A 10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients

OBJECTIVE: To determine the factors affecting the outcome of orthotopic liver transplantation (OLT) for end-stage liver disease caused by hepatitis C virus (HCV) and to identify models that predict patient and graft survival. SUMMARY BACKGROUND DATA: The national epidemic of HCV infection has become the leading cause of hepatic failure that requires OLT. Rapidly increasing demands for OLT and depleted donor organ pools mandate appropriate selection of patients and donors. Such selection should be guided by a better understanding of the factors that influence the outcome of OLT. METHODS: The authors conducted a retrospective review of 510 patients who underwent OLT for HCV during the past decade. Seven donor, 10 recipient, and 2 operative variables that may affect outcome were dichotomized at the median for univariate screening. Factors that achieved a probability value less than 0.2 or that were thought to be relevant were entered into a stepdown Cox proportional hazard regression model. RESULTS: Overall patient and graft survival rates at 1, 5, and 10 years were 84%, 68%, and 60% and 73%, 56%, and 49%, respectively. Overall median time to HCV recurrence was 34 months after transplantation. Neither HCV recurrence nor HCV-positive donor status significantly decreased patient and graft survival rates by Kaplan-Meier analysis. However, use of HCV-positive donors reduced the median time of recurrence to 22.9 months compared with 35.7 months after transplantation of HCV-negative livers. Stratification of patients into five subgroups, based on time of recurrence, revealed that early HCV recurrence was associated with significantly increased rates of patient death and graft loss. Donor, recipient, and operative variables that may affect OLT outcome were analyzed. On univariate analysis, recipient age, serum creatinine, donor length of hospital stay, donor female gender, United Network for Organ Sharing (UNOS) status of recipient, and presence of hepatocellular cancer affected the outcome of OLT. Elevation of pretransplant HCV RNA was associated with an increased risk of graft loss. Of 15 variables considered by multivariate Cox regression analysis, recipient age, UNOS status, donor gender, and log creatinine were simultaneous significant predictors for patient survival. Simultaneously significant factors for graft failure included log creatinine, log alanine transaminase, log aspartate transaminase, UNOS status, donor gender, and warm ischemia time. These variables were therefore entered into prognostic models for patient and graft survival. CONCLUSION: The earlier the recurrence of HCV, the greater the impact on patient and graft survival. The use of HCV-positive donors may accelerate HCV recurrence, and they should be used judiciously. Patient survival at the time of transplantation is predicted by donor gender, UNOS status, serum creatinine, and recipient age. Graft survival is affected by donor gender, warm ischemia time, and pretransplant patient condition. The authors' current survival prognostic models require further multicenter validation.     

The impact of donor variables on the outcome of orthotopic liver transplantation for hepatitis C

Morphologic characteristics of the graft have been proposed as a major contributor to the long-term outcomes in orthotopic liver transplantation (OLT). Our objective was to determine the impact of donor variables, including donor age, donor-recipient HLA match, and type of donation (DCD vs donation after brain death [DBD]), on the outcome of OLT in 192 patients with hepatitis C virus (HCV). Fourteen patients underwent OLT from donation after cardiac death (DCD) donors and 188 from DBD donors. Mean donor age, warm ischemia time at recovery, and cold ischemia time were similar between the groups. Overall graft survival rate at 1 year (55% DCD vs 85% DBD) and 5 years (46% DCD vs 78% DBD) was significantly lower in the DCD group (P = .0003). Similarly, patient survival rate at 1 year (62% DCD vs 93% DBD) and 5 years (62% DCD vs 82% DBD) was significantly lower in the DCD group (P = .0295). Incidences of hepatic artery thrombosis, portal vein thrombosis, and primary nonfunction were similar between the DCD and DBD groups. The incidence of liver abscess with ischemic-type biliary stricture was higher in recipients from DCD as compared with DBD (42% vs 2%). A trend toward lower graft survival was noted in recipients from donors older than 60 years of age in the HCV population (P = .07), with statistically lower patient survival (P = .02). Donor- recipient HLA matching did not appear to correlate with OLT outcome in patients with HCV. DCD donors and donors older than 60 years of age significantly impact patient and graft survival. Lower graft and patient survival in recipients from DCD donors does not appear to be related to early disease recurrence.     

Liver transplantation using donors older than 80 years: a single-center experience

AIM: The shortage of organs for orthotopic liver transplantation (OLT) has forced transplantation centers to expand the donor pool by using donors traditionally labeled as "extended criteria donors." One such example is OLT using a donor with advanced age. MATERIALS AND METHODS: We retrospectively evaluated 10 patients who received a liver graft from cadaveric donors older than 80 years. We analyzed pretransplantation donor and recipient characteristics, as well as the evolution of the recipients. RESULTS: All 10 donors were older than 80 years (median age, 83.5; range, 80-93). No steatosis (>30%) was accepted in the older donor group. Medium follow-up was 19.5 months. The most frequent cause for OLT was hepatitis C virus (HCV) cirrhosis (8/10 patients). We had 1 case of primary nonfunction, 1 patient died immediately after surgery because of extrahepatic complications (cardiac arrest), and 2 other patients had a severe HCV recurrence and died after 1 and 2 years from OLT, respectively. Five patients had HCV recurrence and biliary complications were present in 60% of the patients. No cases of acute or chronic rejection were described. Overall survival rates after 1 and 3 years were 80% and 40%, respectively. CONCLUSIONS: Old donor age is not an absolute contraindication to OLT. Liver grafts from donors older than 80 years can be used knowing that there is a high risk of postoperative complications. Furthermore, the increased risk of developing severe HCV recurrence, related to older donor age, suggests that such livers should be used in HCV-negative recipients.     

The outcome of liver grafts procured from hepatitis C-positive donors

BACKGROUND: The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. The survival of grafts from HCV+ donors has not been studied in detail. METHODS: Two study populations were examined retrospectively to assess the survival of liver grafts procured from HCV+ donors. First, we evaluated the survival of all 13 HCV+ and 103 HCV- grafts that were transplanted at our institution to HCV+ recipients from January 1, 1995 to December 31, 1999. In parallel, we analyzed a subset of the United Network for Organ Sharing (UNOS) liver transplant database from the same 5-year time period that was comprised of 14,195 adult patients for whom donor and recipient HCV serologies were known. Kaplan-Meier graft survival for both patient populations was calculated based on donor and recipient HCV serologic status. A Cox proportional hazards analysis was performed on UNOS data to identify variables independently predicting graft survival. RESULTS: For transplants performed at our institution, we found no statistically significant difference in the Kaplan-Meier graft survival of HCV+ and HCV- grafts transplanted to HCV+ recipients (P=0.68). The incidence of biopsy-proven, recurrent HCV posttransplant was similar in recipients receiving either HCV+ or HCV- grafts (4/13 vs. 18/103, chi-square P=0.211). Analysis of UNOS data revealed that the survival of HCV+ grafts in HCV+ recipients was equivalent to the survival of HCV- grafts in HCV+ recipients. Unexpectedly, the survival of grafts in HCV+ recipients in general was significantly inferior to that of grafts in HCV- recipients. Multivariate analysis of all patients found recipient but not donor HCV status to be independently predictive of graft survival. CONCLUSIONS: Analysis of data from a single center and the national UNOS database suggests that transplantation of liver allografts from HCV+ donors to HCV+ recipients results in graft survival comparable to HCV- grafts transplanted to HCV+ recipients. In contrast, recipient HCV positivity is an independent predictor of graft failure compared with patients transplanted for other causes of liver disease.     

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience

OBJECTIVE: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. METHODS: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. RESULTS: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992-2001) versus the era I (1984-1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. CONCLUSIONS: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.     

Analysis of clinical variables of donors and recipients with respect to short-term graft outcome in human liver transplantation

Donor and recipient factors are closely associated with graft survival after orthotopic liver transplantation (OLT). This study was performed to analyze clinical characteristics of recipients and donors, which affect 30-day graft loss after OLT. MATERIALS AND METHODS: One hundred eighty-six livers from heart-beating donors were accepted between May 1997 and June 1998 at the University of Pittsburgh Medical Center. Donor variables that were analyzed included age, sex, cold ischemia time (CIT), warm ischemia time (WIT), imported versus local procurement, cardiopulmonary arrest, serum sodium level, and dopamine dose. The recipient characteristics included native liver disease and UNOS status. Two-sided Fisher exact test and stepwise logistic regression were used for univariate and multivariate analyses. P-values < .05 were considered statistically significant. RESULTS: Twenty-eight grafts (15.1%) were lost within 30 days of OLT. The following factors were found to adversely affect graft survival: donor sodium > 155 mEq/L (P = .002); CIT > 12 hours (P = .002); WIT > 45 minutes (P = .002); and imported liver graft (P = .048). Logistic regression revealed that donor sodium (odds ratio, 3.03; 95% CI, 1.05 to 8.74), CIT (OR 1.20; 95% CI 1.05 to 1.38), WIT (OR 1.06; 95% CI 1.01 to 1.09) were independent predictors of early graft loss. CONCLUSION: Donor hypernatremia as well as warm and cold ischemia times independently affect graft outcomes in the early postoperative period after OLT. Avoidance of long preservation and correction of donor sodium level are recommended to optimize results and survival in OLT.     

Hepatitis C Positive Grafts may be used in Orthotopic Liver Transplantation: A Matched Analysis

Hepatitis C (HCV)-positive liver grafts have been increasingly used in patients with decompensated liver disease from HCV because of critical shortage of available organs. Fifty-nine recipients of HCV-positive grafts were matched to patients who received HCV-negative grafts. All recipients were transplanted for HCV liver disease. Matching variables were (1) status, (2) pre-transplant creatinine, (3) recipient age, (4) donor age, (5) warm ischemia time, and (6) year of transplantation. Both unmatched and matched analyses were performed on patient survival, graft survival, and time to HCV recurrence. There was no significant statistical difference in patient, graft, or HCV recurrence-free survival between recipients of HCV-positive and HCV-negative grafts with matched and unmatched analyses (p > 0.05). The 3-year estimates of HCV disease-free survival were 12% (+/- 9%) and 19% (+/- 7%) using HCV-positive and -negative grafts, respectively. The use of HCV-positive grafts in recipients with HCV does not appear to affect patient survival, graft survival, or HCV recurrence when compared with the use of HCV-negative grafts. Our results suggest that HCV-positive grafts can be used in a HCV liver transplant recipient.     

Pretransplant model to predict posttransplant survival in liver transplant patients

OBJECTIVE: To develop a prognostic model that determines patient survival outcomes after orthotopic liver transplantation (OLT) using readily available pretransplant variables. SUMMARY BACKGROUND DATA: The current liver organ allocation system strongly favors organ distribution to critically ill recipients who exhibit poor survival outcomes following OLT. A severely limited organ resource, increasing waiting list deaths, and rising numbers of critically ill recipients mandate an organ allocation system that balances disease severity with survival outcomes. Such goals can be realized only through the development of prognostic models that predict survival following OLT. METHODS: Variables that may affect patient survival following OLT were analyzed in hepatitis C (HCV) recipients at the authors' center, since HCV is the most common indication for OLT. The resulting patient survival model was examined and refined in HCV and non-HCV patients in the United Network for Organ Sharing (UNOS) database. Kaplan-Meier methods, univariate comparisons, and multivariate Cox proportional hazard regression were employed for analyses. RESULTS: Variables identified by multivariate analysis as independent predictors for patient survival following primary transplantation of adult HCV recipients in the last 10 years at the authors' center were entered into a prognostic survival model to predict patient survival. Accordingly, mortality was predicted by 0.0293 (recipient age) + 1.085 (log10 recipient creatinine) + 0.289 (donor female gender) + 0.675 urgent UNOS - 1.612 (log10 recipient creatinine times urgent UNOS). The above variables, in addition to donor age, total bilirubin, prothrombin time (PT), retransplantation, and warm and cold ischemia times, were applied to the UNOS database. Of the 46,942 patients transplanted over the last 10 years, 25,772 patients had complete data sets. An eight-factor model that accurately predicted survival was derived. Accordingly, the mortality index posttransplantation = 0.0084 donor age + 0.019 recipient age + 0.816 log creatinine + 0.0044 warm ischemia (in minutes) + 0.659 (if second transplant) + 0.10 log bilirubin + 0.0087 PT + 0.01 cold ischemia (in hours). Thus, this model is applicable to first or second liver transplants. Patient survival rates based on model-predicted risk scores for death and observed posttransplant survival rates were similar. Additionally, the model accurately predicted survival outcomes for HCV and non-HCV patients. CONCLUSIONS: Posttransplant patient survival can be accurately predicted based on eight straightforward factors. The balanced application of a model for liver transplant survival estimate, in addition to disease severity, as estimated by the model for end-stage liver disease, would markedly improve survival outcomes and maximize patients' benefits following OLT.     

Long-term results and modeling to predict outcomes in recipients with HCV infection: results of the NIDDK liver transplantation database.

Hepatitis C virus (HCV)-associated liver disease is the most common indication for liver transplantation (LT). There are, however, no long-term (>5 year) studies of comparative outcomes for recipients with HCV infection, and no models capable of identifying recipients with HCV infection at greatest risk for adverse outcomes. We prospectively determined: 1) long-term outcomes, and 2) whether pretransplant patient or donor variables can be used to predict death and/or graft loss in recipients with HCV infection. A total of 165 HCV-infected recipients were eligible for this study. Pretransplant donor and recipient characteristics and patient and graft survival data were prospectively collected. Model building for outcomes was carried out using logistic regression. Receiver operating characteristic curves for different models were created and compared. Median follow-up was 8.5 years. Adjusted 10 year graft survival was 64% for recipients with HCV infection and 51% for uninfected recipients. A model incorporating pretransplant HCV ribonucleic acid (RNA), cytomegalovirus immunoglobulin (CMV IgG) serostatus, creatinine, bilirubin, prothrombin time international ratio (INR), recipient age, and donor age was developed to identify recipients at greatest risk of short-term mortality or graft loss (area under receiver operating characteristic curve = .83) In conclusion, long-term outcomes following LT for recipients with HCV infection are comparable to those for recipients undergoing LT for other indications. HCV-infected recipients at greatest risk for short-term mortality and graft loss can be identified using several readily identifiable pretransplant variables. Long-term death and graft loss specifically secondary to recurrence of HCV appears, however, to be determined primarily by factors other than those included in this analysis.     

Factors differentially correlated with the outcome of liver transplantation in hcv+ and HCV- recipients

BACKGROUND: Survival following liver transplantation for hepatitis C virus (HCV) is significantly poorer than for liver transplants performed for other causes of chronic liver disease. The factors responsible for the inferior outcome in HCV+ recipients, and whether they differ from factors associated with survival in HCV- recipients, are unknown. METHODS: The UNOS database was analyzed to identify factors associated with outcome in HCV+ and HCV- recipients. Kaplan-Meier graft and patient survival and Cox proportional hazards analysis were conducted on 13,026 liver transplants to identify the variables that were differentially associated with outcome survival in HCV- and HCV+ recipients. RESULTS: Of the 13,026 recipients, 7386 (56.7%) were HCV- and 5640 were HCV+. In HCV- and HCV+ recipient populations, five-year patient survival rates were 83.5% vs. 74.6% (P<0.00001) and five-year graft survival rates 80.6% vs. 69.9% (P<0.00001), respectively. In a multivariate regression model, donor age and recipient creatinine were observed to be significant covariates in both groups, while donor race, cold ischemia time (CIT), female to male transplants, and recipient albumin were independent predictors of survival of HCV- recipients. In the HCV+ cohort, recipient race, warm ischemia time (WIT), and diabetes also independently predicted graft survival. CONCLUSIONS: A number of parameters are differentially correlated with outcome in HCV- and HCV+ recipients of orthotopic liver transplantation. These findings may not only have practical implications in the selection and management of liver transplant patients, but also may shed new insight into the biology of HCV infection posttransplant.     

Use of hepatitis C virus-positive grafts in liver transplantation: a single-centre experience

AIM: Our goal was to evaluate the outcome of HCV(+) recipients after liver transplantation (LT) using HCV(+) donors and the interaction between donor and recipient viral strain. METHODS: We performed a retrospective analysis of 21 LT performed between 1998 and 2004 using livers from HCV(+) donors in HCV(+) recipients. Two hundred thirty-seven patients with HCV cirrhosis who underwent LT with livers from HCV(-) donors were the control group. Ishak score (IS) was evaluated for all HCV(+) grafts. The considered variables included donor age, hepatic enzymes, intensive care unit stay, HCV genotype, ischemia time, recipient age, UNOS status, Child score, HCV genotype (before and 6 months after LT) and IS (after LT). We analyzed patient, graft, and disease-free survival. RESULTS: HCV(+) donors were significantly older than HCV(-) donors. The cumulative 5-year patient and graft survivals and disease free intervals were not different between groups. IS grading was more than 2/18 in two cases; the only graft with a staging score over 2/6 was retransplanted for early nonfunction. In two cases, different HCV genotypes were matched and donor strain took over the recipient strain. In one patient, donor genotyping 2a-2c took over recipient genotyping 1b and 9 months after LT recurrent hepatitis was documented, but antiviral therapy cleared HCV. CONCLUSIONS: Livers from HCV(+) donors can safely be used in HCV(+) recipients. Hepatic biopsy must always be performed; livers with bridging fibrosis should not be used. The takeover of one strain by another may change the prognosis of the patient if the predominant strain is more sensitive to antiviral therapy.     

Impact of Donor Age on the Results of Liver Transplantation in Hepatitis C Virus-Positive Recipients

Objective

Hepatitis C virus (HCV)-cirrhosis is the most frequent indication for orthotopic liver transplantation (OLT) among adults in most European and American transplant centers. The aim of this study was to analyze the impact of donor age on graft survival among HCV-positive cirrhotic transplant patients.

Materials and Methods

We performed an observational, retrospective study between March 1997 and December 2004, analyzing 340 liver transplantations. The patients were divided into 4 groups, considering whether the HCV infection was the indication for OLT and whether the age of the donor was older or younger than 48 years: group 1 (HCV, <48 years); group 2 (HCV, >48 years); group 3 (non-HCV, <48 years); and group 4 (non-HCV, >48 years).

Results

A univariate analysis showed that posttransplantation graft survival was clearly influenced by recipient HCV serologic status (P = .018). However, no graft survival differences were found when the analysis variable was age (>48 or <48 years). When both variables were studied, a positive HCV serology did not modify graft survival when the donor age was <48 years (P = .32), but had a statistically significant negative impact when the age was >48 years (P = .02).

Conclusions

The use of older donors for HCV recipients resulted in worse graft and patient survivals in our study. This difference in survival was not present in non-HCV recipients or when grafts for HCV recipients were procured from younger donors. Donor age <30 years was a protective factor for graft survival among HCV recipients.     

Liver transplantation from old donors into HCV and non-HCV recipients

BACKGROUND: Chronic liver failure due to HCV-related cirrhosis is the leading indication for liver transplantation in Western countries. Inferior long-term results have been reported for liver transplantation in HCV patients, especially when marginal donor livers are utilized. The aim of this study was to retrospectively analyze the outcome of liver transplantation from elderly donors in HCV versus non-HCV recipients. METHODS: One hundred seventy-nine patients receiving 204 liver transplantations were divided into four groups according to HCV positivity and donor age (> or <65 years). Long-term survivals were calculated by the Kaplan-Meier method. RESULTS: Grafts from donors of >65 years into HCV-positive patients displayed lower patient and graft survival rates than HCV-negative cases, although macrosteatosis was more frequent (55% vs 9%, P =.02) among organs used for non-HCV cases. Moreover, HCV-positive recipients transplanted with a donor aged >65 years had significantly lower patient and graft survival (40% vs 78% [P =.01] and 40% vs 68% [P =.06], respectively) than patients receiving a liver from a younger donor. CONCLUSIONS: Our retrospective analysis, although hampered by a small number of patients transplanted with an old liver, suggest that the results of liver transplantation with a donor graft >65 years of age into an HCV-positive recipient shows a worse outcome than those from younger donors. Older livers should be reserved for non-HCV cases.     

The impact of gender and age matching for long-term graft survival in living donor renal transplantation

In renal transplantation, donor age and allograft size are known to have an important influence on the outcome of the graft reflecting functional renal mass. Women tend to have smaller kidneys with 17% fewer nephrons than male kidneys. The number of glomeruli per kidney as well as the mean glomerular volume closely correlate with kidney weight and negatively correlate with subject age. We evaluated the impact of gender and age matching in living-donor renal transplantation on long-term graft survival. MATERIALS AND METHODS: Four groups were discerned among 614 renal transplants, according to donor and recipient gender: Group 1 was male donor to male recipient; Group 2 was male donor to female recipient; Group 3 was female donor to male recipient; and Group 4 was female donor to female recipient. We analyzed long-term graft survival and risk factors between the four groups as well as according to age matching. Statistical significance was determined by the Kaplan-Meier method and log rank test (P < .05). RESULT: The graft survival rates at 1, 3, 5, and 10 years were 92.62%, 88.13%, 82.37%, and 76.07%, respectively. The risk factors affecting long-term graft survival were donor age, donor gender, acute rejection rate, and HLA-DR matching. Among the four groups, the graft survival rates of Group 3 (female donor to male recipient) were significantly different from the other groups (P = .0165). Also, the long-term graft survival rates according to age differences were significantly different between older donors than recipients and younger donors than recipients in each group (P = .0213). CONCLUSION: The importance of inadequate renal mass is magnified in high-risk recipients. Age matching could perhaps improve the results of transplantation, particularly when kidneys from older donors are used. Consideration of age and gender as criteria for the choice of donors and recipients may be considered in organ allocation.     

Orthotopic liver transplantation and living donors. An experimental study in the dog

Orthotopic liver transplantation (OLT) using partial grafts harvested from living donors would represent a further alternative to the limited supply of hepatic grafts, especially in pediatrics. We report herein the results of an original technique of living donor OLT that we have developed in the dog. This study was conducted in male mongrel dogs weighing 25-30 kg for the donors and 10-15 kg for the recipients. The donor operation consisted in harvesting the left lobe of the liver as a graft. The recipient operation consisted in the implantation of the graft in the orthotopic position after total hepatectomy with preservation of the inferior vena cava. Ten survival experiments were undertaken. The first donor died of infected liver necrosis of the quadrate lobe. All other donors survived without major complication. Among the 10 grafts, only 9 were used. Substantial survival could be obtained in 3 dogs. On recipient survived for 48 hours and 2 for 24 hours but their graft was functioning and producing bile. Two dogs died intraoperatively. The 4 other recipients developed an outflow block of the graft after reperfusion leading to lethal hemorrhage from the transected surface. This work is, to our knowledge, the first experimental study of OLT using living donors. It provides a technical basis to the clinical use of living hepatic allograft donors which otherwise depends on ethical issues.     

Impact of donor age on survival and fibrosis progression in patients with hepatitis C undergoing liver transplantation using HCV+ allografts.

Studies have suggested that the use of hepatitis C virus (HCV)-positive (HCV+) donor allografts has no impact on survival. However, no studies have examined the effect that HCV+ donor histology has upon recipient and graft survival. We evaluated the clinical outcome and impact of histological features in HCV patients transplanted using HCV+ livers. We reviewed all patients transplanted for HCV at our institution from 1988 to 2004; 39 received HCV+ allografts and 580 received HCV-negative (HCV-) allografts. Survival curves compared graft and patient survival. Each HCV+ allograft was stringently matched to a control of HCV- graft recipients. No significant difference in survival was noted between recipients of HCV+ livers and controls. Patients receiving HCV+ allografts from older donors (age > or =50 yr) had higher rates of graft failure (hazard ratio, 2.74) and death rates (hazard ratio, 2.63) compared to HCV- allograft recipients receiving similarly-aged older donor livers. Matched case-control analysis revealed that recipients of HCV+ allografts had more severe fibrosis post-liver transplantation than recipients of HCV- livers (P = 0.008). More advanced fibrosis was observed in HCV+ grafts from older donors compared to HCV+ grafts from younger donors (P = 0.012). In conclusion, recipients of HCV+ grafts from older donors have higher rates of death and graft failure, and develop more extensive fibrosis than HCV- graft recipients from older donors. Recipients of HCV+ grafts, regardless of donor age, develop more advanced liver fibrosis than recipients of HCV- grafts.     

DR antigens influence graft outcome and HCV recurrence after liver transplantation

Hepatitis C (HCV) recurrence following liver transplantation is universal. However, the severity of recurrence is highly variable between patients. We speculated that recipient DR antigens or the level of DR mismatching between the recipient and the donor might affect the severity of HCV recurrence and allograft survival. Clinical outcome was compared between HCV+ recipients with DR2, DR3, or DR5 versus HCV+ recipients with all other DR antigens. Recipients with DR3 had reduced allograft survival (P < .02), a higher rate of HCV recurrence (P < .05), and more severe liver disease (P < .05). Recipients with DR5 had superior allograft survival (P < .05), low rates of HCV recurrence (P < .05), and benign liver disease (P < .05). Clinical outcome of recipients with DR2 was equivalent (P = Ns) to the non-DR2, -3, -5 recipients. The incidence of acute rejection was equivalent (P = Ns) in all groups. The level of DR mismatching between donor and recipient did not affect HCV recurrence or severity. However, allograft survival was better (P < .05) in recipients with zero DR mismatches. The data show that host genetic factors play an important role in HCV recurrence and allograft outcome after liver transplantation. In addition, identification of DR antigens may help predict an HCV+ patient's relative risk for severe HCV recurrence.     

Impact of the recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft.

BACKGROUND: The impact of hepatitis C virus (HCV) infection recurrence after orthotopic liver transplantation (OLT) on graft viability is still not accurately defined. Our study aims to evaluate the magnitude and rate of progression of HCV-induced liver damage after OLT in a single institution cohort of 122 HCV-infected recipients. METHODS: All patients transplanted at our institution between 1988 and 1996 with positive serum HCV antibodies before OLT, minimum postoperative survival of 6 months, and without hepatitis B virus coinfection or severe non-HCV-related graft complications were retrospectively included in the study. RESULTS: HCV infection recurrence was almost universal, and genotype 1b was observed in 87% of the cases. After a median histological follow-up of 43 months (range: 7-96), evidences of HCV-induced histological damage were found in 94% of the cases. The actuarial rates of severe graft damage (including cirrhosis, fibrosing cholestatic hepatitis, and submassive liver necrosis) were 15%, 33%, and 44% at 3, 5, and 7 years, respectively, and among these patients, 52% developed decompensated liver disease during the follow-up and 36% lost their grafts. The biochemical severity at the onset of the recurrent hepatitis and the development of cholestasis or cytomegalovirus disease were independent predictors of severe HCV-related graft damage. No differences were found in graft and patient survival when positive-HCV OLT recipients were compared with a coetaneous cohort of 215 non-HCV OLT recipients. CONCLUSIONS: HCV infection recurrence leads to severe liver damage and subsequently to clinical decompensation in a significant proportion of OLT recipients. Some clinical and biochemical characteristics can predict the severity of HCV-induced graft damage.     

Living donor liver transplantation for hepatitis C

Liver cirrhosis and hepatocellular carcinoma related to chronic hepatitis C virus (HCV) infection are currently the most common indications for liver transplantation. The number of living donor liver transplantation (LDLT) procedures has increased given the shortage of donor organs from deceased donors. However, recurrence of HCV infection is universal and affects graft survival. This mini-review compared the outcomes for HCV-positive recipients after LDLT with those after deceased donor liver transplantation.     

Liver transplantation from anti-hepatitis C virus-positive donors: our experience

Background

Hepatitis C (HCV) is among the most common causes of end-stage liver disease worldwide. The donor shortage leads us to consider alternative organ sources such as HCV-positive donors. The outcomes of these transplants must be evaluated thoroughly since there is universal recurrence of disease among HCV-positive liver transplant recipients.

Methods

From January 2005 to April 2011, we performed 143 liver transplants (OLT) to treat end-stage liver disease secondary to HCV infection. Thirteen patients (9,1%) received livers from HCV-positive donors. A control group consisted of 130 HCV-positive patients who underwent OLT during the same period with organs from HCV-negative donors. Donor HCV status was assessed by 2 tests: HCV antibodies and viral load. Not only recipient and graft survivals were analyzed, but also frequency, timing and severity of hepatitis recurrence.

Results

Among 143 transplants performed in HCV-positive recipients during a 6-year period from January 1, 2005, to April 30, 2011, 9.1% of patients received an organ from an anti-HCV-positive donor, 72.7% of whom showed a negative viral load. The vast majority (80%) of our patients suffered hepatitis during their follow-up, 22.4% of which were severe cases.

Conclusions

No significant difference in patient or graft survival was observed between the 2 groups. A high percentage of grafts with initial positive serology for HCV showed no viral replication. Grafts from HCV-positive donors can be considered to be a safe, effective source for liver donation.