R. Cutler Quillin

Interleukin-33 is hepatoprotective during liver ischemia/reperfusion in mice.

Interleukin (IL)‐33 is a recently identified member of the IL‐1 family that binds to the receptor, ST2L. In the current study, we sought to determine whether IL‐33 is an important regulator in the hepatic response to ischemia/reperfusion (I/R). Male C57BL/6 mice were subjected to 90 minutes of partial hepatic ischemia, followed by up to 8 hours of reperfusion. Some mice received recombinant IL‐33 (IL‐33) intraperitoneally (IP) before surgery or anti‐ST2 antibody IP at the time of reperfusion. Primary hepatocytes and Kupffer cells were isolated and treated with IL‐33 to assess the effects of IL‐33 on inflammatory cytokine production. Primary hepatocytes were treated with IL‐33 to assess the effects of IL‐33 on mediators of cell survival in hepatocytes. IL‐33 protein expression increased within 4 hours after reperfusion and remained elevated for up to 8 hours. ST2L protein expression was detected in healthy liver and was up‐regulated within 1 hour and peaked at 4 hours after I/R. ST2L was primarily expressed by hepatocytes, with little to no expression by Kupffer cells. IL‐33 significantly reduced hepatocellular injury and liver neutrophil accumulation at 1 and 8 hours after reperfusion. In addition, IL‐33 treatment increased liver activation of nuclear factor kappa light‐chain enhancer of activated B cells (NF‐κB), p38 mitogen‐activated protein kinase (MAPK), cyclin D1, and B‐cell lymphoma 2 (Bcl‐2), but reduced serum levels of CXC chemokines. In vitro experiments demonstrated that IL‐33 significantly reduced hepatocyte cell death as a result of increased NF‐κB activation and Bcl‐2 expression in hepatocytes. Conclusion: The data suggest that IL‐33 is an important endogenous regulator of hepatic I/R injury. It appears that IL‐33 has direct protective effects on hepatocytes, associated with the activation of NF‐κB, p38 MAPK, cyclin D1, and Bcl‐2 that limits liver injury and reduces the stimulus for inflammation. (HEPATOLOGY 2012)

Impact of recipient morbid obesity on outcomes after liver transplantation

The aim of this study was to analyze the impact of morbid obesity in recipients on peritransplant resource utilization and survival outcomes. Using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 12 445 patients who underwent liver transplantation (LT) between 2007 and 2011 and divided them into two cohorts based on recipient body mass index (BMI; <40 vs. ≥40 kg/m²). Recipients with BMI ≥40 comprised 3.3% (n = 416) of all LTs in the studied population. There were no significant differences in donor characteristics between two groups. Recipients with BMI ≥40 were significant for being female, diabetic, and with NASH cirrhosis. Patients with a BMI ≥40 had a higher median MELD score, limited physical capacity, and were more likely to be hospitalized at LT. BMI ≥40 recipients had higher post‐LT length of stay and were less often discharged to home. With a median follow‐up of 2 years, patient and graft survival were equivalent between the two groups. In conclusion, morbidly obese LT recipients appear sicker at time of LT with an increase in resource utilization but have similar short‐term outcomes.

Neighborhood level effects of socioeconomic status on liver transplant selection and recipient survival.

BACKGROUND & AIMS Previous studies have reported that patients of higher socioeconomic status (SES) have increased access to liver transplantation and reduced waitlist mortality than patients of lower SES. However, little is known about the association between SES and outcomes after liver transplantation. METHODS By using a link between the University HealthSystem Consortium and the Scientific Registry of Transplant Recipients databases, we identified 12,445 patients who underwent liver transplantation from 2007 through 2011. We used a proportional hazards model to assess the effect of SES on patient survival, controlling for characteristics of recipients, donors, geography, and center. RESULTS Compared with liver recipients in the lowest SES quintile, those in the highest quintile were more likely to be male, Caucasian, have private insurance, and undergo transplantation when they had lower Model for End-Stage Liver Disease scores. In proportional hazards model analysis, liver recipients of the lowest SES were at an increased risk for death within a median of 2 years after transplantation (hazard ratio, 1.17; 95% confidence interval, 1.02-1.35). CONCLUSIONS Patients of lower SES appear to face barriers to liver transplantation, but perioperative outcomes (length of stay, in-hospital mortality, or 30-day readmission) do not differ significantly from those of patients of higher SES. However, fewer patients of low SES survive for 2 years after transplantation, independent of features of the recipient, donor, surgery center, or location.

Variation by center and economic burden of readmissions after liver transplantation

The rate and causes of hospital readmissions after liver transplantation (LT) remain largely unknown in the United States. Adult patients (n = 11,937; 43.1% of all LT cases) undergoing LT from 2007 to 2011 were examined with a linkage of the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases to determine the incidence and risk factors for 30‐day readmissions and utilization metrics 90 days after LT. The overall 30‐day hospital readmission rate after LT was 37.9%, with half of patients admitted within 7 days after discharge. Readmitted patients had worse overall graft and patient survival with a 2‐year follow‐up. Multivariate analysis identified risk factors associated with 30‐day hospital readmission, including a higher Model for End‐Stage Liver Disease score, diabetes at LT, dialysis dependence, a high donor risk index allograft, and discharge to a rehabilitation facility. After adjustments for donor, recipient, and geographic factors in a hierarchical model, we found significant variation in readmission rates among hospitals ranging from 26.3% to 50.8% (odds ratio, 0.53‐1.90). In the 90‐day analysis after LT, readmissions accounted for

Is liver transplantation safe and effective in elderly (≥70 years) recipients? A case-controlled analysis

43,785 of added costs in comparison with patients who were not readmitted in the first 90 days. This is the first national report showing that more than one‐third of LT recipients are readmitted to their center within 30 days and that readmissions are associated with center variation and increased resource utilization. Liver Transpl 21:953‐960, 2015.

Cost effectiveness after a pancreaticoduodenectomy: bolstering the volume argument

BACKGROUND Elderly patients are evaluated for liver transplantation (LT) with increasing frequency, but outcomes in this group have not been well defined. METHODS A linkage of the Scientific Registry of Transplant Recipients (SRTR) and the University HealthSystem Consortium (UHC) databases identified 12,445 patients who underwent LT during 2007-2011. Two cohorts were created consisting of, respectively, elderly recipients aged ≥70 years (n = 323) and recipients aged 18-69 years (n = 12,122). A 1:1 case-matched analysis was performed based on propensity scores. RESULTS Elderly recipients had lower Model for End-stage Liver Disease (MELD) scores at LT (median 15 versus 19; P < 0.0001), more often underwent transplantation at high-volume centres (46% versus 33%; P < 0.0001) and more often received grafts from donors aged >60 years (24% versus 15%; P < 0.0001). The two cohorts had similar hospital lengths of stay, in-hospital mortality, hospital costs and 30-day readmission rates. There were no differences in graft survival between the two cohorts (P = 0.10), but elderly recipients had worse longterm overall survival (P = 0.009). However, a case-controlled analysis confirmed similar perioperative hospital outcomes, graft survival and longterm patient survival in the two matched cohorts. CONCLUSIONS Elderly LT recipients accounted for <3% of all LTs performed during 2007-2011. Selected elderly recipients have perioperative outcomes and survival similar to those in younger adults.

Hospital Resource Use with Donation after Cardiac Death Allografts in Liver Transplantation: A Matched Controlled Analysis from 2007 to 2011

BACKGROUND The cost implication of variability in pancreatic surgery is not well described. It was hypothesized that for a pancreaticoduodenectomy (PD), lower volume centres demonstrate worse peri-operative outcomes at higher costs. METHODS From 2009-2011, 9883 patients undergoing a PD were identified from the University HealthSystems Consortium (UHC) database and stratified into quintiles by annual hospital case volume. A decision analytic model was constructed to assess cost effectiveness. Total direct cost data were based on Medicare cost/charge ratios and included readmission costs when applicable. RESULTS The lowest volume centres demonstrated a higher peri-operative mortality rate (3.5% versus 1.3%, P < 0.001) compared with the highest volume centres. When both index and readmission costs were considered, the per-patient total direct cost at the lowest volume centres was

Independent effect of black recipient race on short-term outcomes after liver transplantation

23,005, or 10.9% (i.e.

In 10 years of debate: Pro-machine perfusion for liver preservation will be universal.

2263 per case) more than at the highest volume centres. One-way sensitivity analyses adjusting for peri-operative mortality (1.3% at all centres) did not materially change the cost effectiveness analysis. Differences in cost were largely recognized in the index admission; readmission costs were similar across quintiles. CONCLUSIONS For PD, low volume centres have higher peri-operative mortality rates and 10.9% higher cost per patient. Performance of PD at higher volume centres can lead to both better outcomes and substantial cost savings.

Hypothermic machine perfusion in liver transplantation

BACKGROUND Although donation after cardiac death (DCD) liver allografts have been used to expand the donor pool, concerns exist regarding primary nonfunction and biliary complications. Our aim was to compare resource use and outcomes of DCD allografts with donation after brain death (DBD) liver allografts. STUDY DESIGN Using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 11,856 patients who underwent deceased donor liver transplantation (LT) from 2007 to 2011. Patients were divided into 2 cohorts based on type of allograft (DCD vs DBD). Matched pair analysis (n = 613 in each group) was used to compare outcomes of the 2 donor types. RESULTS Donation after cardiac death allografts comprised 5.2% (n = 613) of all LTs in the studied cohort; DCD allograft recipients were healthier and had lower median Model of End-Stage Liver Disease (MELD) score (17 vs 19; p < 0.0001). Post LT, there was no significant difference in length of stay, perioperative mortality, and discharge to home rates. However, DCD allografts were associated with higher direct cost (