ABSTRACT
UNLABELLED: Data on liver transplantation for patients with alcoholic hepatitis are limited. Using the United Network for Organ Sharing database (2004-2010), adults undergoing liver transplantation for a listing diagnosis of alcoholic hepatitis were matched for age, gender, ethnicity, and model for endstage disease (MELD) score, donor risk index, and year of transplantation with three patients transplanted for a listing diagnosis of alcoholic cirrhosis. Study outcomes of graft and patient survival on follow-up were also analyzed for cohorts based on the diagnosis of the explant (46 alcoholic hepatitis and 138 alcoholic cirrhosis) and diagnosis at both listing as well as of the explant (11 alcoholic hepatitis and 33 alcoholic cirrhosis). Five-year graft and patient survival of alcoholic hepatitis and alcoholic cirrhosis patients were 75% and 73% (P = 0.97) and 80% and 78% (P = 0.90), respectively. Five-year graft and patient survival rates were also similar for cohorts based on diagnosis of the explant and diagnosis at listing as well as explant. Cox proportional regression analysis adjusting for other variables showed no impact of the etiology of liver disease (alcoholic hepatitis versus alcoholic cirrhosis) on the graft and patient survival. The causes of graft loss and patient mortality were similar in the two groups, and were not alcohol-related in any patient. CONCLUSION: Compared with alcoholic cirrhosis, patients with alcoholic hepatitis have similar posttransplantation graft and patient survival. Based on these preliminary findings, liver transplantation may be considered in a select group of patients with alcoholic hepatitis who fail to improve with medical therapy. Prospective studies are needed to assess the long-term outcome after liver transplantation in patients with alcoholic hepatitis.
Subject(s)
Hepatitis, Alcoholic/surgery , Liver Cirrhosis, Alcoholic/surgery , Liver Transplantation/mortality , Liver Transplantation/methods , Adult , Age Factors , Confidence Intervals , Databases, Factual , Female , Graft Rejection , Graft Survival , Hepatitis, Alcoholic/mortality , Hepatitis, Alcoholic/pathology , Humans , Kaplan-Meier Estimate , Liver Cirrhosis, Alcoholic/mortality , Liver Cirrhosis, Alcoholic/pathology , Liver Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/physiopathology , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Sex Factors , Survival Rate , Tissue Donors , Treatment Outcome , United StatesABSTRACT
Although in vitro models have been a cornerstone of anti-cancer drug development, their direct applicability to clinical cancer research has been uncertain. Using a state-of-the-art Taqman-based quantitative RT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of six cancer types, in established cancer cell lines (grown in monolayer, 3D scaffold, or in xenograft) and clinical samples, either containing >75% tumor cells or microdissected. The MDR transcriptome was determined a priori based on an extensive curation of the literature published during the last three decades, which led to the enumeration of 380 genes. No correlation was found between clinical samples and established cancer cell lines. As expected, we found up-regulation of genes that would facilitate survival across all cultured cancer cell lines evaluated. More troubling, however, were data showing that all of the cell lines, grown either in vitro or in vivo, bear more resemblance to each other, regardless of the tissue of origin, than to the clinical samples they are supposed to model. Although cultured cells can be used to study many aspects of cancer biology and response of cells to drugs, this study emphasizes the necessity for new in vitro cancer models and the use of primary tumor models in which gene expression can be manipulated and small molecules tested in a setting that more closely mimics the in vivo cancer microenvironment so as to avoid radical changes in gene expression profiles brought on by extended periods of cell culture.
Subject(s)
Antineoplastic Agents/therapeutic use , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor/methods , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Cell Survival , Female , Gene Expression Profiling , Humans , Ovarian Neoplasms/metabolism , Ovary/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Translational Research, Biomedical/methods , Tumor Cells, Cultured , Tumor Suppressor Protein p53/metabolismABSTRACT
Immune-mediated liver diseases contribute significantly to morbidity and mortality due to liver failure and the need for liver transplantation. The pathogenesis of the immune-mediated chronic liver diseases, primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cirrhosis, is poorly understood. Genetic susceptibility factors may play a role, but increasing attention is being given to the association between environmental factors and these diseases. The existence of such a relationship is supported by epidemiologic surveys, animal models, and geographic clustering analyses. Unearthing the cause of this association may provide insight into the pathogenesis of immune-mediated chronic liver diseases and autoimmunity.
