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African American (AA) liver transplant (LT) recipients with hepatitis C virus (HCV) have higher rates of graft loss than other racial/ethnic groups. The Donor Risk Index (DRI) predicts graft loss but is neither race- nor disease-specific and may not be optimal for assessing donor risk for AA HCV-positive LT recipients. We developed a DRI for AA with HCV with the goal of enhancing graft loss predictions. All U.S. HCV-positive adult AA first deceased donor LTs surviving ≥30 days from March 2002 to December 2009 were included. A total of 1,766 AA LT recipients were followed for median 2.8 (interquartile range [IQR] 1.3-4.9) years. Independent predictors of graft loss were donor age (40-49 years: hazard ratio [HR] 1.54; 50-59 years: HR 1.80; 60+ years: HR 2.34, P < 0.001), non-AA donor (HR 1.66, P < 0.001), and cold ischemia time (CIT) (HR 1.03 per hour >8 hours, P = 0.03). Importantly, the negative effect of increasing donor age on graft and patient survival among AAs was attenuated by receipt of an AA donor. A new donor risk model for AA (AADRI-C) consisting of donor age, race, and CIT yielded 1-year, 3-year, and 5-year predicted graft survival rates of 91%, 77%, and 68% for AADRI <1.60; 86%, 67%, and 55% for AADRI 1.60-2.44; and 78%, 53%, and 39% for AADRI >2.44. In the validation dataset, AADRI-C correctly reclassified 27% of patients (net reclassification improvement P = 0.04) compared to the original DRI.

Conclusion

AADRI-C identifies grafts at higher risk of failure and this information is useful for risk-benefit discussions with recipients. Use of AA donors allows consideration of older donors.

Patients with T1 hepatocellular carcinoma (HCC) are not eligible for Model for End Stage Liver Disease (MELD) exception for liver transplant (LT) in part due to a high rate of misdiagnosis (no HCC on explant). The likelihood of misdiagnosis for T2 HCC and factors associated with misdiagnosis are unknown. We analyzed the Organ Procurement and Transplantation Network database including 5664 adults who underwent LT from 2012 to 2015 with MELD exception for T2 HCC, and searched for no evidence of HCC in the explant pathology file. We focused on those (n = 324) receiving no local-regional therapy (LRT) to evaluate the probability of no HCC found in explant. Median waiting time was short at 1.7 months, and 35 (11%) had no HCC on explant. On multivariable logistic regression, factors associated with no HCC on explant were age <50 (OR: 17.3, P < .001), non-HCV (OR: 5.4, P = .001), and alpha-fetoprotein <10 (OR: 2.9, P = .04). Tumor size and number were not different between groups. The proportion of misdiagnosis did not change significantly after implementation of Liver Imaging Reporting and Data System (LI-RADS) for HCC diagnosis.

Conclusion

The rate of misdiagnosis was 11% among T2 HCC patients who underwent LT without receiving LRT prior to LT and did not change significantly after implementation of LI-RADS. More efforts are needed to eliminate unnecessary LT for patients without HCC.

Unlabelled

Cirrhosis is characterized by sarcopenia and malnutrition, leading to progressive functional decline. We aimed to objectively measure functional decline in patients with cirrhosis awaiting liver transplantation and its association with waiting list mortality. Consecutive adults listed for liver transplantation with laboratory Model for End-Stage Liver Disease (MELD) ≥12 at a single center underwent functional status assessments at every outpatient visit using the Short Physical Performance Battery (0 = impaired to 12 = robust), consisting of gait, chair stands, and balance tests. Joint linear time-to-event analyses modeled the simultaneous impact of the longitudinal trajectory of physical function on waiting list mortality (=death or delisted for being too sick for liver transplantation). Included were 309 liver transplantation candidates. Median laboratory MELD was 15, serum albumin was 3.0 g/dL, 28% had ascites, 18% had hepatic encephalopathy, and 83% were Child class B or C. At a median follow-up of 14 months, 15% died or were delisted and 28% underwent liver transplantation. Average physical function worsened per 3 months on the waiting list: -0.38 kg in grip strength, -0.05 meters/second in gait, 0.03 seconds in chair stands, and -0.16 Short Physical Performance Battery points. In joint models of longitudinal trajectories of physical function and waiting list mortality adjusted for MELD-Na, albumin, hepatocellular carcinoma, and baseline physical function, the longitudinal trajectories of each physical function measure were significantly associated with waiting list mortality: grip (hazard ratio = 0.89, 95% confidence interval 0.83-0.95), gait (hazard ratio = 0.72, 95% confidence interval 0.62-0.84), chair stands (hazard ratio = 1.17, 95% confidence interval 1.09-1.25), and Short Physical Performance Battery <10 (hazard ratio = 1.45, 95% confidence interval 1.15-2.20).

Conclusion

Liver transplantation candidates experience significant functional decline on the waiting list, despite modest wait time and low baseline MELD; decline in physical function is associated with an increased risk of death or delisting, independent of liver disease severity.

In the United States, there are significant geographic disparities in the time to transplantation for patients with hepatocellular carcinoma (HCC); it is possible that rapid transplantation contributes to higher rates of posttransplant HCC recurrence because there is insufficient time for the tumor biology to manifest. In this study, we compared HCC recurrence in rapid transplant patients and their slower transplant counterparts. We identified adult liver transplantation (LT) candidates in the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data set who were granted an initial exception for an HCC diagnosis between January 1, 2006 and September 30, 2010 and underwent transplantation in the same time window. Patients were followed until HCC recurrence, non-HCC-related death, or last follow-up. The cumulative incidence of HCC recurrence was compared for patients waiting ≤ 120 days and patients waiting >120 days from an HCC exception to LT. The association between the risk of posttransplant recurrence and the wait time was further evaluated via competing risks regression with the Fine and Gray model. For 5002 LT recipients with HCC, the median wait time from an exception to LT was 77 days, and it varied from 30 to 169 days by UNOS region. The cumulative incidence of posttransplant HCC recurrence was 3.3% [95% confidence interval (CI) = 2.8%-3.8%] and 5.6% (95% CI = 5.0%-6.3%) within 1 and 2 years, respectively. The rate of observed recurrence within 1 year of transplantation was significantly lower for patients waiting >120 days versus patients waiting ≤ 120 days (2.2% versus 3.9%, P = 0.002); however, the difference did not persist at 2 years (5.0% versus 5.9%, P = 0.09). After we accounted for clinical factors, the HCC recurrence risk was reduced by 40% for patients waiting >120 days (subhazard ratio = 0.6, P = 0.005). In conclusion, the risk of HCC recurrence within the first year after transplantation may be lessened by the institution of a mandatory waiting time after an exception is granted.

Background

Data are limited on marijuana use and its impact on liver transplant (LT) waitlist outcomes. We aimed to assess the risk of waitlist mortality/delisting and likelihood of LT among prior marijuana users and to determine the prevalence and factors associated with marijuana use.

Methods

Retrospective cohort of adults evaluated for LT over 2 years at a large LT center. Marijuana use was defined by self-report in psychosocial assessment and/or positive urine toxicology. Ongoing marijuana use was not permitted for LT listing during study period.

Results

Eight hundred eighty-four adults were evaluated, and 585 (66%) were listed for LT (median follow-up, 1.4 years; interquartile range, 0.5-2.0). Prevalence of marijuana use was 48%, with 7% being recent users and 41% prior users. Marijuana use had statistically significant association with alcoholic cirrhosis (incidence rate ratio [IRR], 1.9) and hepatitis C (IRR, 2.1) versus hepatitis B, tobacco use (prior IRR, 1.4; recent IRR, 1.3 vs never), alcohol use (never IRR 0.1; heavy use/abuse IRR 1.2 vs social), and illicit drug use (prior IRR, 2.3; recent, 1.9 vs never). In adjusted competing risk regression, marijuana use was not associated with the probability of LT (prior hazard ratio [HR], 0.9; recent HR, 0.9 vs never) or waitlist mortality/delisting (prior HR, 1.0; recent HR, 1.0 vs never). However, recent illicit drug use was associated with higher risk of death or delisting (HR, 1.8; P = 0.004 vs never).

Conclusions

Unlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist. Prospective studies are needed to assess ongoing marijuana use on the LT waitlist and post-LT outcomes.

We investigated the possibility that patients with hepatocellular carcinoma (HCC) listed for liver transplant with tumors just outside stage T2 size criteria may be inaccurately reported as just meeting the tumor size criteria for transplant. The United Network for Organ Sharing/Standard Transplant Analysis and Research database identified 12,958 patients listed for liver transplants with HCC exception points from 2006 to 2013, 9,168 of whom were listed with one tumor. A logistic power peak function was fitted to the single-tumor size histogram, with the fitted values representing unbiased expected values. The difference between the observed and expected tumor counts for 2.0 cm and 5.0 cm was 238 (22%) and 66 (57%), respectively. This suggests that up to 304 (3.0%) patients with tumors outside of transplant criteria had their measurements recorded at the margins of eligibility. A risk-adjusted Poisson model evaluated the ratio of observed to expected HCC recurrence by tumor size. There were 435 HCC recurrences among 6,049 transplants. Only 2.0-cm tumors had observed to expected recurrence differing from 1 (ratio 0.73, 95% confidence interval 0.57-0.94), indicating a 27% lower than expected rate of recurrence.

Conclusion

Higher than expected observed tumor counts at the lower transplant criteria margin were corroborated by lower than expected HCC recurrence, suggesting that tumor sizes at the margins of HCC transplant criteria may be subject to inaccurate reporting. (Hepatology 2017;66:1144-1150).

Patients with T1 hepatocellular carcinoma (HCC; 1 lesion < 2 cm) are currently not eligible for priority listing for liver transplantation (LT). A common practice is to wait without locoregional therapy (LRT) until tumor growth occurs from T1 to T2 (1 lesion 2-5 cm or 2-3 lesions ≤ 3 cm) to be eligible for listing with Model for End-Stage Liver Disease exception. We aimed to evaluate the intention to treat outcome of the "wait and not ablate" approach for nonresection candidates with T1 HCC until tumor growth to T2. The study included 114 patients with T1 HCC 1.0-1.9 cm followed by serial imaging every 3 months. Two investigators performed independent imaging reviews to confirm the diagnosis. Median increase in total tumor diameter was 0.14 cm/month. Probabilities of progression from T1 to directly beyond T2 without LT listing were 4.4% at 6 months and 9.0% at both 12 and 24 months. The 1- and 3-year survival was 94.5% and 75.5%. In multivariate analysis, predictors of rapid tumor progression, defined as a > 1 cm increase in total tumor diameter over 3 months, included alcoholic liver disease (odds ratio [OR], 6.52; P = 0.02) and Hispanic race (OR, 3.86; P = 0.047), whereas hepatitis B appeared to be protective (OR, 0.09; P = 0.04). By competing risks regression, predictors of exclusion from LT (with or without listing for LT under T2) were alpha-fetoprotein (AFP) ≥ 500 ng/mL (HR, 12.69; 95% confidence interval, 2.8-57.0; P = 0.001) and rapid tumor progression (HR, 5.68; P < 0.001). In conclusion, the "wait and not ablate" approach until tumor growth from T1 to T2 before LT listing is associated with a <10% risk of tumor progression to directly beyond T2 criteria. However, patients with AFP ≥ 500 ng/mL and rapid tumor progression are at high risk for wait-list dropout and should receive early LRT.

Background and aims

In some states, liver transplantation (LT) for alcohol-associated liver disease (ALD) is covered by Medicaid only with documentation of abstinence and/or alcohol rehabilitation. Different Medicaid policies may affect the distribution of LT for ALD, particularly post-2011, as centers have adopted early (i.e., specific abstinence period not required) LT practices.

Approach and results

We surveyed Medicaid policies in all states actively performing LT and linked state policies to prospectively collected national registry data on LT recipients from 2002 to 2017 with ALD as the primary listing diagnosis. We categorized Medicaid policies for states as "restrictive" (requiring documentation of a specific abstinence period and/or rehabilitation) versus "unrestrictive" (deferring to center eligibility policies). Difference-of-differences analysis, comparing 2002-2011 versus 2012-2017, evaluated whether restrictive policies were associated with decreased proportion of LTs paid by Medicaid among patients with ALD post-2011. We performed sensitivity analyses to account for any differences by diagnosis of hepatocellular carcinoma, hepatitis C virus, nonalcoholic steatohepatitis, or Medicare insurance. We also performed a sensitivity analysis to account for any difference by prevalence of ALD among restrictive versus unrestrictive states. Of 10,836 LT recipients in 2002-2017, 7,091 were from 24 states in the restrictive group and 3,745 from 14 states in the unrestrictive group. The adjusted proportion (95% confidence interval) of LTs paid by Medicaid among restrictive versus unrestrictive states between 2002 and 2011 was 17.6% (15.4%-19.8%) versus 18.9% (15.4%-22.3%) (P = 0.54) and between 2012 and 2017, 17.2% (14.7%-19.7%) versus 23.2% (19.8%-26.6%) (P = 0.005). In difference-of-differences analysis, restrictive (versus unrestrictive) policies were associated with a 4.7% (0.8%-8.6%) (P = 0.02) absolute lower adjusted proportion of LTs for ALD paid by Medicaid post-2011.

Conclusions

Restrictive Medicaid policies are present in most states with active LT centers and are associated with lower proportions of LTs for ALD paid by Medicaid post-2011 compared to states with unrestrictive Medicaid policies. Reevaluation of Medicaid alcohol use policies may be warranted, to align more closely with contemporary center-level practices.

Frailty results from the chronic effects of malnutrition and muscle wasting in patients with cirrhosis. It is well-established that frailty is strongly associated with mortality in this population. However, little is known of its relationship with physical disability, a critical patient-centered outcome. Adults with cirrhosis underwent outpatient testing of frailty using the Liver Frailty Index (LFI) and disability using activities of daily living (ADL; range 0-6) and Instrumental ADL (IADL; range 0-8) scales at one center between 2012 and 2016. We used adjusted multilevel logistic mixed-effects regression to test the association between frailty and current disability (impairment with ≥1 ADL or IADL) and incident disability at 6 months among those without baseline disability. Of the 983 participants, 20% were robust, 32% were less robust, 33% were prefrail, and 15% were frail; 587 (60%) had at least 1 assessment. The percentage of participants with at least 1 baseline ADL or IADL impairment was 28% and 37%, respectively. In adjusted regression models, each point LFI increase was associated with a 3.3 and 4.6 higher odds of current difficulty with at least 1 ADL and IADL (P < 0.001 for each), respectively. Among participants without baseline disability, each point LFI increase was associated with a 2.6 and 1.7 higher odds of having difficulty with at least 1 ADL and IADL at 6 months, respectively. Conclusion: Frailty is strongly associated with concurrent and incident disability in patients with cirrhosis. In the clinic, the LFI can be used to identify those in greatest need for additional support/resources to maintain functional independence. In research settings, the LFI may help to identify an enriched population for clinical trials of interventions aimed at those most vulnerable to disability.