Impact of Donation After Circulatory Death Allografts on Outcomes Following Simultaneous Liver-Kidney Transplant: A Single-Center Experience and Review of the Literature.

OBJECTIVES: Limited data exist on outcomes after simultaneous liver-kidney transplants with extended criteria donor grafts. We compared outcomes in recipients of simultaneous liver-kidney transplants with donation after circulatory death versus donation after brain death grafts. MATERIALS AND METHODS: This retrospective analysis included all liver transplants performed over a 7-year period at a single center. We compared categorical variables using the chi-square test and continuous variables using the t test. We compared survival using the Kaplan-Meier method and performed a univariate analysis of predictors of outcomes using Cox regression method. RESULTS: Over the study period, 196 patients underwent liver transplant, with 33 (16.8%) undergoing simultaneous liver-kidney transplant. In this cohort, 23 and 10 patients, respectively, received grafts from donors after brain death versus circulatory death. Both groups were comparable with respect to age, sex, hepatitis C virus status, and presence of hepatocellular carcinoma. Median (range) Model for End-Stage Liver Disease score was higher in recipients of donation after brain death grafts (37 [26-40] vs 23 [21-24]; P < .01). Liver allograft survival was comparable in donation after brain death versus donation after circulatory death recipients (P = .82) at 1 year (64.0% vs 66.7%), 3 years (57.6% vs 55.6%), and 5 years (57.6% vs 55.6%). Patient survival was also comparable (P = .89) at 1 year (70.1% vs 77.8%), 3 years (63.1% vs 55.6%), and 5 years (63.1% vs 55.6%). Graft outcomes remained similar even after adjustment for Model for End-Stage Liver Disease score at transplant (hazard ratio 0.58; 95% CI, 0.14-2.44; P = .45). Univariate analysis of predictors of patient survival after simultaneous liver- kidney transplant showed a trend toward statistical significance with recipient age and donor male sex. CONCLUSIONS: Grafts from donors after circulatory death could help safely expand the donor pool in patients undergoing simultaneous liver-kidney transplant without compromising outcomes.

Reduction in 90 day readmission rates utilizing ambulatory pulmonary pressure monitoring.

AIMS: In the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association Functional Class III Heart Failure Patients) trial, heart failure hospitalization (HFH) rates were lower in patients with ambulatory pulmonary artery pressure (PAP) monitoring guidance. We investigated the effect of ambulatory haemodynamic monitoring on 90 day readmission rates after HFH. METHODS AND RESULTS: We retrospectively analysed patients across the Advocate Aurora Health hospital network who had undergone PAP sensor implantation between 1 October 2015 and 31 October 2019. Patients with a ventricular assist device (VAD) or transplant prior to implantation were excluded. Rates of total HFH and 30 and 90 day all-cause readmission up to 12 months after implantation were collected, while censoring for an endpoint of heart transplantation, VAD, or death. Event rates were compared using Poisson regression. Of 459 patients included, there were 404 HFHs before and 179 after implantation. Compared with pre-implantation, 30 day all-cause readmission [incidence rate ratio (IRR): 0.55 (0.39-0.77), P = 0.0006] and 90 day all cause readmission rates were lower post-implantation [IRR: 0.45 (0.35-0.58), P < 0.0001]. The effect of PAP sensor implantation on 90 day all-cause readmission incidence rates was consistent across multiple subgroups. CONCLUSIONS: Across a large hospital network, ambulatory haemodynamic monitoring was associated with lower HFH rates, as well as 30 and 90 day all-cause readmission rates. This supports the utility of ambulatory PAP monitoring to improve HF management in the era of value-based medicine.

Impact of Donation After Circulatory Death Allografts on Outcomes After Liver Transplant for Hepatitis C: A Single-Center Experience and Review of the Literature.

OBJECTIVES: We investigated the impact of liver transplant from donors after circulatory death on incidence and severity of recurrent hepatitis C virus infection, graft and patient survival and aimed to identify predictors of outcomes. MATERIALS AND METHODS: We retrospectively reviewed all liver transplants performed at a single center (July 2007-February 2014). Patients with hepatitis C who underwent liver transplant from donors after circulatory death (group 1) were compared with hepatitis C patients who received grafts from donors after brain death (group 2) and patients without hepatitis C who received grafts from donors after circulatory death (group 3).We used the Kaplan-Meier method for survival analysis and performed a multivariable analysis for predictors of outcomes using Cox regression. Competing risk was used to analyze hepatitis C recurrence. RESULTS: Of 196 patients, 107 were included: 25 in group 1, 46 in group 2, and 36 in group 3. All 3 groups were comparable, except for longer cold ischemia time (P < .01) in group 1, lower Model for End-Stage Liver Disease score at transplant in groups 1 and 3 (P < .01), and greater proportion of recipients with hepatocellular carcinoma in groups 1 and 2 (P = .02). Hepatitis C recurrence and severe recurrence at 1 and 3 years were higher in group 1 (but not statistically significant). Severe recurrence was noted in 17% versus 8% at 1 year (P = .12) and 30% versus 14% at 3 years (P = .08). Graft and patient survival rates at 1, 3, and 5 years were comparable in all 3 study groups. CONCLUSIONS: Recurrent hepatitis C, including severe recurrence, was greater following donation after circulatory death compared with donation after brain death liver transplant. However, graft survival and patient survival were comparable, including in recipients of donation after circulatory death grafts without hepatitis C.

Liver Transplant Using Donation After Circulatory Death Donors: A Low-Volume Single-Center Experience.

OBJECTIVES: Although donor shortages have prompted increased use of livers from donors after circulatory death, data are limited on their outcomes in low-volume centers and their applicability in this setting. MATERIALS AND METHODS: We retrospectively reviewed liver transplants from donors after circulatory death performed at our low-volume center over a 7-year period and identified predictors of outcomes. RESULTS: Between 2007 and 2014, of 196 liver transplants (mean 28/year), donations after circulatory death accounted for 31%. Patient/liver graft survival rates were similar in recipients of brain dead donor versus circulatory death donor allografts (P = .47 and P = .87 respectively): 88.4% versus 85.7%/87.7 versus 86.3% at 1 year, 78.5 versus 74.2%/76.5% versus 75.4% at 3 years, and 70.8% versus 62.0%/65.1% versus 63.7% at 5 years. Multivariable analysis identified recipients with hepatitis C virus from donors >50 years old as an independent predictor of graft and patient survival (P < .01). Biliary complications trended higher in recipients of circulatory death donor livers. Among solitary liver transplant recipients, although biliary complications adversely affected graft survival in both groups (circulatory death vs brain dead donor cohorts, P = .02 vs P = .03), patient survival was only affected in the circulatory death donor cohort (P = .01). However, when all transplants were included in graft loss modeling, presence of biliary complications significantly impacted graft survival only in recipients of livers from circulatory death donors (P < .01). Among biliary complications, ischemic cholangiopathy had the greatest impact on graft loss (P ≤ .01). CONCLUSIONS: Donation after circulatory death allografts could be safely used to expand the donor pool even in low-volume liver transplant centers. Outcomes were comparable to grafts from donors after brain death, although biliary complications, mainly because of ischemic cholangiopathy, had a greater effect on liver transplants from circulatory death donors. Efforts to minimize ischemic cholangiopathy could enable their greater utilization, regardless of center volume, without compromising outcomes.

Benefits of Neurohormonal Therapy in Patients With Continuous-Flow Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) have dramatically improved short-term outcomes among patients with advanced heart failure. While neurohormonal blockade (NHB) is the cornerstone of treatment for patients with heart failure with reduced ejection fraction, its effect after LVAD placement has not been established. We reviewed medical records of 307 patients who underwent primary LVAD implantation from January 2006 to September 2015 at two institutions in the United States. Patients were followed for at least 2 years post-LVAD implantation or until explantation, heart transplantation, or death. Cox regression analysis stratifying on center was used to assess associations with mortality. Neurohormonal blockade use was treated as a time-dependent predictor. Stepwise selection indicated treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) (hazard ratio [HR] = 0.53 [0.30-0.95], p = 0.03), age at the time of implantation (HR = 1.28 [1.05-1.56] per decade, p = 0.02), length of stay postimplantation (HR = 1.16 [1.11-1.21] per week, p < 0.01) and INTERMACS profile of 1 or 2 (HR = 1.86 [1.17-2.97], p < 0.01) were independent predictors of mortality. In this large, retrospective study, treatment with ACEIs or ARBs was an independent factor associated with decreased mortality post-LVAD placement.

Beneficial effects of a point-of-care bleeding risk calculator on anticoagulant selection in the coronary catheterization laboratory.

STUDY OBJECTIVES: To estimate periprocedural bleeding risk before elective percutaneous coronary intervention (PCI) by using a point-of-care bleeding risk calculator and to document changes in anticoagulant use and bleeding complications after implementation of use of this calculator. DESIGN: Prospective observational pilot study with a historical control cohort. SETTING: Tertiary care medical center. PATIENTS: The pilot cohort consisted of 100 patients undergoing ad hoc PCI during elective cardiac catheterization procedures between January and May 2013, whose bleeding risk and accompanying PCI anticoagulant recommendations were determined by the use of a pre-PCI point-of-care bleeding risk calculator. The historical control cohort consisted of all patients who underwent elective PCI at the same facility between April 1, 2011, and March 31, 2012, before implementation of use of the bleeding risk calculator. MEASUREMENTS AND MAIN RESULTS: The pre-PCI bleeding risk calculator distinguished patients in the pilot cohort as high risk (score 12 or higher) or low risk (lower than 12) for bleeding after a PCI procedure. The primary outcome was bivalirudin use in the pilot cohort compared with its use in the historical control cohort. Implementation of the bleeding risk calculator significantly decreased bivalirudin use compared with bivalirudin use in the historical control cohort (87% in the control cohort vs 60% in the pilot cohort, p<0.01). Bivalirudin use remained high in patients at high bleeding risk (82.2% in the pilot cohort vs 87.4% in the control cohort, p=0.3) and its use was decreased in patients at low bleeding risk (41.8% in the pilot cohort vs 87.1% in the control cohort, p<0.01). The incidence of bleeding complications in the pilot cohort was comparable with that in the control cohort (1% vs. 0.4%, p=0.37), although this pilot study was underpowered to potentially detect a significant change in the incidence of bleeding complications. CONCLUSION: A simple bleeding risk calculator can substantially reduce overall bivalirudin use by specifically decreasing its use among patients at low bleeding risk while maintaining its use among patients at high bleeding risk. The incidence of bleeding complications remained unchanged despite decreasing bivalirudin use among patients undergoing elective coronary catheterization who were at low risk for bleeding.

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.

Predictors of cardiovascular events after liver transplantation: a role for pretransplant serum troponin levels.

Cardiovascular complications are major causes of morbidity and mortality after liver transplantation. Identifying candidates at highest risk of postoperative complications is a cornerstone of optimizing outcomes and utility. Using traditional cardiac risk factors in addition to C-reactive protein (CRP) levels, troponin levels, and echocardiographic parameters before transplantation, we sought to define cardiac risk so that we could predict cardiovascular events after transplantation. From December 1998 to December 2001, 230 adult patients who underwent liver transplantation with a median follow-up of 8.2 years were studied. The risk factors for cardiac disease were as follows: male gender with a mean age of approximately 50 years (57%), smoking history (60%), diabetes (23%), hypertension (19%), elevated troponin (25%), elevated CRP (25%), and preexisting cardiac disease (16%). Fifty-nine cardiac events occurred over 8.2 years. Risk factors (univariate analysis) for first cardiac events included age in decades [hazard ratio (HR) = 1.31, P = 0.047], diabetes (HR = 2.20, P = 0.004), prior cardiovascular disease (HR = 4.77, P < 0.0001), a troponin I level > 0.07 ng/mL (HR = 2.00, P = 0.023), left ventricular hypertrophy (HR = 2.06, P = 0.047), stress wall abnormalities (HR = 2.25, P = 0.018), and ischemia on stress imaging (HR = 2.89, P = 0.015). Multivariate analysis confirmed age, diabetes, a troponin I level > 0.07, and prior cardiac disease as independent risk factors for posttransplant cardiac events. In conclusion, pretransplant elevated troponin levels, diabetes, and a history of cardiovascular disease, alone or in combination, are strongly associated with the occurrence of posttransplant cardiovascular events.

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.

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.

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.

Alcoholic liver disease-related mortality in the United States: 1980-2003.

OBJECTIVES: Data on temporal changes in alcoholic liver disease (ALD)-related mortality in the United States are lacking. This longitudinal assessment is important, given the divergent data on trends in worldwide ALD-related mortality, concerns for underestimation of mortality attributed to ALD in previous investigations, and shifting attention to hepatitis C virus (HCV)-related mortality. METHODS: We analyzed mortality data compiled in the multiple cause-of-death public-use data file from the National Vital Statistics System from 1980 to 2003 using categorization by both International Classification of Diseases (ICD)-9 and ICD-10 systems. The main outcome measure was age- and sex-adjusted death rates attributable to ALD, HCV, or both (ALD/HCV) listed as immediate or underlying cause of death. RESULTS: A total of 287,365 deaths were observed over the 24-year period. Age- and sex- adjusted incidence rates of ALD-related deaths decreased from 6.9/100,000 persons in 1980 to 4.4/100,000 persons by 2003. After introduction of HCV diagnostic testing, HCV-related liver mortality increased to 2.9/100,000 persons by 2003. Death rates for subjects with concomitant ALD/HCV rose to 0.2/100,000 persons by 1999 and then remained unchanged through 2003. Age-specific mortality related to ALD was highest in the ages of 45-64 years. Between 1980 and 2003, the age- and sex-adjusted ALD-related mortality (per 100,000 persons) decreased from 6.3 to 4.5 among Caucasians, 11.6 to 4.1 among African Americans, and 8.0 to 3.7 among the "other" race group. CONCLUSIONS: Despite a decline in ALD-related mortality, the proportion of alcohol-related liver deaths is still considerably large and comparable in scope to that of HCV.

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.