Strategies to reduce hepatitis C virus recurrence after liver transplantation

Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not retransplanting this patients, as lower patient and graftoutcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pretransplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of posttransplant HCV recurrence and strategies to reduce its impact on our patients.     

Hepatitis C and liver transplantation

Hepatitis C virus (HCV) is important to the liver transplant recipient for several reasons. First, chronic HCV infection is a frequent cause of end-stage liver disease in North America and Europe, where the majority of liver transplants are performed. Second, recurrence of HCV after liver transplantation is almost universal so that many liver transplant recipients with and without overt hepatitis are viraemic. Third, HCV infection in the organ donor and/or in the blood transfused in the peri-transplant period make acquisition of HCV possible. Finally, liver transplantation for chronic HCV infection represents a major financial burden to the health-care system in the USA and worldwide. Histological hepatitis not due to HBV or cytomegalovirus (CMV) is present in 14–35% of allografts from patients undergoing liver transplantation, and the majority of this is due to HCV infection. HCV infection recurs post-transplant in almost all patients with pre-transplant infection. Proof that HCV does recur has been provided by the sequencing of the hypervariable domain of the E2/NS1 region. The magnitude of HCV infection is underestimated by using serological assays in this immunosuppressed population. Using the b-DNA assay, HCV-RNA levels have been shown to increase in patients with recurrent infection. The long-term consequences remain to be defined but post-transplantation HCV infection is generally much less devastating than post-transplantation HBV infection, and many patients have clinically silent disease. It is likely that a carrier state exists in immunosuppressed transplant recipients since high HCV-RNA levels occur in the absence of liver damage. In one study, 1, 2 and 3 year patient survival rates were shown to be comparable in patients with chronic active HCV infection and with cryptogenic cirrhosis (94, 89 and 87%, and 84, 84 and 73%, respectively). A more recent study from the University of Pittsburgh which compared the outcome of a larger number of HCV-infected patients (n= 237) with a large number of control patients with non-viral disease (n= 801), showed that indeed HCV infection does impact negatively on both patient and graft survival (1, 2 and 3 year patient survival in the study and control groups of 78, 68 and 66% and 84, 82 and 78%, respectively, P= 0.001). Undoubtedly with time, the full impact of recurrent HCV infection will become apparent, although short-term survival is sufficiently good to warrant continued transplantation of this group of patients. While the disease course in many patients is benign, aggressive post-transplant HCV infection leading to liver failure is well documented. Factors which determine why some patients are more susceptible to liver damage than others are currently under study. It is likely that many interrelated variables are involved, including the level of pre-transplant viraemia, genotype of the virus, amount of post-transplantation immunosuppression, and ability of the host immune system to recognize HCV and mount an immune response.     

Post-liver transplant hepatitis C virus recurrence: An unresolved thorny problem

Hepatitis C virus (HCV)-related cirrhosis represents the leading cause of liver transplantation in developed, Western and Eastern countries. Unfortunately, liver transplantation does not cure recipient HCV infection: reinfection universally occurs and disease progression is faster after liver transplant. In this review we focus on what happens throughout the peri-transplant phase and in the first 6-12 mo after transplantation: during this crucial period a completely new balance between HCV, liver graft, the recipient’s immune response and anti-rejection therapy is achieved that will deeply affect subsequent outcomes. Nearly all patients show an early graft reinfection, with HCV viremia reaching and exceeding pre-transplant levels; in this setting, histological assessment is essential to differentiate recurrent hepatitis C from acute or chronic rejection; however, differentiating the two patterns remains difficult. The host immune response (mainly cellular mediated) appears to be crucial both in the control of HCV infection and in the genesis of rejection, and it is also strongly influenced by immunosuppressive treatment. At present no clear immunosuppressive strategy could be strongly recommended in HCV-positive recipients to prevent HCV recurrence, even immunotherapy appears to be ineffective. Nonetheless it seems reasonable that episodes of rejection and over-immunosuppression are more likely to enhance the risk of HCV recurrence through immunological mechanisms. Both complete prevention of rejection and optimization of immunosuppression should represent the main goals towards reducing the rate of graft HCV reinfection. In conclusion, post-transplant HCV recurrence remains an unresolved, thorny problem because many factors remain obscure and need to be better determined.     

Early graft dysfunction following adult-to-adult livingrelated liver transplantation： Predictive factors and outcomes

AIM： To describe a condition that we define as early graft dysfunction （EGD） which can be identified preoperatively. METHODS： Small-for-size graft dysfunction following living-related liver transplantation （LRLT） is characterized by EGD when the graft-to-recipient body weight ratio （GRBWR） is below 0.8%. However, patients transplanted with GRBWR above 0.8% can develop dysfunction of the graft. In 73 recipients of LRLT （GRBWR 〉 0.8%）, we identified 10 patients who developed EGD. The main measures of outcomes analyzed were overall mortality, number of re-transplants and length of stay in days （LOS）. Furthermore we analyzed other clinical pre-transplant variables, intraoperative parameters and post transplant data.RESULTS： A trend in favor of the non-EGD group （3-mo actuarial survival 98% vs 88%, P = 0.09; 3-mo graft mortality 4.7% vs 20%, P = 0.07） was observed as well as shorter LOS （13 d vs 41.5 d; P = 0.001） and smaller requirement of peri-operative Units of Plasma （4 vs 14; P = 0.036）. Univariate analysis of pretransplant variables identified platelet count, serum bilirubin, INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score （P = 0.025, OR： 1.175） and pre-transplant platelet count （P = 0.043, OR： 0.956） were independently associated with EGD. CONCLUSION： EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.     

Outcomes after adult isolated small bowel transplantation: experience from a single European centre

BACKGROUND: Adult isolated small bowel transplantation is considered the standard treatment for patients with life-threatening parenteral nutrition-related complications. Here, we report a 3-year experience in a single European centre between December 2000 and December 2003. AIMS: To evaluate and discuss pre-transplant and post-transplant factors that influenced survival rates in our series. PATIENTS: Fourteen patients, with a mean parenteral nutrition course of 27 months, were transplanted. In eight cases they had not experienced any major complication from parenteral nutrition. METHODS: We described pre-transplant evaluation and inclusion criteria, surgical technique and clinical management after transplant. Immunosuppressive therapy was based on induction drugs and Tacrolimus. We reported survival rates, major complications and rejection events. RESULTS: One-year actuarial survival rate was of 92.3% with a mean 21-month follow-up (range 3-36 months). We had no intraoperative deaths. One patient (7.2%) died of sepsis following cytomegalovirus enteritis. One patient underwent graftectomy (7.2%) for intractable severe acute rejection. One-year actuarial graft survival rate of 85.1%. One patient (7.2%) affected by post-transplant lymphoproliferative disease is alive and disease-free after 8 months. CONCLUSION: We believe candidate selection, induction therapy, donor selection and short ischemia time play an important role in survival after small bowel transplantation.     

A concise review of hepatitis C in heart and lung transplantation

Hepatitis C (HCV) infection is prevalent in recipients of, and candidates for, solid organ transplants. The outcomes of HCV infection in cardiac and lung transplant recipients have yet to be clearly established, and future prospective studies are needed. In the absence of safe and effective antiviral treatment for HCV infection in heart and lung transplant recipients, the management of these patients remains a challenge and must be considered on an individual basis. Interferon therapy for HCV before transplantation appears to improve outcomes; however, post-transplant interferon therapy in the cardiac and pulmonary transplant setting may be associated with an increased risk of graft rejection. Given the paucity of information regarding HCV treatment in these transplant recipients, and with appropriate concerns that graft loss from rejection may not be amenable to a second transplant (given the scarcity of suitable cadaveric organs), multicentre, randomized controlled trials are needed to determine the optimal approach for treatment of HCV infection in this population.     

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

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.     

Prevention and Treatment of Recurrent Hepatitis C after Liver Transplantation

Hepatitis C virus (HCV) is the leading indication for liver transplantation in the United States. Recurrent HCV infection after transplant is nearly universal, and the disease course is accelerated. In select patients, pre-transplant antiviral therapy can be given with the aim of preventing recurrent infection. The more common strategy for managing recurrent HCV, however, is post-transplant antiviral therapy with the aim of achieving sustained virologic response. The limited efficacy and poor tolerability of pegylated-interferon and ribavirin among patients with cirrhosis or after liver transplant have been major barriers to preventing or treating recurrent HCV. Preliminary results suggest that virologic response in this patient population is improved with protease inhibitor (PI)-based triple therapy. Although the efficacy of this regimen at preventing or treating recurrent HCV remains to be seen, serious adverse events are frequent when PI-triple therapy is used in the transplant setting. More tolerable and effective treatment regimens are desperately needed in this patient population.     

The natural history of inflammatory bowel disease and primary sclerosing cholangitis after liver transplantation �C a single-centre experience

OBJECTIVE:

To describe the natural history of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) after liver transplant, the predictors of PSC and IBD recurrence, and the interaction of these disease processes.

METHODS:

Data regarding patients who received liver transplants for PSC at the University of Alberta Hospital (Edmonton, Alberta) from 1989 to 2006 were retrospectively reviewed. Recurrent PSC (rPSC) was defined by the Mayo Clinic criteria. Cox proportional hazards modelling and Kaplan-Meier statistics were used.

RESULTS:

Fifty-nine patients were studied, with a median follow-up of 68 months. A total of 71.2% of patients were diagnosed with IBD pre-transplant. Clinical IBD severity post-transplant compared with severity pretransplant was unchanged in 67%, worse in 26.5% and improved in 6.1% of patients. Twenty-five per cent of patients developed rPSC post-transplant. The occurrence of at least one episode of acute cellular rejection (hazard ratio 5.7; 95% CI 1.3 to 25.8) and cytomegalovirus mismatch (hazard ratio 4.2; 95% CI 1.1 to 15.4) were found to be significant predictors of rPSC. Although not statistically significant, there was no rPSC in patients without pre- or post-transplant IBD, and in only one patient with a colectomy. Actuarial patient survival rates at one, five and 10 years post-transplant were 97%, 86% and 79%, respectively. Although a significant proportion of patients experienced worsening IBD post-transplantation, the presence or severity of IBD did not influence rPSC or patient survival.

CONCLUSION:

Acute cellular rejection and cytomegalovirus mismatch were both identified as independent predictors of rPSC. The impact of steroids and the ideal immunosuppressive regimen for the control of both IBD and PSC post-transplant requires further examination in prospective studies.     

Adult living donor versus deceased donor liver transplantation: A 10-year prospective single center experience

It has been 4 years since the first, long-term (> 3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) was reported.¹ In this follow up, prospective, IRB approved, 10-year comparison of A2ALLTx to ADDLTx we expand on our initial observations. This data includes: age, gender, ethnicity, primary liver disease, waiting time, pretrans-plant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications.In 10 years, 465 ADDLTx (81.37) and 107 A2ALLTx (18.7%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (54.5% vs. 48.2%). Data regarding overall patient and graft survival and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (9.6% vs. 21.7%) and more biliary complications (27.1% vs. 17.6%).In conclusion, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.     

Liver transplantation for viral hepatitis in 2015

Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus(HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus(HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.     

A Canadian national retrospective chart review comparing the long term effect of cyclosporine vs. tacrolimus on clinical outcomes in patients with post-liver transplantation hepatitis C virus infection

The transition from regular use of cyclosporine to the newer calcineurin-inhibitors, such as tacrolimus, has been suggested as a contributing factor to the “era effect” of worsening outcomes of post-transplant HCV recurrence. This retrospective medical chart review of 458 patients was undertaken to evaluate the role of immunosuppressant choice (cyclosporine vs. tacrolimus) in determining virologic response and clinical outcomes of post-liver transplant HCV infection recurrence. Our results showed that patients undergoing interferon-based treatment taking cyclosporine have significantly better odds (OR: 2.59, P = 0.043) of presenting a sustained viral response (66.7%) compared to tacrolimus (52.8%). This did not result in a significant effect on post-liver transplantation clinical events including HCV-related deaths, graft loss, fibrosing cholestatic hepatitis, hepatocellular carcinoma or graft rejection. Other variables, which showed a significant relationship with the achievement of sustained viral response included donor age (OR 0.96, P = 0.001) and HCV genotype 1 infection (OR 0.05, P < 0.001). The observed significant increase in the odds of acute/hyperacute (OR 6.49, P = 0.001) and chronic rejection (OR 10.45, P < 0.001) in the cyclosporine to tacrolimus switch group, accompanied by an increase in the odds of HCV-related death (OR 2.30, P < 0.047) compared to tacrolimus merits further study. A significant increase (P < 0.044) in new-onset diabetes mellitus with tacrolimus (28.3%) compared to cyclosporine (18.7%) was also observed. Pre-transplant diabetes mellitus was associated with a significantly increased likelihood of graft fibrosis (HR 1.95, P = 0.003).     

Early outcomes and long-term survival after kidney transplantation in elderly versus younger recipients from the same donor in a matched-pairs analysis

The elderly are the fastest-growing population on waiting lists for kidney transplantation (KTx). Recognized barriers to KTx in the elderly is early post-transplant mortality and morbidity. To analyze the outcomes of KTx in recipients older than 60 years and, simultaneously, in their younger paired recipients, receiving a graft from the same donor.We included 328 kidney transplant recipients in the study. The elderly kidney transplant recipients (EKT) group included 164 patients aged 65 standard deviation (SD4) years. They were paired with younger kidney transplant recipients (YKT) aged 45 (SD12) years.The studied groups (EKT vs YKT) did not differ from the graft function estimated 1 year after the transplantation (50.7 mL/min vs 54.0 mL/min), while the estimated glomerular filtration rate decline was significantly faster in the YKT group. One-year patient survival (93.9% vs 97.0%), 1-year graft survival (90.4% vs 82.3%), and incidences of delayed graft function and acute rejection did not differ between the EKT and YKT groups. Significantly more cardiovascular complications and post-transplant diabetes mellitus were noticed in the EKT group. The long-term patient and graft survivals were poorer in the EKT group versus the YKT group, but death-censored graft survivals were the same. After having excluded donor-derived graft factors, there were no differences in the first-year outcome of KTx between recipients younger and older than 60 years. As life expectancy is lower in the EKT group, the probability of patient and graft survival was also significantly lower in this group. However, death-censored graft survival was not different in the EKT and YKT groups.     

Hepatitis C in non-hepatic solid organ transplant candidates and recipients:A new horizon

Hepatitis C virus(HCV) infection is estimated to affect 130-150 million people globally which corresponds to2%-3% of the total world population. It remains the leading indication for liver transplant worldwide and has been demonstrated to negatively impact both patient and graft survival following non-hepatic organ transplantation. In the era of interferon-based therapy, although treatment and cure of HCV prior to nonhepatic transplant improved survival, tolerability and low cure rates substantially limited therapy. Interferon(IFN)-based therapy following non-hepatic solid organ transplant, due to the risk of allograft rejection, is generally contraindicated. Rapid advances in IFN-free therapy with direct acting antivirals(DAAs) in the last few years have completely changed the paradigm of hepatitis C therapy. Compared to IFN-based regimens, DAAs have less frequent and less severe adverse effects, shorter durations of therapy, and higher cure rates that are minimally impacted by historically negative predictors of response such as cirrhosis, ethnicity, and post-transplant state. Recent studies have shown that liver transplant(LT) recipients can be safely and effectively treated with DAA combination therapies; although data are limited, many of the principles of therapy in LT may be extrapolated to non-hepatic solid organ transplant recipients. Here we review the data on DAA combination therapies in transplantation, discuss the advantages and disadvantages of pre- vs post-transplant HCV therapy and future directions.     

Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT)

BackgroundCorticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT).MethodsWe randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months.ResultsThe incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22).ConclusionFollowing LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.     

Increasing serum levels of IgM anti-HCV are diagnostic of recurrent hepatitis C in liver transplant patients with ALT flares

Summary.  Recurrent hepatitis and acute rejection share common features which make difficult for diagnosis in liver transplant hepatitis C virus (HCV) positive patients. We studied the usefulness of quantitative monitoring of HCV RNA and immunoglobulin (Ig)M anti-HCV in the differential diagnosis between recurrent hepatitis and acute rejection in 98 consecutive anti-HCV positive liver transplant patients. Aminotransferase levels, serum HCV RNA and IgM anti-HCV were measured at the time of transplantation and monthly thereafter. A liver biopsy (LB) was obtained when serum aminotransferase levels increased to twice or more than normal. During a mean follow-up of 16 months 86 aminotransferase flares were observed. Histology was compatible with recurrent hepatitis C in 44 cases and with acute rejection in 28, doubtful in 14. The fluctuations of HCV RNA serum levels were not significantly different in the three groups. Serum IgM anti-HCV levels increased (from negative to positive or with value variations ≥ 0.18) in 36 of 44 cases with recurrent hepatitis C at the time of alanine aminotransferase (ALT) flare. IgM anti-HCV remained unchanged in all rejection cases ( P  < 0.001), but increased in 10 of 11 histologically doubtful cases that were diagnosed as hepatitis at the second LB. Increasing serum levels of IgM anti-HCV at the time of ALT flares are significantly associated with recurrent hepatitis C in liver transplant patients. The quantitative monitoring of IgM anti-HCV appears to be an additional diagnostic tool for distinguishing recurrent hepatitis C from acute graft rejection with a 100% specificity; 100% positive predictive value and 88.9% diagnostic accuracy.     

Long-term follow-up of hearttransplant recipients with pre-transplant malignancies

A pre-existing malignancy has disqualified patients from solid organ transplantation because of concerns regarding recurrence. We reviewed pre-transplant characteristics and long-term results in patients who underwent heart transplantation with a pre-existing malignancy, because there has been no prior study of these patients in the long term. All 214 patients who underwent heart transplantation from July 1985 through June 2004 were studied retrospectively Thirteen of these patients had been treated for a malignancy before transplantation. Pre-transplant characteristics (age, sex, diabetes, and weight) and post-transplant outcomes (rejection, infection, and survival) were compared for the 2 groups. The patients with pre-existing malignancies were younger (47 vs 54 years, P=0.014), less heavy (73 vs 79 kg, P=0.017), and more likely to be female (54% vs 22%, P=0.010), compared with recipients without a pre-malignancy. Pulmonary vascular resistances, histories of tobacco use, and incidence of pre-transplant diabetes were not different between the 2 groups. The mean duration of follow-up for the 2 groups was similar (2,760 days for the pre-malignancy group vs 2,215 days for the non-pre-malignancy group, P=NS). Episodes of treated rejection and infection for the pre-malignancy group vs the non-pre-malignancy group were similar (1.8 episodes of rejection vs 1.6 episodes, P=NS); and (1. 7 episodes of infection vs 0.8 episodes, P=0.098). None of the pre-malignancy patients had recurrence of their original cancer, and long-term survival for the 2 groups was essentially identical (63% vs 62% at 10 years, P=NS). The dissemination of reports such as these may enable more patients with cured malignancies to benefit from transplantation.     

Influence of intensified medical treatment and organ allocation on outcome of transplant candidates

BACKGROUND: To test how the organization of a pre-transplant clinic and changes in organ allocation modus influence the survival of potential transplant candidates, the survival of patients referred for transplant evaluation between 4/93 and 4/96 (group A) was compared to that of patients referred from 5/96 to 7/00(group B). METHODS: After screening for transplant indication, group A was followed by the referring physician up to transplantation or 3-month reevaluation. Group B was closely followed by a specialized heart-failure clinic. Group A was transplanted according to Eurotransplant criteria, with waiting time being the strongest priority criterion. Due to an allocation partnership off our transplant centers, group B could be transplanted according to medical urgency regardless of waiting time. RESULTS: Overall one-year survival after referral was 69.8% for group A vs. 91 %for group B (p <0.0001). Transplantation within 1 year was required in more group A than group B patients (34% vs. 23%)with worse one-year post-transplant survival in group A (82%vs. 93%). CONCLUSIONS: Intensified treatment by a specialized heart failure program and an allocation system that allows for preferred transplantation of the 'sickest' patient improved over-all survival of transplant candidates and reduced the percentage of patients requiring transplantation.     

Challenges of recurrent hepatitis C in the liver transplant patient

Cirrhosis secondary to hepatitis C virus(HCV)is a very common indication for liver transplant.Unfortunately recurrence of HCV is almost universal in patients who are viremic at the time of transplant.The progression of fibrosis has been shown to be more rapid in the post-transplant patients than in the transplant na?ve,hence treatment of recurrent HCV needs to be considered for all patients with documented recurrent HCV.Management of recurrent HCV is a challenging situation both for patients and physicians due to multiple reasons as discussed in this review.The standard HCV treatment with pegylated interferon and Ribavarin can be considered in these patients but it leads to a lower rate of sustained virologic clearance than in the nontransplanted population.Some of the main challenges associated with treating recurrent HCV in post-transplant patients include the presence of cytopenias;need to monitor drug-drug interactions and the increased incidence of renal compromise.In spite of these obstacles all patients with recurrent HCV should be considered for treatment since it is associated with improve-ment in survival and a delay in fibrosis progression.With the arrival of direct acting antiviral drugs there is renewed hope for better outcomes in the treatment of post-transplant HCV recurrence.This review evaluates current literature on this topic and identifies challenges associated with the management of post-transplant HCV recurrence.     

Mortality predictors in liver transplant recipients with recurrent hepatitis C cirrhosis.

BACKGROUND/AIM: Recipients of orthotopic liver transplant for hepatitis C (HCV) invariably develop recurrent disease. The risk factors for death and retransplantation following the development of cirrhosis from HCV are unclear. The aim of this study was to identify predictors of survival in liver transplant recipients who develop cirrhosis from recurrent HCV. METHODS: We reviewed records of patients who underwent liver transplantation for cirrhosis due to HCV between January 1990 and December 2001. Prognostic factors of patient survival following the development of recurrent cirrhosis were identified through multivariate analysis. RESULTS: During the study period, 511 patients underwent transplantation for HCV cirrhosis. Of these, 65 patients (13%) developed biopsy proven recurrent cirrhosis from HCV; 43 (8%) were relisted for transplantation, and 24 (5%) underwent retransplantation. The overall Kaplan-Meier patient survival rates after the histologic diagnosis of cirrhosis at 1 and 5 years were 66% and 30%, respectively. A multivariate Cox proportional hazards model showed patients with higher last (i.e. at follow-up or prior to retransplantation) International normalized ratio (INR) values (hazard ratios (HR)=2.02, 95% confidence interval 1.26, 3.24, P<0.01) to have an increased risk of death. CONCLUSION: Our results suggested survival was decreased after the diagnosis of cirrhosis from recurrent HCV. Higher INR was associated with an increased risk of death following the development of cirrhosis.