Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014

Natalie J. Torok, Jonathan A. Dranoff, Detlef Schuppan, Scott L. Friedman – 27 January 2015 – There is an urgent need to develop antifibrotic therapies for chronic liver disease, and clarify which endpoints in antifibrotic trials will be acceptable to regulatory agencies. The American Association for the Study of Liver Diseases sponsored an endpoints conference to help accelerate the efficient testing of antifibrotic agents and develop recommendations on clinical trial design for liver fibrosis.

Characterization of the genotype and integration patterns of hepatitis B virus in early‐ and late‐onset hepatocellular carcinoma

Hongli Yan, Yuan Yang, Ling Zhang, Guannan Tang, YuZhao Wang, Geng Xue, Weiping Zhou, Shuhan Sun – 27 January 2015 – Early‐onset hepatocellular carcinoma (HCC) accounts for 15%‐20% of total HCC cases in Asia, and the incidence is increasing. The low frequency of cirrhosis and poor prognosis of early‐onset HCC suggests that its mechanisms may differ from late‐onset HCC. Although hepatitis B virus (HBV) infection is epidemiologically associated with HCC, the role of HBV in early‐onset HCC remains poorly understood.

Treatment with ledipasvir and sofosbuvir improves patient‐reported outcomes: Results from the ION‐1, ‐2, and ‐3 clinical trials

Zobair M. Younossi, Maria Stepanova, Patrick Marcellin, Nezam Afdhal, Kris V. Kowdley, Stefan Zeuzem, Sharon L. Hunt – 27 January 2015 – Treatment with interferon (IFN) and ribavirin (RBV) significantly impairs quality of life and other patient‐reported outcomes (PROs). Patient experience with IFN‐ and RBV‐free anti‐HCV (hepatitis C virus) regimens has not been reported. We assessed PROs in patients treated with ledipasvir and sofosbuvir (LDV/SOF) with and without RBV.

Chemokine (C‐X‐C motif) ligand 13 promotes intrahepatic chemokine (C‐X‐C motif) receptor 5+ lymphocyte homing and aberrant B‐cell immune responses in primary biliary cirrhosis

Yongyin Li, Weibin Wang, Libo Tang, Xuanqiu He, Xin Yan, Xiaoyong Zhang, Youfu Zhu, Jian Sun, Yongquan Shi, Xiong Ma, Ian R. Mackay, M. Eric Gershwin, Ying Han, Jinlin Hou – 27 January 2015 – The serological hallmark of primary biliary cirrhosis (PBC) is the presence of high titer and specific antimitochondrial antibodies (AMAs). Although there is no global immune defect in patients with PBC, there is widespread dysregulated B‐cell function, including increased sera levels of immunoglobulin M and enhanced B‐cell responses to cytosine‐phosphate‐guanine stimulation.

Long‐term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus–related cirrhosis

Jeong Won Jang, Jong Young Choi, Young Seok Kim, Hyun Young Woo, Sung Kyu Choi, Chang Hyeong Lee, Tae Yeob Kim, Joo Hyun Sohn, Won Young Tak, Kwang‐Hyub Han – 27 January 2015 – The effect of viral suppression on long‐term disease outcome after decompensation in patients with hepatitis B virus (HBV)‐related cirrhosis has not been established. The aim of this study was to determine the long‐term effect of antiviral therapy (AVT) in patients with HBV‐related decompensated cirrhosis.

All‐oral 12‐week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY‐3 phase III study

David R. Nelson, James N. Cooper, Jacob P. Lalezari, Eric Lawitz, Paul J. Pockros, Norman Gitlin, Bradley F. Freilich, Ziad H. Younes, William Harlan, Reem Ghalib, Godson Oguchi, Paul J. Thuluvath, Grisell Ortiz‐Lasanta, Mordechai Rabinovitz, David Bernstein, Michael Bennett, Trevor Hawkins, Natarajan Ravendhran, Aasim M. Sheikh, Peter Varunok, Kris V. Kowdley, Delphine Hennicken, Fiona McPhee, Khurram Rana, Eric A.

All‐oral 12‐week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY‐3 phase III study

David R. Nelson, James N. Cooper, Jacob P. Lalezari, Eric Lawitz, Paul J. Pockros, Norman Gitlin, Bradley F. Freilich, Ziad H. Younes, William Harlan, Reem Ghalib, Godson Oguchi, Paul J. Thuluvath, Grisell Ortiz‐Lasanta, Mordechai Rabinovitz, David Bernstein, Michael Bennett, Trevor Hawkins, Natarajan Ravendhran, Aasim M. Sheikh, Peter Varunok, Kris V. Kowdley, Delphine Hennicken, Fiona McPhee, Khurram Rana, Eric A.

Activation of aryl hydrocarbon receptor dissociates fatty liver from insulin resistance by inducing fibroblast growth factor 21

Peipei Lu, Jiong Yan, Ke Liu, Wojciech G. Garbacz, Pengcheng Wang, Meishu Xu, Xiaochao Ma, Wen Xie – 22 January 2015 – The aryl hydrocarbon receptor (AHR), also known as the dioxin receptor, was originally characterized as a xenobiotic receptor that senses xenotoxicants. We investigated the endobiotic and hepatic role of AHR in fatty liver and energy metabolism and identified the endocrine factor that mediates the metabolic function of AHR.

Safety of long‐term biologic therapy in rheumatologic patients with a previously resolved hepatitis B viral infection

Michele Barone, Antonella Notarnicola, Giuseppe Lopalco, Maria Teresa Viggiani, Francesco Sebastiani, Michele Covelli, Florenzo Iannone, Alfonso W. Avolio, Alfredo Di Leo, Luca Cantarini, Giovanni Lapadula – 22 January 2015 – European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long‐term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed.

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