Variation in organ quality between liver transplant centers.

A wide spectrum of quality exists among deceased donor organs available for liver transplantation. It is unknown whether some transplant centers systematically use more low quality organs, and what factors might influence these decisions. We used hierarchical regression to measure variation in donor risk index (DRI) in the United States by region, organ procurement organization (OPO) and transplant center. The sample included all adults who underwent deceased donor liver transplantation between January 12, 2005 and February 1, 2009 (n = 23,810). Despite adjusting for the geographic region and OPO, transplant centers' mean DRI ranged from 1.27 to 1.74, and could not be explained by differences in patient populations such as disease severity. Larger volume centers and those having competing centers within their OPO were more likely to use higher risk organs, particularly among recipients with lower model for end-stage liver disease (MELD) scores. Centers using higher risk organs had equivalent waiting list mortality rates, but tended to have higher post-transplant mortality (hazard ratio 1.10 per 0.1 increase in mean DRI). In conclusion, the quality of deceased donor organ patients receive is variable and depends in part on the characteristics of the transplant center they visit.

Estimation of the harm to the waiting list as a crucial factor in the selection of patients with hepatocellular carcinoma for liver transplantation.

BACKGROUND: Long-term survival rates after orthotopic liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) of any size and number may now be predicted using the Metroticket calculator. The aim of this study was to evaluate the minimum post-OLT survival threshold that would justify the selection of a patient with HCC for OLT. METHODS: We used a Markov model, recently developed at the University of Michigan, which assumes that a patient with HCC should undergo OLT if his or her transplant benefit is greater than the cumulative harm to the rest of the waiting list (WL). In the base case, we considered a patient with a low survival perspective without OLT (5-year survival rate, 10%). The data sources to construct and validate the model were as follows: the Organ Procurement and Transplantation Network report, and our prospective database. RESULTS: Our center was generally characterized by lower WL mortalities, although there were lower transplant probabilities for both HCC and non-HCC patients than the average US center. The proportion of HCC patients on the WL was higher in Padua (25%) than in the United States (10%). The calculated harm to the WL was 434 quality-adjusted days of life in Padua, and 957 in the United States (P < .01). The OLT benefit outweighed the harm to the WL when the 5-year post-OLT survival rate was higher than 30% in Padua, and 61% in the United States. CONCLUSIONS: In a decision model including the concepts of transplantation benefit and harm to the WL, the minimum 5-year post-OLT survival threshold justifying the selection of a patient with HCC for OLT in Padua was 30%.

Foreigners traveling to the U.S. for transplantation may adversely affect organ donation: a national survey.

The aims of this study were (1) to determine attitudes among the American public regarding foreigners coming to the United States for the purposes of transplantation, and (2) to investigate the impact this practice might have on the public's willingness to donate organs. A probability-based national sample of adults age > or =18 was asked whether people should be allowed to travel to the United States to receive a transplant, and whether this practice would discourage the respondents from becoming an organ donor. Among 1049 participants, 30% (95% CI 25-34%) felt that people should not be allowed to travel to the United States to receive a deceased donor transplant, whereas 28% felt this would be acceptable in some cases. Thirty-eight percent (95% CI 33-42%) indicated that this practice might prevent them from becoming an organ donor. In conclusion, deceased-donor transplantation of foreigners is opposed by many Americans. Media coverage of this practice has the potential to adversely affect organ donation.

Attitudes of the American public toward organ donation after uncontrolled (sudden) cardiac death.

Concerns about public support for organ donation after cardiac death have hindered expansion of this practice, particularly rapid organ recovery in the context of uncontrolled (sudden) cardiac death (uDCD). A nationally representative Internet-based panel was provided scenarios describing donation in the context of brain death, controlled cardiac death and uncontrolled cardiac death. Participants were randomized to receive questions about trust in the medical system before or after the rapid organ recovery scenario. Among 1631 panelists, 1049 (64%) completed the survey. Participants expressed slightly more willingness to donate in the context of controlled and uncontrolled cardiac death than after brain death (70% and 69% vs. 66%, respectively, p < 0.01). Eighty percent of subjects (95% CI 77-84%) would support having a rapid organ recovery program in their community, though 83% would require family consent or a signed donor card prior to invasive procedures for organ preservation. The idea of uDCD slightly decreased trust in the medical system from 59% expressing trust to 51% (p = 0.02), but did not increase belief that a signed donor card would interfere with medical care (28% vs. 32%, p = 0.37). These findings provide support for the careful expansion of uDCD, albeit with formal consent prior to organ preservation.

Centers for Disease Control 'high-risk' donors and kidney utilization.

The aims of this study were to determine whether Centers for Disease Control high risk (CDCHR) status of organ donors affects kidney utilization and recipient survival. Data from the Scientific Registry of Transplant Recipients were used to examine utilization rates of 45,112 standard criteria donor (SCD) deceased donor kidneys from January 1, 2005, and February 2, 2009. Utilization rates for transplantation were compared between CDCHR and non-CDCHR kidneys, using logistic regression to control for possible confounders. Cox regression was used to determine whether CDCHR status independently affected posttransplant survival among 25,158 recipients of SCD deceased donor kidneys between January 1, 2005, and February 1, 2008. CDCHR kidneys were 8.2% (95% CI 6.9-9.5) less likely to be used for transplantation than non-CDCHR kidneys; after adjusting for other factors, CDCHR was associated with an odds ratio of utilization of 0.67 (95% CI 0.61-0.74). After a median 2 years follow-up, recipients of CDCHR kidneys had similar posttransplant survival compared to recipients of non-CDCHR kidneys (hazard ratio 1.06, 95% CI 0.89-1.26). These findings suggest that labeling donor organs as 'high risk' may result in wastage of approximately 41 otherwise standard kidneys per year.

Geographic variation in organ availability is responsible for disparities in liver transplantation between Hispanics and Caucasians.

The aims of this study were to determine whether disparities in waiting list outcomes exist for Hispanics and African Americans during the post-MELD era, and to investigate interactions between disparities and geography. Scientific Registry of Transplant Recipients data were used to compare Hispanics and African Americans to Caucasians listed between 2003 and 2008. Endpoints included (i) receipt of a liver transplant and (ii) death or removal from the waiting list for being too sick or medically unsuitable. Adjustment for possible confounders was performed using multivariate Cox regression, with adjustment for geographic variation using a fixed-effects multilevel model. In multivariate analysis, African Americans have similar hazard of transplantation and death/removal as Caucasians during the post-MELD era. However, Hispanics are less likely to receive a transplant than Caucasians despite adjustment for potential confounders (HR 0.80, 95% CI 0.77-0.83), while having a similar hazard of death/removal. This effect disappeared after adjusting for unequal regional distribution of Hispanics, who represent 8% of patients in donation service areas (DSAs) having median waiting times of < or = 155 days versus 19% in DSAs with median waiting times of >155 days. In conclusion, disparities in liver transplantation exist for Hispanics during the post-MELD era, caused by geographic variation in organ availability.

Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: A majority of studies investigating the accuracy of ultrasound for detecting hepatocellular carcinoma (HCC) do not reflect how this test is used for surveillance vs. diagnosis. AIM: To determine the performance characteristics of surveillance with ultrasound for the detection of HCC, particularly early HCC as defined by the Milan criteria. METHODS: A systematic literature review using the MEDLINE and SCOPUS databases yielded six studies that evaluated the accuracy of ultrasound for HCC at any stage and 13 studies that were specific to early HCC. RESULTS: Surveillance ultrasound detected the majority of tumours before they presented clinically, with a pooled sensitivity of 94%. However, ultrasound was less effective for detecting early HCC with a sensitivity of 63%. Alpha-fetoprotein provided no additional benefit to ultrasound. Meta-regression analysis demonstrated a significantly higher sensitivity for early HCC with ultrasound every 6 months than with annual surveillance. Current studies have limitations such as verification bias and are of suboptimal quality. CONCLUSIONS: Surveillance with ultrasound demonstrates limited sensitivity for early HCC, although this may be improved by testing at 6-month intervals. Currently available evidence evaluating surveillance ultrasound has significant limitations and future studies are necessary to determine optimal surveillance methods for early HCC.

A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria.

No empirical studies have defined the posttransplant survival that would justify expansion of the Milan criteria for liver transplantation of hepatocellular carcinoma. We created a Markov model comparing the survival benefit of transplantation for a patient with >Milan HCC, versus the harm caused to other patients on the waiting list. In the base-case analysis, the strategy of transplanting the patient with >Milan HCC resulted in a 44% increased risk of death and a utility loss of 3 quality-adjusted years of life across the pre- and posttransplant periods for a nationally representative cohort of patients on the waiting list. This harm outweighed the benefit of transplantation for a patient with >Milan HCC having a 5-year posttransplant survival of less than 61%. This survival threshold was most sensitive to geographic variations in organ shortage, with the threshold varying from 25% (Region 3) to >72% (Regions 1, 5, 7 and 9). In conclusion, expansion of the Milan criteria will require demonstrating high survival rates for the newly eligible patients-approximately 61% at 5 years after transplantation. In regions with less severe organ shortage, a more aggressive approach to transplanting these patients may be justified.

Advances in critical care hepatology.

Complications of liver disease are commonly seen in the intensive care unit (ICU). When evaluating patients with liver disease in the ICU, it is important to determine whether it is acute or chronic liver disease. Because the pathophysiological mechanisms differ among acute and chronic liver, they will be consider separately in this review. Significant advances in the management of acute liver failure highlight the importance of intracranial pressure monitoring for Grade III/IV encephalopathy, and suggest that moderate hypothermia may be a promising treatment for these patients with refractory intracranial hypertension. Chronic liver disease is best discussed in terms of the various complications that may ensue such as ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, variceal hemorrhage and hepatic encephalopathy. Each of these conditions will be discussed with specific attention to critical care management.

Regulators of G protein signaling: rapid changes in mRNA abundance in response to amphetamine.

This study examined mRNAs encoding regulators of G protein signaling (RGSs) expressed within the striatum and determined whether their expression in the caudate putamen was altered by amphetamine. RT-PCR techniques were used to clone cDNA probes of RGSs expressed within the rat striatum. Northern blot analysis of caudate putamen and nucleus accumbens RNA determined the relative abundance of RGS mRNA expressed within the caudate putamen and adjacent nucleus accumbens to be RGS 2 > RGS 5 > RGS 16 > RGS 4 = RGS 9 > RGS 8 = RGS 3. A single injection of amphetamine rapidly and transiently induced RGS 2 mRNA. The temporal pattern of induction of RGS 2 strongly resembled that of the immediate early gene c-fos. Levels of mRNAs of RGS 3 and 5 steadily increased over a 4-h interval, as did that of the 6.6-kb transcript of RGS 8. The level of RGS 9 mRNA, which shows strong striatal-specific expression, steadily decreased over a 4-h interval, whereas RGS 4 and 16 and the 3.9-kb transcript of RGS 8 were not significantly affected at any point examined. The ability of amphetamine to alter RGS mRNA expression within the caudate putamen suggests these proteins may play an important role in adaptive processes to psychostimulant exposure.