Impact of hepatitis B and C on graft loss and mortality of patients after kidney transplantation

BACKGROUND: Mortality or graft loss after renal transplantation might be influenced by hepatitis virus infection. METHODS: Sera from time of transplantation of 927 renal transplant recipients were tested for hepatitis C (HCV) and hepatitis B virus (HBV) in order to investigate the impact of hepatitis virus infection on graft loss and mortality over an observation period of 20 yr. RESULTS: One hundred and twenty three of 927 patients were HCV positive, 30 patients HBV positive and seven patients HBV and HCV positive. The observation period was 9.2 +/- 4.4 yr. Mortality was significantly higher in patients with hepatitis B (p = 0.0005), as well as in patients with concomitant B and C hepatitis (p < 0.0001) and in those who acquired HCV infection after transplantation (n = 30, p = 0.0192) compared with non-infected patients. Patients with replicating HBV infection (HBeAg positive) had the worst prognosis (p < 0.0001). In the multivariate analysis the presence of HBeAg (p < 0.0001), patients' age (p < 0.0001) and HCV infection after transplantation (p = 0.0453) were predictors for death. Graft survival was significantly shorter in patients with concomitant hepatitis B and C (p = 0.0087) as well as in HBeAg positive patients (p = 0.002). HCV infection or HBs antigenemia did not have a significant impact on graft survival compared with non-infected patients. CONCLUSION: HCV infection after transplantation is associated with a high mortality whereas chronic HCV infection before trans plantation does not have a significant impact on mortality. Patients with replicating HBV infection or concomitant HBV and HCV infection have a high risk of graft loss and mortality.     

肾移植前后丙型肝炎病毒感染的管理

丙型肝炎病毒(hepatitis C virus, HCV)除导致肝功能损伤外,约43％～85％的慢性丙型肝炎(chronic hepatitis C,CHC)患者可伴有多种肝外表现(extrahepatic manifestations,EHM)[1-4],包括多种HCV感染相关肾脏疾病[5-6].Ferri等[2]...     

Impact of hepatitis C virus infection on patient and graft survival in kidney transplantation

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease after renal transplantation, which represents a risk factor for graft loss and patient death. Hepatitis C (+) kidney transplant candidates who remain on the waiting list show a greater risk of mortality than those who are transplanted, a risk that escalates with time. The aim of this study was to examine the impact of HCV infection on patient and allograft survival in our transplant population. Among 90 renal transplant patients transplanted between 1991 and 2002 who were retrospectively analyzed, 45 were HCV-positive and 45 HCV-negative by serology. All positive patients had shown positive HCV antibody and/or positive HCV RNA. The mean ages of the patients were 36.2 +/- 9 years among the HCV (+) and 38 +/- 10 years among the HCV (-) patients (P = .31). Eighteen HCV (+) patients and 14 HCV (-) patients received their grafts from deceased donors. The immunosuppressive protocols were similar in both groups. The number of acute rejection episodes were 13 (30%) in HCV (+) and 6 (13%) in the HCV (-) group (P = .006). Diabetes mellitus developed in 10 (23%) HCV (+) and 7 (16%) HCV (-) patients (P = .04). Cytomegalovirus disease occurred in 5 (16%) HCV (+) and 2 (6%) HCV (-) patients (P = .32). The mean serum creatinine was 1.85 +/- 1.1 mg/dL in HCV (+) and 1.8 +/- 1 mg/dL in HCV (-) group (P = .82). The mean graft survivals were 97.1 +/- 52 months in the HCV (+) and 81.1 +/- 37 months in the HCV (-) group (P = .04). Seven HCV (+) patients (16%) and three HCV (-) patients (6%) lost their grafts (P = .04). Advanced cirrhosis developed in three HCV (+) patients (6%). One patient died in the HCV (+) group. Patient survivals were 98% in the HCV (+) and 100% in the HCV (-) cohorts. In this study, the rate of graft loss was higher in HCV (+) patients, whereas the patient survival was similar.     

Different impacts of hepatitis B virus and hepatitis C virus on the outcome of kidney transplantation

Previous studies had shown that HBV and HCV infections lead to increased morbidity and mortality after kidney transplantation when compared with the nonhepatitis group. However, few studies have compared the impact among a population with a high prevalence of HBV and HCV infections. We studied the outcomes of 346 recipients including 23 HBsAg (+) patients (6.6%; group 1), 22 patients with anti-HCV+ (6.3%, group 2), and 301 nonhepatitis patients (group 3) in a single center during a 6-year period. No patient had evidence of precirrhosis or cirrhosis before transplant. The primary end point was graft and patient survival rates. Secondary end point was the rate of progression of chronic allograft, nephropathy. The median follow-up time was 3.7 (0.5-6.8) years. Five-year actuarial graft survival was 80% for group 1, 61% for group 2, and 88 % for group 3 (P = .005). Cox regression showed HCV (hazards ratio 2.96; 95% CI = 1.03-8.51) and acute rejection episode (HR 3.01; 95%CI = 1.86-4.87) to be significant predictors of graft survival. Actuarial 5-year patient survival of group 1 was significantly lower than group 2 or group 3 (79 % vs 89% and 96%; P = .003). Cox regression revealed that the hazards ratio of HBV for death was 7.63 (95%CI = 1.88-30.86; P = .004). In contrast, HCV infection had no significant effect on patient survival (HR 1.59; 95%CI = 0.28-9.02). The rate of chronic allograft nephropathy progression was significantly faster in group 1 (-6.74 mL/min per year) and group 2 (-6.14 mL/min per year) than the controls. We concluded that HBV infection decreased patient survival earlier than HCV and that HCV decreased graft survival more significantly than HBV. Both HBV and HCV were associated with rapid progression of chronic allograft nephropathy. HBV was the strongest risk factor for mortality compared with HCV, with acute rejection episode, with diabetes mellitus, or other hazardous factors.     

Antibodies to hepatitis C virus in kidney transplantation.

Ninety patients on dialysis, 241 cadaveric kidney donors and 27 cadaveric kidney recipients with a follow-up of 2 years, have been investigated as for anti-HCV positivity by means of 3 tests. As for patients on dialysis and cadaveric donors, the prevalence was 32 and 4%, respectively. As for transplanted patients, it must be noted that 4 negative recipients from positive donors seroconverted, but without any change in hepatic enzymes, while in 2 or 9 anti-HCV-positive recipients, hepatic enzymes increased after transplantation. Seroconversion in patients transplanted from a negative donor was not significantly different. We conclude that, according to their experience, anti-HCV positivity in the donors is not associated with a significant risk of infection in recipients of cadaveric grafts.     

Recurrence of hepatitis C virus after liver transplantation

Abstract The hepatitis C virus is a common cause of chronic hepatitis after orthotopic liver transplantation (OLT). We evaluated 95 consecutive patients who underwent OLT at our institute between March 1988 and November 1992 and who had a follow-up period longer than 3 months. All patients had a second-generation test (ELISA + RIBA) for HCV antibodies (HCV Ab) before and monthly after OLT; all had a polymerase chain reaction (PCR) test for detection of viral RNA after the operation. Whenever biochemical abnormalities (hyper-transaminasemia 2 times the normal range) were seen, a percutaneous liver biopsy was performed. Forty-two HCV Ab + patients before OLT remained positive after OLT. In this group the PCR test was positive in 32 cases (78.5%). In 13/42 (30.9%) cases (all PCR +) with hypertransaminasemia histological examination showed signs of viral C hepatitis (score of Knodell minimum 3, maximum 12, median 5.5). Of 53 HCV Ab patients before OLT, only 1 became HCV Ab+ and PCR+ 15 months after OLT. In the remaining 52 patients 15 were PCR+. Twenty of 53 patients (37.7%) had a liver biopsy because of hypertransaminasemia: in no case did histology show any signs of hepatitis C. In conclusion, viral C recurs often after OLT for post-hepatitic C cirrhosis. The histological graft lesions are in most cases moderate. We did not observe any deaths related to viral C infection in grafted patients. According to our results post-hepatic C cirrhosis remains a good indication for OLT.     

Spontaneous clearance of hepatitis C virus after liver transplantation in two patients coinfected with hepatitis C virus and human immunodeficiency virus.

Spontaneous resolution of chronic hepatitis C virus (HCV) infection is exceedingly rare and poorly understood. As HCV and human immunodeficiency virus (HIV) have shared routes of transmission, HCV coinfection is estimated to affect 15%-30% of the HIV-positive population. We report 2 patients with HCV-HIV coinfection who underwent orthotopic liver transplantation at our center and had spontaneous clearance of their chronic HCV infection after transplantation without any anti-HCV treatment. Both patients showed no evidence of HCV recurrence for more than 3 years despite long-term immunosuppressant therapy. Spontaneous clearance of chronic HCV infection can occur in HIV-HCV-coinfected patients after liver transplantation. The mechanism of this phenomenon remains unclear.     

Effect of kidney transplantation on outcomes among patients with hepatitis C

The long-term outcome of kidney transplantation in patients infected with hepatitis C virus (HCV) and end stage renal disease (ESRD) is not well described. We retrospectively identified 230 HCV-infected patients using enzyme immunoassay and nucleic acid testing obtained during the transplant evaluation. Of 207 patients who had a liver biopsy before transplant, 44 underwent 51 follow-up liver biopsies at approximately 5-year intervals either while on the waitlist for a kidney or after kidney transplantation. Advanced fibrosis was present in 10% of patients biopsied, identifying a population that may warrant consideration for combined liver-kidney transplantation. Kidney transplantation does not seem to accelerate liver injury; 77% of kidney recipients who underwent follow-up biopsies showed stable or improved liver histology. There was a higher risk for death during the first 6 months after transplant, but undergoing transplantation conferred a long-term survival advantage over remaining on the waitlist, which was evident by 6 months after transplant (HR, 0.32; 95% CI, 0.17 to 0.62). Furthermore, the risk for death resulting from infection was significantly higher during the first 6 months after transplant (HR, 26.6; 95% CI, 5.01 to 141.3), whereas there was an early (≤6 months) and sustained decrease in the risk for cardiovascular death (HR, 0.20; 95% CI, 0.08 to 0.47). In summary, these data suggest the importance of liver biopsy before transplant and show that kidney transplantation confers a long-term survival benefit among HCV-infected patients with ESRD compared with remaining on the waitlist. Nevertheless, the higher incidence of early infection-related deaths after transplant calls for further study to determine the optimal immunosuppressive protocol.     

Impact of pre-transplant dialysis modality on post-transplant diabetes mellitus after kidney transplantation

Courivaud C, Ladrière M, Toupance O, Caillard S, de Ligny BH, Ryckelynck J‐P, Moulin B, Rieu P, Frimat L, Chalopin J‐M, Chauvé S, Kazory A, Ducloux D. Impact of pre‐transplant dialysis modality on post‐transplant diabetes mellitus after kidney transplantation.
Clin Transplant 2011: 25: 794–799. © 2010 John Wiley & Sons A/S. Abstract: Post‐transplant diabetes mellitus (PTDM) is a well‐known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre‐transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti‐diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre‐transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p < 0.001), body mass index (BMI) (p < 0.001), use of tacrolimus (p = 0.002), and rejection episodes (p < 0.001) were identified as independent risk factors for development of PTDM. Patients in the PD group were younger (p = 0.004), had lower BMI (p = 0.07), and were less likely to have a history of hepatitis C (p = 0.007) and autosomal dominant polycystic kidney disease (p = 0.07). Adjustment for these variables did not modify the results. The results of this study suggest that pre‐transplant dialysis modality does not have an impact on the subsequent development of PTDM in RTRs.     

Hepatobiliary diseases after kidney transplantation unrelated to classic hepatitis virus

Multiple studies during the past decades have identified chronic liver disease as an important cause of morbidity and mortality in kidney transplant recipients. It has been reported that up to 25% of patients will have some degree of abnormal liver functions during the immediate posttransplant period. In these patients, liver failure has been implicated as the cause of death in approximately 30% of the long-term survivors. While infections from hepatitis virus remain the main cause of ongoing liver damage, many other opportunistic infections with various potential to alter liver function have also been identified. In addition, posttransplant patients are also exposed to hepatotoxic adverse effects of many pharmacotherapeutics including immunosuppressive and nonimmunosuppressive agents. Since there are numerous reports dealing with classic viral hepatitis after kidney transplantation, this review primarily focuses on post-kidney transplant liver diseases which are not due to classic hepatitis viruses.     

Cardiovascular events and investigation in patients who are awaiting cadaveric kidney transplantation

The optimal strategy for cardiovascular (CV) disease surveillance in kidney transplant candidates is uncertain. In this observational study of 604 wait-listed patients in British Columbia, the risk for CV event in diabetic and nondiabetic candidates was 12.7 and 4.5% per year, respectively. CV event rates were relatively constant during the first 3 yr of wait-listing (5.3 to 6.6 per 100 patient-years; 95% confidence interval [CI], 3.7 to 9.3) but rose dramatically during the peritransplantation period (39.6/100 patient-years; 95% CI, 20.6 to 76.1) and remained high throughout the first posttransplantation year (4.0 per 100 patient-years; 95% CI, 2.2 to 7.5). The results of noninvasive cardiac investigations before wait-listing were not predictive of the time to CV event after wait-listing. The practice of surveillance cardiac investigation in wait-listed patients on the basis of ongoing clinical assessment of cardiac risk resulted in fewer investigations (n = 171) than with the recommended practice of periodic screening on the basis of waiting time alone (n = 530) and was not associated with an increased frequency of CV events (CV event rate in patients with and without the recommended frequency of investigation was 9.9 [95% CI, 7.1 to 13.7] and 6.7 [95% CI, 5.2 to 8.7] per 100 patient-years). It is concluded that transplant candidates are at high risk for CV events particularly during the perioperative period. Initial cardiac investigations have limited value in guiding the timing of patient reevaluation after wait-listing. Periodic surveillance cardiac investigation after wait-listing may be unnecessary and requires further study.     

Impact of hepatitis C virus infection on short-term outcomes in renal transplantation

Hepatitis C virus is an RNA virus with 6 known genotypes. Prevalence of hepatitis C virus infection in the world is almost 3%. In patients undergoing hemodialysis, prevalence of hepatitis C virus positivity is reported to be from 1%-54% depending on the methods used for detection. Liver disease in kidney transplant recipients has been attributed to hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, ethanol, hemosiderosis, and drugs such as azathioprine and cyclosporine A. Hepatitis C virus infection is currently the main cause of chronic liver disease in this group, and it may affect allograft outcome. Whether hepatitis C virus infection after renal transplantation adversely affects graft and patient survival remains controversial. Several series have reported no impact on short- and long-term patient and graft survival. In fact, comparative studies using different immunosuppressive protocols are not available. The differences in the results of these studies may be explained by confounding factors, for example, differences in immunosuppressive protocols, study design, methodology of diagnosing hepatitis C virus infection, and differences in hepatitis C virus genotypes. Treatment protocols for hepatitis-C-virus--associated liver disease should be considered before renal transplantation. Nevertheless, transplantation is the best option for patients with hepatitis C virus with end-stage renal disease, and less hepatotoxic immunosuppressive agents may decrease the incidence of posttransplant liver disease in patients with hepatitis C virus. This review will discuss the studies with specific emphasis on the impact of hepatitis C virus infection on short-term outcome in renal transplantation.