FoxO3 inactivation promotes human cholangiocarcinoma tumorigenesis and chemoresistance through Keap1‐Nrf2 signaling

Li Guan, Lei Zhang, Zhicheng Gong, Xiaonan Hou, Yuxiu Xu, Xinhua Feng, Hongyang Wang, Han You – 9 February 2016 – FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs in human cancers remain largely unknown. Aberrant expression and activation of Nrf2 often correlate with chemoresistance and poor prognosis. Here, we report that FoxO3 directs the basal transcription of Kelch‐like ECH‐associated protein 1 (Keap1), an adaptor protein that bridges Nrf2 to Cul3 for degradation.

Retreatment with sofosbuvir and simeprevir of patients with hepatitis C virus genotype 1 or 4 who previously failed a daclatasvir‐containing regimen

Christophe Hézode, Stéphane Chevaliez, Giovanna Scoazec, Alexandre Soulier, Anne Varaut, Magali Bouvier‐Alias, Isaac Ruiz, Françoise Roudot‐Thoraval, Ariane Mallat, Cyrille Féray, Jean‐Michel Pawlotsky – 8 February 2016 – Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct‐acting antiviral‐based regimens is commonly associated with emergence of resistance‐associated variants (RAVs).

Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver

Nam‐On Ku, Pavel Strnad, Heike Bantel, M. Bishr Omary – 8 February 2016 – Keratins, formerly known as cytokeratins, are the major epithelial‐specific subgroup of intermediate filament proteins. Adult hepatocytes express keratin polypeptides 8 and 18 (K8/K18), whereas cholangiocytes express K8/K18 and keratins 7 and 19 (K7/K19). Keratins function primarily to protect hepatocytes from apoptosis and necrosis, which was revealed using several genetic mouse models.

P2X1‐regulated IL‐22 secretion by innate lymphoid cells is required for efficient liver regeneration

Ramesh Kudira, Thomas Malinka, Andreas Kohler, Michel Dosch, Mercedes Gomez de Agüero, Nicolas Melin, Stefanie Haegele, Patrick Starlinger, Niran Maharjan, Smita Saxena, Adrian Keogh, Deborah Stroka, Daniel Candinas, Guido Beldi – 8 February 2016 – Paracrine signalling mediated by cytokine secretion is essential for liver regeneration after hepatic resection, yet the mechanisms of cellular crosstalk between immune and parenchymal cells are still elusive. Interleukin‐22 (IL‐22) is released by immune cells and mediates strong hepatoprotective functions.

Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver

Nam‐On Ku, Pavel Strnad, Heike Bantel, M. Bishr Omary – 8 February 2016 – Keratins, formerly known as cytokeratins, are the major epithelial‐specific subgroup of intermediate filament proteins. Adult hepatocytes express keratin polypeptides 8 and 18 (K8/K18), whereas cholangiocytes express K8/K18 and keratins 7 and 19 (K7/K19). Keratins function primarily to protect hepatocytes from apoptosis and necrosis, which was revealed using several genetic mouse models.

Retreatment with sofosbuvir and simeprevir of patients with hepatitis C virus genotype 1 or 4 who previously failed a daclatasvir‐containing regimen

Christophe Hézode, Stéphane Chevaliez, Giovanna Scoazec, Alexandre Soulier, Anne Varaut, Magali Bouvier‐Alias, Isaac Ruiz, Françoise Roudot‐Thoraval, Ariane Mallat, Cyrille Féray, Jean‐Michel Pawlotsky – 8 February 2016 – Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct‐acting antiviral‐based regimens is commonly associated with emergence of resistance‐associated variants (RAVs).

Atrioventricular conduction disturbances immediately after hepatic graft reperfusion and their outcomes in patients undergoing liver transplantation

Sung‐Hoon Kim, Young‐Jin Moon, Sooho Lee, Sung‐Moon Jeong, Jun‐Gol Song, Gyu‐Sam Hwang – 6 February 2016 – Hemodynamic perturbation during hepatic graft reperfusion in patients undergoing liver transplantation (LT) is challenging and is frequently accompanied by bradyarrhythmia and even asystole. However, detailed data on electrocardiographic (ECG) changes during reperfusion are almost nonexistent, although the correct diagnosis by record is important for the treatment. We aimed to identify ECG rhythm disturbances during graft reperfusion and to investigate risk factors and outcomes.

Impaired physical function following pediatric LT

Amy G. Feldman, Katie Neighbors, Shubhra Mukherjee, Melanie Rak, James W. Varni, Estella M. Alonso – 6 February 2016 – The purpose of this article is to investigate the spectrum of physical function of pediatric liver transplantation (LT) recipients 12‐24 months after LT. Review data were collected through the functional outcomes group, an ancillary study of the Studies of Pediatric Liver Transplantation registry. Patients were eligible if they had survived LT by 12‐24 months.

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