Better estimates of survival for patients considering adjuvant chemotherapy after surgery for early non-small-cell lung cancer.

Introduction: The aim of this study was to summarise and describe survival data from contemporary randomised trials of platinum-based adjuvant chemotherapy for patients with non-small-cell lung cancer (NSCLC). The goal was to assist clinicians to provide better estimates of survival for patients considering adjuvant chemotherapy following surgical resection for NSCLC.

Methods: Randomised trials of cisplatin-based adjuvant chemotherapy for resected NSCLC were identified.

Two lymph nodes draining the mouse liver are the preferential site of DC migration and T cell activation.

Background & Aims: Lymph nodes (LNs) play a critical role in host defence against pathogens. In rodents, lymphatic anatomy and drainage have been characterized for many different organs. Surprisingly, the LNs draining the mouse liver have not been clearly identified.

Early on-treatment viral load and baseline METAVIR score: improved prediction of sustained virological response in HCV genotype 1 patients.

Background: On-treatment HCV viral load during early therapy with pegylated interferon (PEG-IFN) and ribavirin is highly predictive of sustained virological response (SVR). We sought to provide further refinement of this prediction through an extensive evaluation of the effect of HCV viral loads at weeks 4, 8 and 12 on SVR, including analysis by liver disease stage grouping.

Methods: A total of 309 patients with genotype 1 chronic HCV and recent liver biopsy enrolled in the CHARIOT study received 180 μg of PEG-IFN-α2a weekly with 1,000/1,200 mg of ribavirin daily.

Tolerance in liver transplantation.

Operational tolerance (OT) in liver transplant patients occurs much more frequently than OT of other transplanted organs; however the rate of OT varies considerably with the centre and patient population. Rates of OT range from 15% of the total liver transplant (LTX) patient population down to less than 5%. This review examines the reports of liver OT and compares the factors that could contribute to this variation.

APASL consensus statements and management algorithms for hepatitis C virus infection.

The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the "APASL Consensus Statements and Management Algorithms for Hepatitis C Virus Infection" in December, 2010, in order to revise "Asian Pacific Association for the Study of the Liver consensus statements on the diagnosis, management and treatment of hepatitis C virus infection (J Gastroenterol Hepatol 22:615-633, 2007)". The working party consisted of expert hepatologists from the Asian-Pacific region gathered at Makuhari, Chiba, Japan on 19 December 2010. New data were presented, discussed and debated to draft a revision.

Prevention of post liver transplant HBV recurrence.

Background: Twenty years ago, liver transplantation for hepatitis B had been a relative contraindication to universal HBV recurrence and poor outcomes. Over the ensuing two decades, there has been refinement of prevention strategies in order to minimize HBV recurrence in the allograft.

Results: Currently, the most efficacious and cost-effective strategies include newer oral antiviral drugs in combination with low doses of hepatitis B immunoglobulin (HBIG).

Hepatocyte entry leads to degradation of autoreactive CD8 T cells.

Although most self-reactive T cells are eliminated in the thymus, mechanisms to inactivate or control T cells specific for extrathymic antigens are required and exist in the periphery. By investigating the site in which autoreactive T cells are tolerized, we identify a unique mechanism of peripheral deletion in which naïve autoreactive CD8 T cells are rapidly eliminated in the liver after intrahepatic activation. T cells actively invade hepatocytes, enter endosomal/lysosomal compartments, and are degraded.

Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed?

Unlabelled: Screening for hepatocellular carcinoma (HCC) is commonly practiced and recommended in published guidelines, but evidence for its efficacy has been controversial. We tested the feasibility of conducting a randomized controlled trial (RCT) of HCC surveillance in patients with cirrhosis and followed up those offered screening to detect clinical outcomes. Participation was offered to patients with cirrhosis attending liver clinics at three university hospitals.

Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index.

Background And Aim: Donor liver steatosis can impact on liver allograft outcomes. The aim of the present study was to comprehensively report on the impact of type and grade of donor steatosis, as well as donor and recipient factors, including the reported Donor Risk Index (DRI), on liver allograft outcomes.

Methods: A review of unit data for all adult liver transplant procedures from 2001 to 2007, as well as donor offers.

A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt.

Background: The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions.

Aim: The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e.

A novel role of dipeptidyl peptidase 9 in epidermal growth factor signaling.

Dipeptidyl peptidase IV (DPP4), DPP8, DPP9, and fibroblast activation protein (FAP), the four proteases of the DPP4 gene family, have unique peptidase and extra-enzymatic activities that have been implicated in various diseases including cancers. We report here a novel role of DPP9 in regulating cell survival and proliferation through modulating molecular signaling cascades. Akt (protein kinase B) activation was significantly inhibited by human DPP9 overexpression in human hepatoma cells (HepG2 and Huh7) and human embryonic kidney cells (HEK293T), whereas extracellular signal-regulated kinases (ERK1/2) activity was unaffected, revealing a pathway-specific effect.

Approaching the promise of operational tolerance in clinical transplantation.

Long-term acceptance of transplanted organs without requirement for indefinite immunosuppression remains the ultimate goal of transplant clinicians and scientists. This clinical state of allograft acceptance termed "operational tolerance" has been elusive in routine practice. However, there are published reports of recipients where immunosuppression has been discontinued, by intention or patient noncompliance, in which the outcome is a nondestructive immune response and normal function.

Virological response is associated with decline in hemoglobin concentration during pegylated interferon and ribavirin therapy in hepatitis C virus genotype 1.

Unlabelled: Anemia may increase the likelihood of achieving a sustained virological response (SVR) during pegylated interferon and ribavirin treatment of hepatitis C virus (HCV) infection. To determine whether hemoglobin decline is associated with SVR, we retrospectively evaluated the CHARIOT study of 871 treatment-naïve HCV genotype 1 patients. Anemia (serum hemoglobin <100 g/L) occurred in 137 (16%) patients, of whom only 14 (10%) received erythropoietin.

Effect of low-level HCV viraemia at week 24 on HCV treatment response in genotype 1 patients.

Background: We examined the detection of low-level viraemia at week 24 as a predictor of sustained virological response (SVR) and viral relapse/breakthrough, and the agreement between the Roche Cobas TaqMan™ HCV RNA assay (TaqMan) and Roche Cobas(®) Amplicor HCV qualitative assay (Amplicor; both Roche Molecular Diagnostics, Pleasanton, CA, USA) for detection of low-level viraemia.

Methods: A total of 871 treatment-naive HCV genotype 1 patients participating in an induction-dose pegylated interferon therapy study had virological responses assessed using TaqMan. A total of 151 patients with HCV RNA levels ≤500 IU/ml had samples tested in parallel using the Amplicor and TaqMan assays.

Discoidin domain receptor 1: isoform expression and potential functions in cirrhotic human liver.

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression.

Spontaneous acceptance of mouse kidney allografts is associated with increased Foxp3 expression and differences in the B and T cell compartments.

Spontaneous acceptance of organ allografts can identify novel mechanisms of drug-free transplantation tolerance. Spontaneous acceptance occurs in both mouse kidney transplants and rat liver transplants however the early immune processes of mouse kidney acceptance have not been studied. Acceptance of C57BL/6 strain kidney allografts in fully MHC-incompatible B10.

Soluble CD26 / dipeptidyl peptidase IV enhances human lymphocyte proliferation in vitro independent of dipeptidyl peptidase enzyme activity and adenosine deaminase binding.

Human CD26 has dipeptidyl peptidase-4 (DPP IV) enzyme activity and binds to adenosine deaminase (ADA). CD26 is costimulatory for lymphocytes and has a circulating soluble form (sCD26). DPP IV enzyme inhibition is a new successful type 2 diabetes therapy.

Diabetes is a progression factor for hepatic fibrosis in a high fat fed mouse obesity model of non-alcoholic steatohepatitis.

Background & Aims: While type 2 diabetes is an independent risk factor for worsening of human non-alcoholic steatohepatitis (NASH) in clinical studies, it has not been systematically reported in any model whether diabetes exacerbates NASH. The study aim was to determine if diabetes causes NASH progression in a mouse model of diet induced obesity.

Methods: C57BL/6 mice were fed a high fat diet (HFD: 45% kcal fat) or standard chow (CHOW: 12% kcal fat) for 20 weeks and some animals (HFD+DM or CHOW+DM) were also rendered diabetic by low dose streptozotocin for the final 5 weeks, to model type 2 diabetes.