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90 Risk factors of mortality for invasive fungal infections complicating orthotopic liver transplantation in children
ProgramAbstracts
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RISK FACTORS O F M O R T A L I T Y FOR INVASIVE FUNGAL INFECTIONS COMPLICATING ORTHOTOPIC LIVER T R A N S P L A N T A T I O N IN C H I L D R E N M. AlaponL R. Debbag, D. Bes, P. Santos, A. Speranza, M. de la RJba, C. Fernandnz, M. T. de Davila, C. Mondiglio, A. Manterola and O. Imventarza. Hospital Nacional de Pediatria "'Juan P. C.rar'rahan "', Buenos Aires, Argentina, Invasive fungal infections (IFI), due to their high morbidity and mortality, are recognized as severe infectious complications in patients undergoing orthctopic liver transplantation (OLT). The purpose of the Study was to analyze risk factors of moo.silty of IFI in patients who have undergone OLT. Material and methods: Retrospective study of pediatric patients with culture documented IFI who have undergone an OLT between November 1992 and September i999 The medical records of the first 00 days of each liver transplant were reviewed for pro, intra and post operative variables, clinical symptoms, cultures and causes of death. The statistical methods employed were chi-squared test, Ficher, univariate and multivariate relative risk analysis (Epiinfo 6.04 and SPSS). Results: Out of 190 transplantations, 22 episodes of IFI were documented. The median age of the infected transplantations was 68 months ( range 12- 217 months). The indications for OLT in the infected patients (pts) were fulminant hepatic failure: I i pts ( Hepatitis A: 6 pts, Non A Non B: 5 pts), biliary atrecia: 5 pts, autoimmune hepatitis: 3 pts, others: 2 pts.). Clinical infections were : sepsis (9 pts), abdominal collections (4 pts), urinary infection (4 pts), peritonitis (4 pts), surgical wound 2 (pts). Candida (C) albicans was isolated in 15 pts, C. parapsilosis: 3pts, C. tropicalis: Ipt, C lipolytica: 1, Aspergillus fumigatus: ipt, T~chophyton sp; ] pt. Fongal specimens were isolated from liver tissue in 8 pts, urine; 4 pts, blood: 4 pts, abdominal collections: 3pts, peritoneal fluid: 2 pts and wound: 2pts. Eight patients died (7 related to infection). The risk factors of mortality (univariate analysis) were bifiary atresia (P< 0.05), sepsis (P<0.00i), positive hepatic culture (13<0.017) , low platelet count < 50000/mL (p<0.002), total hilicrubin >15 mg % (p<0018), GOT > 101 U/L (p<0.0018), GPT > 101 U/L (p<0.041), Prothrombin time < 49 % (p<0.0056). Multiple regression analysis indicated that sepsis (p<0.0001) and fungal culture from hepatic tissue (p<0.003) to be risk factors associated with death. Conclusions: Analysing risk factors for mortality, determine high risk patients and are usefid to create strategies to prevent IFI aRer OLT
INCIDENCE OF INFECTIONS IN LIVER TRANSPLANTATION DUE TO FULMINANT HEPATITIS. A.Valledor, L.Bare/m, L.Clara, A.Oedano. A.Villamil, G.Greco. S.Masias, E.Sorkin, M.Ciardnllo. Hospital Italiano Bs.As. Argentina. In our Hospital,158 Orthatopic Liver Transplants (OLT) were performed in 148 adult patients (pts.) between 1988 end september 1999.Th¢ p ~ s e of the .~ was to know if differencas in the incidence end type of infections in the first 60 days post OLT exists between patients who received OLT due to Fnlminant Hepatitis (FH) or due to other diseases, in order to establish different prophylaxis strategies. A brief description of melhods: Clinical records ofall the patients filled in a data base were analyzed.Second transplants and liver-kidney transplants were excluded from both group. Results: (~ont~ol grOeP: 130 pts.Age average: 44 y.Sex:F: 79, M: 51 pts. Liver disease:HCV: 28 pts., Autnlmmane Chronic Hepatitis (A.C.H.): 22 pts., Primaty Biliary Cirrhosis: 21 pts.. Cryptogenetic cirrhosis: 19, Sclerosing cholangitis: 15 pts., Secondary biliary cirrhosis 5, Alcoholic cirrhosis: 7 ,HBV: 3 and other: 14 pts. H.F. group: 13 pts. Age average: 35 y. Sex: F: 10. M: 3 pts. Liver disease: A.C.H. 6 ( 1 associated to HVA and 3 unknown. INFECTIONS F .H. GROUP CONTROL GROUP P Episodes/pt , % pts. Episodes/pt % pts. 2.6 77% 2 72% NS Total Infections Severe Infections 1.2 54% 0.7 42% NS I Bacterial. Infections 1.7 77% 1.2 61% NS Severe Bacterial infections I 54% 0.5 34% NS NS ; Viral Infections ().2 23% 0.5 39% Severn Viral Infections 0.07 7.6% 0.1 11.5% NS Funsal Infections 0.4 3 I% 0.25 24% NS Severe Funsal Infections 0 0 0.03 4% NS Parasitic infections 0 0 0,014 1.5% NS Severe Parasitic infections 0 0 0.007 0.7% NS Mortality 23% 2 l,,5% No statistical difference was noted in the incidence of bacterial, viral, fungaJ or parasitic infections between both groups, although a tendency was observed to higher number of all type of infections in the FH. group compared with the Control group. No statistical difference was noted in mortality. Conclusions: Our findings do not support special prophylactic strategies in patients with OLT for fulminant hepatitis. However. the H.F.group is small, end this could be the reason for no significant differences found.
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INFECTIONS IN LIVER TRANSPLANTATION FOR HCV CIRRHOSIS. L. Clara, L.Barc/m, A.Va]ledor , A,Gadano , O. Oaldame , A. Villumil , S. Chao. W. Belloso. E. de Santibafies. Hospital Italieno Bs.As. Argentina. In our Hospital 152 Orthotopic Liver Transplants (OLT) were performed in 142 adult patients between 1988 and May 1999.Theourpose of the study is to compare the incidence and type of infections between those who received an OLT for HCV cirrhosis or due to other liver diseases, because of the irnmunodepression caused by HCV itse|f.A brief description of me.thod~.:Clinical records of all the patients who had at least 6 months of. follow-up filled in a data base werc analyzed. Re-transplantation. fulminam hepatitis and bver-kidney transplant were excluded from both groups. Re#ults: Control group: 102 pts.Ag¢ average: 41 y.(19-63 y.).Sex: F:62 M:40 pts.Liver disease: P.B.C: 21 pts.,Sclerosing cholangitis:15. C.A.H 20, Cryptogenctic cirrhosis: 17, Other: 29 pts. 2 pts. presented with associated Hepatocarcinoma (HCC). HCV grou_~: 27 pts,Age average: 56 y.(25-.67 y.). Sex: F: 15, M 12 pts. 8 pts. presented with associated HCC. There were no significant statistical differences in primary immanosupression, rejection episodes nor cumulated steroid dose between both ~roups. INFECTIONS Control Group HCV Group p Ep./pt* % pts. Ep./pt % pts. Total 2.8 74/102 (72.5%) 3.4 23/27 (85%~ NS Total severe i. I 55/! 02 (54%) 1.7 20/27 (74%) NS Bacterial 1.5 641102 (63%) 2 20/27 (74%) NS Bacterial severe 0.9 45/102 (44%) 1.2 15/27 (55.5%) NS Viral 0.8 52/102 (5 I%) 0.7 14/27 (52%.) NS Viral severe 0.2 23/102 (22.5%.) 0.1 4/27 (15%) NS Fungal 0.4 32/102 (31%) 0.5 12/27 (44%) NS Fungalsevere 0.03 4/102 (4%) 0.3 6/27 (22%)** 0.001 I 6/27 (22%) NSMORTALITY 22/102 (21.5%) *Total number episodes/total number of patients in the group. ** Aspergillas: I. P. ('arinii: 2, C~. ptococcus: 2, Histoplasma: I.( "andida: 2 ep. Conclusions: The only significant difference between the 2 groups was the higher incidence of severe fungal infections in the HCV group. Most of these, were opportunistic infections (.4spergdlosis, Cryptococezt~. Histoplasma. I~C.P). Considering that drug indacad immunosaprassion (primary and rejection treatment) was similar in both groups, this increase in severe fungal infections in HVC group, could be attributed to immunodepressor effect of HCV itself. More studies 8re needed to confirm our findings.
Ganciclovir Does Not Increase the Risk of HCV Recurrence After Liver Transplantation: JM Rabkin, SL Orloff, CL Corless, HR Rosen, AJ Olyaei Introduction: Recurrence of hepatitis C (HCV) is a major risk factor for allografi loss following orthotopic liver transplantation (OLTx). Overall immunosuppression likely affects the rote and timing of HCV recurrence. Ganciclovir is a potent and effective antiviral agent for the prevention and treatment of cylomegalovirus (CMV) infection post-OLTx. Ganciclovir is also immunosuppressivc with associated adverse effects of leukopenia and myelosuppressinn. The present study was undertaken to investigate ganciclovir's effect post-OLTx on the rate and timing of HCV recurrence as well as its impact on CMV infection and acute rejection compared to patients treated with acyclovir. Methods: The clinical course e r a consecutive group of HCV positive (+) OLT× recipients who received either high dose acyclovir (n=38) or ganciclovir (n=36) for CMV prophylaxis were retrospectively analyzed for the incidence and timing of HCV recurrence, CMV infection and acute rejection, All patients had a minimum follow-up of one year. Patients received triple immunosuppressinn with calcineurin inhibitors, purine antagonists, and steroids. (Fisber's Exact, Chi-square, or Kaplan Meier Test) Results: The overall incidence of HCV recurrence post-OLTx was 82.4% (61174). The median time to HCV recurrence was 160 days (range 32-1036) for the acynlovir group and 145 days (range 35-541 ) for the ganciclovir group (NS). HCV recurrence was seen in 17 (45%) acyclovir patients and 18 (50%) gancicfovir patJems by six months and 22 (58%) acyclovir patients and 24 (66%) ganciclovir patients by one year (NS). Overall mortality beyond six months was I 1% (8/74). Nine patients (12%) were diagnosed with CI~V infection. The incidence of CMV infection in the acyclovir group (8/38: 21%) was significantly higher compared to the ganciclovir group ( 1/36: 3%). (p=0,029). The incidence of acute rejection in the acyclovir grouP (I 7/38: 45%) was significantly higher compared to the ganciclovir group (8/36: 22%). (p=0.0.4). Conclusion: These data suggest that gancic]ovir is a superior antiviral agent compared to acyclovir for prevention of post-OLTx CMV infection. In addition, less rejection was noted in ganciclovir treated patients. Despite gnnciclovir's immunosuppressive properties, nllograft hepatitis by six months and one year post-OLTx were similar in both groups. Gannlclovir is an effective and safe prophylactic in HCV (+) OLTx recipients and does not increase the risk of HCV recurrence post-OLTx.
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RISK FACTORS O F M O R T A L I T Y FOR INVASIVE FUNGAL INFECTIONS COMPLICATING ORTHOTOPIC LIVER T R A N S P L A N T A T I O N IN C H I L D R E N M. AlaponL R. Debbag, D. Bes, P. Santos, A. Speranza, M. de la RJba, C. Fernandnz, M. T. de Davila, C. Mondiglio, A. Manterola and O. Imventarza. Hospital Nacional de Pediatria "'Juan P. C.rar'rahan "', Buenos Aires, Argentina, Invasive fungal infections (IFI), due to their high morbidity and mortality, are recognized as severe infectious complications in patients undergoing orthctopic liver transplantation (OLT). The purpose of the Study was to analyze risk factors of moo.silty of IFI in patients who have undergone OLT. Material and methods: Retrospective study of pediatric patients with culture documented IFI who have undergone an OLT between November 1992 and September i999 The medical records of the first 00 days of each liver transplant were reviewed for pro, intra and post operative variables, clinical symptoms, cultures and causes of death. The statistical methods employed were chi-squared test, Ficher, univariate and multivariate relative risk analysis (Epiinfo 6.04 and SPSS). Results: Out of 190 transplantations, 22 episodes of IFI were documented. The median age of the infected transplantations was 68 months ( range 12- 217 months). The indications for OLT in the infected patients (pts) were fulminant hepatic failure: I i pts ( Hepatitis A: 6 pts, Non A Non B: 5 pts), biliary atrecia: 5 pts, autoimmune hepatitis: 3 pts, others: 2 pts.). Clinical infections were : sepsis (9 pts), abdominal collections (4 pts), urinary infection (4 pts), peritonitis (4 pts), surgical wound 2 (pts). Candida (C) albicans was isolated in 15 pts, C. parapsilosis: 3pts, C. tropicalis: Ipt, C lipolytica: 1, Aspergillus fumigatus: ipt, T~chophyton sp; ] pt. Fongal specimens were isolated from liver tissue in 8 pts, urine; 4 pts, blood: 4 pts, abdominal collections: 3pts, peritoneal fluid: 2 pts and wound: 2pts. Eight patients died (7 related to infection). The risk factors of mortality (univariate analysis) were bifiary atresia (P< 0.05), sepsis (P<0.00i), positive hepatic culture (13<0.017) , low platelet count < 50000/mL (p<0.002), total hilicrubin >15 mg % (p<0018), GOT > 101 U/L (p<0.0018), GPT > 101 U/L (p<0.041), Prothrombin time < 49 % (p<0.0056). Multiple regression analysis indicated that sepsis (p<0.0001) and fungal culture from hepatic tissue (p<0.003) to be risk factors associated with death. Conclusions: Analysing risk factors for mortality, determine high risk patients and are usefid to create strategies to prevent IFI aRer OLT
INCIDENCE OF INFECTIONS IN LIVER TRANSPLANTATION DUE TO FULMINANT HEPATITIS. A.Valledor, L.Bare/m, L.Clara, A.Oedano. A.Villamil, G.Greco. S.Masias, E.Sorkin, M.Ciardnllo. Hospital Italiano Bs.As. Argentina. In our Hospital,158 Orthatopic Liver Transplants (OLT) were performed in 148 adult patients (pts.) between 1988 end september 1999.Th¢ p ~ s e of the .~ was to know if differencas in the incidence end type of infections in the first 60 days post OLT exists between patients who received OLT due to Fnlminant Hepatitis (FH) or due to other diseases, in order to establish different prophylaxis strategies. A brief description of melhods: Clinical records ofall the patients filled in a data base were analyzed.Second transplants and liver-kidney transplants were excluded from both group. Results: (~ont~ol grOeP: 130 pts.Age average: 44 y.Sex:F: 79, M: 51 pts. Liver disease:HCV: 28 pts., Autnlmmane Chronic Hepatitis (A.C.H.): 22 pts., Primaty Biliary Cirrhosis: 21 pts.. Cryptogenetic cirrhosis: 19, Sclerosing cholangitis: 15 pts., Secondary biliary cirrhosis 5, Alcoholic cirrhosis: 7 ,HBV: 3 and other: 14 pts. H.F. group: 13 pts. Age average: 35 y. Sex: F: 10. M: 3 pts. Liver disease: A.C.H. 6 ( 1 associated to HVA and 3 unknown. INFECTIONS F .H. GROUP CONTROL GROUP P Episodes/pt , % pts. Episodes/pt % pts. 2.6 77% 2 72% NS Total Infections Severe Infections 1.2 54% 0.7 42% NS I Bacterial. Infections 1.7 77% 1.2 61% NS Severe Bacterial infections I 54% 0.5 34% NS NS ; Viral Infections ().2 23% 0.5 39% Severn Viral Infections 0.07 7.6% 0.1 11.5% NS Funsal Infections 0.4 3 I% 0.25 24% NS Severe Funsal Infections 0 0 0.03 4% NS Parasitic infections 0 0 0,014 1.5% NS Severe Parasitic infections 0 0 0.007 0.7% NS Mortality 23% 2 l,,5% No statistical difference was noted in the incidence of bacterial, viral, fungaJ or parasitic infections between both groups, although a tendency was observed to higher number of all type of infections in the FH. group compared with the Control group. No statistical difference was noted in mortality. Conclusions: Our findings do not support special prophylactic strategies in patients with OLT for fulminant hepatitis. However. the H.F.group is small, end this could be the reason for no significant differences found.
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INFECTIONS IN LIVER TRANSPLANTATION FOR HCV CIRRHOSIS. L. Clara, L.Barc/m, A.Va]ledor , A,Gadano , O. Oaldame , A. Villumil , S. Chao. W. Belloso. E. de Santibafies. Hospital Italieno Bs.As. Argentina. In our Hospital 152 Orthotopic Liver Transplants (OLT) were performed in 142 adult patients between 1988 and May 1999.Theourpose of the study is to compare the incidence and type of infections between those who received an OLT for HCV cirrhosis or due to other liver diseases, because of the irnmunodepression caused by HCV itse|f.A brief description of me.thod~.:Clinical records of all the patients who had at least 6 months of. follow-up filled in a data base werc analyzed. Re-transplantation. fulminam hepatitis and bver-kidney transplant were excluded from both groups. Re#ults: Control group: 102 pts.Ag¢ average: 41 y.(19-63 y.).Sex: F:62 M:40 pts.Liver disease: P.B.C: 21 pts.,Sclerosing cholangitis:15. C.A.H 20, Cryptogenctic cirrhosis: 17, Other: 29 pts. 2 pts. presented with associated Hepatocarcinoma (HCC). HCV grou_~: 27 pts,Age average: 56 y.(25-.67 y.). Sex: F: 15, M 12 pts. 8 pts. presented with associated HCC. There were no significant statistical differences in primary immanosupression, rejection episodes nor cumulated steroid dose between both ~roups. INFECTIONS Control Group HCV Group p Ep./pt* % pts. Ep./pt % pts. Total 2.8 74/102 (72.5%) 3.4 23/27 (85%~ NS Total severe i. I 55/! 02 (54%) 1.7 20/27 (74%) NS Bacterial 1.5 641102 (63%) 2 20/27 (74%) NS Bacterial severe 0.9 45/102 (44%) 1.2 15/27 (55.5%) NS Viral 0.8 52/102 (5 I%) 0.7 14/27 (52%.) NS Viral severe 0.2 23/102 (22.5%.) 0.1 4/27 (15%) NS Fungal 0.4 32/102 (31%) 0.5 12/27 (44%) NS Fungalsevere 0.03 4/102 (4%) 0.3 6/27 (22%)** 0.001 I 6/27 (22%) NSMORTALITY 22/102 (21.5%) *Total number episodes/total number of patients in the group. ** Aspergillas: I. P. ('arinii: 2, C~. ptococcus: 2, Histoplasma: I.( "andida: 2 ep. Conclusions: The only significant difference between the 2 groups was the higher incidence of severe fungal infections in the HCV group. Most of these, were opportunistic infections (.4spergdlosis, Cryptococezt~. Histoplasma. I~C.P). Considering that drug indacad immunosaprassion (primary and rejection treatment) was similar in both groups, this increase in severe fungal infections in HVC group, could be attributed to immunodepressor effect of HCV itself. More studies 8re needed to confirm our findings.
Ganciclovir Does Not Increase the Risk of HCV Recurrence After Liver Transplantation: JM Rabkin, SL Orloff, CL Corless, HR Rosen, AJ Olyaei Introduction: Recurrence of hepatitis C (HCV) is a major risk factor for allografi loss following orthotopic liver transplantation (OLTx). Overall immunosuppression likely affects the rote and timing of HCV recurrence. Ganciclovir is a potent and effective antiviral agent for the prevention and treatment of cylomegalovirus (CMV) infection post-OLTx. Ganciclovir is also immunosuppressivc with associated adverse effects of leukopenia and myelosuppressinn. The present study was undertaken to investigate ganciclovir's effect post-OLTx on the rate and timing of HCV recurrence as well as its impact on CMV infection and acute rejection compared to patients treated with acyclovir. Methods: The clinical course e r a consecutive group of HCV positive (+) OLT× recipients who received either high dose acyclovir (n=38) or ganciclovir (n=36) for CMV prophylaxis were retrospectively analyzed for the incidence and timing of HCV recurrence, CMV infection and acute rejection, All patients had a minimum follow-up of one year. Patients received triple immunosuppressinn with calcineurin inhibitors, purine antagonists, and steroids. (Fisber's Exact, Chi-square, or Kaplan Meier Test) Results: The overall incidence of HCV recurrence post-OLTx was 82.4% (61174). The median time to HCV recurrence was 160 days (range 32-1036) for the acynlovir group and 145 days (range 35-541 ) for the ganciclovir group (NS). HCV recurrence was seen in 17 (45%) acyclovir patients and 18 (50%) gancicfovir patJems by six months and 22 (58%) acyclovir patients and 24 (66%) ganciclovir patients by one year (NS). Overall mortality beyond six months was I 1% (8/74). Nine patients (12%) were diagnosed with CI~V infection. The incidence of CMV infection in the acyclovir group (8/38: 21%) was significantly higher compared to the ganciclovir group ( 1/36: 3%). (p=0,029). The incidence of acute rejection in the acyclovir grouP (I 7/38: 45%) was significantly higher compared to the ganciclovir group (8/36: 22%). (p=0.0.4). Conclusion: These data suggest that gancic]ovir is a superior antiviral agent compared to acyclovir for prevention of post-OLTx CMV infection. In addition, less rejection was noted in ganciclovir treated patients. Despite gnnciclovir's immunosuppressive properties, nllograft hepatitis by six months and one year post-OLTx were similar in both groups. Gannlclovir is an effective and safe prophylactic in HCV (+) OLTx recipients and does not increase the risk of HCV recurrence post-OLTx.