B surface antigen–positive).

Antiviral activity and safety of LB80380 in hepatitis B e antigen–positive chronic hepatitis B patients with lamivudine‐resistant disease

Man‐Fung Yuen, Kwang‐Hyub Han, Soon‐Ho Um, Seung Kew Yoon, Hye‐Ryon Kim, John Kim, Chung Ryeol Kim, Ching‐Lung Lai – 30 November 2009 – We aimed to determine the antiviral activity and safety of a new nucleotide analogue, LB80380, in chronic hepatitis B (CHB) patients with lamivudine‐resistant virus. Sixty‐five patients with lamivudine‐resistant virus were randomized to receive five ascending daily doses (30, 60, 90, 150, 240 mg) of LB80380. LB80380 was given together with lamivudine for the first 4 weeks, followed by 8 weeks of LB80380 monotherapy.

The histogenesis of regenerative nodules in human liver cirrhosis

Wey‐Ran Lin, Siew‐Na Lim, Stuart A. C. McDonald, Trevor Graham, Victoria L. Wright, Claire L. Peplow, Adam Humphries, Hemant M. Kocher, Nicholas A. Wright, Amar P. Dhillon, Malcolm R. Alison – 30 November 2009 – Here, we investigate the clonality and cells of origin of regenerative nodules in human liver cirrhosis using mitochondrial DNA (mtDNA) mutations as markers of clonal expansion. Mutated cells are identified phenotypically by deficiency in the entirely mtDNA encoded cytochrome c oxidase (CCO) enzyme by histochemical and immunohistochemical methods.

Outcome of recurrent hepatitis C virus after liver transplantation in a randomized trial of tacrolimus monotherapy versus triple therapy

Pinelopi Manousou, Dimitrios Samonakis, Evangelos Cholongitas, David Patch, James O'Beirne, Amar P. Dhillon, Keith Rolles, Aiden McCormick, Peter Hayes, Andrew K. Burroughs – 24 November 2009 – Less potent immunosuppression is considered to reduce the severity of hepatitis C virus (HCV) recurrence after liver transplantation. An optimal regimen is unknown. We evaluated tacrolimus monotherapy versus triple therapy in a randomized trial of 103 first transplants for HCV cirrhosis.

Prospective validation of a noninvasive index for predicting liver fibrosis in hepatitis C virus–infected liver transplant recipients

Salvador Benlloch, Laura Heredia, Claudia Barquero, José‐Miguel Rayón, Ramón Pina, Victoria Aguilera, Martín Prieto, Marina Berenguer – 24 November 2009 – We previously developed a mathematical model, the Hospital Universitario La Fe (HULF) index, as an alternative to protocol liver biopsy (PLB) to estimate significant fibrosis (SF) in patients who underwent liver transplantation (LT) for liver damage caused by chronic HCV infection. In the present study, we sought to validate this noninvasive index.

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