African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models. CONCLUSIONS: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.

Cannabinoid Use Among Liver Transplant Recipients.

The effect of cannabinoids on liver transplant outcomes is an area of active research. We aimed to investigate marijuana (MJ) and cannabidiol (CBD) use among liver transplant recipients at the University of Colorado Hospital (UCH), specifically prevalence, habits, and predictors of use. Liver transplant recipients followed at UCH with valid email addresses were sent an informed consent postcard and survey invitation. This exploratory survey was conducted using REDCap. IBM SPSS Statistics software was used for statistical analysis. Of 1227 recipients who were sent surveys, 538 people responded. On average, respondents were 59 years old, with 63.7% male and 81.7% White. Hepatitis C virus (HCV; 30.4%) and alcohol use (17.7%) were the most common etiologies of liver disease. Among respondents, 23.8% reported current MJ use. Methods of use included smoking (72.4%), ingestion (55.3%), and vaporization (31.7%). Top reasons for MJ use were recreation (56.5%), anxiety (54.8%), and pain (53.2%). Among respondents, 21.0% currently used CBD, usually in the form of creams or lotions (58.9%) and to relieve pain (84.9%) and anxiety (31.1%). In multivariable analysis, age (odds ratio [OR], 0.941; 95% confidence interval [CI], 0.923-0.959; P < 0.001), diabetes mellitus (OR, 0.357; 95% CI, 0.171-0.746; P = 0.01), HCV cirrhosis (OR, 3.949; 95% CI, 2.281-6.835; P < 0.001), alcohol-related cirrhosis (OR, 2.101; 95% CI, 1.202-3.671; P = 0.01), and current tobacco use (OR, 2.918; 95% CI, 1.065-7.990; P = 0.04) were significant predictors of MJ use. Our study shows that cannabinoid use after liver transplant is common. MJ use is associated with decreasing age, alcohol-related and HCV cirrhosis, and tobacco use. Anxiety, pain, and recreation were top reasons for its use. Transplant teams should address reasons why their patients use MJ and CBD and develop programs to mitigate anxiety and pain after transplant. Further studies are needed to examine effects of cannabinoids on liver transplant outcomes.

Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) is an autoimmune disease characterized by bile duct destruction that can progress to cirrhosis. A liver biopsy substudy was conducted in the PBC obeticholic acid (OCA) International Study of Efficacy (POISE) to determine the long-term effects of OCA on liver damage and fibrosis in patients with PBC. POISE is a phase 3, double-blind, placebo-controlled, randomized trial with a 5-year open-label extension that evaluated 5 to 10 mg OCA daily in patients who were intolerant or unresponsive to ursodeoxycholic acid. METHODS: Liver biopsy specimens were collected from 17 patients at time of enrollment in the double-blind phase and after 3 years of OCA treatment. Histologic evaluations were performed by 2 pathologists in a blinded, randomized fashion to determine the effects of OCA on fibrosis and other histologic parameters. Collagen morphometry assessments were performed by automated second harmonic generation and 2-photon excitation microscopy to observe quantitative measures of fibrosis. RESULTS: From the time of enrollment until 3 years of treatment, most patients had improvements or stabilization in fibrosis (71%), bile duct loss (76%), ductopenia (82%), ductular reaction (82%), interface hepatitis (100%), and lobular hepatitis (94%). Over the 3-year period, we found significant reductions in collagen area ratio (median, -2.1; first quartile, -4.6, third quartile, -0.3; P = .013), collagen fiber density (median, -0.8; first quartile, -2.5; third quartile, 0; P = .021), collagen reticulation index (median, -0.1; first quartile, -0.3; third quartile, 0; P = .008), and fibrosis composite score (median, -1.0; first quartile, -2.5; third quartile, -0.5; P = .002). CONCLUSIONS: A subanalysis of data from the POISE study showed that long-term OCA treatment in patients with PBC is associated with improvements or stabilization of disease features, including ductular injury, fibrosis, and collagen morphometry features (ClinicalTrials.gov no: NCT01473524 and EudraCT no: 2011-004728-36).

Transfemoral Transcatheter Aortic Valve Replacement for Mixed Aortic Valve Disease in Child's Class C Liver Disease Prior to Orthotopic Liver Transplantation: A Case Report.

The American Association for the Study of Liver Diseases practice guidelines list severe cardiac disease as a contraindication to liver transplantation. Transcatheter aortic valve replacement has been shown to decrease all-cause mortality in patients with severe aortic stenosis who are not considered candidates for surgical aortic valve replacement. We report our experience of liver transplantation in a patient with severe aortic stenosis and moderate aortic insufficiency who underwent transcatheter aortic valve replacement with Child-Pugh Class C disease at a Model For End-Stage Liver Disease score of 29. The patient had a difficult post procedure course that was successfully medically managed. After liver transplantation the patient was discharged to home on postoperative day 11. The combination of cardiac disease and end stage liver disease is challenging but these patients can have a successful outcome despite very severe illness.

Bioethics and the Right to Health: Advancing a Complementary Agenda.

This special section in Health and Human Rights Journal explores the relationship between bioethics and the right to health. Although bioethics scholars may argue for a right to health, particularly in the domains of universal health coverage and global health governance, and human rights scholars may advance ethical norms in their work, there has been little scholarly attention to the intersections, synergies, and contrasts between these two areas of study. At first glance, this is surprising given that bioethics and human rights share conceptual and normative terrain in articulating guidance for action on health-related issues and international policy and practice is explicitly interrelating human rights and ethics.

Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation.

BACKGROUND & AIMS: IL28B single nucleotide polymorphisms are strongly associated with spontaneous HCV clearance and treatment response in non-transplant populations. A DDX58 single nucleotide polymorphism is associated with the antiviral response of innate lymphocytes. We aimed at evaluating the associations of donor and recipient IL28B (rs12979860 and rs8099917) and DDX58 (rs10813831) genotypes with severity of HCV recurrence after liver transplantation. METHODS: In a case-control study of 523 liver transplantation recipients with HCV, we matched severe with mild recurrent HCV based on 2-year clinical and histologic follow-up. A total of 440 liver transplantation recipients (severe, n=235; mild, n=205) with recipient DNA and 225 (severe, n=123; mild, n=102) with both recipient and donor DNA were analyzed. RESULTS: IL28B [rs12979860, non-CC (vs. CC) and rs8099917, non-TT (vs. TT)] in the recipient-only analysis had higher risk of severe recurrent HCV [OR 1.57 and 1.58, p<0.05]. However, for the 225 with donor and recipient DNA, IL28B rs12979860 CC (vs. non-CC) and rs8099917 TT (vs. non-TT) and DDX58 rs10813831 non-GG (vs. GG) were associated with more (not less) severe recurrent HCV. The greatest risk of severe recurrent HCV was for rs12979860 CC donors in non-CC recipients (OR 7.02, p <0.001, vs. non-CC donor/recipient) and for rs8099917 TT donors in non-TT recipients (OR 5.78, p=0.001, vs. non-TT donor/recipient). These associations persisted after controlling for donor age, donor race, and donor risk index. CONCLUSIONS: IL28B and DDX58 single nucleotide polymorphisms that are favorable when present in the non-transplant setting or in the recipient are unfavorable when present in a donor liver graft.

Risk of waitlist mortality in patients with primary sclerosing cholangitis and bacterial cholangitis.

Patients with primary sclerosing cholangitis (PSC) are at increased risk for bacterial cholangitis because of biliary strictures and bile stasis. A subset of PSC patients suffer from repeated episodes of bacterial cholangitis, which can lead to frequent hospitalizations and impaired quality of life. Although waitlist candidates with PSC and bacterial cholangitis frequently receive exception points and/or are referred for living donor transplantation, the impact of bacterial cholangitis on waitlist mortality is unknown. We performed a retrospective cohort study of all adult waitlist candidates with PSC who were listed for initial transplantation between February 27, 2002 and June 1, 2012 at the University of Pennsylvania and the University of Colorado-Denver. During this period, 171 PSC patients were waitlisted for initial transplantation. Before waitlisting, 38.6% (66/171) of the patients had a history of bacterial cholangitis, whereas 28.0% (44/157) of the patients with at least 1 Model for End-Stage Liver Disease update experienced cholangitis on the waitlist. During follow-up, 30 patients (17.5%) were removed from the waitlist for death or clinical deterioration, with 46.7% (14/30) developing cholangiocarcinoma. Overall, 12 of the 82 waitlist candidates (14.6%) who ever had an episode of cholangitis were removed for death or clinical deterioration, whereas 18 of the 89 candidates (20.2%) without cholangitis were removed (P = 0.34 for a comparison of the 2 groups). No patients were removed because of bacterial cholangitis. In multivariate competing-risk models, a history of bacterial cholangitis was not associated with an increased risk of waitlist removal for death or clinical deterioration (subhazard ratio = 0.67, 95% confidence interval = 0.65-0.70, P < 0.001). In summary, waitlist transplant candidates with PSC and bacterial cholangitis do not have an increased risk of waitlist mortality. The data call into question the systematic granting of exception points or referral for living donor transplantation due to a perceived risk of increased waitlist mortality.

Human rights impact assessment of trade-related Intellectual property rights: a key strategy in post-2015 efforts to improve access to safe and accessible medicines

In 2013, more than half the world's poor continue to lack access to essential medicines, despite a multitude of global health diplomacy efforts to increase access to affordable medicines in low and middle-income countries. This failure is exemplified in Millennium Development Goal (MDG) Target 8E which aims to increase access to affordable medicines, yet fails to address key causes of unaffordability, including trade-related intellectual property rights under World Trade Organization (WTO) and bilateral and regional free trade agreement rules. This commentary argues that addressing these price impacts is key to effectively advancing access to medicines and that such measures should be incorporated into goals to replace the MDGs after they expire in 2015. One way to do so is through the use of human rights impact assessment (HRIA) of trade-related intellectual property rights to mitigate the price impacts of these rights and realize state duties in order to provide access to affordable essential medicines. An HRIA requires policy makers to assess the impacts of trade-related intellectual property rights on medicine affordability and access, and to accordingly remedy any negative impacts on medicines access. Multiple global health and human rights actors and institutions endorse their use, and significant attention has been brought to developing effective, robust and user-friendly methodologies. Global policy makers formulating post-2015 access-to-medicine goals should ensure that HRIAs are adopted as a pragmatic and widely agreed upon means of protecting drugs from a key structural determinant of inaccessibility, and realizing universal access as a prioritized aspect of the right to health.

Risk of advanced fibrosis with grafts from hepatitis C antibody-positive donors: a multicenter cohort study.

Over the last decade, the use of liver grafts from hepatitis C virus antibody-positive donors [HCV(+)Ds] has tripled in the United States. Although previous studies have demonstrated no association between an HCV(+)D status and graft loss, the effects of an HCV(+)D on histological outcomes are not well known. Hepatitis C virus (HCV)-infected recipients at 5 US centers (2002-2007) who survived more than 30 days with 1 or more posttransplant biopsy samples were included. Cox regression was used to examine the association between an HCV(+)D status and advanced fibrosis (stage 3/4 or higher). Ninety-nine of the 1206 patients (8%) received an HCV(+)D graft. Recipients of HCV(+)D grafts were older than recipients of hepatitis C virus antibody-negative donor [HCV(-)D] grafts (P = 0.03), but they were otherwise similar. HCV(+)D grafts were significantly lower in quality according to the donor risk index (P < 0.001). Advanced fibrosis occurred in 32% of HCV(+)D graft recipients and in 28% of HCV(-)D graft recipients (P = 0.39). The unadjusted 1- and 3-year rates of advanced fibrosis were significantly higher for HCV(+)D graft recipients (14% and 48%) versus HCV(-)D graft recipients (7% and 33%, P = 0.01). Transplantation with HCV(+)D grafts was associated with a 58% increased risk of advanced fibrosis [95% confidence interval (CI) = 1.05-2.36, P = 0.03]. However, in an analysis stratified by the mean donor age of 45 years, an HCV(+)D status was associated with advanced fibrosis only with donors >45 years old [hazard ratio (HR) = 1.76, 95% CI = 1.06-2.93, P = 0.03] and not with donors ≤45 years old (HR = 0.94, 95% CI = 0.47-1.87, P = 0.85). In conclusion, a careful consideration of the risks and benefits is needed with HCV(+)D grafts. Recipients of HCV(+)D grafts (especially from older donors) should undergo close monitoring for more rapidly progressive fibrosis. Studies are needed to determine whether early HCV therapy modifies this risk.

Hepatitis C virus-infected women have a higher risk of advanced fibrosis and graft loss after liver transplantation than men.

UNLABELLED: In natural history studies of hepatitis C virus (HCV) infection, women have a lower risk of disease progression to cirrhosis. Whether female sex influences outcomes of HCV in the posttransplantation setting is unknown. All patients transplanted for HCV-related liver disease from 2002-2007 at five United States transplantation centers were included. The primary outcome was development of advanced disease, defined as biopsy-proven bridging fibrosis or cirrhosis. Secondary outcomes included death, graft loss, and graft loss with advanced recurrent disease. A total of 1,264 patients were followed for a median of 3 years (interquartile range, 1.8-4.7), 304 (24%) of whom were women. The cumulative rate of advanced disease at 3 years was 38% for women and 33% for men (P=0.31), but after adjustment for recipient age, donor age, donor anti-HCV positivity, posttransplantation HCV treatment, cytomegalovirus infection and center, female sex was an independent predictor of advanced recurrent disease (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.02-1.70; P=0.04). Among women, older donor age and treated acute rejection were the primary predictors of advanced disease. The unadjusted cumulative 3-year rates of patient and graft survival were numerically lower in women (75% and 74%, respectively) than men (80% and 78%, respectively), and in multivariable analyses, female sex was an independent predictor for death (HR, 1.30; 95% CI, 1.01-1.67; P=0.04) and graft loss (HR, 1.31; 95% CI, 1.02-1.67; P=0.03). CONCLUSION: Female sex represents an underrecognized risk factor for advanced recurrent HCV disease and graft loss. Further studies are needed to determine whether modification of donor factors, immunosuppression, and posttransplantation therapeutics can equalize HCV-specific outcomes in women and men.

Hepaticoduodenostomy is an alternative to Roux-en-Y hepaticojejunostomy for biliary reconstruction in live donor liver transplantation.

INTRODUCTION: A Roux-en-Y hepaticojejunostomy (HJ) is usually performed during live donor liver transplantation (LDLT) when a duct-to-duct reconstruction is not possible. However, direct anastomosis of the bile duct to the duodenum (hepaticoduodenostomy [HD]) is an alternative technique for biliary repair that has been previously used for conventional biliary surgery and at our center for cadaveric liver transplant. We provide the first evidence that HD is an alternative technique for biliary reconstruction in LDLT. METHODS: We performed a total of 71 LDLT between 2002 and 2008. An end-to-end anastomosis was used in 30 patients. Forty-one patients had a biliary enteric anastomosis in which seven were reconstructed with an HD. Accessory ducts were fashioned into a common duct or implanted into the duodenum separately. RESULTS: There were no patient deaths or retransplants in a follow-up period that ranged from 90 to 771 days after surgery. One patient was diagnosed with cholangitis that responded to intravenous antibiotics and removal of the stent by endoscopy. CONCLUSIONS: This preliminary case series suggests that that HD is a feasible alternative to HJ biliary anastomosis when a duct-to-duct anastomosis cannot be performed. HD offers the possible advantage of simple postoperative access to the biliary system by endoscopy and avoids complications caused by HJ bowel anastomosis.

Impact of hepatopulmonary syndrome on quality of life and survival in liver transplant candidates.

BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS) affects 10%-30% of patients with cirrhosis and portal hypertension, but the impact on functional status, quality of life, and survival is poorly defined. We assessed the impact of HPS in patients evaluated for liver transplantation. METHODS: We performed a prospective multicenter cohort study of patients being evaluated for liver transplantation in 7 academic centers in the United States. Patients with HPS (defined as an increased alveolar-arterial oxygen gradient with intrapulmonary vasodilation) were compared with those without HPS in terms of demographics and clinical variables. New York Heart Association functional class, quality of life, and survival were assessed. RESULTS: Seventy-two patients with HPS and 146 patients without HPS were compared. There were no differences in age, sex, or etiology or severity of liver disease between the groups; however, patients with HPS were less likely to have a history of smoking (P = .03). Patients with HPS had worse New York Heart Association functional class (P = .005) and had significantly worse quality of life in certain domains compared with patients without HPS. In addition, patients with HPS also had a significantly increased risk of death compared with patients without HPS despite adjustment for age, sex, race/ethnicity, Model for End-Stage Liver Disease score, and liver transplantation (adjusted hazard ratio = 2.41; 95% confidence interval, 1.31-4.41; P = .005). CONCLUSIONS: HPS was associated with a significant increase in risk of death as well as worse functional status and quality of life in patients evaluated for liver transplantation.

Atrial septal perforation from TIPS stent migration.

Transjugular intrahepatic portosystemic shunts (TIPS) are safe and effective for the treatment of portal hypertension. Cardiac complications are unusual. This study reports a case of TIPS stent migration to the right atrium causing perforation of the atrial septum in a patient with end-stage liver disease. The shunt was removed transvenously but attempts at transvenous occlusion of the septal perforation were unsuccessful. The patient went on to undergo combined open-heart surgery with septum repair and liver transplantation. The case highlights a rare complication of TIPS and methods for treatment including transvenous removal, transvenous repair, and combined cardiotomy-liver transplantation surgery.

Hepatic artery chemoembolization for hepatocellular carcinoma in patients listed for liver transplantation.

We retrospectively analyzed all listed patients having hepatic artery chemoembolization (HACE) for hepatocellular carcinoma (HCC) stage T2 or less. Outcomes were transplantation, waiting list removal, death, and HCC recurrence. Twenty patients (mean age 55.7 years; 15 males) were identified. Twelve (60%) were transplanted, seven (35%) were removed from the list and one (5%) remains listed. Fourteen (70%) are alive. All 12 transplanted patients are alive (mean 2.94 years); one of seven removed from the list is alive (mean 1.45 years). Survival was significantly higher for those transplanted or listed vs. removed from the list (100% vs. 14.3%, p = 0.0002). No HCC's recurred. Three patients (15%) were removed from the list after prolonged waiting times before MELD. Hepatic artery chemoembolization induced deterioration and removal from the list of one (5%) patient. Survival for those transplanted was excellent(100%), but overall survival was significantly lower (61.3%) at a mean 5.48 years. Hepatic artery chemoembolization for listed patients with

Impact of pretransplant diagnosis of hepatocellular carcinoma on cadveric liver allocation in the era of MELD.

The allocation system based on the Model for End-stage Liver Disease (MELD) has led to more patients diagnosed with hepatocellular carcinoma (HCC) being transplanted. We hypothesized that more patients misdiagnosed with HCC are also being transplanted, leading to inappropriate organ allocation. Therefore, we retrospectively analyzed all liver transplants at our center from July 14, 2000, to October 22, 2002 (N = 172; 129 pre-MELD, 43 post-MELD), comparing pretransplant HCC diagnosis to explant histology. Thirty patients met the United Network for Organ Sharing (UNOS) diagnostic criteria for pretransplant HCC diagnosis. There were 25 men (median age, 52.5 yr), and 80% had hepatitis C. The proportion of patients transplanted who had an HCC diagnosis increased from 12% (15/129) pre-MELD to 35% (15/43) post-MELD implementation (P < 0.01). Three of 15 (20%) transplanted pre-MELD and 5 of 15 (33%) transplanted post-MELD lacked HCC in the explant (P = 0.10). Of the three false-positives pre-MELD, one was Status 2B already, and two received living-donor livers. Of the 5 false-positives post-MELD, three had score upgrades that led to early transplantation (13 to 29, 20 to 29, and 9 to 24) while two had MELD scores of 35 and 36 already. The percentage of organs that could have gone to patients with more advanced liver disease without HCC increased from 0% (0/129) pre-MELD to 7% (3/43) post-MELD (P < 0.01). Since the implementation of MELD, the proportion of patients transplanted who had an HCC diagnosis nearly tripled, and a small but significant proportion of organs are now going to patients misdiagnosed with HCC. More stringent HCC diagnostic criteria will be required to decrease the effect that misdiagnosis has on organ allocation.

Survival following liver transplantation from non-heart-beating donors.

OBJECTIVE: To determine whether patient and graft survival following transplantation with non-heart-beating donor (NHBD) hepatic allografts is equivalent to heart-beating-donor (HBD) allografts. SUMMARY BACKGROUND DATA: With the growing disparity between the number of patients awaiting liver transplantation and a limited supply of cadaveric organs, there is renewed interest in the use of hepatic allografts from NHBDs. Limited outcome data addressing this issue exist. METHODS: Retrospective evaluation of graft and patient survival among adult recipients of NHBD hepatic allografts compared with recipients of HBD livers between 1993 and 2001 using the United Network of Organ Sharing database. RESULTS: NHBD (N = 144) graft survival was significantly shorter than HBD grafts (N = 26856). One- and 3-year graft survival was 70.2% and 63.3% for NHBD recipients versus 80.4% and 72.1% (P = 0.003 and P = 0.012) for HBD recipients. Recipients of an NHBD graft had a greater incidence of primary nonfunction (11.8 vs. 6.4%, P = 0.008) and retransplantation (13.9% vs. 8.3%, P = 0.04) compared with HBD recipients. Prolonged cold ischemic time and recipient life support were predictors of early graft failure among recipients of NHBD livers. Although differences in patient survival following NHBD versus HBD transplant did not meet statistical significance, a strong trend was evident that likely has relevant clinical implications. CONCLUSIONS: Graft and patient survival is inferior among recipients of NHBD livers. NHBD donors remain an important source of hepatic grafts; however, judicious use is warranted, including minimization of cold ischemia and use in stable recipients.

To transplant or not to transplant recurrent hepatitis C and liver failure.

In summary, re-OLT accounts for 10% of all OLTs performed and is associated with significantly increased resource use, and decreased survival compared with primary OLT. After transplantation into an HCV-infected recipient, infection of the allograft by HCV is invariable. As patients survive longer after liver transplantation, it is likely that allograft failure related to HCV recurrence will occur. Results of re-OLT for HCV are inferior to those of primary grafting, paralleling the results for retransplantation for other indications. Many studies have demonstrated that HCV infection significantly impairs patient and allograft survival after liver retransplantation, regardless of etiology of allograft failure. Patient survival rates with HCV infection are 57% to 65% at 1 year, as compared with 65% to 82% among patients without HCV infection. Experience with retransplantation is limited, however, and studies are difficult to interpret because of small sample sizes and lack of uniform definitions of survival, HCV recurrence, and allograft failure. Similar to outcomes after retransplantation for non-HCV related indications, the most common causes of death are sepsis and multi-organ failure. The high mortality associated with retransplantation has not universally been caused by recurrent disease, however recent studies have demonstrated that re-recurrent HCV occurs and the natural history is similar, if not more accelerated, after the second transplant. HCV infection may, in fact, increase mortality in a group of patients already predisposed to an inferior outcome. Preoperative serum creatinine and bilirubin have been consistently associated with survival after retransplantation and favorable results are attainable with strict selection criteria. The increasing use of expanded donor criteria, in particular, LRLT, raises important practical and ethical issues with regards to the HCV-positive transplant recipient and will become a challenge to the transplant community as a whole. With the donor morbidity and mortality associated with LRLT currently estimated at 32% and 0.3%, respectively, one must determine how much risk is acceptable to the donor in relation to the outcome in the recipient. This is especially true in HCV-infected recipients, in whom HCV re-recurrence may occur in the second allograft and lead to accelerated failure. LRLT, however, would not deplete the organ pool and would lead to the use of scarce cadaveric organs to patients who are awaiting primary liver transplantation. Despite inferior outcomes, a better tactic may be to consider retransplantation for recurrent HCV in those whose primary transplant was a LDLT, as the initial allograft did not deplete the donor pool. Given the shortage of donor organs and the increasing number of patients with HCV-induced allograft cirrhosis, identifying ways to improve allograft survival in HCV-infected patients represents an important focus for further research. Additional studies are needed to further explore the mechanisms underlying the reduction in survival and to identify which HCV-positive individuals are at greatest risk for poor survival. Studies are beginning to emerge that demonstrate that HCV recurrence can be modified with combination antiviral therapy and that the HCV virus can be eliminated. Additional longitudinal prospective studies are needed to assess the exact impact of HCV on survival after retransplantation, the effects of the newer immunosuppressive agents such as sirolimus and mycophenolate mofetil on HCV, the use of preemptive antiviral therapy on HCV eradication and fibrosis modification, and the appropriateness of expanded donor criteria. Until we have longer follow-up and greater experience with the HCV-positive recipient with allograft failure, retransplantation should be considered a viable option for highly selected patients, particularly in patients in whom renal failure and severe hyperbilirubinemia have not occurred.