Michael L. Volk

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation

The availability of direct‐acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end‐stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV‐viremic patients into non–HCV‐viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C–infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

Performance-based measures associate with frailty in patients with end-stage liver disease.

Background Physical frailty, as measured by the Fried Frailty Index, is increasingly recognized as a critical determinant of outcomes in patients with cirrhosis. However, its utility is limited by the inclusion of self-reported components. We aimed to identify performance-based measures associated with frailty in patients with cirrhosis. Methods Patients with cirrhosis, aged 50 years or older, underwent: 6-minute walk test (cardiopulmonary endurance), chair stands in 30 seconds (muscle endurance), isometric knee extension (lower extremity strength), unipedal stance time (static balance), and maximal step length (dynamic balance/coordination). Linear regression associated each physical performance test with frailty. Principal components exploratory factor analysis evaluated the interrelatedness of frailty and the 5 physical performance tests. Results Of 40 patients with cirrhosis, with a median age of 64 years and Model for End-stage Liver Disease (MELD) MELD of 12.10 (25%) were frail by Fried Frailty Index ≥3. Frail patients with cirrhosis had poorer performance in 6-minute walk test distance (231 vs 338 m), 30-second chair stands (7 vs 10), isometric knee extension (86 vs 122 Newton meters), and maximal step length (22 vs 27 in. (P ⩽ 0.02 for each). Each physical performance test was significantly associated with frailty (P < 0.01), even after adjustment for MELD or hepatic encephalopathy. Principal component factor analysis demonstrated substantial, but unique, clustering of each physical performance test to a single factor—frailty. Conclusions Frailty in cirrhosis is a multidimensional construct that is distinct from liver dysfunction and incorporates endurance, strength, and balance. Our data provide specific targets for prehabilitation interventions aimed at reducing frailty in patients with cirrhosis in preparation for liver transplantation.

Palliative care for patients with end‐stage liver disease: An overview

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Analysis of Liver Offers to Pediatric Candidates on the Transplant Wait List

BACKGROUND & AIMSnApproximately 10% of children on the liver transplant wait-list in the United States die every year. We examined deceased donor liver offer acceptance patterns and their contribution to pediatric wait-list mortality.nnnMETHODSnWe performed a retrospective cohort study of children on the US liver transplant wait-list from 2007 through 2014 using national transplant registry databases. We determined the frequency, patterns of acceptance, and donor and recipient characteristics associated with deceased donor liver organ offers for children who died or were delisted compared with those who underwent transplantation. Children who died or were delisted were classified by the number of donor liver offers (0 vs 1 or more), limiting analyses to offers of livers that were ultimately transplanted into pediatric recipients. The primary outcome was death or delisting on the wait-list.nnnRESULTSnAmong 3852 pediatric liver transplant candidates, children who died or were delisted received a median 1 pediatric liver offer (inter-quartile range, 0-2) and waited a median 33 days before removal from the wait-list. Of 11,328 donor livers offered to children, 2533 (12%) were transplanted into children; 1179 of these (47%) were immediately accepted and 1354 (53%) were initially refused and eventually accepted for another child. Of 27,831 adults, 1667 (6.0%; median, 55 years) received livers from donors younger than 18 years (median, 15 years), most (97%) allocated locally or regionally. Of children who died orxa0were delisted, 173 (55%) received an offer of 1 or more liver that was subsequently transplanted into another pediatric recipient, and 143 (45%) died or were delisted with no offers.nnnCONCLUSIONSnAmong pediatric liver transplant candidates in the US, children who died or were delisted received a median 1 pediatric liver offer and waited a median of 33 days. Of livers transplanted into children, 47% were immediately accepted and 53% were initially refused and eventually accepted for another child. Of children who died or were delisted, 55% received an offer of 1 or more liver that was subsequently transplanted into another pediatric recipient, and 45% died or were delisted with no offers. Pediatric prioritization in the allocation and development of improved risk stratification systems is required to reduce wait-list mortality among children.

Strategies to Reduce 30-Day Readmissions in Patients with Cirrhosis

Purpose of ReviewApproximately, one quarter of patients discharged after a hospitalization for decompensated cirrhosis will be readmitted within 30xa0days. These readmissions have been associated with increased morbidity and mortality, can be financially harmful to the health system, and may be partially preventable. This review summarizes the literature on readmissions, providing clinicians with tools for risk prediction and a taxonomy for preventative interventions.Recent FindingsReadmission strategies can be categorized according to complexity (simple versus complex) and specificity (focused versus broad). The literature thus far provides the following generalizable inferences: 1) Interventions should be integrated in the clinical workflow, 2) default options are more powerful than voluntary actions, 3) knowledge improvement should focus on the front line clinicians, 4) process improvements do not always translate into better outcomes, and 5) any successful intervention must include viable alternatives to hospitalization.SummaryA growing body of literature provides concrete and actionable guidance for interventions to reduce readmissions in patients with cirrhosis.

The "pHS Increased Risk" Label Is Associated with Nonutilization of Hundreds of Organs per Year

Background The Public Health Service “Increased Risk” (PHS IR) designation identifies donors at increased risk of transmitting hepatitis B, C, and human immunodeficiency virus. Although the risk remains very low in the era of nucleic acid testing, we hypothesized that this label may result in decreased organ utilization. Methods Organ Procurement and Transplantation Network data were used to compare utilization rates between PHS-IR and non–PHS-IR donors, as well as to compare export rates and variation in utilization. Results Among adult standard criteria donors between 2010 and 2013 with a known PHS-IR status, covariate-adjusted utilization rates were lower among PHS-IR donors than non–PHS-IR donors for all organs. For example, 4073 (76.7%) of 5314 PHS-IR kidneys were used, compared with 25 490 (83.7%) of 30 456 non–PHS-IR kidneys—an absolute difference of 7%. Furthermore, all PHS-IR organs had higher export rates than non–PHS-IR organs. For example, 28.7% of PHS-IR kidneys were exported versus 19.7% of non–PHS-IR kidneys. Finally, the utilization rate of PHS-IR organs varied by Donation Service Area; utilization ranged from 20% to 100% among adult kidneys, suggesting significant variation in practices. Similar patterns were seen among pediatric donors. Based on the covariate-adjusted model, if the PHS-IR label did not exist, there could be an additional 313 transplants performed in the United States each year. Conclusions The PHS “increased risk” label appears to be associated with nonutilization of hundreds of organs per year, despite the very low risk of disease transmission. Better tools are needed to communicate the magnitude of risk to patients and their families.

Decision support for organ offers in liver transplantation

Organ offers in liver transplantation are high‐risk medical decisions with a low certainty of whether a better liver offer will come along before death. We hypothesized that decision support could improve the decision to accept or decline. With data from the Scientific Registry of Transplant Recipients, survival models were constructed for 42,857 waiting‐list patients and 28,653 posttransplant patients from 2002 to 2008. Daily covariate‐adjusted survival probabilities from these 2 models were combined into a 5‐year area under the curve to create an individualized prediction of whether an organ offer should be accepted for a given patient. Among 650,832 organ offers from 2008 to 2013, patient survival was compared by whether the clinical decision was concordant or discordant with model predictions. The acceptance benefit (AB)—the predicted gain or loss of life by accepting a given organ versus waiting for the next organ—ranged from 3 to −2 years (harm) and varied geographically; for example, the average benefit of accepting a donation after cardiac death organ ranged from 0.47 to −0.71 years by donation service area. Among organ offers, even when AB was >1 year, the offer was only accepted 10% of the time. Patient survival from the time of the organ offer was better if the model recommendations and the clinical decision were concordant: for offers with ABu2009>u20090, the 3‐year survival was 80% if the offer was accepted and 66% if it was declined (Pu2009<u20090.001). In conclusion, augmenting clinical judgment with decision support may improve patient survival in liver transplantation. Liver Transpl 21:784–791, 2015.

Hospital resource intensity and cirrhosis mortality in United States

AIM To determine whether hospital characteristics predict cirrhosis mortality and how much variation in mortality is attributable to hospital differences. METHODS We used data from the 2005-2011 Nationwide Inpatient Sample and the American Hospital Association Annual survey to identify hospitalizations for decompensated cirrhosis and corresponding facility characteristics. We created hospital-specific risk and reliability-adjusted odds ratios for cirrhosis mortality, and evaluated patient and facility differences based on hospital performance quintiles. We used hierarchical regression models to determine the effect of these factors on mortality. RESULTS Seventy-two thousand seven hundred and thirty-three cirrhosis admissions were evaluated in 805 hospitals. Hospital mean cirrhosis annual case volume was 90.4 (range 25-828). Overall hospital cirrhosis mortality rate was 8.00%. Hospital-adjusted odds ratios (aOR) for mortality ranged from 0.48 to 1.89. Patient characteristics varied significantly by hospital aOR for mortality. Length of stay averaged 6.0 ± 1.6 days, and varied significantly by hospital performance (P < 0.001). Facility level predictors of risk-adjusted mortality were higher Medicaid case-mix (OR = 1.00, P = 0.029) and LPN staffing (OR = 1.02, P = 0.015). Higher cirrhosis volume (OR = 0.99, P = 0.025) and liver transplant program status (OR = 0.83, P = 0.026) were significantly associated with survival. After adjusting for patient differences, era, and clustering effects, 15.3% of variation between hospitals was attributable to differences in facility characteristics. CONCLUSION Hospital characteristics account for a significant proportion of variation in cirrhosis mortality. These findings have several implications for patients, providers, and health care delivery in liver disease care and inpatient health care design.

The high burden of alcoholic cirrhosis in privately insured persons in the United States

Alcoholic cirrhosis (AC) is a major cause of liver‐related morbidity and mortality in the United States. Rising rates of alcohol use disorders in the United States will likely result in more alcoholic liver disease. Our aim was to determine the prevalence, health care use, and costs of AC among privately insured persons in the United States. We collected data from persons aged 18‐64 with AC (identified by codes from the International Classification of Diseases, Ninth and Tenth Revisions) enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009‐2015). We determined yearly prevalence, weighted to the national employer‐sponsored, privately insured population. Using competing risk analysis, we estimated event rates for portal hypertensive complications and estimated the association between AC and costs as well as admissions and readmissions. In 2015, 294,215 people had cirrhosis and 105,871 (36%) had AC. Mean age at AC diagnosis was 53.5 years, and 32% were women. Over the 7 years queried, estimated national cirrhosis prevalence rose from 0.19% to 0.27% (P < 0.001) and for AC from 0.07% to 0.10% (P < 0.001). Compared to non‐AC, AC enrollees were significantly more likely to have portal hypertensive complications at diagnosis and higher yearly cirrhosis and alcohol‐related admissions (25 excess cirrhosis admissions and 6.3 excess alcohol‐related admissions per 100 enrollees) as well as all‐cause readmissions. Per‐person costs in the first year after diagnosis nearly doubled for AC versus non‐AC persons (US

Hospital readmissions for decompensated cirrhosis

44,835 versus 23,319). Conclusion: In a nationally representative cohort of privately insured persons, AC enrollees were disproportionately sicker at presentation, were admitted and readmitted more often, and incurred nearly double the per‐person health care costs compared to those with non‐AC. (Hepatology 2018).