Objectives Adherence to the American Association for the Study of Liver Disease (AASLD) guidelines for the management of chronic hepatitis B (CHB) has not been systematically assessed. We sought to comprehensively evaluate adherence to five key areas of these guidelines. We also evaluated physician and patient factors underlying nonadherence, and predictors of nonadherence such as physician type, patient demographic factors, and phase of CHB infection. Methods Nine hundred and sixty-two adult patients were retrospectively identified. Each patient chart was reviewed in detail. The primary outcome was adherence to five areas of the AASLD guidelines: (i) timely alanine aminotransferase (ALT)/hepatitis B virus DNA level checks needed to monitor inactive carrier and immune-tolerant phases; (ii) liver biopsy to guide decisions on initiating treatment; (iii) treatment initiation when indicated; (iv) hepatocellular carcinoma (HCC) screening; (v) testing for hepatitis A virus (HAV) immunity, HIV, and hepatitis C virus (HCV) co-infections. Results Sixty percent did not undergo clinically indicated liver biopsies, largely owing to physician nonadherence. Eighty-nine percent of these missed biopsies were needed to further assess possible e-antigen-negative CHB. A high treatment initiation rate was found for the treatment eligible, but 121 patients had unclear treatment eligibility as they warranted, but did not undergo, liver biopsy. Forty-five percent did not have timely HCC screening, although gastroenterology physicians had the highest odds of adherence, and 29% did not have timely CHB lab assessment; patients seen by gastroenterologists had twice the odds compared with primary care physicians of undergoing timely lab monitoring. Thirty-five, 24, and 54% were not tested for HAV, HCV, and HIV co-infections. Conclusions Our findings show remarkably poor adherence to AASLD guidelines, particularly in the areas of liver biopsy, timely HCC and ALT monitoring, and testing for co-infection. These findings call for greater efforts to meet physician knowledge gaps, incorporation of decision support tools, and improved communication among providers.

Lipids and lipoproteins have emerged as key constituents of the immune response to microbial infection. We, therefore, sought to understand the complex interaction between lipoprotein metabolism and sepsis. Apolipoprotein E (apoE), a component of plasma lipoproteins, has been suggested to bind and traffic Ags for NKT cell activation. However, apoE’s role in sepsis has not been demonstrated. In this study, we examined the effect of exogenous apoE in a rat model of septic peritonitis, induced by cecal ligation and puncture. We demonstrate that 48 h after serial injections of apoE, septic mortality increased in a dose-dependent manner. While sepsis resulted in increased splenic and decreased hepatic and circulating NKT cell populations, serial injections of apoE for 24 h after cecal ligation and puncture increased the frequency, cell number, and BrdU uptake in splenic and hepatic NKT cell populations, while concomitantly depleting these populations in the circulation. These changes were correlated with elevated alanine amino transferase levels, an indicator of liver injury. Interestingly, while sepsis increased hepatic T cell apoptosis and necrosis, apoE reversed these changes. apoE also promoted increases in predominantly Th1 cytokine levels in sera and a decrease in IL-4, the main NKT cell-derived Th2 cytokine. Consequently, apoE treatment is associated with increased sepsis-induced mortality, and increased NKT cell frequency and proliferation in the liver and spleen, with concomitant decreases in these NKT cell parameters in the peripheral circulation. apoE treatment also promoted a Th1 cytokine response, increased the degree of liver injury, and decreased apoptosis in hepatic lymphocytes.

This data from a large, single-center experience demonstrates that LT is the treatment of choice for FHF and results in durable survival. Analysis revealed 4 novel outcome predictors. Young children with rapid onset acute liver failure are a high-risk subpopulation. Unique to this study, cCrCl and PELD accurately predicted the end-points. This analysis identifies patient subpopulations requiring early aggressive intervention with LT.

Background Despite recent advances in intestinal transplantation (ITx), infection (INF) and acute cellular rejection (ACR) remain major causes of patient and graft loss. Studies in other solid-organ transplantations indicate that low levels of serum immunoglobulin G (IgG) negatively impact outcomes. To date, there have been no studies on IgG after ITx. Methods A retrospective review of an IgG measurement protocol in primary ITx recipients between 2007 and 2011 was undertaken. IgG levels were measured at the time of evaluation, transplantation, and at weekly intervals for 2 months. Hypogammaglobulinemia (HGG) was defined as IgG levels below the lower limit of the 95% confidence interval for age. Associations between HGG, INF, and ACR were tested, and the incidence and timing of INF and ACR were compared. Results Thirty-four patients were transplanted at a mean (SD) age of 12.4 (17.2) years. Most were Latino children with gastroschisis who received multivisceral grafts. Relative to pre-ITx levels, a statistically significant decrease in IgG levels was observed after ITx (PG0.05). Twenty patients (59%) developed HGG during the post-ITx period at a mean (SD) of 9.8 days. No significant associations were identified between HGG and INF or ACR. Conclusions This is the first study to describe serum IgG levels after ITx. A marked decrease in serum IgG levels was observed early on, in most patients. The etiology is potentially related to immunotherapy. HGG was not associated with INF or ACR, possibly related to the sample size and our practice of exogenous intravenous immunoglobulin replacement.