Liver Transplantation Cohort Research Articles

Living Donor Liver Transplantation (LDLT)

Liver transplant (LT) has become the standard of care of end-stage liver disease (ESLD) or unresectable hepatocellular carcinoma. There are at least 18,000 patients on the wait list for a deceased donor liver donation. However, there is a critical shortage of donor organs, contributing to increasing wait-list mortality as well as profound acuity of patients when organs do become available. Living donor liver transplantation (LDLT) has become widely accepted in United States (US) as a potential alternative source of organs for patients eligible for liver transplantation. Several important factors have limited the significant growth of LDLT. LDLT is a technically challenging procedure that requires significant training and institutional and programmatic commitment and support. Furthermore, there are risks associated with donor procedure including potential liver failure and death, which call the ethics of LDLT into question. For these reasons and since LDLT is relatively new procedure, there are a few major transplant centers in the US performing this procedure. The National Institute of Health organized a network of nine leading transplant centers establishing the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) to study outcomes for LDLT in the US in 2002. The study was dedicated to reporting and investigating short and long-term outcomes for both recipients and donors. As the funding cycle concludes in 2015, the observations and publications of the consortium have contributed tremendously to the North American development of LDLT as an option for patients with ESLD and complications requiring transplantation.

Costs and absence of HCV-infected employees by disease stage

Objectives:Quantify the costs and absenteeism associated with stages of the Hepatitis C virus (HCV).Study design:Retrospective analysis of the HCMS integrated database from multiple geographically diverse, US-based employers with employee information on medical, prescription, and absenteeism claims.Methods:Employee data were extracted from July 2001–March 2013. Employees with HCV were identified by ICD-9-CM codes and classified into disease severity cohorts using diagnosis/procedure codes assigning the first date of most severe claim as the index date. Non-HCV employees (controls) were assigned random index dates. Inclusion required 6-month pre-/post-index eligibility. Medical, prescription, and absenteeism cost and time were analyzed using two-part regression (logistic/generalized linear) models, controlling for potentially confounding factors. Costs were inflation adjusted to September 2013.Results:All direct costs comparisons were statistically significant (p ≤ 0.05) with mean medical costs of $1813 [SE = $3] for controls (n = 727,588), $4611 [SE = $211] for non-cirrhotic (n = 1007), $4646 [SE = $721] for compensated cirrhosis (CC, n = 87), $12,384 [SE = $1122] for decompensated cirrhosis (DCC, n = 256), $33,494 [SE = $11,753] for hepatocellular carcinoma (HCC, n = 17) and $97,724 [SE = $32,437] for liver transplant (LT, n = 19) cohorts. Mean short-term disability days/costs were significantly greater for the non-cirrhotic (days = 2.03 [SE = 0.36]; $299 [SE = $53]), DCC (days = 6.20 [SE = 1.36]; $763 [SE = $169]), and LT cohorts (days = 21.98 [SE = 8.21]; $2537 [SE = $972]) compared to controls (days = 1.19 [SE = 0.01]; $155 [SE = $1]). Mean sick leave costs were significantly greater for non-cirrhotic ($373 [SE = $22]) and DCC ($460 [SE = $54]) compared to controls ($327 [SE = $1]).Conclusions:Employees with HCV were shown to have greater direct and indirect costs compared to non-HCV employee controls. Costs progressively increased in the more severe HCV disease categories. Slowing or preventing disease progression may avert the costs of more severe liver disease stages and enable employees with HCV to continue as productive members of the workforce.

Patterns and predictors of sexual function after liver donation: The Adult-to-Adult Living Donor Liver Transplantation Cohort study.

Although sexual functioning is an important facet of a living donor's quality of life, it has not received an extensive evaluation in this population. Using data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, we examined donor sexual functioning across the donation process from the predonation evaluation to 3 months and 1 year after donation. Donors (n = 208) and a comparison group of nondonors (n = 155) completed self-reported surveys with specific questions on sexual desire, satisfaction, orgasm, and (for men) erectile function. Across the 3 time points, donor sexual functioning was lower at the evaluation phase and 3 months after donation versus 1 year after donation. In the early recovery period, abdominal pain was associated with difficulty reaching orgasm [odds ratio (OR), 3.98; 95% confidence interval (CI), 1.30-12.16], concerns over appearance were associated with lower sexual desire (OR, 4.14; 95% CI, 1.02-16.79), and not feeling back to normal was associated with dissatisfaction with sexual life (OR, 3.58; 95% CI, 1.43-8.99). Efforts to educate donors before the surgery and prepare them for the early recovery phase may improve recovery and reduce distress regarding sexual functioning.

Immunodiagnostic Tests' Predictive Values for Progression to Tuberculosis in Transplant Recipients: A Prospective Cohort Study.

Little is known about the predictive value for progression to tuberculosis (TB) of interferon-γ release assays and how they compare with the tuberculin skin test (TST) in assessing the risk of TB infection in transplant recipients. We screened 50 liver transplant (LT) and 26 hematopoietic stem cell transplant (HSCT) recipients with both QuantiFERON-TB Gold In-tube (QFT-GT) and TST and prospectively followed them for a median of 47 months without preventive chemoprophylaxis. In the LT cohort, 1 in 22 (4.5%) QFT-GT-positive patients developed posttransplant TB, compared with none of the QFT-GT-negative patients. In the HSCT cohort, none of the 7 QFT-GT-positive patients developed TB, whereas 1 case (5.3%) progressed to active TB among the 19 QFT-GT-negative patients. Comparable results were obtained with the TST: in the LT group, 1 of 23 TST-positive and none of the 27 TST-negative patients developed TB; and in the HSCT group, none of the 8 TST-positive and one of the 18 TST-negative patients progressed to active TB. In this cohort of transplant recipients, the positive predictive value of QFT-GT for progression to active TB was low and comparable to that of TST. Although the risk of developing TB in patients with negative results at baseline is very low, some cases may still occur.

Liver Transplantation-Associated Lung Cancer: Comparison of Clinical Parameters and Outcomes

BackgroundThe incidence of lung cancer (LC) is increased in patients with a history of liver transplantation (LT). The purpose of our study was to compare the clinical characteristics and outcomes of patients with postliver transplantation LC (PLTLC) with cohorts of patients with “transplant-naive” LC, and LT patients without LC. Patients and MethodsAll the patients who had undergone LT or had been diagnosed with LC from 1987 to 2012 were included in the present analysis. The PLTLC cohort was compared with a LT cohort (n = 725) and the local LC registry (n = 2803). The standardized incidence ratios (SIRs) were computed in the classic manner after adjustment for sex, age, and year of follow-up. ResultsWithin the LT cohort, 22 patients (5 women) developed PLTLC (2.3%). The SIR for LC in LT recipients was 4.4 in the women and 2.6 in the men. The PLTLC cohort was older at LT (58.4 vs. 53.3 years; P = .028). Also, 90.5% of the PLTLC group had a history of smoking; 8 patients (42.1%) had had LC detected by annual routine lung cancer screening. The median post-LT survival was significantly inferior in the PLTLC cohort (117.1 vs. 182.6 months; P = .041). The median overall survival (OS), starting from the diagnosis of LC, was similar in the PLTLC and LC cohort (14.7 vs. 15.1 months; P = .519). ConclusionThe incidence of LC is significantly increased in the LT population. Therefore, LC screening might be an option for LT patients with a history of smoking. The prognosis of LC does not seem to be impaired by LT, suggesting a minor effect of LT on OS in patients with lung cancer.

Changes in liver and spleen volumes after living liver donation: a report from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL).

Previous reports have drawn attention to persistently decreased platelet counts among liver donors. We hypothesized an etiologic association between altered platelet counts and postdonation splenomegaly and sought to explore this relationship. This study analyzed de-identified computed tomography/magnetic resonance scans of 388 donors from 9 Adult-to-Adult Living Donor Liver Transplantation Cohort Study centers read at a central computational image analysis laboratory. Resulting liver and spleen volumes were correlated with time-matched clinical laboratory values. Predonation liver volumes varied 2-fold in healthy subjects, even when they were normalized by the body surface area (BSA; range = 522-1887 cc/m(2) , n = 346). At month 3 (M3), postdonation liver volumes were, on average, 79% of predonation volumes [interquartile range (IQR) = 73%-86%, n = 165] and approached 88% at year 1 (Y1; IQR = 80%-93%, n = 75). The mean spleen volume before donation was 245 cc (n = 346). Spleen volumes greater than 100% of the predonation volume occurred in 92% of donors at M3 (n = 165) and in 88% at Y1 after donation (n = 75). We sought to develop a standard spleen volume (SSV) model to predict normal spleen volumes in donors before donation and found that decreased platelet counts, a younger age, a higher predonation liver volume, higher hemoglobin levels, and a higher BSA predicted a larger spleen volume (n = 344, R(2) = 0.52). When this was applied to postdonation values, some large volumes were underpredicted by the SSV model. Models developed on the basis of the reduced sample of postdonation volumes yielded smaller underpredictions. These findings confirm previous observations of thrombocytopenia being associated with splenomegaly after donation. The results of the SSV model suggest that the biology of this phenomenon is complex. This merits further long-term mechanistic studies of liver donors with an investigation of the role of other factors such as thrombopoietin and exposure to viral infections to better understand the evolution of the spleen volume after liver donation.

Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL)

Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL)

Liver regeneration after living donor transplantation: Adult‐to‐adult living donor liver transplantation cohort study

Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676 ± 251 g (mean ± SD), and percentage reconstitution was 80% ± 13%. Among recipients, GRWR was 1.3% ± 0.4% (8 < 0.8%). Graft weight was 60% ± 13% of SLV. Three-month absolute growth was 549 ± 267 g, and percentage reconstitution was 93% ± 18%. Predictors of greater 3-month liver volume included larger patient size (donors and recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (P = 0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR = 4.50, P = 0.001) but not by GRWR or graft fraction (P > 0.90 for each). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3-month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction affects postresection function. Liver Transpl 21:79-88, 2015. © 2014 AASLD.

Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL)

There are few long-term studies of the health-related quality of life (HRQOL) in living liver donors. This study aimed to characterize donor HRQOL in the Adult to Adult Living Donor Liver Transplantation Study (A2ALL) up to 11 years post-donation. Between 2004 and 2013, HRQOL was assessed at evaluation, at 3 months, and yearly post-donation in prevalent liver donors using the short-form survey (SF-36), which provides a physical (PCS) and a mental component summary (MCS). Of the 458 donors enrolled in A2ALL, 374 (82%) had SF-36 data. Mean age at evaluation was 38 (range 18-63), 47% were male, 93% white, and 43% had a bachelor's degree or higher. MCS and PCS means were above the US population at all time points. However, at every time point there were some donors who reported poor scores (>1/2 standard deviation below the age and sex adjusted mean) (PCS: 5.3-26.8%, 10.0-25.0%). Predictors of poor PCS and MCS scores included recipient's death within the two years prior to the survey and education less than a bachelor's degree; poor PCS scores were also predicted by time since donation, Hispanic ethnicity, and at the 3-month post-donation time point. In summary, most living donors maintain above average HRQOL up to 11 years prospectively, supporting the notion that living donation does not negatively affect HRQOL. However, targeted support for donors at risk for poor HRQOL may improve overall HRQOL outcomes for living liver donors.

Predictors of donor follow-up after living donor liver transplantation.

Donor safety in living liver donation is of paramount importance; however, information on long-term outcomes is limited by incomplete follow-up. We sought to ascertain factors that predicted postdonation follow-up in 456 living liver donors in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study. Completed donor follow-up was defined as physical, phone, or laboratory contact at a given time point. Univariate and multivariate mixed effects logistic regression models, using donor and recipient demographic and clinical data and donor quality-of-life data, were developed to predict completed follow-up. Ninety percent of the donors completed their follow-up in the first 3 months, and 83% completed their follow-up at year 1; rates of completed follow-up ranged from 57% to 72% in years 2 to 7 and from 41% to 56% in years 8 to 10. The probability of completed follow-up in the first year was higher for white donors [odds ratio (OR) = 3.27, 95% confidence interval (CI) = 1.25-8.58] but lower for donors whose recipients had hepatitis C virus or hepatocellular carcinoma (OR = 0.34, 95% CI = 0.17-0.69). After the first year, an older age at donation predicted more complete follow-up. There were significant center differences at all time points (OR range = 0.29-10.11), with center variability in both returns for in-center visits and the use of phone/long-distance visits. Donor follow-up in the first year after donation was excellent but decreased with time. Predictors of follow-up varied with the time since donation. In conclusion, adapting best center practices (enhanced through the use of telephones and social media) to maintain contact with donors represents a significant opportunity to gain valuable information about long-term donor outcomes.

Plenary Sessions

Purpose: To study long-term complications in recipients of deceased donor liver transplant (DDLT) and living donor liver transplant (LDLT) in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Methods: We analyzed 471 DDLT and 565 LDLT from 1998 to 2010 followed up to 10 years for 39 categories of complications graded by Clavien-Dindo classification. Kaplan-Meier was used to estimate probability of complication and resolution over time, and predictors of complications were tested in Cox models. Results: Recipients of LDLT were more likely to be white, have cholestatic liver disease. DDLT recipients were more likely to have HCC, be in the ICU, on a ventilator, or have ascites. 85% and 47% of LDLT and DDLT recipients had a physiologic MELD less than 21 at the time of the transplant. Median follow-up for DDLT and LDLT was 3.12 and 3.52 years, respectively. Complications more probable in LDLT included bile leak, biliary stricture, HAT and bacteremia. In DDLT, ascites, intra-abdominal bleeding, cardiac complications and recurrent cirrhosis were more probable.Figure: No Caption available.At least one complication occurred in 70% and 73% of DDLT and LDLT, respectively. A higher probability of grade 3 or 4 complications was observed in LDLT recipients (28 % vs. 20% at 8 years, p=0.03). We found that risk factors for Grade 4 complications were DCD, dialysis at transplant, ascites, and duration of operation, but no significant difference between DDLT and LDLT (HR=0.89, p=0.60). Development of chronic kidney disease was less likely in LDLT recipients (HR 0.41, p=0.02). 95% of complications resolved in 5 years, with 86% of complications resolving in 12 months and no statistical difference between DDLT and LDLT. Biliary strictures, hernia, vascular and psychological complications had the lowest probability of resolution within 12 months. Conclusions: Biliary and vascular complications remain a challenge in LDLT while renal impairment, cardiac complications and recurrent cirrhosis are more probable in DDLT.

Post-Transplant Complications in Recipients of Deceased and Living Donor Liver Transplant.

Purpose: To study long-term complications in recipients of deceased donor liver transplant (DDLT) and living donor liver transplant (LDLT) in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Methods: We analyzed 471 DDLT and 565 LDLT from 1998 to 2010 followed up to 10 years for 39 categories of complications graded by Clavien-Dindo classification. Kaplan-Meier was used to estimate probability of complication and resolution over time, and predictors of complications were tested in Cox models. Results: Recipients of LDLT were more likely to be white, have cholestatic liver disease. DDLT recipients were more likely to have HCC, be in the ICU, on a ventilator, or have ascites. 85% and 47% of LDLT and DDLT recipients had a physiologic MELD less than 21 at the time of the transplant. Median follow-up for DDLT and LDLT was 3.12 and 3.52 years, respectively. Complications more probable in LDLT included bile leak, biliary stricture, HAT and bacteremia. In DDLT, ascites, intra-abdominal bleeding, cardiac complications and recurrent cirrhosis were more probable.Figure: No Caption available.At least one complication occurred in 70% and 73% of DDLT and LDLT, respectively. A higher probability of grade 3 or 4 complications was observed in LDLT recipients (28 % vs. 20% at 8 years, p=0.03). We found that risk factors for Grade 4 complications were DCD, dialysis at transplant, ascites, and duration of operation, but no significant difference between DDLT and LDLT (HR=0.89, p=0.60). Development of chronic kidney disease was less likely in LDLT recipients (HR 0.41, p=0.02). 95% of complications resolved in 5 years, with 86% of complications resolving in 12 months and no statistical difference between DDLT and LDLT. Biliary strictures, hernia, vascular and psychological complications had the lowest probability of resolution within 12 months. Conclusions: Biliary and vascular complications remain a challenge in LDLT while renal impairment, cardiac complications and recurrent cirrhosis are more probable in DDLT.

Improving Outcomes in DCDD Liver Transplantation: There Can Only Be Strength in Numbers

In the United States, liver transplantation using donation after circulatory determination of death (DCDD) donors is challenged by persistently inferior graft survival compared with donation after neurological death (DND), along with declining rates of liver transplantation relative to the total number of DCDD donors. Advances in adult-to-adult living donor liver transplantation graft survival temporally related to the Adult-to-Adult Living Donor Liver Transplantation Cohort Study consortium suggest that a similarly focused collaborative effort may serve to stimulate evolution within DCDD liver transplantation. Without a multi-center consortium to support innovative trials, the current state of DCDD liver transplantation is unlikely to progress.

Hepatitis C disease severity in living versus deceased donor liver transplant recipients: An extended observation study

Donor factors influence hepatitis C virus (HCV) disease severity in liver transplant (LT) recipients. Living donors, because they are typically young and have short cold ischemic times, may be advantageous for HCV-infected patients. Among HCV-infected patients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) surviving >90 days and followed for a median 4.7 years, advanced fibrosis (Ishak stage ≥3) and graft loss were determined. The 5-year cumulative risk of advanced fibrosis was 44% and 37% in living donor LT (LDLT) and deceased donor LT (DDLT) patients (P = 0.16), respectively. Aspartate aminotransferase (AST) activity at LT (hazard ratio [HR] = 1.38 for doubling of AST, P = 0.005) and biliary strictures (HR = 2.68, P = 0.0001) were associated with advanced fibrosis, but LDLT was not (HR = 1.11, 95% confidence interval [CI] 0.73-1.69, P = 0.63). The 5-year unadjusted patient and graft survival probabilities were 79% and 78% in LDLT, and 77% and 75% in DDLT (P = 0.43 and 0.32), with 27% and 20% of LDLT and DDLT graft losses due to HCV (P = 0.45). Biliary strictures (HR = 2.25, P = 0.0006), creatinine at LT (HR = 1.74 for doubling of creatinine, P = 0.0004), and AST at LT (HR = 1.36 for doubling of AST, P = 0.004) were associated with graft loss, but LDLT was not (HR = 0.76, 95% CI: 0.49-1.18, P = 0.23). Donor type does not affect the probability of advanced fibrosis or patient and graft survival in HCV-infected recipients. Thus, while LDLT offers the advantage of shorter wait times, there is no apparent benefit for HCV disease progression. Biliary strictures have a negative effect on HCV fibrosis severity and graft survival, and a high AST at LT may be an important predictor of fibrosis risk post-LT.

P236 Disease severity after 3 years of treating newly diagnosed pediatric Crohn's disease patients (the BELCRO cohort)

Background: In IBD, primary sclerosing cholangitis (PSC) confers an increased risk of colorectal neoplasia (CRN). The aim of this study was to evaluate the effect of liver transplantation (LT) on development of CRN in patients with PSC and IBD. Methods: From our LT cohort (n = 275, period 1992 2011), 21 patients were identified with PSC and IBD and a follow-up post LT >6 months (PSC+LT). We further identified 39 patients with PSC and IBD without LT (PSC). In these patients with PSC and IBD, we performed a Cox regression analysis with LT as a timedependent covariate. We additionally compared development of CRN after LT between patients with PSC and IBD and the non-PSC LT population. To this end, we compared PSC+LT to a group of LT patients without PSC or IBD that was matched for sex, age and duration of post LT follow up (LT). Results: In patients with PSC, LT increased the risk of CRN in PSC patients with IBD in the univariate analysis; this effect was no longer present in the multivariate analysis. Cumulative incidence of CRN was 29% in the PSC+LT group vs. 10% in the PSC group (ns). CRN-free survival did not differ between PSC+LT and LT groups. Cumulative incidence of CRN for the groups was similar (resp. 29% vs. 32%, ns). Conclusions: Liver transplantation did not increase the rate of CRN in patients with both PSC and IBD. Furthermore, the rate of development of CRN did not differ between PSC+LT patients and the general LT population.

P237 Differential diagnosis between intestinal tuberculosis and Crohn's disease – A prospective multicenter study from China

Background: In IBD, primary sclerosing cholangitis (PSC) confers an increased risk of colorectal neoplasia (CRN). The aim of this study was to evaluate the effect of liver transplantation (LT) on development of CRN in patients with PSC and IBD. Methods: From our LT cohort (n = 275, period 1992 2011), 21 patients were identified with PSC and IBD and a follow-up post LT >6 months (PSC+LT). We further identified 39 patients with PSC and IBD without LT (PSC). In these patients with PSC and IBD, we performed a Cox regression analysis with LT as a timedependent covariate. We additionally compared development of CRN after LT between patients with PSC and IBD and the non-PSC LT population. To this end, we compared PSC+LT to a group of LT patients without PSC or IBD that was matched for sex, age and duration of post LT follow up (LT). Results: In patients with PSC, LT increased the risk of CRN in PSC patients with IBD in the univariate analysis; this effect was no longer present in the multivariate analysis. Cumulative incidence of CRN was 29% in the PSC+LT group vs. 10% in the PSC group (ns). CRN-free survival did not differ between PSC+LT and LT groups. Cumulative incidence of CRN for the groups was similar (resp. 29% vs. 32%, ns). Conclusions: Liver transplantation did not increase the rate of CRN in patients with both PSC and IBD. Furthermore, the rate of development of CRN did not differ between PSC+LT patients and the general LT population.

P235 Does liver transplantation affect the risk for colorectal neoplasia in PSC-IBD patients?

Background: In IBD, primary sclerosing cholangitis (PSC) confers an increased risk of colorectal neoplasia (CRN). The aim of this study was to evaluate the effect of liver transplantation (LT) on development of CRN in patients with PSC and IBD. Methods: From our LT cohort (n = 275, period 1992 2011), 21 patients were identified with PSC and IBD and a follow-up post LT >6 months (PSC+LT). We further identified 39 patients with PSC and IBD without LT (PSC). In these patients with PSC and IBD, we performed a Cox regression analysis with LT as a timedependent covariate. We additionally compared development of CRN after LT between patients with PSC and IBD and the non-PSC LT population. To this end, we compared PSC+LT to a group of LT patients without PSC or IBD that was matched for sex, age and duration of post LT follow up (LT). Results: In patients with PSC, LT increased the risk of CRN in PSC patients with IBD in the univariate analysis; this effect was no longer present in the multivariate analysis. Cumulative incidence of CRN was 29% in the PSC+LT group vs. 10% in the PSC group (ns). CRN-free survival did not differ between PSC+LT and LT groups. Cumulative incidence of CRN for the groups was similar (resp. 29% vs. 32%, ns). Conclusions: Liver transplantation did not increase the rate of CRN in patients with both PSC and IBD. Furthermore, the rate of development of CRN did not differ between PSC+LT patients and the general LT population.

Functional distal splenorenal shunt and splenic artery ligation as portal flow modulation in left lobe living donor transplantation

Functional distal splenorenal shunt and splenic artery ligation as portal flow modulation in left lobe living donor transplantation

Resource Utilization and Direct Medical Costs of Chronic Hepatitis C in Thailand: A Heavy but Manageable Economic Burden

ObjectiveTo estimate the cost for the management of chronic hepatitis C (CHC) and related morbidities by using a payer perspective in Thailand. MethodsData elements were extracted from medical records of 542 patients newly diagnosed with CHC in five tertiary care hospitals across Thailand. All patients were divided into five health states: noncirrhotic CHC, hepatitis C virus (HCV)-related compensated cirrhosis, HCV-related decompensated cirrhosis, HCV-related hepatocellular carcinoma, and HCV-related liver transplantation. Resource utilization data for each patient during a 12-month follow-up study period were compiled, and reference prices published by the Thai government were used to estimate the cost for each health state. The average cost was calculated and categorized into various groups, for example, laboratory and diagnostic tests, procedures, medication, and hospitalization. ResultsThe average number of outpatient visits per patient was approximately six visits in all cohorts. The HCV-related hepatocellular carcinoma and liver transplantation cohorts had a higher average number of inpatient admissions per patient. The average number of days per admission varied from fewer than 3 days to 1 week or more across all the health states. The average annual total cost per patient varied across all health states from approximately 170,000 to 600,000 baht, and medication cost was the largest portion in every cohort, except the HCV-related liver transplantation cohort in year 1. Among all medications, the average annual antiviral medication cost per patient was the largest portion in the noncirrhotic CHC and HCV-related compensated cirrhosis cohorts. ConclusionsCHC was a costly disease in Thailand. The average annual medication cost was the largest portion in every health state, except HCV-related liver transplantation.

Norovirus Causing Chronic Diarrhea in Renal Transplant Recipients

Purpose: The incidence of diarrhea after renal transplant is common, varying from 13-64%, depending on the immunosupressant regime. Post-transplant diarrhea doubles the risk of renal graft loss and mortality. Studies of liver transplant cohorts have suggested that the most common causes of post-transplant diarrhea are Clostridium difficile, cytomegalovirus, and the use of immnosupressive regimes, including mycophenolate mofetil, cyclosporine, tacrolimus, and sirolimus. Recently, norovirus has been implicated as a cause of chronic diarrhea post-renal transplant. Norovirus is the most common cause of acute gastroenteritis worldwide. In immunocompetent individuals, it is self-limiting. A literature review found two case series of patients (n=9 and n=15) demonstrating persistent norovirus infection following renal transplant. Other cases have been documented in immunosupressed patients. In our center, we have identified two cases of chronic diarrhea in renal transplant recipients caused by chronic Norovirus infection. The first was a 65 year-old male with a two-year history of diarrhea following an episode of acute gastroenteritis. Stool frequency was 3-6 bowel movements per day. Stool studies and tests for C. difficile were negative, but tested positive for norovirus. A colonoscopy was normal. Norovirus PCR was performed three times during the course of the diarrhea, and was positive each time, remaining positive for over 16 months. The second patient was a 67-year-old female with an 18-month history of chronic diarrhea following a severe self-limited gastroenteritis. She presented with 5-6 bowel movements a day, and scant blood on a few occasions. Again, colonoscopy and stool studies were normal, as were multiple tests for C. difficile. Norovirus PCR was positive throughout the course of her illness -- in this case for a duration of over 15 months. While diarrhea is common after kidney transplantation, we present two cases of chronic diarrhea post-renal transplant with persistently positive Norovirus PCR. Norovirus may persist in renal transplant recipients or immunocompromised individuals, and should be considered when these patients present with chronic diarrhea.