The biliary HCO3− umbrella: A unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies

Ulrich Beuers, Simon Hohenester, Lucas J. Maillette de Buy Wenniger, Andreas E. Kremer, Peter L. M. Jansen, Ronald P. J. Oude Elferink – 16 June 2010 – This review focuses on the hypothesis that biliary HCO secretion in humans serves to maintain an alkaline pH near the apical surface of hepatocytes and cholangiocytes to prevent the uncontrolled membrane permeation of protonated glycine‐conjugated bile acids.

Histologic outcomes in hepatitis C–infected patients with varying degrees of virologic response to interferon‐based treatments

Paul J. Pockros, Fayez M. Hamzeh, Paul Martin, Ellen Lentz, Xiaolei Zhou, Sugantha Govindarajan, Anna S. Lok – 16 June 2010 – Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon‐based therapies can experience treatment‐related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression.

Polymorphism in xeroderma pigmentosum complementation group C codon 939 and aflatoxin B1–related hepatocellular carcinoma in the Guangxi population

Xi‐Dai Long, Yun Ma, Yuan‐Feng Zhou, Ai‐Min Ma, Guo‐Hui Fu – 16 June 2010 – Genetic polymorphisms in DNA repair genes may influence individual variations in DNA repair capacity, and this may be associated with the risk and outcome of hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) exposure. In this study, we focused on the polymorphism of xeroderma pigmentosum complementation group C (XPC) codon 939 (rs#2228001), which is involved in nucleotide excision repair.

Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis

Laura K. Cole, René L. Jacobs, Dennis E. Vance – 16 June 2010 – Tamoxifen is an anti‐estrogen drug widely used for the treatment of hormone‐sensitive breast cancer. Approximately 43% of breast cancer patients treated with tamoxifen develop hepatic steatosis. The mechanism or mechanisms by which tamoxifen may induce lipid accumulation in the liver are unclear. Mice were injected with tamoxifen or vehicle (sesame oil containing 1% benzyl alcohol) for 5 consecutive days. In comparison with the vehicle, tamoxifen increased hepatic triacylglycerol levels by 72%.

Liver‐specific β‐catenin knockout mice have bile canalicular abnormalities, bile secretory defect, and intrahepatic cholestasis

Tzu‐Hsuan Yeh, Lindsay Krauland, Vijay Singh, Baobo Zou, Prathab Devaraj, Donna B. Stolz, Jonathan Franks, Satdarshan P. S. Monga, Eizaburo Sasatomi, Jaideep Behari – 11 June 2010 – Beta‐catenin plays important roles in liver physiology and hepatocarcinogenesis. While studying the role of β‐catenin in diet‐induced steatohepatitis, we recently found that liver‐specific β‐catenin knockout (KO) mice exhibit intrahepatic cholestasis. This study was undertaken to further characterize the role of β‐catenin in biliary physiology.

A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B

Henry Lik‐Yuen Chan, Vincent Wai‐Sun Wong, Grace Lai‐Hung Wong, Chi‐Hang Tse, Hoi‐Yun Chan, Joseph Jao‐Yao Sung – 11 June 2010 – Serum hepatitis B surface antigen (HBsAg) quantification has been suggested to reflect the concentration of covalently closed circular DNA in the liver. We aimed to investigate the HBsAg levels at different stages of chronic hepatitis B and the changes in HBsAg level during the natural progression of disease. One hundred seventeen untreated patients with chronic hepatitis B were studied with longitudinal follow‐up for 99 ± 16 months.

CX3CL1‐CX3CR1 interaction prevents carbon tetrachloride‐induced liver inflammation and fibrosis in mice

Tomonori Aoyama, Sayaka Inokuchi, David A. Brenner, Ekihiro Seki – 11 June 2010 – Chronic liver disease is associated with hepatocyte injury, inflammation, and fibrosis. Chemokines and chemokine receptors are key factors for the migration of inflammatory cells such as macrophages and noninflammatory cells such as hepatic stellate cells (HSCs). The expression of CX3CR1 and its ligand, CX3CL1, is up‐regulated in chronic liver diseases such as chronic hepatitis C. However, the precise role of CX3CR1 in the liver is still unclear.

A novel role for thyroid‐stimulating hormone: Up‐regulation of hepatic 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme a reductase expression through the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate–responsive element binding protei

Limin Tian, Yongfeng Song, Mingzhao Xing, Wei Zhang, Guang Ning, Xiaoying Li, Chunxiao Yu, Chengkong Qin, Jun Liu, Xingsong Tian, Xianglan Sun, Rui Fu, Lin Zhang, Xiujuan Zhang, Yan Lu, Jianwen Zou, Laicheng Wang, Qingbo Guan, Ling Gao, Jiajun Zhao – 11 June 2010 – Elevated thyroid‐stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in hypothyroidism, but there is no known mechanism directly linking the two.

Role and cellular source of nicotinamide adenine dinucleotide phosphate oxidase in hepatic fibrosis

Samuele De Minicis, Ekihiro Seki, Yong‐Han Paik, Christoph H. Österreicher, Yuzo Kodama, Johannes Kluwe, Luciano Torozzi, Katsumi Miyai, Antonio Benedetti, Robert F. Schwabe, David A. Brenner – 11 June 2010 – Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) is required for liver fibrosis. This study investigates the role of NOX in ROS production and the differential contribution of NOX from bone marrow (BM)‐derived and non–BM‐derived liver cells.

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