- Email: [email protected]
Increased systemic production of carbon monoxide in patients with cirrhosis and ascites with and without spontaneous bacterial peritonitis (SBP)
Friday, April 19, 2002
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nist, Tezosentan in cirrhotic rats following endotoxin (lipopolysaccharide, LPS) administration. Two groups of rats with cirrhosis received LPS (1 mg/kg iv) and either Tezosentan (5 mg/kg iv) or placebo one hour later. Four hours after LPS administration, hemodynamic studies and laboratory tests were performed and rats were killed for hepatic measurements of inducible NOS activity and protein expression, myeloperoxidase (MPO) and COX-2 expression. Hepatic polynuclear infiltration was also evaluated. At four hours, the survival rate was significantly lower in rats receiving LPS and Tezosentan (80 + 10%) than in rats receiving LPS and placebo (50 4- 11%). Following LPS and Tezosentan, ASAT and ALAT concentrations remained normal while they increased by more than 700% with LPS alone. TNF-alpha levels remained significantly lower in rats receiving LPS and Tezosentan (182 4- 38 pg/ml) and those receiving LPS alone (821 4212 pg/ml). Tezosentan significantly decreased hepatic MPO activity and polynuclear infiltration following LPS administration. Tezosentan had no significant effect on hepatic inducible NOS and COX-2. In conclusion, Tezosentan decreased mortality rate and liver injury in rats with cirrhosis receiving endotoxin. These beneficial effects might be due to a decrease in TNF-alpha production and polymorphonuclear infiltration in the liver.
-'] THE CANNABINOID RECEPTOR CB1 COMPENSATES FOR DEFICIENT ENOS ACTIVITY IN ecNOS-KNOCKOUT MICE AND IS MARKEDLY UPREGULATED IN MURINE AND HUMAN CIRRHOSIS Erwin Biecker ~, Hans Saegesser ] , Markus Neef 2, Tilman Sauerbruch 2, Juerg Reichen 1 . 1 Department of Clinical Pharmacology, University of
Berne, Berne, Switzerland; 2Department of Internal Medicine 1, University of Bonn, Bonn, Germany Aim: Recently, it has been shown that endogenous cannabinoids and their receptors are involved in the regulation of portal blood flow and that NO - at least in part - mediates this effect. We therefore hypothesized that the CB 1-receptor is upregulated in livers of cirrhotic mice and that ecNOS knock-out (KO) mice, lacking eNOS activity, exhibit higher CB 1-receptor levels than wild type (WT) mice. To assess whether animal data can be translated to the situation in man, mRNA levels of the CB 1-receptor were determined in hepatic arteries of cirrhotic and control patients. Methods: ecNOS-KO and WT mice were rendered cirrhotic by bile duct ligation (BDL); sham-operated mice served as controls. Hepatic arteries of cirrhotic patients were collected during liver transplantation; donor vessels served as controls, mRNA was quantitated by TaqMan real-time PCR. Results are expressed as x-fold increase in delta-delta Ct values (deltaCt = Ct target sequence-Ct GAPDH). Protein levels were estimated by Western blotting. Statistical analysis was done using the Mann-Whitney U test. Results: ecNOS-KO mice exhibited higher CB 1 mRNA (5.6-fold increase; p = 0.01) and protein levels (3.7-fold increase; p = 0.02) than WT mice. Bile duct ligation induced marked elevation of CB 1-receptor mRNA (95fold increase; p = 0.0005) and protein (3.1-fold increase; p = 0.02) in WT animals. Due to the higher basal levels in sham-operated controls, this effect was less pronounced in BDL ecNOS KO mice on the mRNA (6.6-fold increase; p = 0.04) and protein level (1.7-fold increase; p = 0.02). Human hepatic artery CB1 mRNA levels are upregulated in cirrhotic subjects compared to controls (5-fold increase; p = 0.04). Conclusions: The upregulation of the CBl-receptor in ecNOS-KO mice compared to WT mice supports the hypothesis that NO mediates part of the vasodilator effect of carmabinoids. The CB 1-receptor upregulation in livers of cirrhotic WT mice and - less pronounced - in ecNOS-KO mice as well as the increased mRNA levels in human hepatic arteries of cirrhotic patients outlines the importance of the endocannabinoids and their receptor in portal hypertension.
•]
RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL OF RHU-EPO TO IMPROVE PLATELET COUNT AND PLATELET FUNCTION IN ALCOHOLIC CIRRHOTICS WITH THROMBOCYTOPENIA
Monika Homoncik l, Markus Peck-Radosavljevic t, Napo Laya 2, Alfred Gangl 1, Peter Ferenci i, Bernd Jilma 2. 1Department of
Gastroenterology And Hepatology, Vienna University Hospital, Vienna; 2Department of Clinical Pharmacology, Vienna University Hospital, Vienna, Austria Background: Patients with liver cirrhosis have a complex hemostasis disturbance including thrombocytopenia and abnormal bleeding time. Erythropoietin is the primary stimulator of erythrocyte production and was reported to increase megakaryocyte formation. In addition erythropoietin was shown to increase platelet count and platelet reactivity in healthy volunteers. We therefore hypothesized that the administration of erythropoietin to patients with thrombocytopenia may result in an increase of platelet count and platetet function. Methods: A total of 21 thrombocytopenic patients with alcoholic liver cirrhosis (abstaining at study entry) received either 100 IF_Ykgerythropoietin (Erypo ®, Janssen-Cilag, Vienna) or placebo on day 1, 3 and 5 in a 2:1 randomized, double-blinded fashion. Platelet count, platelet reactivity (flow cytometry, thrombin receptor activating peptide induced P-selectin expression), in-vivo (Simplate II) and in-vitro (PFA-100) bleeding times were determined on study days 1, 3, 5 and 9. Results: Baseline median platelet count was 80 G/L (range, 39-127) and was not significantly different between groups (p > 0.05). Treatment with erythropoietin increased platelet count by 20% (p = 0.01) and platelet reactivity up to 70% (p < 0.01) versus baseline. This increase in platelet count and platelet reactivity had no effect on primary hemostasis measured by in-vivo and in-vitro bleeding times (p > 0.05). No significant effect was observed in the placebo group. Conclusions: Treatment with erythropoietin increased significantly platelet count and platelet reactivity in patients with alcoholic liver cirrhosis. However, these changes had no effect on platelet function. Thus, erythropoitin appears to be unable to reduce the risk for bleeding in thrombocytopenic patients suffering from liver cirrhosis.
~ - ' ] INCREASED SYSTEMIC PRODUCTION OF CARBON MONOXIDE IN PATIENTS WITH CIRRHOSIS AND ASCITES WITH AND WITHOUT SPONTANEOUS BACTERIAL PERITONITIS (SBP) D. De Las Hems 1, R. Ortega I, P. Gines I , A. Cardenas l , J. Fernandez I , M. Guevara 1, B. Calahorra I , J. A. Barbera 2, M. Navasa I , W. Jimenez 3, V. Arroyo I , J. Rodts 1 . 1 Liver Unit Diseases," 2pneumology Unit,"
SHormonal Laboratory, Hospital Clinic, ID1BAPS, Barcelona, Catalunya, Spain Carbon monoxide (CO) is a gas with a potent vasodilator action synthetized from the catabolism of heme by the action of the heme oxygenase, which exists in two isoforms, constitutive (HO-2) and inducible (HO-1) by bacterial products and cytokines. Studies in animals with portal hypertension have found an increased activity of the HO-1, which could participate in the pathogenesis of splanchnic vasodilation. No studies have been reported assessing the production of CO in human cirrhosis. In the current study, the concentration of CO in the exhaled air (COexh) and the concentration of carboxihemoglobin in venous blood (COHb), as indexes of the systemic production of CO, were assessed in 12 healthy subjects, 12 patients with cirrhosis and ascites and 24 patients with SBP. Smokers and patients with lung diseases were excluded. COexh and COHb were significantly higher in patients with ascites than values in healthy subjects (3 4- 0.4 vs. 0.9 + 0.7 ppm and 1.3 4- 0.5 vs 0.6 4- 0.3%, respectively, p < 0.005 for both). In patients with SBP, values of COexh and COHb were even higher than those in patients with ascites without SBP (5.6 4- 3 ppm and 1.9 4- 1%, p < 0.01 for both). Resolution of SBP was associated with a significant reduction
Parallel Session 3: Portal Hypertension & Complications in Chronic Liver Disease in both parameters, which reached values similar to those of patients without SBP one month after resolution of the infection. These results support the existence of an increased systemic production of CO in cirrhosis with ascites and in SBP, which could participate in the pathogenesis of arterial vasodilation present in these conditions.
[-~
ORAL GLUTAMINE CHALLENGE CORRELATES WITH MINIMAL HEPATIC ENCEPHALOPATHY AND PREDICTS OVERT EPISODES
Lourdes Grande I , Ines Camacho 2, Soledad Benitez 2 , Manuel Romero-Gomez 1. 1Hepatology Unit, Valme U. Hospital, Sevilla;
2Biochemistry Unit, Valme U. Hospital, Sevilla, Spain Aims: We assessed the usefulness of oral glutamine challenge (OGC) in the management of patients with minimal hepatic encephalopathy (MHE). Methods: Seventy cirrhotic patients and ten healthy volunteers were enrolled. MHE was deduced when a patient had a Z score >2.3 in at least one test from among number connection test, digit symbol test and block design test. Venous ammonia concentrations were measured before and 60 minutes (NH3-60m) after a l0 g oral glutamine load. A pathological glutamine tolerance value was an ammonia value > 128 mg/dl (ROC curve). We also determined the blood concentrations of Mn, Zn, glutamine, glutamate and BCAA/AAA ratio. Results: In healthy controls ammonia remains unchanged (from 40.4 + 22.2 to 44.2 + 13.6). No patient developed signs of overt hepatic encephalopathy or adverse events following the glutamine load. Ammonia increased significantly in cirrhotic patients (from 70.41 + 45.2 to 127.43 + 78.6; p < 0.001). In multivariate analysis (logistic regression) OGC was related to liver dysfunction (OR = 7.69; 95% CI = 1.72 - 33.3; p < 0.01), presence of esophageal varices (OR = 7.14; 95% CI = 1.9 - 25; p < 0.005) and MHE (OR = 5.45; 95% CI = 1.17 - 25.4; p < 0.05). In a mean follow-up of 10.2 + 2.9 months, 11 patients (15%) developed overt HE. In multivariate analysis OGC (OR = 14.5; 95% CI = 1.26 - 126.3) and MHE (OR = 1.56; 95% CI = 1.02 - 21.9) achieved statistical significance. Patients who developed overt HE showed a greater NH3-60m than those patients who did not develop overt HE (from 95.9 + 49 to 181 + 62 vs. from 65.6 + 46 to 117 + 77, respectively; p < 0.01). Conclusions: A pathological OGC correlates with MHE and could predict the development of overt HE. A combination of biochemical and neuropsychological tests could provide a new index to assess overt HE risk in cirrhotic patients.
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LIVER DISEASE IS A MAJOR CAUSE OF MORTALITY FOLLOWING ALLOGENIC BONE MARROW TRANSPLANTATION
Manal El-Saved 1, Alaa El-Haddad 2, Omar Fahmy 2, Iman Salama 3, Hossam Mahmoud 2. 1Pediatric Dept., Hematology/Oncology Division,
Ain Shams University, Cairo; 2Bone Marrow Transplantation Center of National Cancer Institute, Cairo; 3Community Medicine Department of National Research Center, Cairo, Egypt Objective: This retrospective study aimed at determining prevalence and risk factors for liver dysfunction within 6 months following allogenic bone marrow transplantation (BMT). A total of 103 patients, median age 23 ys (33% < 18 ys; 66% males), transplanted in a single institution were enrolled. Data on donors and recipients were collected including hematological disease, bilirubin, alanine transaminase (ALT), alkaline phosphatase (ALP), hepatitis B (HBV), and hepatitis C (HCV) markers (including HCVRNA). Results: Fifty-one of 103 patients died and liver disease was the major cause of death (25 of 51,49.5%). Incidence of severe venoocclusive disease (VOD) was 7.8% and hepatic failure attributed to liver graft-versus-hostdisease (GVHD) was 22.3% (23/103). Of those, 44.5% were anti-HCV and/or HCV-RNA, 24.1% HBcAb, 6.9% HBsAg and 62.1% HBsAb positive. Only 4 had ALT > 500 U/L (normal <= 42 U/L), Multiple logistic analyses showed that ALP could predict hepatic GVHD (Adjusted Odds Ratio, AOR: 7.4, p = 0.02) and VOD (AOR: 9.24, p = 0.047). Donors' HCV-RNA and HBsAg were also predictive of liver GVHD (AOR: 102, p = 0.018 and AOR: 18.5, p = 0.057 respectively). The most significant risk factors for mortality following BMT were liver GVHD (AOR: 9.28, 95% CI = 1.89-45.4, p = 0.006) and VOD (AOR: 7.55, 95% CI = 0.95-65.3, p = 0.05). Conclusions: Hepatic GVHD is a common complication following BMT and is a strong predictor of potentially lethal liver complications. The high prevalence of HCV and HBV might have contributed to outcome of liver GVHD and VOD. However, the study could not rule out fulminant reactivation due to lack of HBV-DNA and liver histology results. Antiviral therapy should be commenced early to prevent relentless progression of liver disease.
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nist, Tezosentan in cirrhotic rats following endotoxin (lipopolysaccharide, LPS) administration. Two groups of rats with cirrhosis received LPS (1 mg/kg iv) and either Tezosentan (5 mg/kg iv) or placebo one hour later. Four hours after LPS administration, hemodynamic studies and laboratory tests were performed and rats were killed for hepatic measurements of inducible NOS activity and protein expression, myeloperoxidase (MPO) and COX-2 expression. Hepatic polynuclear infiltration was also evaluated. At four hours, the survival rate was significantly lower in rats receiving LPS and Tezosentan (80 + 10%) than in rats receiving LPS and placebo (50 4- 11%). Following LPS and Tezosentan, ASAT and ALAT concentrations remained normal while they increased by more than 700% with LPS alone. TNF-alpha levels remained significantly lower in rats receiving LPS and Tezosentan (182 4- 38 pg/ml) and those receiving LPS alone (821 4212 pg/ml). Tezosentan significantly decreased hepatic MPO activity and polynuclear infiltration following LPS administration. Tezosentan had no significant effect on hepatic inducible NOS and COX-2. In conclusion, Tezosentan decreased mortality rate and liver injury in rats with cirrhosis receiving endotoxin. These beneficial effects might be due to a decrease in TNF-alpha production and polymorphonuclear infiltration in the liver.
-'] THE CANNABINOID RECEPTOR CB1 COMPENSATES FOR DEFICIENT ENOS ACTIVITY IN ecNOS-KNOCKOUT MICE AND IS MARKEDLY UPREGULATED IN MURINE AND HUMAN CIRRHOSIS Erwin Biecker ~, Hans Saegesser ] , Markus Neef 2, Tilman Sauerbruch 2, Juerg Reichen 1 . 1 Department of Clinical Pharmacology, University of
Berne, Berne, Switzerland; 2Department of Internal Medicine 1, University of Bonn, Bonn, Germany Aim: Recently, it has been shown that endogenous cannabinoids and their receptors are involved in the regulation of portal blood flow and that NO - at least in part - mediates this effect. We therefore hypothesized that the CB 1-receptor is upregulated in livers of cirrhotic mice and that ecNOS knock-out (KO) mice, lacking eNOS activity, exhibit higher CB 1-receptor levels than wild type (WT) mice. To assess whether animal data can be translated to the situation in man, mRNA levels of the CB 1-receptor were determined in hepatic arteries of cirrhotic and control patients. Methods: ecNOS-KO and WT mice were rendered cirrhotic by bile duct ligation (BDL); sham-operated mice served as controls. Hepatic arteries of cirrhotic patients were collected during liver transplantation; donor vessels served as controls, mRNA was quantitated by TaqMan real-time PCR. Results are expressed as x-fold increase in delta-delta Ct values (deltaCt = Ct target sequence-Ct GAPDH). Protein levels were estimated by Western blotting. Statistical analysis was done using the Mann-Whitney U test. Results: ecNOS-KO mice exhibited higher CB 1 mRNA (5.6-fold increase; p = 0.01) and protein levels (3.7-fold increase; p = 0.02) than WT mice. Bile duct ligation induced marked elevation of CB 1-receptor mRNA (95fold increase; p = 0.0005) and protein (3.1-fold increase; p = 0.02) in WT animals. Due to the higher basal levels in sham-operated controls, this effect was less pronounced in BDL ecNOS KO mice on the mRNA (6.6-fold increase; p = 0.04) and protein level (1.7-fold increase; p = 0.02). Human hepatic artery CB1 mRNA levels are upregulated in cirrhotic subjects compared to controls (5-fold increase; p = 0.04). Conclusions: The upregulation of the CBl-receptor in ecNOS-KO mice compared to WT mice supports the hypothesis that NO mediates part of the vasodilator effect of carmabinoids. The CB 1-receptor upregulation in livers of cirrhotic WT mice and - less pronounced - in ecNOS-KO mice as well as the increased mRNA levels in human hepatic arteries of cirrhotic patients outlines the importance of the endocannabinoids and their receptor in portal hypertension.
•]
RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL OF RHU-EPO TO IMPROVE PLATELET COUNT AND PLATELET FUNCTION IN ALCOHOLIC CIRRHOTICS WITH THROMBOCYTOPENIA
Monika Homoncik l, Markus Peck-Radosavljevic t, Napo Laya 2, Alfred Gangl 1, Peter Ferenci i, Bernd Jilma 2. 1Department of
Gastroenterology And Hepatology, Vienna University Hospital, Vienna; 2Department of Clinical Pharmacology, Vienna University Hospital, Vienna, Austria Background: Patients with liver cirrhosis have a complex hemostasis disturbance including thrombocytopenia and abnormal bleeding time. Erythropoietin is the primary stimulator of erythrocyte production and was reported to increase megakaryocyte formation. In addition erythropoietin was shown to increase platelet count and platelet reactivity in healthy volunteers. We therefore hypothesized that the administration of erythropoietin to patients with thrombocytopenia may result in an increase of platelet count and platetet function. Methods: A total of 21 thrombocytopenic patients with alcoholic liver cirrhosis (abstaining at study entry) received either 100 IF_Ykgerythropoietin (Erypo ®, Janssen-Cilag, Vienna) or placebo on day 1, 3 and 5 in a 2:1 randomized, double-blinded fashion. Platelet count, platelet reactivity (flow cytometry, thrombin receptor activating peptide induced P-selectin expression), in-vivo (Simplate II) and in-vitro (PFA-100) bleeding times were determined on study days 1, 3, 5 and 9. Results: Baseline median platelet count was 80 G/L (range, 39-127) and was not significantly different between groups (p > 0.05). Treatment with erythropoietin increased platelet count by 20% (p = 0.01) and platelet reactivity up to 70% (p < 0.01) versus baseline. This increase in platelet count and platelet reactivity had no effect on primary hemostasis measured by in-vivo and in-vitro bleeding times (p > 0.05). No significant effect was observed in the placebo group. Conclusions: Treatment with erythropoietin increased significantly platelet count and platelet reactivity in patients with alcoholic liver cirrhosis. However, these changes had no effect on platelet function. Thus, erythropoitin appears to be unable to reduce the risk for bleeding in thrombocytopenic patients suffering from liver cirrhosis.
~ - ' ] INCREASED SYSTEMIC PRODUCTION OF CARBON MONOXIDE IN PATIENTS WITH CIRRHOSIS AND ASCITES WITH AND WITHOUT SPONTANEOUS BACTERIAL PERITONITIS (SBP) D. De Las Hems 1, R. Ortega I, P. Gines I , A. Cardenas l , J. Fernandez I , M. Guevara 1, B. Calahorra I , J. A. Barbera 2, M. Navasa I , W. Jimenez 3, V. Arroyo I , J. Rodts 1 . 1 Liver Unit Diseases," 2pneumology Unit,"
SHormonal Laboratory, Hospital Clinic, ID1BAPS, Barcelona, Catalunya, Spain Carbon monoxide (CO) is a gas with a potent vasodilator action synthetized from the catabolism of heme by the action of the heme oxygenase, which exists in two isoforms, constitutive (HO-2) and inducible (HO-1) by bacterial products and cytokines. Studies in animals with portal hypertension have found an increased activity of the HO-1, which could participate in the pathogenesis of splanchnic vasodilation. No studies have been reported assessing the production of CO in human cirrhosis. In the current study, the concentration of CO in the exhaled air (COexh) and the concentration of carboxihemoglobin in venous blood (COHb), as indexes of the systemic production of CO, were assessed in 12 healthy subjects, 12 patients with cirrhosis and ascites and 24 patients with SBP. Smokers and patients with lung diseases were excluded. COexh and COHb were significantly higher in patients with ascites than values in healthy subjects (3 4- 0.4 vs. 0.9 + 0.7 ppm and 1.3 4- 0.5 vs 0.6 4- 0.3%, respectively, p < 0.005 for both). In patients with SBP, values of COexh and COHb were even higher than those in patients with ascites without SBP (5.6 4- 3 ppm and 1.9 4- 1%, p < 0.01 for both). Resolution of SBP was associated with a significant reduction
Parallel Session 3: Portal Hypertension & Complications in Chronic Liver Disease in both parameters, which reached values similar to those of patients without SBP one month after resolution of the infection. These results support the existence of an increased systemic production of CO in cirrhosis with ascites and in SBP, which could participate in the pathogenesis of arterial vasodilation present in these conditions.
[-~
ORAL GLUTAMINE CHALLENGE CORRELATES WITH MINIMAL HEPATIC ENCEPHALOPATHY AND PREDICTS OVERT EPISODES
Lourdes Grande I , Ines Camacho 2, Soledad Benitez 2 , Manuel Romero-Gomez 1. 1Hepatology Unit, Valme U. Hospital, Sevilla;
2Biochemistry Unit, Valme U. Hospital, Sevilla, Spain Aims: We assessed the usefulness of oral glutamine challenge (OGC) in the management of patients with minimal hepatic encephalopathy (MHE). Methods: Seventy cirrhotic patients and ten healthy volunteers were enrolled. MHE was deduced when a patient had a Z score >2.3 in at least one test from among number connection test, digit symbol test and block design test. Venous ammonia concentrations were measured before and 60 minutes (NH3-60m) after a l0 g oral glutamine load. A pathological glutamine tolerance value was an ammonia value > 128 mg/dl (ROC curve). We also determined the blood concentrations of Mn, Zn, glutamine, glutamate and BCAA/AAA ratio. Results: In healthy controls ammonia remains unchanged (from 40.4 + 22.2 to 44.2 + 13.6). No patient developed signs of overt hepatic encephalopathy or adverse events following the glutamine load. Ammonia increased significantly in cirrhotic patients (from 70.41 + 45.2 to 127.43 + 78.6; p < 0.001). In multivariate analysis (logistic regression) OGC was related to liver dysfunction (OR = 7.69; 95% CI = 1.72 - 33.3; p < 0.01), presence of esophageal varices (OR = 7.14; 95% CI = 1.9 - 25; p < 0.005) and MHE (OR = 5.45; 95% CI = 1.17 - 25.4; p < 0.05). In a mean follow-up of 10.2 + 2.9 months, 11 patients (15%) developed overt HE. In multivariate analysis OGC (OR = 14.5; 95% CI = 1.26 - 126.3) and MHE (OR = 1.56; 95% CI = 1.02 - 21.9) achieved statistical significance. Patients who developed overt HE showed a greater NH3-60m than those patients who did not develop overt HE (from 95.9 + 49 to 181 + 62 vs. from 65.6 + 46 to 117 + 77, respectively; p < 0.01). Conclusions: A pathological OGC correlates with MHE and could predict the development of overt HE. A combination of biochemical and neuropsychological tests could provide a new index to assess overt HE risk in cirrhotic patients.
-~
13
LIVER DISEASE IS A MAJOR CAUSE OF MORTALITY FOLLOWING ALLOGENIC BONE MARROW TRANSPLANTATION
Manal El-Saved 1, Alaa El-Haddad 2, Omar Fahmy 2, Iman Salama 3, Hossam Mahmoud 2. 1Pediatric Dept., Hematology/Oncology Division,
Ain Shams University, Cairo; 2Bone Marrow Transplantation Center of National Cancer Institute, Cairo; 3Community Medicine Department of National Research Center, Cairo, Egypt Objective: This retrospective study aimed at determining prevalence and risk factors for liver dysfunction within 6 months following allogenic bone marrow transplantation (BMT). A total of 103 patients, median age 23 ys (33% < 18 ys; 66% males), transplanted in a single institution were enrolled. Data on donors and recipients were collected including hematological disease, bilirubin, alanine transaminase (ALT), alkaline phosphatase (ALP), hepatitis B (HBV), and hepatitis C (HCV) markers (including HCVRNA). Results: Fifty-one of 103 patients died and liver disease was the major cause of death (25 of 51,49.5%). Incidence of severe venoocclusive disease (VOD) was 7.8% and hepatic failure attributed to liver graft-versus-hostdisease (GVHD) was 22.3% (23/103). Of those, 44.5% were anti-HCV and/or HCV-RNA, 24.1% HBcAb, 6.9% HBsAg and 62.1% HBsAb positive. Only 4 had ALT > 500 U/L (normal <= 42 U/L), Multiple logistic analyses showed that ALP could predict hepatic GVHD (Adjusted Odds Ratio, AOR: 7.4, p = 0.02) and VOD (AOR: 9.24, p = 0.047). Donors' HCV-RNA and HBsAg were also predictive of liver GVHD (AOR: 102, p = 0.018 and AOR: 18.5, p = 0.057 respectively). The most significant risk factors for mortality following BMT were liver GVHD (AOR: 9.28, 95% CI = 1.89-45.4, p = 0.006) and VOD (AOR: 7.55, 95% CI = 0.95-65.3, p = 0.05). Conclusions: Hepatic GVHD is a common complication following BMT and is a strong predictor of potentially lethal liver complications. The high prevalence of HCV and HBV might have contributed to outcome of liver GVHD and VOD. However, the study could not rule out fulminant reactivation due to lack of HBV-DNA and liver histology results. Antiviral therapy should be commenced early to prevent relentless progression of liver disease.