Development and First Clinical Use of an Extracorporeal Artificial Multiorgan System in Acute-on-Chronic Liver Failure Patients.

Multiple organ failure (MOF) is a common and deadly condition. Patients with liver cirrhosis with acute-on-chronic liver failure (AOCLF) are particularly susceptible. Excess fluid accumulation in tissues makes routine hemodialysis generally ineffective because of cardiovascular instability.

LIVER TRANSPLANTATION: WILL XENOTRANSPLANTATION BE THE ANSWER TO THE DONOR ORGAN SHORTAGE?

Since the first report of a successful liver transplant in 1968, access to this operation has dramatically improved. In 2018, 8,250 patients underwent liver transplantation in the United States. Despite this remarkable advance, a persistent shortage of donor organs remains the primary obstacle to optimal utilization of this life-saving operation.

Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data From Controlled Trials.

Background & Aims: We performed a meta-analysis of individual patient data from 11 randomized controlled trials comparing corticosteroids, pentoxifylline, or their combination in patients with severe alcoholic hepatitis. We compared the effects of the treatments on survival for 28 days or 6 months, and response to treatment based on the Lille model.

Methods: We searched PubMed for randomized controlled trials of pharmacologic therapy for severe alcoholic hepatitis.

Recent trends in liver transplantation for alcoholic liver disease in the United States.

Aim: To examine temporal changes in the indications for liver transplantation (LT) and characteristics of patients transplanted for alcoholic liver disease (ALD).

Methods: We performed a retrospective cohort analysis of trends in the indication for LT using the United Network for Organ Sharing (UNOS) database between 2002 and 2015. Patients were grouped by etiology of the liver disease and characteristics were compared using χ and -tests.

Hepatitis B Virus--Specific and Global T-Cell Dysfunction in Chronic Hepatitis B.

Background & Aims: T cells play a critical role in viral infection. We examined whether T-cell effector and regulatory responses can define clinical stages of chronic hepatitis B (CHB).

Methods: We enrolled 200 adults with CHB who participated in the National Institutes of Health-supported Hepatitis B Research Network from 2011 through 2013 and 20 uninfected individuals (controls).

D-MELD risk capping improves post-transplant and overall mortality under markov microsimulation.

Aim: To hypothesize that the product of calculated Model for End-Stage Liver Disease score excluding exception points and donor age (D-MELD) risk capping ± Rule 14 could improve post liver transplant and overall survival after listing.

Methods: Probabilities derived from the United Network for Organ Sharing database between 2002 and 2004 were used to simulate potential outcomes for all patients listed for transplantation. The Markov simulation was then modified by screening matches using a 1200 or 1600 D-MELD risk cap ± allowing transplants for Model for End-Stage Liver Disease (MELD) ≤ 14 (Rule 14).

Congestive hepatic fibrosis score: a novel histologic assessment of clinical severity.

Chronic right heart failure predisposes to hepatic passive congestion and centrizonal necrosis that may lead to hepatic fibrosis (cardiac sclerosis). Although there have been several studies on the histologic features of congestive hepatopathy, there is no available grading system. In this study we developed a novel grading system for congestive hepatic fibrosis.

Advancing the high throughput identification of liver fibrosis protein signatures using multiplexed ion mobility spectrometry.

Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications.

The HALOS-ND model: a step in the journey of predicting hospital length of stay after liver transplantation.

Hospital length of stay (LOS) after liver transplantation has been determined to correlate with liver disease severity, post-transplant survival rates, and transplant-associated costs. A patient's model for end-stage liver disease (MELD) score and an organ's Donor risk index (DRI) have both been found to be significant predictors of LOS, but these two factors alone are insufficient to form an accurate prediction. Previous studies have identified other factors predictive of LOS, which can be incorporated with MELD and DRI to create more specific results.

Phase I adjuvant trial of sorafenib in patients with hepatocellular carcinoma after orthotopic liver transplantation.

Background: Post-transplant hepatocellular carcinoma recurrence has been reported to be between 15-18% and is higher among patients with high-risk features (bilobar tumor, macrovascular invasion, or multifocality). There are no known treatments which reduce risk of recurrence post-transplant. Sorafenib is currently approved for the treatment of advanced hepatocellular carcinoma.

Clinical factors predicting readmission after orthotopic liver transplantation.

Hospitals with the highest readmission rates for high-cost conditions may be targeted for payment penalties. The primary aim of this study was to determine clinical predictors of 30-day readmission after discharge for patients undergoing orthotopic liver transplantation (OLT) at the University of Washington from January 2003 to October 2010. Secondary aims included the determination of predictors of institutional care after OLT and differences in survival between patients requiring 30-day readmission and patients not requiring 30-day readmission.

Proteome and computational analyses reveal new insights into the mechanisms of hepatitis C virus-mediated liver disease posttransplantation.

Unlabelled: Liver transplant tissues offer the unique opportunity to model the longitudinal protein abundance changes occurring during hepatitis C virus (HCV)-associated liver disease progression in vivo. In this study, our goal was to identify molecular signatures, and potential key regulatory proteins, representative of the processes influencing early progression to fibrosis. We performed global protein profiling analyses on 24 liver biopsy specimens obtained from 15 HCV(+) liver transplant recipients at 6 and/or 12 months posttransplantation.

Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant patients.

Unlabelled: Liver failure resulting from chronic hepatitis C virus (HCV) infection is a major cause for liver transplantation worldwide. Recurrent infection of the graft is universal in HCV patients after transplant and results in a rapid progression to severe fibrosis and end-stage liver disease in one third of all patients. No single clinical variable, or combination thereof, has, so far, proven accurate in identifying patients at risk of hepatic decompensation in the transplant setting.

The use of hepatitis B core antibody-positive donor livers does not appear to have a deleterious effect on graft survival in liver transplantation for hepatitis C.

Introduction: The use of hepatitis B core antibody-positive donor livers (HBcAb(+)) has steadily increased. According to a recent multivariate analysis of United Network for Organ Sharing (UNOS) data, there was no significant increase in the risk of using these donors. The increased risk among the hepatitis C virus (HCV)-positive subgroup noted in a univariate model disappeared upon multivariate analysis.

Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data.

Introduction: A meta-analysis was performed using individual patient data from the five most recent randomised controlled trials (RCTs) which evaluated corticosteroids in severe alcoholic hepatitis (Maddrey discriminant function (DF) ≥ 32 or encephalopathy). This approach overcomes limitations associated with the use of literature data and improves the relevance of the study and estimates of effect size.

Aims: To compare 28-day survival between corticosteroid- and non-corticosteroid-treated patients and to analyse the response to treatment using the Lille model.

Use of an automated clinical management system improves outpatient immunosuppressive care following liver transplantation.

Objective: Immunosuppressive therapy following transplantation, if not managed well, can lead to increased drug toxicity or rejection episodes. We investigated whether use of an automated clinical management system in our liver transplant program would improve clinical outcomes in managing transplant recipients' immunosuppressive medications.

Design: We performed a retrospective cohort study of two patient groups receiving liver transplants at our institution.

Genetic diversity of hepatitis C virus predicts recurrent disease after liver transplantation.

Approximately 20% of patients receiving liver transplants for end-stage hepatitis C rapidly develop severe allograph fibrosis within the first 24 months after transplant. Hepatitis C virus (HCV) variants were studied in 56 genotype-1-infected subjects with end-stage hepatitis C disease at the time before and 12 months after liver transplant, and post-transplant outcome was followed with serial liver biopsies. In 15 cases, pre-transplant HCV genetic diversity was studied in detail in liver (n=15), serum (n=15), peripheral blood mononuclear cells (n=13), and perihepatic lymph nodes (n=10).

Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1.

Background And Aims: Hepatitis C virus (HCV)-induced chronic inflammation may induce oxidative stress which could compromise the repair of damaged DNA, rendering cells more susceptible to spontaneous or mutagen-induced alterations, the underlying cause of liver cirrhosis and hepatocellular carcinoma. In the current study we examined the induction of reactive oxygen species (ROS) resulting from HCV infection and evaluated its effect on the host DNA damage and repair machinery.

Methods: HCV infected human hepatoma cells were analyzed to determine (i) ROS, (ii) 8-oxoG and (iii) DNA glycosylases NEIL1, NEIL2, OGG1.

Liver transplantation at the extremes of the body mass index.

Controversies exist regarding the morbidity and mortality of patients undergoing liver transplantation at the extremes of the body mass index (BMI). A review of the United Network for Organ Sharing database from 1987 through 2007 revealed 73,538 adult liver transplants. Patients were stratified into 6 BMI categories established by the World Health Organization: underweight, <18.

Should liver transplantation in patients with model for end-stage liver disease scores

Studies have shown that liver transplantation offers no survival benefits to patients with Model for End-Stage Liver Disease (MELD) scores View Article and Find Full Text PDF

Investigation of putative multisubtype hepatitis C virus infections in vivo by heteroduplex mobility analysis of core/envelope subgenomes.

The frequency that multiple different subtypes of hepatitis C virus (HCV) simultaneously infect a given individual is controversial. To address this question, heteroduplex mobility analysis (HMA) of portions of the HCV core and envelope 1 region was optimized for sensitive and specific detection of mixtures of HCV genomes of different genotype or subtype. Using the standard HCV genotyping approach of 5'-untranslated region (UTR) analysis, 28 of 374 (7.

Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival.

Background & Aims: Since February 27, 2002, patients with early-stage hepatocellular carcinoma (HCC) have received priority for liver transplantation in the United States under the Model for End-Stage Liver Disease (MELD) allocation system. We aimed to determine the impact of this system on liver transplantation for HCC.

Methods: Data were provided by the United Network for Organ Sharing on 19,404 first-time, cadaveric, adult liver transplantations performed in the United States between 2002 and 2007 and 15,906 performed between 1997 and 2002, an equal-duration period immediately preceding the MELD allocation system.

Clinical trial: interferon alpha-2b continuous long-term therapy vs. repeated 24-week cycles for re-treating chronic hepatitis C.

Background: Treatment options are limited for patients with hepatitis C virus who do not experience sustained viral eradication with pegylated interferon and ribavirin therapy.

Aim: To compare, in an open-label, randomized study, long-term continuous interferon alpha-2b treatment with repeated 24-week courses in patients with chronic hepatitis C virus that relapsed after prior interferon monotherapy.

Methods: A total of 499 patients received 24 weeks of interferon alpha-2b, 3 MIU administered 3 TIW.