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Impact of Cytomegalovirus Infection on Long-Term Survival After Orthotopic Liver Transplantation
Impact of Cytomegalovirus Infection on Long-Term Survival After Orthotopic Liver Transplantation L. Hoppe, C.A. Marroni, R. Bressane, L. Lago, F.L. Schiavo, G.C. Cigerza, A.B.M. Brandão, M.L. Zanotelli, and G.P.C. Cantisani ABSTRACT Cytomegalovirus (CMV) is one of the most common and serious opportunistic infections in solid organ transplant patients. In different series the incidence of CMV infection ranges from 25% to 85%. An indirect effect of infection includes reduced long-term patient and allograft survival. Our objective was to determine the relationship between CMV infection and patient survival after orthotopic liver transplantation. Patients and methods. From January 1999 to December 2001, 163 orthotopic liver transplantations were performed in 154 patients. The inclusion criteria for this analysis were the absence of retransplantation and survival of more than 6 months. One hundred fifteen patients met the inclusion criteria. CMV infection was detected by positive antigenemia. Results. CMV infection occurred in 65.8% of patients after orthotopic liver transplantation. Their 5-year survival was 85%, with no difference observed between patients with or without infection (P ⫽ .8). Conclusion. CMV infection did not interfere with patient survival after orthotopic liver transplantation.
C
YTOMEGALOVIRUS (CMV) infection is a frequent complication in transplant recipients.1 Solid organ recipients experience direct effects of infection, such as pneumonitis, hepatitis, encephalitis, and gastrointestinal disease. Indirect effects include reduced long-term patient survival, other opportunistic infections, allograft dysfunction, and acute and chronic allograft rejection.2 Among kidney and lung transplant recipients, the use of CMV Ig G positive allografts has been associated with decreased patient and allograft survival. In cases of orthotopic liver transplants (OLT), CMV infection is an independent predictor for 1-year survival.3 The aim of the study was to assess the impact of CMV infection on long-term survival after OLT. PATIENTS AND METHODS From January 1999 to December 2001, 163 liver transplantations were performed in 154 patients. The inclusion criteria for this study were absence of retransplantation and more than 6 months survival. The indications for liver transplantation were cirrhosis in all patients, except two: one with fulminant hepatitis and one with familial paramyloidosis. CMV infection was diagnosed based on positive results using CMV-pp65 antigenemia (APAAP technique-Clonab, Biotest,
Dreieich, Germany). CMV screening was performed once a week from postoperative day 10 to discharge. Antigenemia was then measured at each outpatient visit. Conditional survival was analyzed once all patients were alive for at least 6 months.
Statistical Analysis An epidemic curve of infectious episodes was obtained using weekly intervals after transplant. The occurrence of death among infected versus noninfected patients was evaluated by KaplanMeier curves. The level of significance was set at 5% (P ⫽ .05). All statistical analyses were performed using SPSS 12.0.
RESULTS
Antigenemia was positive in 75 of 115 patients (65.8%) including 103 episodes, mostly during the first 3 postoperative months (Fig 1). Patients were followed for 6 to 60 months after OLT, and conditional survival was 96% after the first year, 83% after From Santa Casa, Porto Alegre, FFFCMPA, Rio Grande do Sul, Brazil. Address reprint requests to Lisia Hoppe, Rua Uruguai, 2001, 312/B, Passo Fundo, Rio Grande do Sul, CEP 99010-112, Brasil. E-mail: [email protected]
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.06.074
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
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the third year, and 73% after the fifth year. We did not observe a significant difference between infected and noninfected patients (Fig 2).
DISCUSSION
Our data confirmed that CMV infection is common after OLT. It occurs frequently in the second and third months after OLT.4 CMV infection was not an important factor to decrease patient survival in this cohort in contrast to the report of Falagas et al who claimed that CMV infection was an important, independent factor decreasing long-term patient survival.3
Fig 2. Kaplan-Meier curve showing the occurrence of death in 115 CMV infected and non-infected patients submitted to liver transplant.
REFERENCES
Fig 1. Epidemical curve representing the occurrence of CMV infection episodes in 115 liver transplant patients.
1. Angelis M, Cooper JT, Freeman RB: Impact of donor infection on outcome of orthotopic liver transplantation. Liver Transpl 9:451, 2003 2. Freeman RB, Paya C, Pescovitz MD, et al: Risk factors for cytomegalovirus viremia and disease developing after prophylaxis in high-risk solid-organ transplant recipients. Transplantation 78: 1765, 2004 3. Falagas ME, Paya C, Ruthazer R, et al: Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: a prospective derivation and validation cohort analysis. Transplantation 66:1020, 1998 4. Meer JTM, Drew WL, Bowden RA, et al: Summary of the international consensus symposium on advances in the diagnosis, treatment and prophylaxis of cytomegalovirus infection. Antiviral Res 32:119, 1996
C
YTOMEGALOVIRUS (CMV) infection is a frequent complication in transplant recipients.1 Solid organ recipients experience direct effects of infection, such as pneumonitis, hepatitis, encephalitis, and gastrointestinal disease. Indirect effects include reduced long-term patient survival, other opportunistic infections, allograft dysfunction, and acute and chronic allograft rejection.2 Among kidney and lung transplant recipients, the use of CMV Ig G positive allografts has been associated with decreased patient and allograft survival. In cases of orthotopic liver transplants (OLT), CMV infection is an independent predictor for 1-year survival.3 The aim of the study was to assess the impact of CMV infection on long-term survival after OLT. PATIENTS AND METHODS From January 1999 to December 2001, 163 liver transplantations were performed in 154 patients. The inclusion criteria for this study were absence of retransplantation and more than 6 months survival. The indications for liver transplantation were cirrhosis in all patients, except two: one with fulminant hepatitis and one with familial paramyloidosis. CMV infection was diagnosed based on positive results using CMV-pp65 antigenemia (APAAP technique-Clonab, Biotest,
Dreieich, Germany). CMV screening was performed once a week from postoperative day 10 to discharge. Antigenemia was then measured at each outpatient visit. Conditional survival was analyzed once all patients were alive for at least 6 months.
Statistical Analysis An epidemic curve of infectious episodes was obtained using weekly intervals after transplant. The occurrence of death among infected versus noninfected patients was evaluated by KaplanMeier curves. The level of significance was set at 5% (P ⫽ .05). All statistical analyses were performed using SPSS 12.0.
RESULTS
Antigenemia was positive in 75 of 115 patients (65.8%) including 103 episodes, mostly during the first 3 postoperative months (Fig 1). Patients were followed for 6 to 60 months after OLT, and conditional survival was 96% after the first year, 83% after From Santa Casa, Porto Alegre, FFFCMPA, Rio Grande do Sul, Brazil. Address reprint requests to Lisia Hoppe, Rua Uruguai, 2001, 312/B, Passo Fundo, Rio Grande do Sul, CEP 99010-112, Brasil. E-mail: [email protected]
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.06.074
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1924
Transplantation Proceedings, 38, 1924 –1925 (2006)
CYTOMEGALOVIRUS INFECTION AND SURVIVAL
1925
the third year, and 73% after the fifth year. We did not observe a significant difference between infected and noninfected patients (Fig 2).
DISCUSSION
Our data confirmed that CMV infection is common after OLT. It occurs frequently in the second and third months after OLT.4 CMV infection was not an important factor to decrease patient survival in this cohort in contrast to the report of Falagas et al who claimed that CMV infection was an important, independent factor decreasing long-term patient survival.3
Fig 2. Kaplan-Meier curve showing the occurrence of death in 115 CMV infected and non-infected patients submitted to liver transplant.
REFERENCES
Fig 1. Epidemical curve representing the occurrence of CMV infection episodes in 115 liver transplant patients.
1. Angelis M, Cooper JT, Freeman RB: Impact of donor infection on outcome of orthotopic liver transplantation. Liver Transpl 9:451, 2003 2. Freeman RB, Paya C, Pescovitz MD, et al: Risk factors for cytomegalovirus viremia and disease developing after prophylaxis in high-risk solid-organ transplant recipients. Transplantation 78: 1765, 2004 3. Falagas ME, Paya C, Ruthazer R, et al: Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: a prospective derivation and validation cohort analysis. Transplantation 66:1020, 1998 4. Meer JTM, Drew WL, Bowden RA, et al: Summary of the international consensus symposium on advances in the diagnosis, treatment and prophylaxis of cytomegalovirus infection. Antiviral Res 32:119, 1996