Immunobiology of hepatocarcinogenesis: Ways to go or almost there?

Hepatocellular carcinoma is on the rise and occurs in the setting of chronic liver disease and cirrhosis.Though treatment modalities are available,mortality from this cancer remains high.Medical therapy with the utilization of biologic compounds such as the Food and Drug Administration approved sorafenib might be the only option that can increase survival.Immunotherapy,with modern pharmacologic developments,is a new frontier in cancer therapy and therefore the immunobiology of hepatocarcinogenesis is under investigation.This review will discuss current concepts of immunobiology in hepatocarcinogenesis along with current treatment modalities employing immunotherapy.The tumor microenvironment along with a variety of immune cells coexists and interplays to lead to tumorigenesis.Tumor infiltrating lymphocytes including CD8+ T cells,CD4+ T cells along with regulatory T cells,tumor associated macrophages,tumor associated neutrophils,myeloid derived suppressor cells,and natural killer cells interact to actively provide anti-tumor or pro-tumor effects.Furthermore,oncogenic pathways such as Raf/mitogenactivated protein kinase/extracellular-signal-regulated kinase pathway,phosphatidyl-3-kinase/AKT/mammalian target or rapamycin,Wnt/β-catenin,nuclear factor-κB and signal transducers and activators of transcription 3 may lead to activation and proliferation of tumor cells and are also considered cornerstones in tumorigenesis.Immunotherapy directed at this complex milieu of cells has been showned to be successful in cancer treatment.The use of vaccines,adoptive cell therapy and immune checkpoint inhibitor modulation are current options for therapy.Further translational research will shed light to concepts such as anti-tumor immunity which can add another alternative in the therapeutic armamentarium.

Hospital teaching status on the outcomes of patients with esophageal variceal bleeding in the United States

BACKGROUND Acute variceal bleeding is a major complication of portal hypertension and is a leading cause of death in patients with cirrhosis.There is limited data on the outcomes of patients with esophageal variceal bleeding in teaching versus nonteaching hospitals.Because esophageal variceal bleeding requires complex management,it may be hypothesized that teaching hospitals have lower mortality.AIM To assess the differences in mortality,hospital length of stay(LOS)and cost of admission for patients admitted for variceal bleed in teaching versus nonteaching hospitals across the US.METHODS The National Inpatient Sample is the largest all-payer inpatient database consisting of approximately 20%of all inpatient admissions to nonfederal hospitals in the United States.We collected data from the years 2008 to 2014.Cases of variceal bleeding were identified using the International Classification of Diseases,Ninth Edition,Clinical Modification codes.Differences in mortality,LOS and cost were evaluated for patients with esophageal variceal bleed between teaching and nonteaching hospitals and adjusted for patient characteristics and comorbidities.RESULTS Between 2008 and 2014,there were 58362 cases of esophageal variceal bleeding identified.Compared with teaching hospitals,mortality was lower in nonteaching hospitals(8.0%vs 5.3%,P<0.001).Median LOS was shorter in nonteaching hospitals as compared to teaching hospitals(4 d vs 5 d,P<0.001).A higher proportion of non-white patients were managed in teaching hospitals.As far as procedures in nonteaching vs teaching hospitals,portosystemic shunt insertion(3.1%vs 6.9%,P<0.001)and balloon tamponade(0.6%vs 1.2%)were done more often in teaching hospitals while blood transfusions(64.2%vs 59.9%,P=0.001)were given more in nonteaching hospitals.Using binary logistic regression models and adjusting for baseline patient demographics and comorbid conditions the mortality,LOS and cost in teaching hospitals remained higher.CONCLUSION In patients admitted for esophageal variceal bleeding,mortality,length of stay and cost were higher in teaching hospitals versus nonteaching hospitals when controlling for other confounding factors.

Superior Performance of Teaching and Transplant Hospitals in the Management of Hepatic Encephalopathy from 2007 to 2014

Background and Aims:Hepatic encephalopathy is a liver disease complication with significant mortality and costs.The aim of this study was to evaluate the relative performance of facilities based on their teaching status and transplant capability by correlating their connections to mortality,cost,and length of stay from 2007 to 2014.Methods:The Nationwide Inpatient Sample database was utilized to collect information on(USA)American patients admitted with a primary diagnosis of hepatic encephalopathy from 2007-2014.Hospitals were placed into one of four categories using their teaching and transplant status.Using regression analysis,mortality,length of stay and cost adjusted rate ratios were calculated.Results:The study revealed that teaching transplant centers had a mortality risk ratio of 0.783(95%confidence interval(CI):0.750-0.819,p<0.001).Blacks had the highest mortality risk ratio,of 1.273(95%CI:1.217-1.331,p<0.001).Furthermore,teaching transplant hospitals had a cost rate ratio of 1.226(95%CI:1.214-1.238,p<0.001)and a length of stay rate ratio of 1.104(95%CI:1.093-1.115,p<0.001).Conclusions:It appears that admission to transplant facilities for hepatic encephalopathy is associated with reduced mortality but increased costs and longer stay independent of transplantation.Moreover,factors impacting black mortality should also be examined more closely.