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Impact of Anti-Hepatitis C Virus (HCV) Antibody on Outcomes in Renal Transplant Recipients Infected With HCV
Impact of Anti-Hepatitis C Virus (HCV) Antibody on Outcomes in Renal Transplant Recipients Infected With HCV M. Minz, A. Sharma, A. Das, and Y. Chawla
ABSTRACT Objective. Hepatitis C virus (HCV) infection remains an important risk factor for mortality and morbidity in transplant recipients. In this study, we retrospectively analyzed the impact of pretransplantation hepatitis C antibody status in HCV-infected renal allograft recipients on graft and patient survivals. Patients and Methods. From February 1998 to August 2007, 933 renal transplantations were performed at our center. Of these, 104 patients were identified to be harboring HCV infection: 59 (group I) were anti-HCV positive prior to transplantation and 45 (group II) were HCV RNA/antibody positive in the posttransplantation period. The patients transplanted in different eras received different immunosuppressive regimens. Complete follow-up data were available for 72.3% (43/59) in group I and 80% (36/45) in group II. Both groups had a similar number of patients on cyclosporine (62.8% vs 61.1%), tacrolimus (37.2% vs 38.8%), and mycophenolate mofetil (MMF; 58.1% vs 61.1%). These patients were analyzed for differences in patient and graft survivals by log-rank test. Results. The overall mean ages were 35.1 ⫾ 10.4 and 32.4 ⫾ 10.4 years, male to female ratios 37:6 and 31:5, mean donor ages 41.5 ⫾ 10.9 and 41.2 ⫾ 13.1 years, and mean follow-up durations 29.4 ⫾ 24 (range, 1–107.7) and 32.6 ⫾ 24.2 (range, 3.1–97.2) months in groups I and II, respectively. The patients in group I had received a significantly greater number of blood transfusions compared with patients in group II (6.2 ⫾ 5.7 vs 2.1 ⫾ 2.9) and a significantly greater number of dialysis treatments prior to transplantation (84.5 ⫾ 62.0 vs 33.8 ⫾ 43.2), respectively. Liver function tests—SGOT (22.6 ⫾ 16.1 vs 18.3 ⫾ 12.1 IU/L) and SGPT (24.2 ⫾ 28.9 vs 20.4 ⫾ 20.2 IU/L)—were similar in the 2 groups in the pretransplantation period, respectively. The patient and graft survivals at 5 years were similar: 88.6% vs 82.3% (P ⫽ .81) and 60.1% vs 62.5% (P ⫽ .75) in groups I and II, respectively. The serum creatinine values at last follow-up were 1.38 ⫾ 0.6 vs 1.7 ⫾ 2.4 mg% (P ⫽ not significant), SGOT 33.4 ⫾ 25.6 vs 38.3 ⫾ 47 IU/L, and SGPT 39.3 ⫾ 46.7 vs 59.2 ⫾ 89 IU/L in groups I and II, respectively. Liver decompensation occurred in 4 patients, 2 in each group at a mean duration of 36.5 months. Conclusion. Absence of HCV antibody does not confer any survival disadvantage in HCV-infected renal allograft recipients undergoing renal transplantation.
H
EPATITIS C VIRUS (HCV) infection is an important risk factor for mortality and morbidity in transplant recipients.1 HCV infection is diagnosed by presence of anti-HCV antibodies in the serum prior to transplantation. In about 15% of infected patients, these antibodies may not be detectable. These seronegative patients may have a worse prognosis after transplantation.2 In this study, we retrospectively compared the outcomes after transplanta-
From the Departments of Transplant Surgery (M.M., A.S.), Histology (A.D.), and Hepatology (Y.C.), Postgraduate Institute of Medical Education and Research, Chandigarh, India. Address reprint requests to Dr Mukut Minz, Department of Transplant Surgery, PGIMER, Sector 12, Chandigarh, India 160012. E-mail: [email protected]
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.07.068
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2386
Transplantation Proceedings, 40, 2386 –2388 (2008)
IMPACT OF ANTI-HCV ANTIBODY ON OUTCOMES
tion in seronegative versus seropositive HCV-infected renal failure patients to assess the impact of hepatitis C antibody status on graft and patient survivals. PATIENTS AND METHODS From February 1998 to August 2007, 933 renal transplantations were performed at our center. Of these, 104 (11.1%) patients were identified to be harboring HCV infection: 59 (63.2%; group I) were anti-HCV positive prior to transplantation and 45 (36.8%; group II) were anti-HCV negative prior to transplantation but found to be anti-HCV positive in the posttransplantation period based on routine surveillance or positive for HCV RNA done for liver function test abnormalities. The patients transplanted in different eras received different immunosuppressive regimens. Follow-up data were available for 72.3% (43/59) in group I and 80% (36/45) in group II, which were compared. Both groups had a similar number of patients on cyclosporine (62.8% vs 61.1%), tacrolimus (37.2% vs 38.8%), and mycophenolate mofetil (MMF; 58.1% vs 61.1%). These patients were analyzed for differences in patient and graft survivals by log-rank test.
RESULTS
The overall mean ages were 35.1 ⫾ 10.4 and 32.4 ⫾ 10.4 years, male to female ratios 37:6 and 31:5, mean donor ages 41.5 ⫾ 10.9 and 41.2 ⫾ 13.1 years, and mean follow-up durations 29.4 ⫾ 24 (range, 1–107.7) and 32.6 ⫾ 24.2 (range, 3.1–97.2) months in groups I and II, respectively. The patients in group I had received a significantly greater number of blood transfusions compared with patients in group II (6.2 ⫾ 5.7 vs 2.1 ⫾ 2.9) and a significantly greater number of dialysis treatments prior to transplantation (84.5 ⫾ 62. vs 33.8 ⫾ 43.2), respectively. Liver function tests— SGOT (22.6 ⫾ 16.1 vs 18.3 ⫾ 12.1 IU/L) and SGPT (24.2 ⫾ 28.9 vs 20.4 ⫾ 20.2 IU/L)—were similar in the 2 groups in the pretransplantation period, respectively. The patient and graft survivals at 5 years were similar: 88.6% vs 82.3% (P ⫽ .81) and 60.1% vs 62.5% (P ⫽ .75) in groups I and II, respectively. The serum creatinine values at last follow-up were 1.38 ⫾ 0.6 vs 1.7 ⫾ 2.4 mg% (P ⫽ not significant), SGOT 33.4 ⫾ 25.6 vs 38.3 ⫾ 47 IU/L, and SGPT 39.3 ⫾ 46.7 vs 59.2 ⫾ 89 IU/L in groups I and II, respectively. Liver decompensation occurred in 4 patients, 2 in each group at a mean duration of 36.5 months. Two patients in group II developed fibrosing cholestatic hepatitis (FCH) which responded to immunosuppression withdrawal in 1 patient. DISCUSSION
Hepatitis C infection has been established as a risk factor for graft loss and death in renal transplant recipients.1 The HCV infection in these patients in the pretransplantation period may remain undiagnosed as conventional enzymelinked immunosorbent assay (ELISA) testing used for routine screening of these patients may falsely report a negative result and the patients may then be transplanted. The literature on outcomes of these patients after transplantation is limited to a few studies with a small number of patients which suggest that HCV infection in these patients
2387
undergoes an unusually severe course.2– 4 In the present study we assessed the impact of absence of antibody status in HCV positive transplant patients on the outcomes after transplantation. The present study had an 11.1% prevalence of HCV infection. A large number of HCV positive patients (43.3%) in this study were not detected by the preoperative testing and were detected only in the posttransplantation period based on routine checking or deterioration of liver function tests. This highlights the failure of serological methods to accurately diagnose HCV infection in pretransplant recipients. The reason for failure of antibody to appear in these patients has been attributed to either the immunocompromised status of renal failure patients, poor response to lower levels of viremia in these patients,5 or transplantation during the period of infection when the antibody has yet to appear in the blood.2 Our study did not find any difference in outcomes in patient and graft survivals of seronegative HCV patients versus seropositive patients. In contrast, earlier studies have documented rapidly worsening liver functions in the posttransplantation period. Ok et al reported liver decompensation in 6/15 such patients over a mean period of 11 months and jaundice in 12/15 patients.6 All of these patients responded to a decrease/temporary withdrawal in immunosuppression.6 However, this was a selected cohort of patients who showed liver function abnormalities in the follow-up period and were then detected to be HCV RNA positive, unlike the patients in the present study who were routinely screened for presence of anti-HCV antibody in the posttransplantation period. Similarly progressive liver disease has been reported in isolated case reports among patients infected with HCV during or just before transplantation.3,4 In the present study, 2 seronegative patients developed FCH but the majority of seronegative patients had comparable liver function to the seropositive patients. Liver decompensation with cirrhosis also occurred with similar frequency in the 2 groups. Presence of HCV infection with negative anti-HCV antibody has also been associated with increased mortality after a mean follow-up of 9.2 ⫾ 4.4 years7 when compared with anti-HCV positive patients. However, in the present study, no difference in survival was found. This may be related to the shorter follow-up period of the present study. Another limitation of the present study was an incomplete follow-up of the cohort, but ours is a referral hospital and patients often choose to follow up with a local nephrologist after the initial posttransplantation period. In conclusion, absence of HCV antibody does not confer any survival disadvantage in HCV-infected renal allograft recipients undergoing renal transplantation.
REFERENCES 1. Fabrizi F, Martin P, Dixit V, et al: Hepatitis C virus antibody status and survival after renal transplantation. Meta-analysis of observational studies. Am J Transplant 5:1452, 2005
2388 2. Delladetsima I, Psichogiou M, Sypsa V, et al: The course of hepatitis C virus infection in pretransplantation anti-hepatitis C virus-negative renal transplant recipients: a retrospective follow-up study. Am J Kidney Dis 47:309, 2006 3. Chan TM, Wu PC, Lok AS, et al: Clinicopathological features of hepatitis C virus antibody negative fatal chronic hepatitis C after renal transplantation. Nephron 71:213, 1995 4. Dussol B, Brunet P, Cantaloube JF, et al: Hepatitis C virus infection contracted just before kidney transplantation. Nephron 71:229, 1995
MINZ, SHARMA, DAS ET AL 5. Hanuka N, Sikuler E, Tovbin D, et al: Hepatitis C virus infection in renal failure patients in the absence of anti-hepatitis C virus antibodies. J Viral Hepat 9:141, 2002 6. Ok E, Unsal A, Celik A, et al: Clinicopathological features of rapidly progressive hepatitis C virus infection in HCV antibody negative renal transplant recipients. Nephrol Dial Transplant 13: 3103, 1998 7. Breitenfeldt MK, Rasenack J, Berthold H, et al: Impact of hepatitis B and C on graft loss and mortality of patients after kidney transplantation. Clin Transplant 16:130, 2002
ABSTRACT Objective. Hepatitis C virus (HCV) infection remains an important risk factor for mortality and morbidity in transplant recipients. In this study, we retrospectively analyzed the impact of pretransplantation hepatitis C antibody status in HCV-infected renal allograft recipients on graft and patient survivals. Patients and Methods. From February 1998 to August 2007, 933 renal transplantations were performed at our center. Of these, 104 patients were identified to be harboring HCV infection: 59 (group I) were anti-HCV positive prior to transplantation and 45 (group II) were HCV RNA/antibody positive in the posttransplantation period. The patients transplanted in different eras received different immunosuppressive regimens. Complete follow-up data were available for 72.3% (43/59) in group I and 80% (36/45) in group II. Both groups had a similar number of patients on cyclosporine (62.8% vs 61.1%), tacrolimus (37.2% vs 38.8%), and mycophenolate mofetil (MMF; 58.1% vs 61.1%). These patients were analyzed for differences in patient and graft survivals by log-rank test. Results. The overall mean ages were 35.1 ⫾ 10.4 and 32.4 ⫾ 10.4 years, male to female ratios 37:6 and 31:5, mean donor ages 41.5 ⫾ 10.9 and 41.2 ⫾ 13.1 years, and mean follow-up durations 29.4 ⫾ 24 (range, 1–107.7) and 32.6 ⫾ 24.2 (range, 3.1–97.2) months in groups I and II, respectively. The patients in group I had received a significantly greater number of blood transfusions compared with patients in group II (6.2 ⫾ 5.7 vs 2.1 ⫾ 2.9) and a significantly greater number of dialysis treatments prior to transplantation (84.5 ⫾ 62.0 vs 33.8 ⫾ 43.2), respectively. Liver function tests—SGOT (22.6 ⫾ 16.1 vs 18.3 ⫾ 12.1 IU/L) and SGPT (24.2 ⫾ 28.9 vs 20.4 ⫾ 20.2 IU/L)—were similar in the 2 groups in the pretransplantation period, respectively. The patient and graft survivals at 5 years were similar: 88.6% vs 82.3% (P ⫽ .81) and 60.1% vs 62.5% (P ⫽ .75) in groups I and II, respectively. The serum creatinine values at last follow-up were 1.38 ⫾ 0.6 vs 1.7 ⫾ 2.4 mg% (P ⫽ not significant), SGOT 33.4 ⫾ 25.6 vs 38.3 ⫾ 47 IU/L, and SGPT 39.3 ⫾ 46.7 vs 59.2 ⫾ 89 IU/L in groups I and II, respectively. Liver decompensation occurred in 4 patients, 2 in each group at a mean duration of 36.5 months. Conclusion. Absence of HCV antibody does not confer any survival disadvantage in HCV-infected renal allograft recipients undergoing renal transplantation.
H
EPATITIS C VIRUS (HCV) infection is an important risk factor for mortality and morbidity in transplant recipients.1 HCV infection is diagnosed by presence of anti-HCV antibodies in the serum prior to transplantation. In about 15% of infected patients, these antibodies may not be detectable. These seronegative patients may have a worse prognosis after transplantation.2 In this study, we retrospectively compared the outcomes after transplanta-
From the Departments of Transplant Surgery (M.M., A.S.), Histology (A.D.), and Hepatology (Y.C.), Postgraduate Institute of Medical Education and Research, Chandigarh, India. Address reprint requests to Dr Mukut Minz, Department of Transplant Surgery, PGIMER, Sector 12, Chandigarh, India 160012. E-mail: [email protected]
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.07.068
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2386
Transplantation Proceedings, 40, 2386 –2388 (2008)
IMPACT OF ANTI-HCV ANTIBODY ON OUTCOMES
tion in seronegative versus seropositive HCV-infected renal failure patients to assess the impact of hepatitis C antibody status on graft and patient survivals. PATIENTS AND METHODS From February 1998 to August 2007, 933 renal transplantations were performed at our center. Of these, 104 (11.1%) patients were identified to be harboring HCV infection: 59 (63.2%; group I) were anti-HCV positive prior to transplantation and 45 (36.8%; group II) were anti-HCV negative prior to transplantation but found to be anti-HCV positive in the posttransplantation period based on routine surveillance or positive for HCV RNA done for liver function test abnormalities. The patients transplanted in different eras received different immunosuppressive regimens. Follow-up data were available for 72.3% (43/59) in group I and 80% (36/45) in group II, which were compared. Both groups had a similar number of patients on cyclosporine (62.8% vs 61.1%), tacrolimus (37.2% vs 38.8%), and mycophenolate mofetil (MMF; 58.1% vs 61.1%). These patients were analyzed for differences in patient and graft survivals by log-rank test.
RESULTS
The overall mean ages were 35.1 ⫾ 10.4 and 32.4 ⫾ 10.4 years, male to female ratios 37:6 and 31:5, mean donor ages 41.5 ⫾ 10.9 and 41.2 ⫾ 13.1 years, and mean follow-up durations 29.4 ⫾ 24 (range, 1–107.7) and 32.6 ⫾ 24.2 (range, 3.1–97.2) months in groups I and II, respectively. The patients in group I had received a significantly greater number of blood transfusions compared with patients in group II (6.2 ⫾ 5.7 vs 2.1 ⫾ 2.9) and a significantly greater number of dialysis treatments prior to transplantation (84.5 ⫾ 62. vs 33.8 ⫾ 43.2), respectively. Liver function tests— SGOT (22.6 ⫾ 16.1 vs 18.3 ⫾ 12.1 IU/L) and SGPT (24.2 ⫾ 28.9 vs 20.4 ⫾ 20.2 IU/L)—were similar in the 2 groups in the pretransplantation period, respectively. The patient and graft survivals at 5 years were similar: 88.6% vs 82.3% (P ⫽ .81) and 60.1% vs 62.5% (P ⫽ .75) in groups I and II, respectively. The serum creatinine values at last follow-up were 1.38 ⫾ 0.6 vs 1.7 ⫾ 2.4 mg% (P ⫽ not significant), SGOT 33.4 ⫾ 25.6 vs 38.3 ⫾ 47 IU/L, and SGPT 39.3 ⫾ 46.7 vs 59.2 ⫾ 89 IU/L in groups I and II, respectively. Liver decompensation occurred in 4 patients, 2 in each group at a mean duration of 36.5 months. Two patients in group II developed fibrosing cholestatic hepatitis (FCH) which responded to immunosuppression withdrawal in 1 patient. DISCUSSION
Hepatitis C infection has been established as a risk factor for graft loss and death in renal transplant recipients.1 The HCV infection in these patients in the pretransplantation period may remain undiagnosed as conventional enzymelinked immunosorbent assay (ELISA) testing used for routine screening of these patients may falsely report a negative result and the patients may then be transplanted. The literature on outcomes of these patients after transplantation is limited to a few studies with a small number of patients which suggest that HCV infection in these patients
2387
undergoes an unusually severe course.2– 4 In the present study we assessed the impact of absence of antibody status in HCV positive transplant patients on the outcomes after transplantation. The present study had an 11.1% prevalence of HCV infection. A large number of HCV positive patients (43.3%) in this study were not detected by the preoperative testing and were detected only in the posttransplantation period based on routine checking or deterioration of liver function tests. This highlights the failure of serological methods to accurately diagnose HCV infection in pretransplant recipients. The reason for failure of antibody to appear in these patients has been attributed to either the immunocompromised status of renal failure patients, poor response to lower levels of viremia in these patients,5 or transplantation during the period of infection when the antibody has yet to appear in the blood.2 Our study did not find any difference in outcomes in patient and graft survivals of seronegative HCV patients versus seropositive patients. In contrast, earlier studies have documented rapidly worsening liver functions in the posttransplantation period. Ok et al reported liver decompensation in 6/15 such patients over a mean period of 11 months and jaundice in 12/15 patients.6 All of these patients responded to a decrease/temporary withdrawal in immunosuppression.6 However, this was a selected cohort of patients who showed liver function abnormalities in the follow-up period and were then detected to be HCV RNA positive, unlike the patients in the present study who were routinely screened for presence of anti-HCV antibody in the posttransplantation period. Similarly progressive liver disease has been reported in isolated case reports among patients infected with HCV during or just before transplantation.3,4 In the present study, 2 seronegative patients developed FCH but the majority of seronegative patients had comparable liver function to the seropositive patients. Liver decompensation with cirrhosis also occurred with similar frequency in the 2 groups. Presence of HCV infection with negative anti-HCV antibody has also been associated with increased mortality after a mean follow-up of 9.2 ⫾ 4.4 years7 when compared with anti-HCV positive patients. However, in the present study, no difference in survival was found. This may be related to the shorter follow-up period of the present study. Another limitation of the present study was an incomplete follow-up of the cohort, but ours is a referral hospital and patients often choose to follow up with a local nephrologist after the initial posttransplantation period. In conclusion, absence of HCV antibody does not confer any survival disadvantage in HCV-infected renal allograft recipients undergoing renal transplantation.
REFERENCES 1. Fabrizi F, Martin P, Dixit V, et al: Hepatitis C virus antibody status and survival after renal transplantation. Meta-analysis of observational studies. Am J Transplant 5:1452, 2005
2388 2. Delladetsima I, Psichogiou M, Sypsa V, et al: The course of hepatitis C virus infection in pretransplantation anti-hepatitis C virus-negative renal transplant recipients: a retrospective follow-up study. Am J Kidney Dis 47:309, 2006 3. Chan TM, Wu PC, Lok AS, et al: Clinicopathological features of hepatitis C virus antibody negative fatal chronic hepatitis C after renal transplantation. Nephron 71:213, 1995 4. Dussol B, Brunet P, Cantaloube JF, et al: Hepatitis C virus infection contracted just before kidney transplantation. Nephron 71:229, 1995
MINZ, SHARMA, DAS ET AL 5. Hanuka N, Sikuler E, Tovbin D, et al: Hepatitis C virus infection in renal failure patients in the absence of anti-hepatitis C virus antibodies. J Viral Hepat 9:141, 2002 6. Ok E, Unsal A, Celik A, et al: Clinicopathological features of rapidly progressive hepatitis C virus infection in HCV antibody negative renal transplant recipients. Nephrol Dial Transplant 13: 3103, 1998 7. Breitenfeldt MK, Rasenack J, Berthold H, et al: Impact of hepatitis B and C on graft loss and mortality of patients after kidney transplantation. Clin Transplant 16:130, 2002