Influence of socioeconomic factors on liver transplant survival outcomes in patients with autoimmune liver disease in the United States.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILDs): autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) have different survival outcomes after liver transplant (LT). Outcomes are influenced by factors including disease burden, medical comorbidities, and socioeconomic variables. MATERIALS AND METHODS: Using the United Network for Organ Sharing database (UNOS), we identified 13,702 patients with AILDs listed for LT between 2002 and 2021. Outcomes of interest were waitlist removal, post-LT patient survival, and post- LT graft survival. A stepwise multivariate analysis was performed adjusting for transplant recipient gender, race, diabetes mellitus, model for end-stage liver disease (MELD) score, and additional social determinants including the presence of education, reliance on public insurance, working for income, and U.S. citizenship status. RESULTS: Lack of college education and having public insurance increased the risk of waitlist removal (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.09; 95 % CI, 1.00-1.18; respectively), and negatively influenced post-LT patient survival (HR, 1.16; 95 % CI, 1.06-1.26, and HR, 1.15; 95 % CI, 1.06-1.25; respectively) and graft survival (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.15; 95 % CI, 1.06-1.25; respectively). Not working for income proved to have the greatest detrimental impact on both patient survival (HR, 1.41; 95 % CI, 1.24-1.6) and graft survival (HR, 1.21; 95 % CI, 1.09-1.35). CONCLUSIONS: Our study highlights that lack of college education and public insurance have a detrimental impact on waitlist mortality, patient survival, and graft survival. Not working for income negatively affects post-LT survival outcomes. Not having U.S. citizenship does not affect survival outcomes in AILDs patients.

Living-Donor Liver Transplant and Improved Post-Transplant Survival in Patients with Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is the leading indication of liver transplantation (LT) among autoimmune liver disease patients. There is a scarcity of studies comparing survival outcomes between living-donor liver transplants (LDLT)s and deceased-donor liver transplants (DDLTs) in this population. Using the United Network for Organ Sharing database, we compared 4679 DDLTs and 805 LDLTs. Our outcome of interest was post-LT patient survival and post-LT graft survival. A stepwise multivariate analysis was performed, adjusting for recipient age, gender, diabetes mellitus, ascites, hepatic encephalopathy, cholangiocarcinoma, hepatocellular carcinoma, race, and the model for end-stage liver disease (MELD) score; donor' age and sex were also included to the analysis. According to univariate and multivariate analysis, LDLT had a patient and graft survival benefit compared to DDLT (HR, 0.77, 95% CI 0.65-0.92; p < 0.002). LDLT patient survival (95.2%, 92.6%, 90.1%, and 81.9%) and graft survival (94.1%, 91.1%, 88.5%, and 80.5%) at 1, 3, 5, and 10 years were significantly better than DDLT patient survival (93.2%, 87.6%, 83.3%, and 72.7%) and graft survival (92.1%, 86.5%, 82.1%, and 70.9%) (p < 0.001) in the same interval. Variables including donor and recipient age, male recipient gender, MELD score, diabetes mellitus, hepatocellular carcinoma, and cholangiocarcinoma were associated with mortality and graft failure in PSC patients. Interestingly, Asians were more protected than Whites (HR, 0.61; 95% CI, 0.35-0.99; p < 0.047), and cholangiocarcinoma was associated with the highest hazard of mortality (HR, 2.07; 95% CI, 1.71-2.50; p < 0.001) in multivariate analysis. LDLT in PSC patients were associated with greater post-transplant patient and graft survival compared to DDLT patients.

Management of Primary Biliary Cholangitis: Current Treatment and Future Perspectives.

Primary biliary cholangitis is an autoimmune cholestatic liver disease characterized by progressive destruction of bile ducts, which can ultimately progress to chronic liver disease and cirrhosis. Ursodeoxycholic acid and obeticholic acid are the only 2 Food and Drug Administration (FDA)-approved medications for primary biliary cholangitis. Unfortunately, up to 40% of patients with primary biliary cholangitis have an incomplete response to ursodeoxycholic acid, warranting an essential need for additional therapeutics. Peroxisome proliferator-activated receptor agonists have shown promising data supporting their use as disease-modifying therapies. Fibroblast growth factor-19 agonists, farnesoid X receptor agonists, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 3 inhibitors are additional agents under investigation as potential disease-modifying therapy. However, evidence supporting the use of certain novel therapies over others is sparse. There is a need for additional clinical trials as well as research aimed at the underlying pathophysiology of primary biliary cholangitis to discover additional therapeutic targets.

Early treatment with terlipressin in patients with hepatorenal syndrome yields improved clinical outcomes in North American studies.

Hepatorenal syndrome type 1 (HRS-1) is a serious complication of advanced cirrhosis and a potentially reversible form of acute kidney injury that is associated with rapidly deteriorating kidney function. Liver transplantation remains the only curative treatment for decompensated cirrhosis. However, terlipressin, a vasopressin analog, successfully reverses HRS-1, and may improve patient survival while awaiting liver transplantation. Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin. These post hoc analyses examined pooled data from 352 patients with HRS-1 treated with terlipressin in 3 North American-centric, Phase III, placebo-controlled clinical studies (i.e. OT-0401, REVERSE, and CONFIRM)-across 3 serum creatinine subgroups (i.e. <3, ≥3-<5, and ≥5 mg/dL)-to further delineate their correlation with HRS reversal, renal replacement therapy-free survival, and overall survival. Serum creatinine was significantly associated with HRS reversal in univariate and multivariate logistic regression analyses (P<0.001). The incidence of HRS reversal inversely correlated with serum creatinine subgroup (<3 mg/dL, 49.2%; ≥3-<5 mg/dL, 28.0%; ≥5 mg/dL, 9.1%). At Day 30 follow-up, renal replacement therapy-free survival was significantly higher for patients with HRS-1 in the lower serum creatinine subgroups than in the higher subgroup (<5 vs. >5 mg/dL; p=0.01). Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival (p<0.001) and higher transplant-free survival at Day 90 (p=0.04). Patients with HRS-1 and lower serum creatinine levels who were treated with terlipressin had higher HRS reversal and survival outcomes, highlighting the significant need to identify and treat patients with HRS-1 early when they often have lower serum creatinine levels, and likely a greater response to terlipressin.

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation.

BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001). CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Echocardiographic and Other Preprocedural Predictors of Heart Failure After TIPS Placement in Patients With Cirrhosis: A Single-Center 15-Year Analysis.

BACKGROUND. Heart failure (HF) is an uncommon complication after TIPS placement; its development represents a poor prognostic factor. OBJECTIVE. The purpose of our study was to evaluate the frequency, risk factors, and association with survival of HF developing within 90 days after TIPS placement in patients with cirrhosis. METHODS. This retrospective single-center study included patients with cirrhosis who underwent nonemergent covered-stent TIPS placement from June 2003 to December 2018 and who underwent echocardiography within 2 months before TIPS placement and had at least 90 days of post-TIPS follow-up. Development of HF within 90 days after TIPS was recorded. Frequency of TIPS reduction for post-TIPS HF was determined. Univariable logistic regression analysis and ROC curve analysis were performed to assess potential risk factors for post-TIPS HF. Association of post-TIPS HF and 1-year survival was assessed by the log rank test. RESULTS. The study sample included 107 patients (71 men and 36 women; median age, 58 years). Post-TIPS HF developed in 11 of 107 (10%) patients; median time to development of HF was 16 days (range, 2-62 days). Of these 11 patients, three (27%) required TIPS reduction to achieve resolution of HF symptoms after unsuccessful diuretic therapy. Pre-TIPS right atrium size (odds ratio [OR], 3.26 [95% CI, 1.22-10.16]; p = .03], left ventricle (LV) end-systolic dimension (OR, 5.43 [95% CI, 1.44-24.50], p = .02), LV end-diastolic dimension (OR, 4.12 [95% CI, 1.51-13.47]; p = .009), and estimated peak pulmonary artery systolic pressure (PASP) (OR, 1.27 [95% CI, 1.12-1.50]; p = .001) were associated with post-TIPS HF. AUC of right atrium size, LV end-systolic dimension, LV end-diastolic dimension, and estimated peak PASP for development of post-TIPS HF were 0.71, 0.74, 0.72, and 0.83, respectively. At a cutoff of 31 mm Hg, PASP achieved sensitivity of 70% and specificity of 86% for post-TIPS HF. Patients with post-TIPS HF and those without post-TIPS HF had 1-year survival of 46% versus 73% (p = .06). CONCLUSION. Multiple pre-TIPS echocardiographic variables predict the development of post-TIPS HF in patients with cirrhosis. CLINICAL IMPACT. Preprocedural echocardiography may guide risk stratification in patients with cirrhosis being considered for TIPS placement.

Increased Posttransplant Mortality for Autoimmune Hepatitis Compared With Other Autoimmune Liver Diseases.

GOALS: We sought to compare posttransplant outcomes between autoimmune liver disease. BACKGROUND: Autoimmune liver diseases, namely primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) generally have favorable posttransplant outcomes. PSC is known to require more retransplantation compared with PBC, however, comparisons to AIH are lacking. We sought to compare graft survival and the need for retransplant in AIH compared with other autoimmune liver disease. STUDY: We compared posttransplant graft survival among the 3 entities using Cox regression and competing for risk analyses using the United Network for Organ Sharing (UNOS) database. RESULTS: We found AIH is associated with significantly decreased graft survival compared with PBC [hazard ratio: 0.86; 95% confidence interval (CI): 0.77-0.96] and PSC (hazard ratio: 0.89; 95% CI: 0.8-0.99) after controlling for potential confounders. This is mainly driven by posttransplant death. On competing for risk analysis, AIH was associated with higher risk of death compared with PBC [subdistribution hazard ratio (SHR): 0.79; 95% CI: 0.7-0.89] and PSC (SHR: 0.72; 95% CI: 0.64-0.82) and lower risk of retransplant compared with PSC (SHR: 1.48; 95% CI: 1.19-1.8). CONCLUSION: As prior studies have shown the similar risk of disease recurrence in AIH and PSC, our study indicates at least part of the increased posttransplant mortality in AIH may be due lower retransplantation rate in this population.

Hyperlipidaemia in primary biliary cholangitis: treatment, safety and efficacy.

Primary biliary cholangitis (PBC) is an autoimmune liver disease associated with altered lipoprotein metabolism, mainly cholesterol. Hypercholesterolaemia, a major modifiable risk factor for cardiovascular disease in the general population, occurs in 75%-95% of individuals with PBC. The impact of hypercholesterolaemia on cardiovascular risk in PBC, however, is controversial. Previous data have shown that hypercholesterolaemia in PBC is not always associated with an increase in cardiovascular events. However, patients with PBC with cardiovascular risk factors may still warrant cholesterol-lowering therapy. Treatment of hypercholesterolaemia in PBC poses unique challenges among primary care providers due to concerns of hepatotoxicity associated with cholesterol-lowering medications. This review summarises the current understanding of the pathophysiology of hypercholesterolaemia in PBC and its pertinent cardiovascular risk. We will also discuss indications for treatment and the efficacy and safety of available agents for hypercholesterolaemia in PBC.

Evidence of Significant Ceftriaxone and Quinolone Resistance in Cirrhotics with Spontaneous Bacterial Peritonitis.

OBJECTIVES: There are few studies addressing the impact of cephalosporin and quinolone resistance on hospital length of stay and mortality in spontaneous bacterial peritonitis (SBP). We aim to describe the shifting epidemiology of SBP at our institution and its impact on clinical outcomes. METHODS: We performed a single-center retrospective cohort study of all cases of SBP from 2005 to 2015 at a transplant center. Cases were identified using hospital billing data. Patient data were confirmed using the electronic medical record. Univariate and multivariate logistic regression and Cox proportional hazards models were used to identify factors that were associated with prolonged hospital length of stay and reduced survival. Culture-positive cases (N = 56) were compared to culture-negative cases (N = 104). Subpopulation analysis of the culture-positive cases compared ceftriaxone-resistant (N = 25) to ceftriaxone-susceptible (N = 31) cases. RESULTS: We identified 160 cases of SBP (56 culture positive and 104 culture negative; 21 nosocomial, 79 hospital associated, and 60 community acquired). Forty-five percent (N = 25 total, 13 hospital associated and 6 nosocomial) of bacterial isolates were resistant to ceftriaxone, with 37.5% (N = 21) being gram positive, including 8 methicillin-resistant staphylococcus and 6 vancomycin-resistant enterococcus. Multivariate analysis identified hospital-associated SBP, age, alcoholic cirrhosis, and MELD-Na score as variables associated with worse survival (P < 0.05), with a trend toward worse survival in culture-positive cases (P = 0.123). Only MELD-Na was associated with prolonged length of stay. CONCLUSIONS: The burden of resistant pathogens causing SBP is significant, notably in hospital-associated SBP. Culture-positive SBP may represent a higher risk group compared to culture-negative SBP.

Treatment of Fatigue in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Fatigue is the most common complication of primary biliary cholangitis (PBC) and can be debilitating. Numerous interventions have been trialed targeting several proposed mechanisms of PBC-associated fatigue. We sought to summarize and perform a meta-analysis to determine the efficacy of these interventions. METHODS: A comprehensive database search was conducted from inception through March 27, 2018. The primary outcome was proportion of fatigued patients or reduction in degree of fatigue. Adverse events were a secondary outcome. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same class. RESULTS: We identified 16 studies evaluating ursodeoxycholic acid (UDCA) (7), liver transplantation (2), serotonin reuptake inhibitors (2), colchicine (1), methotrexate (1), cyclosporine (1), modafinil (1), and obeticholic acid (1). On meta-analysis, UDCA was not associated with a reduction in risk of fatigue (RR = 0.86, 95% CI 0.69-1.08, p = 0.19, I2 = 56.2%). While liver transplantation did reduce degree of fatigue (SMD - 0.57, 95% CI - 0.89 to - 0.24, p = 0.001, I2 = 67.3%), fatigue did not return to baseline indicating the underlying cause may not be addressed. CONCLUSIONS: While there is some improvement in fatigue with liver transplantation, there is a lack of high-quality evidence supporting the efficacy of any other intervention in the treatment of PBC-related fatigue. Further research into the underlying pathophysiology may help guide future trials.

A Multicenter Study Into Causes of Severe Acute Liver Injury.

The differential diagnosis of an increase in alanine aminotransferase (ALT) level and/or aspartate aminotransferase (AST) level of ≥1000 IU/L often is stated to include 3 main etiologies: ischemic hepatitis, acute viral hepatitis (typically hepatitis A and hepatitis B), and drug-induced (more specifically, acetaminophen/paracetamol) liver injury (DILI).1 Unfortunately, there are a paucity of studies examining the most common causes of acute liver injury (ALI) and those that have been published have been small,2 single-center,2 or examined less severe increases in ALT or AST levels.3,4 We conducted a multicenter study of all patients with an ALT and/or AST level ≥1000 IU/L. Our study had 3 main goals: (1) to determine the most common causes of an ALT and/or AST level ≥1000 IU/L, along with their relative frequencies; (2) to determine differences in etiology based on hospital type (liver transplant center, community hospital, Veterans Affairs hospital); and (3) to confirm or disprove the differential heuristic that ischemic hepatitis, acute viral hepatitis, and acetaminophen toxicity are the most common etiologies.

Chronic hepatitis C infection - Noninvasive assessment of liver fibrosis in the era of direct acting antivirals.

Significant advancements in the diagnosis and treatment of chronic hepatitis C infection and its associated fibrosis have revolutionized treatment of these patients over the last several years. Liver biopsy, the gold standard diagnostic method for evaluating liver fibrosis level, was routinely used prior to initiation of hepatitis C therapy, placing patients at an inherent risk of adverse events. The recent advent of noninvasive serologic and nonserologic measures of hepatic fibrosis level has reduced the need for liver biopsy significantly, thereby minimizing its associated risks. These noninvasive methods have been extensively studied in the era of interferon therapies and are increasingly recognized in the realm of direct acting antiviral agents as well. Their validation of use after having achieved a sustained virologic response is yet to occur, but the future remains promising. This review focuses on the various non-invasive diagnostic modalities of liver fibrosis and discusses how they can be applied to the care of patients undergoing direct acting antiviral therapy for hepatitis C. In the constantly evolving landscape of hepatitis C therapy, the review underscores the important prognostic value of fibrosis staging prior to HCV treatment and suggests potential uses for non-invasive fibrosis assessment following successful HCV eradication.

Expanding the differential diagnosis for transaminitis in patients with anorexia nervosa.

Aminotransferase elevations have been described in patients with anorexia nervosa. Hypothesized etiologies have included ischemic hepatitis, refeeding-induced transaminitis, and the process of autophagy. Supervised enteral nutrition is the mainstay of treatment for severe anorexia, but an increase in aminotransferase levels after initiation of enteral feeding presents clinicians with a diagnostic dilemma. We present a 31-year-old woman with anorexia nervosa (body mass index [BMI] of 13.5 kg/m2) who experienced a worsening of aminotransferase elevations even after the initiation of enteral feeding. Despite nutritional supplementation, the patient's weight continued to fall for 6 days. Peak aminotransferase concentrations correlated with the patient's lowest weight and improved only after an increase in BMI was eventually achieved. Secondary causes of severe transaminitis were investigated, and after no cause was found, a liver biopsy was performed. Pathology was consistent with liver injury secondary to severe malnutrition rather than from refeeding syndrome. This case highlights malnutrition as an important cause of aminotransferase elevations and underscores the need for judicious early weight restoration in patients with anorexia and abnormal liver chemistry.

Serum Ammonia is Associated With Transplant-free Survival in Hospitalized Patients With Acutely Decompensated Cirrhosis [corrected].

BACKGROUND: As ammonia metabolism is a complex multiorgan process, we sought to determine whether serum ammonia concentrations were associated with transplant-free survival in patients with acutely decompensated cirrhosis and acute-on-chronic liver failure (ACLF). METHODS: We studied 494 consecutive patients hospitalized with cirrhosis between April 2007 and September 2012 with venous ammonia measured on hospital admission. The primary outcome was transplant-free survival. RESULTS: Overall, rates of death or transplant within 30 and 90 days were 23.1% (n=114) and 37.7% (n=186), respectively. Forty-six patients (9.2%) underwent liver transplantation within 90 days. In a multivariate Cox proportional hazards model, ammonia concentration was independently associated with death or transplantation within 30 and 90 days after adjusting for model for end-stage liver disease, sodium, white blood cells, and number of ACLF organ failures; every doubling of ammonia was associated with respective hazard ratios of 1.22 (95% confidence interval, 1.03-1.38) and 1.21 (95% confidence interval, 1.04-1.44) for 90- and 30-day transplant or mortality. Notably, after adjusting for ammonia, organ failures were not predictive of outcomes. In a Kaplan-Meier analysis, patients with admission ammonia concentrations >60 µmol/L had significantly lower 90-day transplant-free survival (P=0.0004). Patients with admission ammonia concentrations >60 µmol/L had higher 90- and 30-day risk of death or transplantation (45.2% vs. 31.2%, P=0.001; and 31.6% vs. 15.7%, P<0.0001, respectively). CONCLUSION: For patients with acutely decompensated cirrhosis, an elevated serum ammonia concentration on admission is associated with reduced 90-day transplant-free survival after adjusting for established predictors.

Fellowship Colonoscopy Training and Preparedness for Independent Gastroenterology Practice.

GOALS: To objectively assess when gastroenterology (GI) fellows achieve technical competency to perform colonoscopy independently. BACKGROUND: New guidelines to assess the procedural competency of GI fellows in training have been developed. Although comprehensive, they do not account for the quality metrics to which independently practicing gastroenterologists are held. STUDY: We performed a prospective study examining consecutive colonoscopies performed by GI fellows from November 2013 through March 2014 at an academic medical center. Using a brief postprocedure questionnaire and the online medical record, we measured rates of independent fellow cecal intubation rate (CIR), insertion time to the cecum (cecal IT), and independent polypectomy rate. Our secondary outcomes were adenoma detection rate and polyp detection rate. RESULTS: A total of 898 colonoscopies performed by 10 GI fellows were analyzed. In the multivariate analysis, CIR [odds ratio (OR)=1.29, P=0.012], cecal IT (ß-coefficient=0.19, P=0.006), and rates of unassisted independent snare polypectomy (OR=1.36, P<0.001) all improved significantly with increased number of procedures performed (OR and ß-coefficient per 100 colonoscopies performed). After performing 500 colonoscopies, fellows achieved a mean CIR>90%, cecal IT between 7 and 10 minutes, and independent polypectomy rate of 90% with further improvement in cecal IT to <7 minutes, and independent snare polypectomy of >95% after 700 cases. CONCLUSIONS: Current procedural recommendations for fellowship training may underestimate the technical skill necessary for independent GI practice upon completion of fellowship. Technical proficiency in snare polypectomy may lag behind proficiency in cecal intubation.

High Glasgow Blatchford Score at admission is associated with recurrent bleeding after discharge for patients hospitalized with upper gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: Upper gastrointestinal bleeding (UGIB) is associated with significant morbidity. The Glasgow Blatchford Score (GBS) can predict endoscopic intervention and in-hospital death, but the ability to predict post-discharge outcomes is unknown. The aims of the study were to determine whether the admission GBS is associated with post-discharge rebleeding and 30-day readmission following hospitalization for UGIB. PATIENTS AND METHODS: In this prospective, observational, cohort study, consecutive patients who were hospitalized with UGIB were enrolled. Admission GBS scores were calculated, and patients with GBS > 7 were classified as high risk. Patients were contacted 30 days following discharge to determine: 1) rate of hospital readmission due to rebleeding, 2) all-cause readmissions, and 3) mortality. Multivariable Cox regression was used to determine associations between GBS, rebleeding, and readmission. RESULTS: A total of 336 patients with UGIB were identified. Patients with high risk GBS were older (68 vs. 62 years; P = 0.01), and were more likely to receive blood (85 % vs. 39 %; P < 0.01) and require intensive care unit admission (64 % vs. 50 %; P = 0.02). Of the 309 patients who survived to discharge, 61 (20 %) were readmitted within 30 days, 25 (8 %) of whom had rebleeding. On multivariable analysis adjusting for the need for endoscopic intervention, high risk GBS patients had higher rebleeding rates (hazard ratio [HR] 3.32, 95 % confidence interval [CI] 1.26 - 11.4). On multivariable analysis, patients with more co-morbidities (HR 1.06, 95 %CI 1.01 - 1.11) and cirrhosis (HR 2.23, 95 %CI 1.19 - 4.04) had higher 30-day readmission rates. CONCLUSIONS: High GBS scores were associated with higher rebleeding rates following discharge. Patients with high GBS scores (> 7) should be monitored following discharge as they have a high risk of rebleeding.

Risk Factors for Adverse Outcomes in Patients Hospitalized With Lower Gastrointestinal Bleeding.

OBJECTIVE: To determine which risk factors and subtypes of lower gastrointestinal bleeding (LGIB) are associated with adverse outcomes after hospital discharge (30-day readmissions, recurrent LGIB, and death). PATIENTS AND METHODS: We conducted a prospective observational study of consecutive patients admitted with LGIB to Beth Israel Deaconess Medical Center from April 1, 2013, through March 30, 2014. Patients were contacted 30 days after discharge to determine hospital readmissions, recurrent LGIB, and death. Multivariable Cox proportional hazards regression models were used to describe associations of variables with 30-day readmissions or recurrent LGIB. Logistic regression was used to determine association with mortality. RESULTS: There were 277 patients hospitalized with LGIB. Of the 271 patients surviving to discharge, 21% (n=57) were readmitted within 30 days, 21 of whom were admitted for recurrent LGIB. The following factors were associated with 30-day readmissions: developing in-hospital LGIB (hazard ratio [HR], 2.26; 95% CI, 1.08-4.28), anticoagulation (HR, 1.82; 95% CI, 1.05-3.10), and active malignancy (HR, 2.33; 95% CI, 1.11-4.42). Patients discharged while taking anticoagulants had higher rates of recurrent bleeding (HR, 2.93; 95% CI, 1.15-6.95). Patients with higher Charlson Comorbidity Index scores (odds ratio [OR], 1.57; 95% CI, 1.25-2.08), active malignancy (OR, 6.57; 95% CI, 1.28-28.7), and in-hospital LGIB (OR, 11.5; 95% CI, 2.56-52.0) had increased 30-day mortality risk. CONCLUSION: In-hospital LGIB, anticoagulation, and active malignancy are risk factors for 30-day readmissions in patients hospitalized with LGIB. In-hospital LGIB, Charlson Comorbidity Index scores, and active malignancy are risk factors for 30-day mortality.

Reappraisal of the hepatitis C virus-positive donor in solid organ transplantation.

PURPOSE OF REVIEW: Hepatitis C virus (HCV)-positive donor allografts may be considered for HCV-positive recipients, but are underutilized. With new effective antiviral treatments, we aim to review data on the use of HCV-positive allografts in solid organ transplantation and place them in the context of the changing HCV landscape. RECENT FINDINGS: Hepatitis C is the most common indication for liver transplant in the USA and Europe and a significant comorbidity in patients on the waitlist for nonliver solid organ transplantation. Patients with HCV on the waitlist for nonliver solid organ transplantation have worse outcomes compared with those without HCV. However, survival after transplantation is improved compared with those who remain on the waitlist. There has been concern that use of HCV-positive allografts would lead to worse post-transplant outcomes. However, more recent data suggest that transplant outcomes for recipients who accept HCV-positive donor allografts may be comparable with those who receive HCV-negative allografts. Emerging treatments to eradicate HCV have further improved the course of HCV-positive individuals, with improved efficacy and reduced side-effects. SUMMARY: In view of the changing landscape of hepatitis C treatment and reduced wait time on the transplant waiting lists for those accepting HCV-positive donors, future use of select HCV-positive donors in solid organ transplantation should be encouraged.

Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy.

Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the ammonia hypothesis to account for these other factors instructs a solid foundation for the effective treatment and prevention of hepatic encephalopathy.

Low yield and utilization of confirmatory testing in a cohort of patients with liver disease assessed for alpha-1 antitrypsin deficiency.

BACKGROUND: Alpha-1 antitrypsin (AAT) deficiency is often evaluated in patients with liver disease of unknown etiology. AIMS: We aimed to describe the practice and yield of AAT testing at a large clinical laboratory. METHODS: This is the retrospective cohort study of all patients with AAT measurements at one major clinical laboratory between 2003 and 2012. RESULTS: AAT was measured in 4,985 patients by more than 339 physicians. Eight (0.16 %) patients were found to have AAT deficiency disease. Low AAT levels were associated with two clinical factors. Aspartate aminotransferase (>40 IU/L) was inversely related, odds ratio (OR) 0.53, 95 % CI (0.32-0.88), while comorbid pulmonary disease was positively correlated, OR 4.00, 95 % CI (1.37-9.30). Non-directed testing was common. More than 90 % of patients with ALT > 40 were simultaneously assessed for AAT deficiency, hepatitis B or C, hemochromatosis, and autoimmune hepatitis. Rates of phenotype utilization were low for patients with low AAT (23, 31.5 %). Phenotype utilization was inversely related to the practice of simultaneous testing for simultaneous autoimmune hepatitis [OR 0.34 (95 % CI 0.13-0.88)], hepatitis B [OR 0.32 (95 % CI 0.11-0.89)], hepatitis C [OR 0.36 (95 % CI 0.13-1.00)], and Wilson disease evaluation [OR 0.35 (95 % CI 0.14-0.92)]. CONCLUSION: The yield of AAT testing for patients with elevated liver enzymes is low. Utilization of phenotype testing is low and related to non-directed liver testing patterns. These data suggest a role for guidelines and laboratory protocols to encourage directed testing and phenotype utilization.