Model to estimate survival in ambulatory patients with hepatocellular carcinoma.

UNLABELLED: Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics. Internal and external validation of the model was performed. Discrimination and calibration of this new model were compared against existing models including Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS) scores. The majority of the patients had viral hepatitis as the underlying liver disease (100% in the derivation cohort and 85% in the validation cohort). The survival model incorporated MELD, age, number of tumor nodules, size of the largest nodule, vascular invasion, metastasis, serum albumin, and alpha-fetoprotein. In cross-validation, the coefficients remained largely unchanged between iterations. Observed survival in the validation cohort matched closely with what was predicted by the model. The concordance (c)-statistic for this model (0.77) was superior to that for BCLC (0.71), CLIP (0.70), or JIS (0.70). The score was able to further classify patient survival within each stage of the BCLC classification. CONCLUSION: A new model to predict survival of HCC patients based on objective parameters provides refined prognostication and supplements the BCLC classification.

Hepatocellular carcinoma in olmsted county, Minnesota, 1976-2008.

OBJECTIVE: To analyze longitudinal trends in the incidence, etiology, and treatment of hepatocellular carcinoma (HCC) in community residents in Olmsted County, Minnesota, and their survival. PATIENTS AND METHODS: Olmsted County residents 20 years or older with HCC newly diagnosed from January 1, 1976, through December 31, 2008, were identified using a community-wide medical record linkage system (Rochester Epidemiology Project). The incidence rate of HCC was calculated by age and sex according to the 2000 US Census population. Temporal trends of HCC etiology, treatment, and patient survival were assessed. RESULTS: The age- and sex-adjusted incidence rate for HCC in Olmsted County was 3.5 per 100,000 person-years for the first era (1976-1990), 3.8 per 100,000 for the second era (1991-2000), and 6.9 per 100,000 for the third era (2001-2008). Alcohol use was the most common risk factor in the first and second eras and chronic hepatitis C virus in the third. The proportion attributed to nonalcoholic fatty liver disease was small (5/47 [10.6%] in the third era). Because the proportion of patients receiving curative treatment increased over time, survival also improved, with a median survival time of 3, 6, and 9 months in the first, second, and third eras, respectively (P=.01). CONCLUSION: In this midwestern US community, the incidence of HCC has increased, primarily due to hepatitis C virus. Although there was a demonstrable improvement in the outcome of HCC in community residents over time, the overall prognosis remains poor.

Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States.

BACKGROUND & AIMS: The relative frequency of nonalcoholic steatohepatitis (NASH) as an indication for liver transplantation and comparative outcomes following transplantation are poorly understood. METHODS: We analyzed the Scientific Registry of Transplant Recipients for primary adult liver transplant recipients from 2001 to 2009. RESULTS: From 2001 to 2009, 35,781 patients underwent a primary liver transplant, including 1959 for who NASH was the primary or secondary indication. The percentage of patients undergoing a liver transplant for NASH increased from 1.2% in 2001 to 9.7% in 2009. NASH is now the third most common indication for liver transplantation in the United States. No other indication for liver transplantation increased in frequency during the study period. Compared with other indications for liver transplantation, recipients with NASH are older (58.5±8.0 vs 53.0±8.9 years; P<.001), have a larger body mass index (>30 kg/m2) (63% vs 32%; P<.001), are more likely to be female (47% vs 29%; P<.001), and have a lower frequency of hepatocellular carcinoma (12% vs 19%; P<.001). Survival at 1 and 3 years after liver transplantation for NASH was 84% and 78%, respectively, compared with 87% and 78% for other indications (P=.67). Patient and graft survival for liver recipients with NASH were similar to values for other indications after adjusting for level of creatinine, sex, age, and body mass index. CONCLUSIONS: NASH is the third most common indication for liver transplantation in the United States and is on a trajectory to become the most common. Outcomes for patients undergoing a liver transplant for NASH are similar to those for other indications.

Use of sirolimus in liver transplant recipients with renal insufficiency: a systematic review and meta-analysis.

UNLABELLED: Sirolimus is used in patients with renal insufficiency after liver transplantation (LT) and especially in those with calcineurin inhibitor (CNI)-associated nephrotoxicity. We conducted a systematic review of all randomized controlled trials and observational studies to test the hypothesis that the use of sirolimus is associated with an improvement in renal function at 1 year in LT recipients with renal insufficiency [glomerular filtration rate (GFR) < 60 mL/minute or creatinine level ≥ 1.5 mg/dL]. We performed a search of all major databases, conference proceedings, and relevant journals through December 2009 and contacted content experts, corresponding authors, and the pharmaceutical manufacturer. A random effects model was used to determine the pooled estimate of the change in renal function and pooled risk estimates of adverse events that may be associated with sirolimus-based therapy at 1 year. Eleven studies (three randomized controlled trials and eight observational studies) met the final inclusion criteria. A nonsignificant improvement of 3.38 mL/minute [95% confidence interval (CI) = -2.93 to 9.69] was observed in methodologically sound observational studies and controlled trials reporting the primary outcome. In controlled trials, baseline GFR >50 mL/min sirolimus use was associated with an improvement of 10.35 mL/minute (95% CI = 3.98-16.77) in GFR or creatinine clearance. Sirolimus was not significantly associated with death [relative risk (RR) = 1.12, 95% CI = 0.66-1.88] or graft failure (RR = 0.80, 95% CI = 0.45-1.41), although reporting was incomplete. It was associated with a statistically significant risk of infection (RR = 2.47, 95% CI = 1.14-5.36), rash (RR = 7.57, 95% CI = 1.75-32.70), ulcers (RR = 7.44, 95% CI = 2.03-27.28), and discontinuation of therapy (RR = 3.61, 95% CI = 1.32-9.89). CONCLUSION: Conversion to sirolimus from CNIs is associated with a nonsignificant improvement in renal function in LT recipients with renal insufficiency, although the results are limited by heterogeneity, a risk of bias, and a lack of standardized reporting.

Endothelial nitric oxide synthase gene variation associated with chronic kidney disease after liver transplant.

OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT). PATIENTS AND METHODS: This study consists of a cohort of adult (> or =18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, > or =40 mL/min per 1.73 m(2) during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m(2) after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables. RESULTS: The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables). CONCLUSION: Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD.

Pretransplant serum troponin levels are highly predictive of patient and graft survival following liver transplantation.

Optimizing the utility of liver transplantation requires the identification of factors that confer increased risk of posttransplant mortality. Elevated serum troponin (TN) levels are strongly predictive of posttransplant mortality after kidney transplantation. We sought to determine whether pretransplant TN levels were predictive of mortality and graft loss after liver transplantation in 236 liver transplant recipients from 1998 to 2001 with 8.2 years of follow-up. Elevated TN levels [hazard ratio (HR) = 2.19, P = 0.004] and a pretransplant history of cardiovascular disease (CVD; HR = 1.90, P = 0.031) were predictive of patient mortality. Elevated TN levels (HR = 2.44, P < 0.001), a history of CVD (HR = 1.83, P = 0.031), and a combination of elevated TN levels and CVD (HR = 2.75, P = 0.027) were associated with increased graft loss. Multivariate analysis confirmed TN and CVD as independent predictors of mortality and graft loss. CVD (HR = 2.39, P = 0.032) and a combination of elevated TN levels and a history of CVD (HR = 6.67, P < 0.001) were predictive of graft loss within 1 year. Age, smoking, diabetes, hypertension, obesity, creatinine levels, and Model for End-Stage Liver Disease scores were not predictive of posttransplant mortality or graft loss. In summary, elevated pretransplant serum TN levels are strongly predictive of mortality and graft loss after liver transplantation and may be helpful in risk stratification of potential liver transplant recipients.

Donor race does not predict graft failure after liver transplantation.

BACKGROUND & AIMS: Donor race has been proposed to predict graft failure after liver transplantation. We evaluated the extent to which the center where the transplantation surgery was performed and other potential confounding factors might account for the observed association between donor race and graft failure. METHODS: We analyzed data from the Organ Procurement and Transplantation Network (January 2003-December 2005) for adult patients undergoing primary liver transplantation in the United States. We examined the association between graft failure and the donor races of African American (AA), Caucasian, Asian/Pacific Islander (API), or those classified as other. RESULTS: Of 10,874 livers that were donated for transplantation, 7631 came from Caucasians, 1579 from AAs, 243 from APIs, and 1421 from others. After 36 months of follow-up evaluation, 2687 grafts failed. Without any adjustments, AA donors (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.00-1.24), API donors (HR, 1.41; 95% CI, 1.12-1.77), and other donors (HR, 1.16; 95% CI, 1.04-1.29) were associated with graft failure. After stratification by center and adjustments for age, height, and hepatitis B core antibody status of donors as well as serum creatinine and hepatitis C status of recipients, donor race was no longer statistically significant for AA (HR, 1.06; 95% CI, 0.95-1.20) and API (HR, 1.15; 95% CI, 0.89-1.49) donors. However, livers donated from members of other race still had an increased risk of graft failure (HR, 1.19; 95% CI, 1.05-1.35), although the effect was not uniform across donor-recipient pairs. CONCLUSIONS: Donor race is not a uniform predictor of graft failure and should not be construed as an indicator of donor quality.

Epidemiology of infections requiring hospitalization during long-term follow-up of pancreas transplantation.

BACKGROUND.: Pancreas transplantation (PT) provides the best glycemic control option for diabetes mellitus but is associated with significant morbidities related to infectious disease. METHODS.: We performed a retrospective study of a cohort of consecutive PT recipients in whom PT was performed from 1998 to 2006 (n=216) and followed up them until July 2008. Data regarding infections, rejection, infection chemoprophylaxis, graft failure, absolute lymphocyte counts (ALCs), and mortalities were collected. RESULTS.: Simultaneous pancreas and kidney, pancreas transplantation alone, and pancreas after kidney (PAK) transplantations were performed in 42, 67, and 107 patients, with a mean (standard deviation) age at transplantation of 46.8 (8.03), 40.6 (10.1), and 43.7 (8.19) years. Of the simultaneous pancreas and kidney, pancreas transplantation alone, and PAK transplant recipients, 54.7%, 37.3%, and 58.8% were men. Overall, 63% developed a serious infection during the median follow-up of 6.4 years. Mean (range) number of infectious episodes was 2.3 (1-12), with mostly bacterial infections both within (68%) and after 1 year (78%). Incidence of bacterial and viral infections was greatest in the first 3 months after transplantation. Fungal infections were more constant. Bladder exocrine drainage was associated with higher risk of infection (hazard ratio=2.5, P<0.001). Infection within the first 3 months after transplantation was related to higher mortality after the first 3 months (hazard ratio=3.19). ALC was associated with the risk of first infections (P=0.005) and bacterial infections (P<0.001). CONCLUSIONS.: Incidence of infections after PT was 63% and mostly bacterial. Bladder drainage increases infection risk and low ALC partially predicts episodes. Limitations include retrospective design, unequal composition of PT groups, and lack of data between kidney and PT for PAK.

Utility of Serum YKL-40 as a Tumor-Specific Marker of Hepatobiliary Malignancies.

BACKGROUND/AIMS: Serum YKL-40 has been linked to several human cancers. We investigated the potential role of serum YKL-40 as a marker of hepatobiliary malignancies. METHODS: Archived serum samples of patients undergoing liver transplantation evaluation at the Mayo Clinic Rochester were used to measure YKL-40 levels. Patients were divided into three groups: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and end-stage liver disease (ESLD) without malignancies. The Model for ESLD (MELD) score was used to quantify the severity of liver disease. RESULTS: The median serum YKL-40 level was highest in the ESLD group at 296 ng/mL, compared to 259 ng/mL in the HCC group and 80 ng/mL in the CCA group (p<0.01). There was a significant correlation between the MELD score and serum YKL-40 level (r=0.50, p<0.01). In a multivariate analysis, there was no significant difference in serum YKL-40 level between ESLD and HCC. CCA was associated with lower YKL-40 levels, a finding that was attributable to a lower prevalence of cirrhosis. CONCLUSIONS: The serum YKL-40 level has little utility as a cross-sectional screening tool for hepatobiliary malignancies, namely HCC and CCA. The role of YKL-40 as a surveillance marker in the follow-up of individual patients remains to be determined.

Long-term probability of and mortality from de novo malignancy after liver transplantation.

BACKGROUND & AIMS: Information about malignancies that arise in patients after liver transplantation comes from volunteer registry databases and single-center retrospective studies. We analyzed a multicenter, prospectively obtained database to assess the probabilities of and risk factors for de novo malignancies in patients after liver transplantation. METHODS: We analyzed the National Institute of Diabetes and Digestive and Kidney Diseases' liver transplantation database of 798 adults who received transplants from April 1990 to June 1994 and long-term follow-up data through January 2003. In this patient population, 171 adult patients developed 271 de novo malignancies. Of these malignancies, 147 were skin-related, 29 were hematologic, and 95 were solid organ cancers; we focused on nonskin malignancies. RESULTS: The probability of developing any nonskin malignancy was highest in patients with primary sclerosing cholangitis (PSC; 22% at 10 years) or alcohol-related liver disease (ALD; 18% at 10 years); all other diagnoses had a 10% probability. Multivariate analysis indicated that increased age by decade (hazard ratio [HR] = 1.33, P = .01), a history of smoking (HR = 1.6, P = .046), PSC (HR = 2.5, P = .001), and ALD (HR = 2.1, P = .01) were associated with development of solid malignancies after liver transplantation. The probabilities of death after diagnosis of hematologic and solid malignancy were 44.0% and 38.0% at 1 year and 57.6% and 53.1% at 5 years, respectively. CONCLUSIONS: De novo malignancy primarily affects patients with PSC or ALD, compared to other transplant recipients, with a significant impact on long-term survival.

Trends in waiting list registration for liver transplantation for viral hepatitis in the United States.

BACKGROUND & AIMS: In the last decade, significant progress has been made in the treatment of liver disease associated with chronic hepatitis, especially in patients infected with the hepatitis B virus (HBV). To investigate whether the population-wide application of antiviral therapies has impacted liver transplant waiting list registration, we analyzed longitudinal trends in waiting list registration for patients with hepatitis B and C and those with nonviral liver disease. METHODS: This study represented a retrospective analysis of registry data containing all US liver transplant centers. All adult, primary liver transplantation candidates registered to the Organ Procurement and Transplantation Network between 1985 and 2006 were included in the analysis. Standardized incidence rates were calculated for waiting list registration for liver transplantation by underlying disease (HBV and HCV infection and other) and by indication for transplantation (fulminant liver disease, hepatocellular carcinoma [HCC], and end-stage liver disease [ESLD]). RESULTS: Of 113,927 unique waiting list registrants, 4793 (4.2%) had HBV, and 40,923 (35.9%) had HCV infections; the remaining 68,211 (59.9%) had neither. The incidence of waiting list registration for ESLD and fulminant liver disease decreased, whereas that for HCC increased. The decrease in ESLD registration was most pronounced, and the increase in HCC was least dramatic among registrants with hepatitis B. The decrease in registration for ESLD secondary to HCV infection was also significantly larger than that for ESLD patients with nonviral etiologies. CONCLUSIONS: The pattern of liver transplantation waiting list registration among patients with hepatitis B suggests that the widespread application of oral antiviral therapy for HBV contributed to the decreased incidence of decompensated liver disease.

Delayed-onset primary cytomegalovirus disease and the risk of allograft failure and mortality after kidney transplantation.

BACKGROUND: During the contemporary era of antiviral prophylaxis, the impact of delayed-onset primary cytomegalovirus (CMV) disease on the outcome of kidney transplantation is not known. We evaluated the incidence, clinical features, risk factors, and outcomes of CMV disease among high-risk kidney transplant recipients. METHODS: The medical records of CMV-seronegative recipients of kidney transplants from CMV-seropositive donors were reviewed. Cox proportional hazards regression was used to identify factors associated with CMV disease and to assess its impact on allograft loss and mortality. RESULTS: None of the 176 CMV-seronegative recipients of kidney transplants from CMV-seropositive donors developed breakthrough CMV disease during a median of 92 days (interquartile range, 90-92 days) of oral ganciclovir or valganciclovir prophylaxis. Thereafter, 51 patients (29%) developed CMV disease at a median of 61 days (interquartile range, 40-143 days) after stopping antiviral prophylaxis. Early-onset bacterial and fungal infection (hazard ratio, 3.61; 95% confidence interval, 1.78-7.33; p < .001) and a Charlson comorbidity index > or =3 (hazard ratio, 2.21; 95% confidence interval, 1.15-4.22; p = .011) were associated with a higher risk of delayed-onset primary CMV disease, and postrejection antiviral prophylaxis (hazard ratio, 0.29; 95% confidence interval, 0.09-0.94; P = .039) was associated with a lower risk of such CMV disease. A time-dependent Cox regression analysis revealed a statistically significant association between tissue-invasive CMV disease and allograft loss or mortality (hazard ratio, 2.85; 95% confidence interval, 1.22-6.67; P = .016). CONCLUSION: This study of a large cohort of CMV-seronegative recipients of kidney transplants from CMV-seropositive donors illustrates the ongoing challenge of delayed-onset primary CMV disease and its impact on transplantation outcomes despite antiviral prophylaxis. Better strategies for CMV disease prevention after kidney transplantation are warranted.

Delayed-onset primary cytomegalovirus disease after liver transplantation.

Clinical practice guidelines recommend antiviral prophylaxis to cytomegalovirus (CMV) donor-positive/recipient-negative (D+/R-) liver transplant recipients. We assessed the outcome of this strategy by determining the incidence, clinical features, and risk factors of CMV disease among CMV D+/R- liver transplant recipients who received antiviral prophylaxis. Sixty-seven CMV D+/R- liver transplant recipients (mean age+/-standard deviation: 49.5+/-11.4 years; 75% male) received oral ganciclovir [n=9 (13%)] or valganciclovir [n=58 (87%)] prophylaxis for a median duration of 92 days (interquartile range: 91-100). No breakthrough CMV disease was observed during antiviral prophylaxis. However, primary CMV disease was observed in 2%, 25%, 27%, 27%, and 29% of patients at 1, 3, 6, 12, and 24 months, respectively, after antiviral prophylaxis was stopped. The incidence of delayed-onset primary CMV disease was similar between those who received oral ganciclovir and valganciclovir. Nine (47%) patients had CMV syndrome, 8 (42%) had gastrointestinal CMV disease, and 2 (11%) had CMV hepatitis. Female patients (P=0.01) and younger age at transplant (P=0.03) were associated with an increased risk, whereas diabetes mellitus (P<0.001) was significantly associated with a lower risk of delayed-onset primary CMV disease. Allograft loss or mortality occurred in 8 (12%) patients during the median follow-up period of 3.31 (range: 0.8-5.9) years. No significant association was observed between CMV disease and patient and allograft survival. In conclusion, CMV disease remains a common complication in CMV D+/R- liver transplant patients during the contemporary era of antiviral prophylaxis. Female patients and younger patients are at increased risk of delayed-onset primary CMV disease.

Survival after liver transplantation: Is racial disparity inevitable?

UNLABELLED: Previous analyses have reported that minority patients undergoing orthotopic liver transplantation (OLT) have poorer survival than Caucasian recipients. The reason for this disparity is unclear. We examined whether racial differences in survival exist at select academic OLT centers. OLT recipients from 4 academic centers were prospectively enrolled in 2 multicenter databases. Data including demographics, liver disease diagnosis, and post-OLT follow-up were obtained for 2823 (135 African, 2448 Caucasian, and 240 other race) adult patients undergoing primary OLT between 1985 and 2000. The survival of patients and grafts after OLT was compared across race. The Kaplan-Meier estimates for 1-year recipient survival were 90.8% [95% confidence interval (CI): 86.0-95.9] for African Americans, 86.5% (95% CI: 85.1-87.9) for Caucasians, and 84.4% (95% CI: 79.8-89.2) for other races. The 5-year recipient survival probability was 69.2% (95% CI: 60.1-79.7) for African Americans, 72.2% (95% CI: 70.1-74.4) for Caucasians, and 67.5% (95% CI: 60.5-75.3) for other races. The 10-year recipient survival probability for African Americans was 54.4% (95% CI: 41.1-72.1), for Caucasians 50.7% (95% CI: 46.4-55.3), and for other races 55.7% (95% CI: 41.5-74.8). There was no difference in patient survival (P = 0.162) or graft survival (P = 0.582) among racial groups. A multivariable proportional hazards model confirmed the absence of an association between race and post-OLT survival after adjustments for age, gender, total bilirubin, creatinine, prothrombin time, and diagnosis. CONCLUSION: These data demonstrate that as a proof of principle, minority OLT recipients should not necessarily expect an OLT outcome inferior to that of Caucasians.

Clinical features and outcomes of delayed-onset primary cytomegalovirus disease in cardiac transplant recipients.

BACKGROUND: Cytomegalovirus (CMV)-seronegative recipients of cardiac allografts from CMV-seropositive donors (CMV D(+)/R(-)) are at highest risk of CMV disease after transplantation. This study was conducted to investigate the incidence, clinical features, risk factors and outcome of delayed-onset primary CMV disease in cardiac recipients who received anti-CMV prophylaxis. METHODS: This study enrolled all CMV D(+)/R(-) cardiac recipients during the period from 2000 to 2004. The medical records of patients were reviewed to assess clinical variables and outcomes. The data were analyzed using descriptive statistics and survival analysis. RESULTS: During the 5-year study period, a total of 31 cardiac recipients had CMV D(+)/R(-) serostatus (mean age +/- SD: 49.2 +/- 13.7 years; 74% male). All patients received oral ganciclovir (n = 6) or valganciclovir (n = 25) prophylaxis for a median duration of 95 days (interquartile range: 90 to 100). No breakthrough CMV disease was observed. However, 9 (29%) patients developed delayed-onset primary CMV disease (3 with CMV syndrome, 6 with gastrointestinal disease) during the period from 120 to 444 days after transplantation. No demographic or clinical variable was significantly associated with delayed-onset primary CMV disease. However, acute rejection with a severity of Grade >or=2 showed a trend toward association with CMV disease (hazards ratio: 2.46; 95% confidence interval: 0.66 to 9.2; p = 0.18). During the mean (+/-SD) follow-up period of 2.9 (+/-1.68) years, 3 patients died. CMV disease was not associated with all-cause mortality. CONCLUSIONS: In the contemporary era of anti-viral prophylaxis, delayed-onset primary CMV disease remains a common complication among CMV D(+)/R(-) cardiac recipients. This finding warrants a better strategy for CMV prevention.

The utility of right ventricular endomyocardial biopsy for the diagnosis of xenograft rejection after CD46 pig-to-baboon cardiac transplantation.

INTRODUCTION: Endomyocardial biopsy is the standard means of establishing cardiac allograft rejection diagnosis. The efficacy of this procedure in xenotransplantation has not been determined. In this study we compare the histology of right ventricular endomyocardial biopsy specimens with the corresponding full cross sections of explanted right ventricle (RV). We also compare RV with the related left ventricle (LV) cross sections. METHODS: Heterotopic CD46 pig-to-baboon cardiac xenotransplants (n = 64) were studied. RV endomyocardial biopsy specimens were taken at cardiac explant by using a standard bioptome (n = 24) or by sharp dissection (n = 40). Hematoxylin and eosin stained sections of RV and LV cross-section and RV endomyocardial biopsy specimens were compared in a blinded fashion. Characteristics of delayed xenograft rejection and a global assessment of ischemia were scored from 0 to 4 according to the percentage of myocardium involved (0, 0%; 1, 1%-25%; 2, 26%-50%; 3, 51%-75%; and 4, 76%-100%). RESULTS: Median graft survival was 30 days (range, 3-137 days). Linear regression analysis of histology scores demonstrated that specimens from both bioptome and sharp dissection equally represented the histology of the RV cross section. Global ischemic injury was strongly correlated between RV and RV endomyocardial biopsy (R(2) = 0.84) and between RV and LV cross sections (R(2) = 0.84). Individual characteristics of delayed xenograft rejection showed no significant variation between RV and RV endomyocardial biopsy or between RV and LV (p < 0.05). CONCLUSIONS: These results indicate that delayed xenograft rejection is a widespread process involving both right and left ventricles similarly. This study shows that histologic assessment of RV endomyocardial biopsy specimens is an effective method for the monitoring of delayed xenograft rejection after cardiac xenotransplantation.

Employment and health insurance in long-term liver transplant recipients.

This study was conducted to examine factors affecting health insurance and employment status in long-term liver transplant (OLT) recipients. All adult primary OLT recipients surviving at least 1 year were surveyed using existing questionnaires. Out of 217 eligible recipients, 186 (86%) responded. The median age of respondents was 55 years with a median survival after OLT of 3.4 years. The majority (98%) of respondents had health insurance coverage. Thirty-four (18%) reported having lost and/or having been denied health insurance since OLT, and 63 (34%) switched health insurance since OLT. Of the 179 that reported employment status, 98 (55%) were employed, including homemakers and students, while 39 (22%) were retired and 42 (24%) unemployed. The majority (76%) of those unemployed cited poor health as the reason for unemployment, followed by 5 (12%) who feared loss of disability or Medicaid benefits. Fourteen reported to have been denied or terminated from employment because of their transplant. In the regression analysis, employment prior to transplantation (odds ratio (OR)=5.1), age less than 57 (OR=5.1), physical function score>52.4 (OR=3.6) and general health score>33.3 (OR=7.6) were significantly associated with employment. These data may help identify high-risk pre-OLT patients for intervention measures such as work rehabilitation.