Patients listed for liver transplantation (LT) as status 1a currently receive the highest priority on the waiting list. The presence of acute on chronic liver failure (ACLF) with three or more organs failing (ACLF‐3) portends low survival without transplantation, which may not be reflected by the Model for End‐Stage Liver Disease‐Sodium (MELD‐Na) score. We compared short‐term waitlist mortality for patients listed status 1a and those with ACLF‐3 at listing. Data were analyzed from the United Network for Organ Sharing database, years 2002‐2014, for 3,377 patients listed status 1a and 5,099 patients with ACLF‐3. Candidates with ACLF were identified based on the European Association for the Study of the Liver Chronic Liver Failure Consortium criteria. MELD‐Na score was treated as a categorical variable of scores <36, 36‐40, and >40. We used competing risks regression to assess waitlist mortality risk. Evaluation of outcomes through 21 days after listing demonstrated a rising trend in mortality among ACLF‐3 patients at 7 days (18.0%), 14 days (27.7%), and 21 days (32.7%) (P < 0.001) compared to a stable trend in mortality among individuals listed as status 1a at 7 days (17.9%), 14 days (19.3%), and 21 days (19.8%) (P = 0.709). Multivariable modeling with adjustment for MELD‐Na category revealed that patients with ACLF‐3 had significantly greater mortality (subhazard ratio, 1.45; 95% confidence interval, 1.31‐1.61) within 14 days of listing compared to status‐1a candidates. Analysis of the interaction between MELD‐Na category and ACLF‐3 showed that patients with ACLF‐3 had greater risk of 14‐day mortality than status‐1a‐listed patients, across all three MELD‐Na categories. Conclusion: Patients with ACLF‐3 at the time of listing have greater 14‐day mortality than those listed as status 1a, independent of MELD‐Na score; these findings illustrate the importance of early transplant evaluation and consideration of transplant priority for patients with ACLF‐3.

Biologics are among the most commonly prescribed medications for several chronic inflammatory diseases. Tumor necrosis factor alpha inhibitors, more so than other agents, have been observed to cause drug-induced liver injury. Additionally, because the approval and popularity of checkpoint inhibitors have grown, similar patterns of liver injury have been documented, with a majority of cases describing immune-mediated hepatitis. Although the exact mechanism of injury is unknown, various host and medication characteristics play a role in the outcome of the molecular cascade invoked by biologics. Prognosis is usually favorable with cessation of the offending agent, but cases of acute liver failure requiring liver transplantation have also been observed. Therefore, algorithms have been created to assist clinicians in treating drug-induced autoimmune hepatitis, mostly with corticosteroids. Additionally, case reports have documented successfully rechallenging patients with a different biologic without recurrence of liver injury, but data are limited. Further investigation is warranted regarding the potential for cross-reactivity and mechanism of injury to develop guidelines to aid clinicians in further management of these patients. (Hepatology Communications 2020;4:172-184).

Summary Background Mortality for patients with acute‐on‐chronic liver failure (ACLF) may be underestimated by the model for end‐stage liver disease‐sodium (MELD‐Na) score. Aim To assess waitlist outcomes across varying grades of ACLF among a cohort of patients listed with a MELD‐Na score ≥35, and therefore having similar priority for liver transplantation. Methods We analysed the United Network for Organ Sharing (UNOS) database, years 2010‐2017. Waitlist outcomes were evaluated using Fine and Gray's competing risks regression. Results We identified 6342 candidates at listing with a MELD‐Na score ≥35, of whom 3122 had ACLF‐3. Extra‐hepatic organ failures were present primarily in patients with four to six organ failures. Competing risks regression revealed that candidates listed with ACLF‐3 had a significantly higher risk for 90‐day waitlist mortality (Sub‐hazard ratio (SHR) = 1.41; 95% confidence interval [CI] 1.12‐1.78) relative to patients with lower ACLF grades. Subgroup analysis of ACLF‐3 revealed that both the presence of three organ failures (SHR = 1.40, 95% CI 1.20‐1.63) or four to six organ failures at listing (SHR = 3.01; 95% CI 2.54‐3.58) was associated with increased waitlist mortality. Candidates with four to six organ failures also had the lowest likelihood of receiving liver transplantation (SHR = 0.61, 95% CI 0.54‐0.68). The Share 35 rule was associated with reduced 90‐day waitlist mortality among the full cohort of patients listed with ACLF‐3 and MELD‐Na score ≥35 (SHR = 0.59; 95% CI 0.49‐0.70). However, Share 35 rule implementation was not associated with reduced waitlist mortality among patients with four to six organ failures (SHR = 0.76; 95% CI 0.58‐1.02). Conclusions The MELD‐Na score disadvantages patients with ACLF‐3, both with and without extra‐hepatic organ failures. Incorporation of organ failures into allocation policy warrants further exploration.

BaCKgRoUND aND aIMS:We assessed the burden of nonalcoholic fatty liver disease (NAFLD)-related acute on chronic liver failure (ACLF) among transplant candidates in the United States, along with waitlist outcomes for this population.appRoaCH aND ReSUltS: We analyzed the United Network for Organ Sharing registry from 2005 to 2017. Patients with ACLF were identified using the European Association for the Study of the Liver/Chronic Liver Failure criteria and categorized into NAFLD, alcohol-associated liver disease (ALD), and hepatitis C virus (HCV) infection. We used linear regression and Chow's test to determine significance in trends and evaluated waitlist outcomes using Fine and Gray's competing risks regression and Cox proportional hazards regression. Between 2005 and 2017, waitlist registrants for NAFLD-ACLF rose by 331.6% from 134 to 574 candidates (P < 0.001), representing the largest percentage increase in the study population. ALD-ACLF also increased by 206.3% (348-1,066 registrants; P < 0.001), whereas HCV-ACLF declined by 45.2% (P < 0.001). As of 2017, the NAFLD-ACLF population consisted primarily of persons aged ≥60 years (54.1%), and linear regression demonstrated a significant rise in the proportion of patients aged ≥65 in this group (β = 0.90; P = 0.011). Since 2014, NAFLD-ACLF grade 1 was associated with a greater risk of waitlist mortality relative to ALD-ACLF (subhazard ratio [SHR] = 1.24; 95% confidence interval [CI], 1.05-1.44) and HCV-ACLF (SHR = 1.35; 95% CI, 1.08-1.71), among patients aged ≥60 years. Mortality was similar among the three groups for patients with ACLF grade 2 or 3.CoNClUSIoNS: NAFLD is the fastest rising etiology of cirrhosis associated with ACLF among patients listed in the United States. As the NAFLD population continues to grow and age, patients with NAFLD-ACLF will likely have the highest risk of waitlist mortality.

AIMTo avoid desensitization protocols and ABO incompatible kidney transplantation (KT) due to high costs and increased risk of infections from intense immunosuppression.METHODSWe present institutional ethical review board - approved study of single center 6-way kidney exchange transplantation. The participants comprised ABO incompatibility (n = 1); positive cross-match and/or presence of donor specific antibody (n = 5). The average time required from registration in kidney paired donation (KPD) registry to find suitable donors was 45 d and time required to perform transplants after legal permission was 2 mo.RESULTSGraft and patient survival were 100%, and 100%, respectively. One patient had biopsy-proven acute borderline T cell rejection (Banff update 2013, type 3). Mean serum creatinine was 0.8 mg/dL at 9 mo follow-up. The waiting time in KPD was short as compared to deceased donor KT.CONCLUSIONWe report first non-simultaneous, single center, 6-way kidney exchange transplantation from India. Our experience will encourage other centers in India to undertake this practice.

Rectal irrigation can be a useful tool in the management of functional bowel disorders and should be tried prior to the consideration of any surgery. However, further work is needed to define the precise indications and patient selection criteria.

BackgroundTo ascertain the validity of kidney paired donations (KPDs) as an alternative strategy for increasing living donor kidney transplantations (LDKTs) in an LDKT-dominated transplant programme since directed kidney transplantation, ABO-incompatible or crossmatch-positive pairs are not feasible due to costs and infectious complications.MethodsThis was a prospective single-centre study of 77 KPD transplantations (25 two-way, 7 three-way and 1 six-way exchange) from 1 January 2015 to 1 January 2016 of 158 registered donor recipient pairs. During this period, a total of 380 kidney transplantations [71 deceased donor kidney transplantations (DDKTs), 309 LDKTs] were performed. The reasons for opting for KPD were ABO incompatibility (n = 45), sensitization (n = 26) and better matching (n = 6).ResultsKPD matching was facilitated in 62% (n = 98) of transplants. In all, 48.7% (n = 77) of the transplants were completed in 2015, whereas 13.3% (n = 21) of the matched patients were to undergo transplant surgery in early 2016 after getting legal permission. The waiting time for KPD was shorter compared with DDKT. The death-censored graft survival and patient survival were 98.7% (n = 76) and 93.5% (n = 72), respectively. In all, 14.2% (n = 11) of patients had acute rejection. Match rates among sensitized (n = 60) and O group patients (n = 62) were 58.3% (n = 35) and 41.9% (n = 26), respectively. Of these, 43.3% (n = 26) and 29% (n = 18) of transplants were completed and 15% (n = 9) and 12.9% (n = 8), respectively, are waiting for legal permission.ConclusionsLDKT increased by 25% in 1 year in our single-centre KPD programme. Our key to success was the formation of a KPD registry, awareness and active counselling programs and developing a dedicated team.

Renal transplantation (RTx) has now become an accepted therapeutic modality of choice for elderly ESRD patients. This single-center study was undertaken to evaluate the outcome of RTx in ESRD patients ≥55 years. A total of 103 patients underwent RTx 79 living related living donors [LD], 24 deceased donors [DD]) at our center. Post-transplant immunosuppression consisted of calcineurin inhibitor–based regimen. The mean donor age was 58.3 years in the LD group and 59.5 years in the DD group. Male recipients constituted 92% in LD and 75% in DD group. In living donor renal transplantation, 1- and 5-year patient survival was 93% and 83.3% respectively and death-censored graft survival was 97.3% and 92.5% respectively. There were 12.6% biopsy proven acute rejection (BPAR) episodes and 12.6% patients were lost, mainly due to infections. In deceased donor renal transplantation, 1- and 5-year patient survival was 79.1% and 74.5% respectively and death-censored graft survival was 95.8% and 85.1% respectively. There were 12.5% BPAR episodes and 25% of patients were lost, mainly due to infections. RTx in ESRD (≥55 years) patients has acceptable patient and graft survival if found to have cardiac fitness and therefore should be encouraged.