LIVER TRANSPLANTATION 21:96–100, 2015
ORIGINAL ARTICLE
Long-Term Outcome After Liver Transplantation for Hepatic Schistosomiasis: A Single-Center Experience Over 15 Years Walid El Moghazy,1,2 Samy Kashkoush,1,3 Wael O’hali,1 and Khalid Abdallah1 Department of Hepatobiliary Surgery and Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 2Department of Surgery, Sohag University, Sohag, Egypt; and 3Department of Surgery, National Liver Institute, Menofyia University, Al-Menofyia, Egypt
1
Our objective was to study the long-term outcomes of patients who had undergone liver transplantation because of schistosomiasis at our institute over the last 15 years. Four hundred forty-one patients underwent liver transplantation at our institute, and 14 did so for schistosomiasis. The survival of patients who underwent transplantation for schistosomiasis was compared with that of patients who underwent transplantation for other liver diseases. Survival curves were drawn via the Kaplan-Meier method and were compared with the log-rank test. P < 0.05 was considered significant. All 14 patients were male, and the average age was 56.8 6 8.4 years. The average Model for End-Stage Liver Disease score was 18.2 6 5.6, and the average Child-Pugh score was 10.6 6 1.2. All patients had splenomegaly; pretransplant variceal bleeding occurred in 7 patients (50%), and portal vein thrombosis was diagnosed in 5 patients (36%). Patient survival was 75% 1 year after transplantation and 75% at the end of follow-up because no patients were lost after the first year. Patients who underwent transplantation for other causes achieved survival rates of 86% and 76% 1 and 10 years after transplantation, respectively. There was no significant survival difference between the 2 groups (P 5 0.66). All patients who survived the early posttransplant period had functioning liver grafts with no reported diagnoses of schistosomiasis in the new grafts. In conclusion, liver transplantation for patients with schistosomiasis C 2014 AASLD. has a favorable outcome with no risk of reactivation. Liver Transpl 21:96-100, 2015. V Received June 22, 2014; accepted September 14, 2014. Schistosomiasis results from long-lived infections by trematode blood flukes of the genus Schistosoma.1 It remains one of the world’s most prevalent diseases and affects more than 200 million people. The genus has 5 species, 4 of which can lead to hepatic disease.1,2 In Saudi Arabia, the prevalence of schistosomiasis is 2.78/100,000; 75% of those affected have intestinal schistosomiasis. Approximately 55% of cases are discovered among Saudi individuals, and 45% are among non-Saudi individuals. Two species, Schistosoma mansoni and Schistosoma haematobium, are endemic in Saudi Arabia.3 The adult S. mansoni worms reside in mesenteric veins of the bowel and produce emboli of ova moving to
the liver; this results in a chronic inflammatory reaction, presinusoidal inflammation, periportal fibrosis, and portal hypertension. This sequence occurs in fewer than 10% of patients who have chronic infections and takes many years to develop. Progressive periportal fibrosis, severe portal hypertension, variceal bleeding, huge splenomegaly, and hypersplenism are characteristic features of hepatic schistosomiasis.4 These changes are related to sustained heavy infections over many years. Despite this, hepatocellular function is preserved until the late stage of the disease.4,5 Liver transplantation represents the definitive treatment for end-stage liver disease.1 Several reports have discussed individual cases of liver grafts infected with
Abbreviations: COP, circumoval precipitin; HBV, hepatitis B virus; HCV, hepatitis C virus; MELD, Model for End-Stage Liver Disease; POD, postoperative day. Potential conflict of interest: Nothing to report. Address reprint requests to Walid El Moghazy, M.D., MSc, Ph.D., Department of Hepatobiliary Sciences and Liver Transplantation, Mail Box 1440, King Abul Aziz Medical City, Kingdom of Saudia Arabia, Riyadh 11426, P.O Box: 22490. Tel: 1966-1180-11111 (Ext. 16792); Fax: 19661180-16737; E-mail: [email protected] DOI 10.1002/lt.24010 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2014 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 21, No. 1, 2015
schistosomiasis after transplantation1 and the transmission of schistosomal infections from living liver donors6 and deceased donors;6-8 however, data on the long-term outcomes of schistosomiasis after liver transplantation are still lacking. This report summarizes the long-term outcomes of patients who underwent liver transplantation for schistosomiasis at our institute over the last 15 years.
PATIENTS AND METHODS Between January 2000 and March 2014, 441 patients underwent liver transplantation at King Abdulaziz Medical City in the Kingdom of Saudi Arabia; 14 of these patients underwent transplantation for hepatic schistosomiasis. Three of the 14 patients had associated liver pathologies, whereas 11 patients had schistosomiasis as the only cause of end-stage liver disease after an extensive diagnostic workup. The diagnosis was based on physical, serological, radiological, and histopathological findings. The ethics committee approved this study to conduct. As part of our workup protocol for liver transplant candidates, all patients were examined for the presence of antischistosomal antibodies with the circumoval precipitin (COP) test.9 Patients who were suspected of having an active schistosomal infection underwent a stool analysis for S. mansoni eggs and a rectal snip in case of a negative stool analysis. Patients who had schistosomal infections were treated with a single dose of praziquantel (15 mg/kg) at the time of diagnosis before liver transplantation, and they were instructed to avoid exposure to water contaminated with Schistosoma. In our cohort, patients with the diagnosis of hepatic schistosomiasis had a pathological confirmation of schistosomal eggs surrounded by fibrous tissue in liver explants. After transplantation, follow-up for serum antischistosomal antibodies was performed with the COP test 1 year after transplantation. Patients with a reactive test were given another single dose of praziquantel. The COP test is used for the screening of potential donors for schistosomiasis, and no potential donors have a reactive test. For deceased donors, liver biopsy is a routine procedure before the graft is used. The rate of donation is low in our region, so marginal grafts are not accepted at our center because retransplantation is not a feasible option in the case of graft nonfunction. Retrospectively, we reviewed medical reports of patients for the following: age at the time of transplantation, sex, weight, height, body mass index, history of variceal bleeding, encephalopathy, spontaneous bacterial peritonitis, ascites, Model for End-Stage Liver Disease (MELD) score,10 Child-Pugh score,11 pretransplant laboratory results, graft type (deceased donor liver grafts versus living donor liver grafts), posttransplant rejection, infection, surgical complications, and graft and patient survival.
Surgery Five patients received living donor liver grafts, and all of them were right lobe grafts without the middle
EL MOGHAZY ET AL. 97
hepatic vein. Nine patients received whole liver grafts from deceased donors.
Immunosuppression Our protocol is based on the induction of immunosuppression with 500 mg of methylprednisolone at the time of graft reperfusion; this is decreased to 100 mg on postoperative day (POD) 1, 80 mg on POD 2, 60 mg on POD 3, 40 mg on POD 4, and 20 mg on POD 5, and it is then tapered gradually and discontinued within the first 3 months after transplantation. Tacrolimus is started on POD 1 after transplantation with a target trough level of 8 to 10 ng/mL, and this is reduced gradually to a target level of approximately 6 ng/mL by the end of the first year. Mycofenolate mofetil is given at 750 mg twice daily, and it is discontinued by the end of the first year after transplantation.
Statistical Analysis Data are summarized as means and standard deviations. Survival curves were drawn via the KaplanMeier method and were compared with the log-rank test. P < 0.05 was considered significant. SPSS 17 (SPSS, Inc., Chicago, IL) was used for all calculations.
RESULTS Fourteen patients (3%) underwent transplantation for hepatic schistosomiasis. All were adult males, and their ages ranged from 36 to 67 years with a mean age of 56.8 6 8.4 years. The mean follow-up for our patients was 4.9 6 3.8 years. Two patients had concomitant hepatitis C virus (HCV) infections, and 1 patient had a hepatitis B virus (HBV) infection. Their MELD scores ranged from 10 to 29 with a mean score of 18.2 6 5.6. Child-Pugh scores ranged from 8 to 12 with a mean score of 10.6 6 1.2 (Table 1). Pretransplant variceal bleeding was reported in 7 patients (50%), ascites was reported in 12 patients (86%), and encephalopathy was reported in only 4 patients (29%). Splenomegaly was diagnosed in all patients, and the mean maximal diameter was 16.4 6 2.7 cm. Portal vein thrombosis was diagnosed in 5 patients (36%); 3 of them were managed intraoperatively with thrombectomy, and the remaining 2 patients had interposition grafts with iliac veins from deceased donors. Patients were maintained on oral anticoagulant therapy for 6 months after transplantation, and they were all alive with functioning liver grafts at the time of this writing. Hepatocellular carcinoma was discovered incidentally in only 1 patient (7%) who had a concomitant HCV infection (Table 1). A serological examination revealed schistosomal antibodies ranging from 1:64 to 1:4096. These numbers improved dramatically after transplantation to
ORIGINAL ARTICLE
Long-Term Outcome After Liver Transplantation for Hepatic Schistosomiasis: A Single-Center Experience Over 15 Years Walid El Moghazy,1,2 Samy Kashkoush,1,3 Wael O’hali,1 and Khalid Abdallah1 Department of Hepatobiliary Surgery and Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 2Department of Surgery, Sohag University, Sohag, Egypt; and 3Department of Surgery, National Liver Institute, Menofyia University, Al-Menofyia, Egypt
1
Our objective was to study the long-term outcomes of patients who had undergone liver transplantation because of schistosomiasis at our institute over the last 15 years. Four hundred forty-one patients underwent liver transplantation at our institute, and 14 did so for schistosomiasis. The survival of patients who underwent transplantation for schistosomiasis was compared with that of patients who underwent transplantation for other liver diseases. Survival curves were drawn via the Kaplan-Meier method and were compared with the log-rank test. P < 0.05 was considered significant. All 14 patients were male, and the average age was 56.8 6 8.4 years. The average Model for End-Stage Liver Disease score was 18.2 6 5.6, and the average Child-Pugh score was 10.6 6 1.2. All patients had splenomegaly; pretransplant variceal bleeding occurred in 7 patients (50%), and portal vein thrombosis was diagnosed in 5 patients (36%). Patient survival was 75% 1 year after transplantation and 75% at the end of follow-up because no patients were lost after the first year. Patients who underwent transplantation for other causes achieved survival rates of 86% and 76% 1 and 10 years after transplantation, respectively. There was no significant survival difference between the 2 groups (P 5 0.66). All patients who survived the early posttransplant period had functioning liver grafts with no reported diagnoses of schistosomiasis in the new grafts. In conclusion, liver transplantation for patients with schistosomiasis C 2014 AASLD. has a favorable outcome with no risk of reactivation. Liver Transpl 21:96-100, 2015. V Received June 22, 2014; accepted September 14, 2014. Schistosomiasis results from long-lived infections by trematode blood flukes of the genus Schistosoma.1 It remains one of the world’s most prevalent diseases and affects more than 200 million people. The genus has 5 species, 4 of which can lead to hepatic disease.1,2 In Saudi Arabia, the prevalence of schistosomiasis is 2.78/100,000; 75% of those affected have intestinal schistosomiasis. Approximately 55% of cases are discovered among Saudi individuals, and 45% are among non-Saudi individuals. Two species, Schistosoma mansoni and Schistosoma haematobium, are endemic in Saudi Arabia.3 The adult S. mansoni worms reside in mesenteric veins of the bowel and produce emboli of ova moving to
the liver; this results in a chronic inflammatory reaction, presinusoidal inflammation, periportal fibrosis, and portal hypertension. This sequence occurs in fewer than 10% of patients who have chronic infections and takes many years to develop. Progressive periportal fibrosis, severe portal hypertension, variceal bleeding, huge splenomegaly, and hypersplenism are characteristic features of hepatic schistosomiasis.4 These changes are related to sustained heavy infections over many years. Despite this, hepatocellular function is preserved until the late stage of the disease.4,5 Liver transplantation represents the definitive treatment for end-stage liver disease.1 Several reports have discussed individual cases of liver grafts infected with
Abbreviations: COP, circumoval precipitin; HBV, hepatitis B virus; HCV, hepatitis C virus; MELD, Model for End-Stage Liver Disease; POD, postoperative day. Potential conflict of interest: Nothing to report. Address reprint requests to Walid El Moghazy, M.D., MSc, Ph.D., Department of Hepatobiliary Sciences and Liver Transplantation, Mail Box 1440, King Abul Aziz Medical City, Kingdom of Saudia Arabia, Riyadh 11426, P.O Box: 22490. Tel: 1966-1180-11111 (Ext. 16792); Fax: 19661180-16737; E-mail: [email protected] DOI 10.1002/lt.24010 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2014 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 21, No. 1, 2015
schistosomiasis after transplantation1 and the transmission of schistosomal infections from living liver donors6 and deceased donors;6-8 however, data on the long-term outcomes of schistosomiasis after liver transplantation are still lacking. This report summarizes the long-term outcomes of patients who underwent liver transplantation for schistosomiasis at our institute over the last 15 years.
PATIENTS AND METHODS Between January 2000 and March 2014, 441 patients underwent liver transplantation at King Abdulaziz Medical City in the Kingdom of Saudi Arabia; 14 of these patients underwent transplantation for hepatic schistosomiasis. Three of the 14 patients had associated liver pathologies, whereas 11 patients had schistosomiasis as the only cause of end-stage liver disease after an extensive diagnostic workup. The diagnosis was based on physical, serological, radiological, and histopathological findings. The ethics committee approved this study to conduct. As part of our workup protocol for liver transplant candidates, all patients were examined for the presence of antischistosomal antibodies with the circumoval precipitin (COP) test.9 Patients who were suspected of having an active schistosomal infection underwent a stool analysis for S. mansoni eggs and a rectal snip in case of a negative stool analysis. Patients who had schistosomal infections were treated with a single dose of praziquantel (15 mg/kg) at the time of diagnosis before liver transplantation, and they were instructed to avoid exposure to water contaminated with Schistosoma. In our cohort, patients with the diagnosis of hepatic schistosomiasis had a pathological confirmation of schistosomal eggs surrounded by fibrous tissue in liver explants. After transplantation, follow-up for serum antischistosomal antibodies was performed with the COP test 1 year after transplantation. Patients with a reactive test were given another single dose of praziquantel. The COP test is used for the screening of potential donors for schistosomiasis, and no potential donors have a reactive test. For deceased donors, liver biopsy is a routine procedure before the graft is used. The rate of donation is low in our region, so marginal grafts are not accepted at our center because retransplantation is not a feasible option in the case of graft nonfunction. Retrospectively, we reviewed medical reports of patients for the following: age at the time of transplantation, sex, weight, height, body mass index, history of variceal bleeding, encephalopathy, spontaneous bacterial peritonitis, ascites, Model for End-Stage Liver Disease (MELD) score,10 Child-Pugh score,11 pretransplant laboratory results, graft type (deceased donor liver grafts versus living donor liver grafts), posttransplant rejection, infection, surgical complications, and graft and patient survival.
Surgery Five patients received living donor liver grafts, and all of them were right lobe grafts without the middle
EL MOGHAZY ET AL. 97
hepatic vein. Nine patients received whole liver grafts from deceased donors.
Immunosuppression Our protocol is based on the induction of immunosuppression with 500 mg of methylprednisolone at the time of graft reperfusion; this is decreased to 100 mg on postoperative day (POD) 1, 80 mg on POD 2, 60 mg on POD 3, 40 mg on POD 4, and 20 mg on POD 5, and it is then tapered gradually and discontinued within the first 3 months after transplantation. Tacrolimus is started on POD 1 after transplantation with a target trough level of 8 to 10 ng/mL, and this is reduced gradually to a target level of approximately 6 ng/mL by the end of the first year. Mycofenolate mofetil is given at 750 mg twice daily, and it is discontinued by the end of the first year after transplantation.
Statistical Analysis Data are summarized as means and standard deviations. Survival curves were drawn via the KaplanMeier method and were compared with the log-rank test. P < 0.05 was considered significant. SPSS 17 (SPSS, Inc., Chicago, IL) was used for all calculations.
RESULTS Fourteen patients (3%) underwent transplantation for hepatic schistosomiasis. All were adult males, and their ages ranged from 36 to 67 years with a mean age of 56.8 6 8.4 years. The mean follow-up for our patients was 4.9 6 3.8 years. Two patients had concomitant hepatitis C virus (HCV) infections, and 1 patient had a hepatitis B virus (HBV) infection. Their MELD scores ranged from 10 to 29 with a mean score of 18.2 6 5.6. Child-Pugh scores ranged from 8 to 12 with a mean score of 10.6 6 1.2 (Table 1). Pretransplant variceal bleeding was reported in 7 patients (50%), ascites was reported in 12 patients (86%), and encephalopathy was reported in only 4 patients (29%). Splenomegaly was diagnosed in all patients, and the mean maximal diameter was 16.4 6 2.7 cm. Portal vein thrombosis was diagnosed in 5 patients (36%); 3 of them were managed intraoperatively with thrombectomy, and the remaining 2 patients had interposition grafts with iliac veins from deceased donors. Patients were maintained on oral anticoagulant therapy for 6 months after transplantation, and they were all alive with functioning liver grafts at the time of this writing. Hepatocellular carcinoma was discovered incidentally in only 1 patient (7%) who had a concomitant HCV infection (Table 1). A serological examination revealed schistosomal antibodies ranging from 1:64 to 1:4096. These numbers improved dramatically after transplantation to
