Access to liver transplantation under the new exception policy for HCC and non-HCC candidates

ABSTRACT BACKGROUND: In October 2015, the Organ Procurement and Transplantation Network (OPTN) implemented a revised liver exception point policy to address the disparity between Hepatocellular Carcinoma (HCC) and non-HCC patients in access to deceased-donor liver transplant (DDLT). Under the new policy, HCC patients obtain exception points only after 6 months on the waitlist. The impact of this policy change on access to DDLT and waitlist mortality for HCC and non-HCC patients has not been described. METHODS: Using Scientific Registry of Transplant Recipients (SRTR) data on 29,759 adult, first-time DDLT waitlist registrants from 2014 to 2016, we compared access to DDLT and mortality risk in HCC vs. non-HCC patients, pre-implementation (10/8/2014-10/7/2015) and post-implementation (10/8/2015-6/30/2016). Waitlist dropout due to deteriorating condition was classified as mortality. We estimated cumulative incidence of DDLT accounting for the competing risk of waitlist mortality overall and for four different strata of calculated MELD (6-10, 11-18, 19-24, and 25-40). We used Cox regression to model cause-specific hazard, and Fine and Gray methods to model mortality accounting for the competing risk of transplantation, adjusting for age, gender, race, and time-varying calculated MELD. RESULTS: During the pre-implementation period, HCC patients had 5-fold higher access to DDLT than non-HCC patients. During the post-implementation period, HCC and non-HCC patients had comparable chances of receiving DDLT experiencing access to DDLT (aCSHR =0.93; 95% CI: 0.81-1.07, p>0.1). HCC candidates in all MELD strata also had higher rates of DDLT than comparable non-HCC candidates during the pre-implementation period (aCSHR = 114.49, 95% CI: 82.26 - 159.35 for MELD 6-10; aCSHR =10.70, 95% CI: 9.67 -11.83 for MELD 11-18; aCSHR =2.18, 95% CI: 1.85-2.57 for MELD 19-24) except among candidates with MELD of 25-40 (aCSHR = 0.58; 95% CI: 0.48 -0.69). In the post-implementation period, HCC candidates had a higher rate of DDLT in MELD stratum 6-10 (aCSHR = 2.91, 95% CI: 1.64 -5.18), similar rate of DDLT in MELD stratum 11-18 (aCSHR = 0.94, 95% CI: 0.75 -1.18) and lower rates of DDLT in higher MELD strata (aCSHR = 0.39, 95% CI: 0.27 -0.58 for MELD 19-24; aCSHR = 0.27, 95% CI: 0.18-0.40 for MELD 25-40) compared to non-HCC candidates. After accounting for the reduction in mortality due to transplant in both groups, risk of waitlist mortality/dropout for HCC candidates compared to non-HCC candidates increased from 1.3-fold higher risk of waitlist mortality/dropout pre-implementation (asHR =1.30, 95% CI: 1.15-1.46, p=0.005) to 2.18-fold higher risk of waitlist mortality/dropout post-implementation (aSHR = 2.18, 95% CI: 1.69-2.80, p<0.001). During both eras, the risk of waitlist mortality/dropout was similar among HCC and non-HCC candidates in lower MELD strata (6-10, 11-18). In higher MELD strata, the risk of waitlist mortality/dropout was higher among HCC candidates compared to non-HCC candidates in the pre-implementation period (asHR = 1.64, 95% CI: 1.27-2.11 for MELD 19-24; 1.31, 95% CI: 1.08-1.58 for MELD 25-40); the higher risk of waitlist mortality/dropout among HCC candidates compared to non-HCC candidates in the higher MELD strata increased further during the post-implementation period (asHR = 1.82, 95% CI: 1.02-3.25 for MELD 19-24; 3.11, 95% CI: 2.18-4.42 for MELD 25-40). CONCLUSIONS: The October 2015 HCC exception policy change eliminated the disparity in access to DDLT between HCC and non-HCC patients. However, risk of waitlist mortality/dropout increased in HCC candidates compared to non-HCC candidates. In lower MELD strata (6-10, 11-18), the policy change reduced discrimination against non-HCC candidates without changing their risk of waitlist mortality/dropout. In higher MELD strata (19-24, 25-40), the policy change reduced access to DDLT for HCC candidates while also increasing the risk of waitlist mortality/dropout within this group

Barriers to access in pediatric living‐donor liver transplantation

Children receiving a LDLT have superior post‐transplant outcomes, but this procedure is only used for 10% of transplant recipients. Better understanding about barriers toward LDLT and the sociodemographic characteristics that influence these underlying mechanisms would help to inform strategies to increase its use. We conducted an online, anonymous survey of parents/caregivers for children awaiting, or have received, a liver transplant regarding their knowledge and attitudes about LDLT. The survey was completed by 217 respondents. While 97% of respondents understood an individual could donate a portion of their liver, only 72% knew the steps in evaluation, and 69% understood the donor surgery was covered by the recipient's insurance. Individuals with public insurance were less likely than those with private insurance to know the steps for LDLT evaluation (44% vs 82%; P < 0.001). Respondents with public insurance were less likely to know someone that had been a living donor (44% vs 56%; P = 0.005) as were individuals without a college degree (64% vs 85%; P = 0.007). Nearly all respondents generally trusted their healthcare team. Among respondents, 82% believed they were well‐informed about LDLT but individuals with public insurance were significantly less likely to feel well‐informed (67% vs 87%; P = 0.03) and to understand how donor surgery might impact donor work/time off (44% vs 81%; P = 0.001). Substantial gaps exist in parental understanding about LDLT, including its evaluation, potential benefits, and complications. Greater emphasis on addressing these barriers, especially to individuals with fewer resources, will be helpful to expand the use of LDLT

Association Between Living Kidney Donor Postdonation Hypertension and Recipient Graft Failure.

BACKGROUND: Recipients of kidneys from living donors who subsequently develop end-stage renal disease (ESRD) also have higher graft failure, suggesting the 2 donor kidneys share risk factors that could inform recipient outcomes. Given that donor ESRD is rare, an earlier and more common postdonation outcome could serve as a surrogate to individualize counseling and management for recipients. Hypertension is a frequent event before donor ESRD; thus, early postdonation hypertension might indicate higher risk of graft failure. METHODS: We studied Scientific Registry of Transplant Recipients data to quantify the association between early postdonation hypertension and recipient graft failure using propensity score-weighted Cox proportional hazards regression. We also examined the association between postdonation systolic blood pressure and graft failure. RESULTS: Of 37 901 recipients, 2.4% had a donor who developed hypertension within 2 years postdonation. Controlling for donor and recipient characteristics, recipients whose donors developed hypertension had no higher risk for graft failure (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.85-1.25, P = 0.72). This was consistent among subgroups of recipients at higher risk for adverse outcomes due to hyperfiltration: African American recipients (aHR 1.10, 95% CI 0.70-1.73, P = 0.68) and those with ESRD caused by hypertension (aHR 1.10, 95% CI 0.65-1.85, P = 0.73) or diabetes (aHR 0.80, 95% CI 0.56-1.13, P = 0.20). However, graft failure was associated with postdonation systolic blood pressure (per 10 mm Hg, aHR 1.05, 95% CI 1.03-1.08, P &lt; 0.001). CONCLUSIONS: Although postdonation systolic blood pressure is associated with graft failure, the reported diagnosis of hypertension as determined by the requirement for blood pressure treatment early postdonation did not portend a higher risk of recipient graft failure in the same way as eventual postdonation ESRD

Assessing Community Based Improved Maternal Neonatal Child Survival (IMNCS) Program in Rural Bangladesh

<div><p>Objectives</p><p>A community based approach before, during and after child birth has been proven effective address the burden of maternal, neonatal and child morbidity and mortality in the low and middle income countries. We aimed to examine the overall change in maternal and newborn health outcomes due the “Improved Maternal Newborn and Child Survival” (IMNCS) project, which was implemented by BRAC in rural communities of Bangladesh.</p><p>Methods</p><p>The intervention was implemented in four districts for duration of 5-years, while two districts served as comparison areas. The intervention was delivered by community health workers who were trained on essential maternal, neonatal and child health care services. A baseline survey was conducted in 2008 among 7, 200 women with pregnancy outcome in last year or having a currently alive child of 12–59 months. A follow-up survey was administered in 2012–13 among 4, 800 women of similar characteristics in the same villages.</p><p>Findings</p><p>We observed significant improvements in maternal and essential newborn care in intervention areas over time, especially in health care seeking behaviors. The proportion of births taking place at home declined in the intervention districts from 84.3% at baseline to 71.2% at end line (P<0.001). Proportion of deliveries with skilled attendant was higher in intervention districts (28%) compared to comparison districts (27.4%). The number of deliveries was almost doubled at public sector facility comparing with baseline (P<0.001). Significant improvement was also observed in healthy cord care practice, delayed bathing of the new-born and reduction of infant mortality in intervention districts compared to that of comparison districts.</p><p>Conclusions</p><p>This study demonstrates that community-based efforts offer encouraging evidence and value for combining maternal, neonatal and child health care package. This approach might be considered at larger scale in similar settings with limited resources.</p></div

Outcome and confounding variables used in evaluation measurement.

<p>Outcome and confounding variables used in evaluation measurement.</p

Living donor postnephrectomy kidney function and recipient graft loss: A dose-response relationship.

Development of end-stage renal disease (ESRD) in living kidney donors is associated with increased graft loss in the recipients of their kidneys. Our goal was to investigate if this relationship was reflected at an earlier stage postdonation, possibly early enough for recipient risk prediction based on donor response to nephrectomy. Using national registry data, we studied 29 464 recipients and their donors from 2008-2016 to determine the association between donor 6-month postnephrectomy estimated GFR (eGFR) and recipient death-censored graft failure (DCGF). We explored donor BMI as an effect modifier, given the association between obesity and hyperfiltration. On average, risk of DCGF increased with each 10 mL/min decrement in postdonation eGFR (adjusted hazard ratio [aHR] 1.06, 95% confidence interval [CI] 1.02-1.10, P = .007). The association was attenuated with higher donor BMI (interaction P = .049): recipients from donors with BMI = 20 (aHR 1.12, 95% CI 1.04-1.19, P = .002) and BMI = 25 (aHR 1.07, 95% CI 1.03-1.12, P = .001) had a higher risk of DCGF with each 10 mL/min decrement in postdonation eGFR, whereas recipients from donors with BMI = 30 and BMI = 35 did not have a higher risk. The relationship between postdonation eGFR, donor BMI, and recipient graft loss can inform counseling and management of living donor kidney transplant recipients

Study flow chart.

<p>Study flow chart.</p

Pretransplant Hepatitis C Virus Treatment Decreases Access to High-quality Livers

Background. Despite the revolutionary role of direct-acting antivirals for hepatitis C virus (HCV), the treatment timing for liver transplant candidates remains controversial. We hypothesize that deferring treatment until after liver transplantation improves access to a larger and higher-quality donor pool without a detrimental impact on post-liver transplantation outcomes. Methods. This single-center study includes recipients that underwent deceased-donor liver transplant with HCV as the primary indication January 1, 2014, to December 31, 2018. For recipients that were untreated (n = 87) versus treated (n = 42) pre-LT, we compared post-LT mortality using Cox regression with inverse probability of treatment-weighted data. Results. Among pre-LT untreated recipients, 95% were willing to accept an HCV+ donor, and 44.8% received a positive HCV antibody and nucleic acid amplification test (NAT) liver. Among pre-LT treated recipients, 5% were willing to accept an HCV+ donor, and 100% received a negative HCV antibody and NAT liver. The median calculated model for end-stage liver disease at transplant was similar between pre-LT untreated (13, IQR = 9–22) and treated recipients (11, IQR = 8–14) (P = 0.1). Pre-LT treated recipients received livers from older (47 y old versus 37, P < 0.01) and higher body mass index donors (30.2 versus 26.6; P = 0.04) and spent longer on the waiting list (319 d 180, P < 0.001). Unadjusted post-LT mortality at 1 year was higher in the pre-LT treated recipients (14.6% versus 3.5%, P = 0.02). After adjusting for recipient factors, pre-LT treated recipients trended toward a 3.9 times higher risk of mortality compared with the pre-LT untreated recipients (adjusted hazard ratio = 0.973.8615.4) (P = 0.06). Conclusions. Deferring HCV treatment improves access to higher-quality donors and may improve post-LT survival