Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

Emerging Biomarkers in Alcohol-associated Hepatitis.

Alcohol-associated hepatitis (AH) is a clinical syndrome of jaundice, abdominal pain, and anorexia due to prolonged heavy alcohol intake. AH is associated with changes in gene expression, cytokines, immune response, and the gut microbiome. There are limited biomarkers to diagnose and prognosticate in AH, but several non-invasive biomarkers are emerging. In this review, clinical risk-stratifying algorithms, promising AH biomarkers like cytokeratin-18 fragments, genetic polymorphisms, and microRNAs will be reviewed.

Acute Alcoholic Hepatitis.

Alcoholic hepatitis is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by prolonged heavy alcohol use. Treatment is mostly supportive. The short-term prognosis of acute alcoholic hepatitis depends on liver recovery, and ranges widely from rapid improvement to grim multiorgan failure despite treatment. Refinement of scoring systems have enhanced prognostication to guide clinical decision making in alcoholic hepatitis. Recent advances in the treatment of alcoholic hepatitis have solidified corticosteroids as the cornerstone of treatment to enhance short-term survival, but not intermediate or long-term survival.

Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis.

BACKGROUND & AIMS: Patients with severe alcoholic hepatitis (AH) have a high risk of death within 90 days. Corticosteroids, which can cause severe adverse events, are the only treatment that increases short-term survival. It is a challenge to predict outcomes of patients with severe AH. Therefore, we developed a scoring system to predict patient survival, integrating baseline molecular and clinical variables. METHODS: We obtained fixed liver biopsy samples from 71 consecutive patients diagnosed with severe AH and treated with corticosteroids from July 2006 through December 2013 in Brussels, Belgium (derivation cohort). Gene expression patterns were analyzed by microarrays and clinical data were collected for 180 days. We identified gene expression signatures and clinical data that are associated with survival without liver transplantation at 90 and 180 days after initiation of corticosteroid therapy. Findings were validated using liver biopsies from 48 consecutive patients with severe AH treated with corticosteroids, collected from March 2010 through February 2015 at hospitals in Belgium and Switzerland (validation cohort 1) and in liver biopsies from 20 patients (9 received corticosteroid treatment), collected from January 2012 through May 2015 in the United States (validation cohort 2). RESULTS: We integrated data on expression patterns of 123 genes and the model for end-stage liver disease (MELD) scores to assign patients to groups with poor survival (29% survived 90 days and 26% survived 180 days) and good survival (76% survived 90 days and 65% survived 180 days) (P < .001) in the derivation cohort. We named this assignment system the gene signature-MELD (gs-MELD) score. In validation cohort 1, the gs-MELD score discriminated patients with poor survival (43% survived 90 days) from those with good survival (96% survived 90 days) (P < .001). The gs-MELD score also discriminated between patients with a poor survival at 180 days (34% survived) and a good survival at 180 days (84% survived) (P < .001). The time-dependent area under the receiver operator characteristic curve for the score was 0.86 (95% confidence interval 0.73-0.99) for survival at 90 days, and 0.83 (95% confidence interval 0.71-0.96) for survival at 180 days. This score outperformed other clinical models to predict survival of patients with severe AH in validation cohort 1. In validation cohort 2, the gs-MELD discriminated patients with a poor survival at 90 days (12% survived) from those with a good survival at 90 days (100%) (P < .001). CONCLUSIONS: We integrated data on baseline liver gene expression pattern and the MELD score to create the gs-MELD scoring system, which identifies patients with severe AH, treated or not with corticosteroids, most and least likely to survive for 90 and 180 days.

A Real-World Evaluation of Repeat Paracentesis-guided Management of Spontaneous Bacterial Peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a common infection in cirrhosis associated with high mortality. More than 20% of patients with SBP do not respond to initial antibiotics. Guidelines differ in recommendations to repeat paracentesis (retap) to confirm antibiotic efficacy. We aim to evaluate the effect of retap-guided management of SBP on antibiotic escalation and 30-day transplant-free survival. MATERIALS AND METHODS: Retrospective cohort study of cirrhotic patients with SBP admitted to a single transplant center from 2010 to 2014. Patients were divided into 2 groups: retap-guided management versus no retap. Prevalence of initial antibiotic treatment failure, defined as <25% decrease in ascitic polymorphonuclear cells, and factors associated with treatment failure, antibiotic escalation and 30-day transplant-free survival were evaluated. RESULTS: Out of 210 patients, 146 (age 58, 74% male, mean model for end-stage liver disease score, 25) had retap and treatment failure was noted in 28 (22%). Gram-positive bacteria accounted for 44% of all positive cultures and third-generation cepahalosporin resistance was noted in 23%. Thirty-day transplant-free survival was 72% and 62% in retap and control groups, respectively (P=0.07). Treatment failure independently doubled the 30-day mortality rate (hazard ratio: 2.15, 1.03 to 4.50, P=0.04). After adjusting for age, model for end-stage liver disease and nosocomial infection, retap-guided management was not associated with improved survival (P=0.34). CONCLUSIONS: The prevalence of initial treatment failure is high (22%) in patients with SBP and doubles the 30-day mortality risk, supporting recommendations to retap all patients with SBP.

Surgery in patients with portal hypertension: a preoperative checklist and strategies for attenuating risk.

Patients with liver disease and portal hypertension are at increased risk of complications from surgery. Recent advances have allowed better optimization of patients with cirrhosis before surgery and a reduction in postoperative complications. Despite this progress, the estimation of surgical risk in a patient with cirrhosis is challenging. The MELD score has shown promise in predicting postoperative mortality compared with the Child-Turcotte-Pugh score. This article addresses current concepts in the perioperative evaluation of patients with liver disease and portal tension, including a preoperative liver assessment (POLA) checklist that may be useful towards mitigating perioperative complications.

A case of undulating fevers and elevated liver tests after pancreas-kidney transplantation.

The patient is a 50-year-old Caucasian woman with a history of a pancreas and two kidney transplants complicated by chronic rejection of her latest kidney allograft and currently undergoing hemodialysis, who was referred for fever of unknown origin and elevated liver tests. She suffered a self-limited acute diarrheal illness with fever 3 months prior to referral and then experienced a persistent, undulating fever pattern. An exhaustive evaluation involving many consultants was undertaken, but failed to determine the etiology of her symptoms. Given her history, persistently elevated liver tests, and abnormal but nonspecific liver biopsy findings, infection with hepatitis E virus (HEV) was entertained. Several serum and stool samples were sent to the Centers for Disease Control for detection of HEV that were positive and ultimately consistent with autochthonous chronic HEV infection. The patient was treated with ribavirin and achieved normalization of her transaminase activities and resolution of her fever after 1 month, and undetectable HEV polymerase chain reaction at treatment month 6 and 10, at which time treatment was stopped. There has been renewed interest in HEV in light of recent studies demonstrating the existence of a chronic form of HEV infection occurring in immunosuppressed patients, such as solid-organ-transplant recipients. This report highlights a case of chronic HEV infection in a pancreas-kidney-transplant recipient with an unusual clinical presentation and highlights the need for increased awareness of chronic HEV infection in the hepatology and transplant community.

High yield of same-session EUS-guided liver biopsy by 19-gauge FNA needle in patients undergoing EUS to exclude biliary obstruction.

BACKGROUND: EUS-guided liver biopsy by Trucut yields variable specimen adequacy at high cost, limiting its utility. A modified EUS-guided technique with reliable adequacy could be a viable alternative to standard techniques in cost-effective clinical settings. OBJECTIVE: To describe our experience with EUS-guided liver biopsy by 19-gauge FNA, non-Trucut, needle in a cost-effective setting: patients with abnormal liver test results of unclear etiology referred for EUS to exclude biliary obstruction in whom an unrevealing EUS would have prompted a next-step liver biopsy by the referring physician. DESIGN: Prospective case series. SETTING: Tertiary-care teaching hospital. PATIENTS: Consecutive patients with abnormal liver tests referred for EUS. INTERVENTIONS: EUS-guided liver biopsy by 19-gauge FNA needle (non-Trucut). MAIN OUTCOME MEASUREMENTS: Diagnostic yield, specimen adequacy, and complications. An adequate specimen was defined as a length of 15 mm or longer and 6 or more complete portal tracts (CPTs). RESULTS: Between July 2008 and July 2011, 22 of 31 consecutive patients meeting inclusion criteria underwent unrevealing EUS with same-session EUS-guided liver biopsy by 19-gauge FNA needle. A median of 2 FNA passes (range 1-3) yielded a median specimen length of 36.9 mm (range 2-184.6 mm) with a median of 9 CPTs (range 1-73 CPTs). EUS-guided liver biopsies yielded a histologic diagnosis and adequate specimens in 20 of 22 patients (91%). Expanded experience led to improved specimen adequacy. There were no complications. LIMITATION: Small study size. CONCLUSIONS: EUS-guided liver biopsy by using a 19-gauge FNA needle appears to be feasible and safe and provides excellent diagnostic yield and specimen adequacy.

A maxed-out liver: a case of acute-on-chronic liver failure.

A 51-year-old man from Puerto Rico with Child-Turcotte-Pugh Class C decompensated cirrhosis due to genotype 1a chronic hepatitis C was referred for worsening jaundice and diuretic-resistant ascites. He began experiencing symptoms of hepatic decompensation 5 months prior to referral with new-onset ascites and spontaneous bacterial peritonitis, evolving into diuretic-resistant ascites, increasing jaundice, and a MELD increase from 12 to 29. During his hospitalization, his MELD score increased to >40 from a rapidly increasing international normalized ratio (INR) and evolving type 1 hepatorenal syndrome. Clinically, the patient appeared quite well despite such a high MELD score. After an extensive pretransplant evaluation and exclusion of infection, he underwent successful orthotopic liver transplantation. After histologic examination of the explanted liver, he subsequently admitted to 5 months of daily use of a detoxifying supplement known as MaxOne (®), containing D-ribose- L-cysteine, consistent with a drug-induced acute-on-chronic liver failure. The use of complementary and alternative medicines and its potential for causing drug-induced liver injury and acute-on chronic liver failure requires a high index of suspicion and increased awareness among health care providers.