- Email: [email protected]
“Human Babesiosis” an Emerging Transfusion Dilemma: Acridine Orange as a Feasible Diagnostic Technology
one patient lived only 23 days and died of hepatocellular carcinoma rupture, whose autopsy findings revealed that CP was completely successful. Among these successful 9 patients, significant improvements were recognized in ECOG performance status scores (from 2.2 to 0.8, in the mean value) and in Child-Pugh scores (from 10.0 to 8.6, in the mean value) at one month after the therapy. The sole unsuccessful case with cirrhosis of unknown etiology and with poor PS(4) died during the procedure without decreasing pleural effusion exudation. Conclusion: CP using NPPV is a simple and very effective therapy, and it significantly improves patient's QOL without significant hepatic function loss.
of GI symptoms. They are also associated with a decreased energy intake as measured by a satiety drinking test. GI symptoms dramatically improve post-transplant.
Treatment of Recurrent Hepatitis C in Liver Transplant Recipients With Extended Duration of Pegylated Interferon and Ribavirin Richard Arrigo, Arun Samanta, Shanthini Griffith, Ravish M. Parekh, Maria Korogodsky, Kiran V. Rao, Adrian Fisher, Dorian Wilson, Kenneth M. Klein, Baburao Koneru
Su1326
Background: Recurrence of HCV infection after liver transplant runs an aggressive course resulting in graft loss. Antiviral therapy using pegylated interferon (P-IFN) and Ribavirin (RBV) is the main treatment but its efficacy in eradicating the virus is poor. Besides other variables, interruption of the antiviral treatment in OLT recipients may adversely impact the anti-HCV treatment. Outcome of extended duration of treatment beyond the standard 48wks of P-IFN and RBV for HCV genotype-1 infection in non-transplant patients has been evaluated. Outcome of this regimen following HCV recurrence in OLT recipients is scarce. Aim: Compare the efficacy of P-IFN and RBV in achieving SVR in patients treated with standard duration of 48 weeks with those treated for extended duration of ≥72 weeks in post OLT genotype 1 HCV recurrence. Patients and Methods: This is a retrospective analysis of our post-OLT patient database with HCV genotype 1 recurrence in 51 patients. Twentyone patients who failed to achieve ETR at 48wks of treatment with P-IFN and RBV were treated for an extended duration(1.8-2.5 yrs from start of treatment). SVR of these patients was compared (1:1.5 ratio)with 30 patients treated for 48wks. All patients had biopsy proven post-OLT HCV. Patients with hepatocellular carcinoma, biliary stricture, hepatic artery thrombosis and acute cellular rejection were excluded. Patients received weekly P-IFN (90180 mcg SQ) and daily RBV (400mg to 600 mg BID). Erythropoietin and G-CSF were given when necessary. Results: Age and pretreatment HCV-RNA was 53.9 + 2.0 years and 3.6 + 0.8 mil IU/ml respectively and 52.5 + 1.6 years and 3.3 + 0.7 mil IU/ml in the extended treatment. There were 42 males and 9 females. ETR was achieved in 13/30 (43%) and SVR in 8/30 (27%) patients treated for 48 weeks. Extended treatment achieved ETR in 4/21 (19%) additional patients and SVR enhanced in 3/21 (14%) more patients. Treatment interruption with either PEG-IFN, RBV or both was required in 8/30 (27%) patients treated for 48 weeks and in 9/21 (43%) patients treated for extended duration. Of the 3/21 (14%) patients in the extended treatment who achieved SVR, 2 had no treatment interruptions and the other had a near 2-log drop at 12 weeks of therapy. Conclusion: Our study indicates that extension of treatment with PEG-IFN and RBV in post-transplant HCV genotype 1 only mildly enhances the SVR in patients who fail 48wks of standard treatment. It is likely that the high rate of treatment interruptions (27% to 43%) in post OLT HCV impacts treatment outcome. Our study suggests that extended treatment for post-OLT HCV may be of value in select individuals with favorable viral kinetics who experience treatment interruptions due to their post OLT co-morbid conditions. More studies are needed to evaluate such an intervention in the post transplant population.
The Presence of Cryptogenic Cirrhosis is Significantly Increased in Patients With Idiopathic Pulmonary Fibrosis but is Not Dependent on Telomerase Mutations Natasha J. Schneider, Lisa H. Lancaster, Joy D. Cogan, Roman Perri Introduction: Cryptogenic cirrhosis is a common clinical problem, but the etiology of this condition remains unclear. The coexistence of cryptogenic cirrhosis with idiopathic pulmonary fibrosis (IPF) has been reported but the overall prevalence of this association has not been fully described. Familial IPF has been linked to mutations in a specific telomerase subunit; thus a unifying mechanism of fibrosis in the lung and liver may provide a framework to understand the pathogenesis of cryptogenic cirrhosis. Aim: To determine the prevalence of idiopathic cirrhosis in a large population of patients with IPF and to assess for telomerase mutations in patients with both IPF and cirrhosis. Methods: We reviewed the medical records of all the patients in a large IPF database at an academic medical center. Information collected included: age, gender, BMI, alcohol use, and laboratory results. Imaging studies reviewed included high resolution CT scans of the chest and, when available, imaging studies of the abdomen and liver biopsies. Genomic DNA harvested from peripheral blood leukocytes isolated from patients identified with both IPF and cirrhosis was examined for mutations in the telomerase complex. Results: 427 patients were included. 84 patients were eliminated because they did not have a definitive diagnosis of IPF. The remaining 343 patients had a mean age of 67 (range 31-85) and all had documented IPF based on classic findings of high resolution CT, open lung biopsy, or both. The majority of the patients were male (71%). Ten patients (2.9%) had cirrhosis as determined by laboratory data, clinical examination and imaging studies, which was nearly ten-fold higher than would be expected in the general population (estimated 0.25-0.8%). One patient without obvious cirrhosis had hepatocellular carcinoma. Only two patients with IPF and cirrhosis had a documented history of heavy alcohol use and one patient had evidence of exposure to hepatitis B and C. Eight patients in the database had a family history significant for a first degree relative with cirrhosis. One patient with IPF and cryptogenic cirrhosis had a sister with cryptogenic cirrhosis and a brother with IPF. Seven of the 10 patients with concomitant IPF and cirrhosis were deceased and one patient had undergone orthotopic liver transplantation. Eight of 10 patients (80%) with IPF and cirrhosis had blood available for telomerase sequencing; 6 patients have been sequenced and no mutations have been identified in the telomerase complex. Conclusions: Our data reveals a strikingly high prevalence of cirrhosis in patients with IPF, suggesting that a common mechanism may underlie the pathogenesis of these fibrotic conditions. However, telomerase mutations were not identified in these patients, implying that an undiscovered mechanism underlies the development of fibrosis in these two organ systems.
Su1329 “Human Babesiosis” an Emerging Transfusion Dilemma: Acridine Orange as a Feasible Diagnostic Technology Helieh S. Oz, Willem J. de Villiers
Su1327
Babesiosis, a common disease of animals, can infect humans via vector “tick bite”, particularly in endemic areas, New England, Northwest, Midwest and California. Recent reports from non-endemic area including fatal cases in Hepatitis C and postliver transplant patients resulting from contaminated blood transfusion should alert the Hepatology and Gastroenterology community regarding this emerging dilemma, and an urgent need for accurate blood screening technology. Here we present the progression of babesiosis in an immunocompromised hamster model and a feasible florescent technique to detect the parasitemia. Methods: Male golden hamsters were immunosuppressed with depomedrol injection followed by addition of dexamethasone in daily drinking water. Animals were bled via tail vein every 3 days until the full progression of disease on day 12. Blood smears stained with different florescent and non-florescent techniques were compared. In addition, infected blood cells were processed for scanning and transmission electron microscopy. Results: Animals developed parasitemia (8%) detected on day 4 post-infection and progressed (90% day 12) in a time dependent manner. Pathology revealed, enlarged internal organs (25-30%), splenomegaly, glomerulonephritis, hematuria, and hemolytic anemia. Animals has moderate to severe hepatitis with hepatocytes degeneration and necrosis, periportal infiltration of inflammatory cells, lymphocytes and macrophages, and bile stasis. In addition, animals demonstrated severe edematous pneumonitis and myocarditis with hemocidrin deposits. Blood smears stained with florescent Acridine orange were superior to Wright, Giemsa or Rodamine Red in detecting parasitemia. Scanning and transmission electron micrographs revealed different stages of the parasite lifecycle. In conclusion, this study alerts the profession of the Babesial transfusion dilemma and offers a simple and feasible staining technique to screen the blood. This study was supported in part by a grant from NIH NIDCRDE19177 (HO).
Gastrointestinal Symptoms Are Associated With Reduced Energy Intake as Well as Psychological Distress and Hormonal Abnormalities in Patients With Liver Cirrhosis Evangelos Kalaitzakis, Axel Josefsson, Maria Castedal, Pia Henfridsson, Irene Hugosson, Maria Bengtsson, Einar Bjornsson Gastrointestinal (GI) symptoms are common in patients with liver cirrhosis (LC). Diabetes mellitus and abnormalities in thyroid and adrenal hormones are common in LC but their relation to GI symptoms is unexplored. Also it is unknown if GI symptoms are related to energy intake and if they improve after liver transplantation. Methods A total of 108 LC patients (mean age 53(SD9); 36F; 25 viral, 24 alcoholic, and 21 cholestatic LC; Child score 9(2); MELD 15(6); 20 HCC) under pretransplant evaluation were prospectively enrolled. Two validated questionnaires were used to measure GI symptoms (GI Symptom Rating Scale-GSRS) and anxiety and depression (Hospital Anxiety and Depression-HAD). Results were compared with reference values from the general population. Fasting serum glucose, insulin, thyrotropin, free T3 and T4, and cortisol were measured. Insulin resistance was defined as homeostasis model assessment index >2.29 (Exp Clin Endocrinol Diabetes 2006). Transplant recipients (n=66) were followed up one year post-transplant. Forty LC patients (age 58(10); 17F) underwent a high-caloric satiety drinking test(ST) where a caloric drink (1.5kcal/ml) was ingested at a constant rate, 15ml/min, until maximal satiety. Ten healthy subjects also underwent ST and served as controls. Results LC patients had more severe GI symptoms than controls (mean total GSRS score 2.27, 95%CI 2.09-2.47 vs 1.53, 95%CI 1.50-1.55, respectively). In all, 50% of patients had moderate to severe GI symptoms (total GSRS score >2), 15% significant depression and 13% anxiety according to HAD, 30% diabetes, 69% insulin resistance, 33% low T3, 5% increased thyrotropin, and 17% low cortisol at baseline. All patients were euthyroid and had normal T4. All GSRS domain scores improved significantly one year post-transplant (p<0.05 vs pre-transplant, p>0.05 vs controls). In multivariate analysis moderate to severe GI symptoms were related to anxiety according to HAD (b=4.1, p=0.003), lower T3 (b=0.42, p=0.028) and lower cortisol (b= 0.99, p=0.029) but not to diabetes or insulin resistance. At ST, patients ingested similar amounts of kcal as controls (1405(607) vs 1505(525), p>0.05). However, patients with moderate to severe GI symptoms (16/40) ingested fewer kcal at ST compared to other LC patients and controls (1123kcal (389) vs 1594kcal (659), p=0.02 and 1505kcal (525), p= 0.04 respectively). The amount of kcal ingested was negatively related to cirrhosis severity, assessed as the Child score (r=-0.35,p=0.03), and recent weight loss (r=-0.31,p=0.06). Conclusion GI symptoms are common in cirrhosis. Psychological distress, low T3 (sick euthyroid syndrome) and low cortisol but not insulin resistance are important determinants
Su1330 Prevalence of Nephrolithiasis is Significantly Higher in Hepatitis C Cirrhosis Compared to Patients Without Cirrhosis Imran S. Farooq, Douglas M. Heuman, Jasmohan S. Bajaj Background: Nephrolithiasis predisposes to urinary tract infections (UTI) that, in cirrhosis, may precipitate acute-on-chronic renal failure. Renal failure is a common accompaniment of end stage liver disease, but subtle changes in renal function may occur early in cirrhosis. It is not known whether cirrhosis can predispose to development of urinary tract calculi. Aim: We undertook a case control study in a homogeneous population of men with HCV to determine whether prevalence of nephrolithiasis (asymptomatic and symptomatic) is associated with presence of cirrhosis. Methods: Records of all male HCV patients undergoing
S-459
AGA Abstracts
AGA Abstracts
Su1328
of GI symptoms. They are also associated with a decreased energy intake as measured by a satiety drinking test. GI symptoms dramatically improve post-transplant.
Treatment of Recurrent Hepatitis C in Liver Transplant Recipients With Extended Duration of Pegylated Interferon and Ribavirin Richard Arrigo, Arun Samanta, Shanthini Griffith, Ravish M. Parekh, Maria Korogodsky, Kiran V. Rao, Adrian Fisher, Dorian Wilson, Kenneth M. Klein, Baburao Koneru
Su1326
Background: Recurrence of HCV infection after liver transplant runs an aggressive course resulting in graft loss. Antiviral therapy using pegylated interferon (P-IFN) and Ribavirin (RBV) is the main treatment but its efficacy in eradicating the virus is poor. Besides other variables, interruption of the antiviral treatment in OLT recipients may adversely impact the anti-HCV treatment. Outcome of extended duration of treatment beyond the standard 48wks of P-IFN and RBV for HCV genotype-1 infection in non-transplant patients has been evaluated. Outcome of this regimen following HCV recurrence in OLT recipients is scarce. Aim: Compare the efficacy of P-IFN and RBV in achieving SVR in patients treated with standard duration of 48 weeks with those treated for extended duration of ≥72 weeks in post OLT genotype 1 HCV recurrence. Patients and Methods: This is a retrospective analysis of our post-OLT patient database with HCV genotype 1 recurrence in 51 patients. Twentyone patients who failed to achieve ETR at 48wks of treatment with P-IFN and RBV were treated for an extended duration(1.8-2.5 yrs from start of treatment). SVR of these patients was compared (1:1.5 ratio)with 30 patients treated for 48wks. All patients had biopsy proven post-OLT HCV. Patients with hepatocellular carcinoma, biliary stricture, hepatic artery thrombosis and acute cellular rejection were excluded. Patients received weekly P-IFN (90180 mcg SQ) and daily RBV (400mg to 600 mg BID). Erythropoietin and G-CSF were given when necessary. Results: Age and pretreatment HCV-RNA was 53.9 + 2.0 years and 3.6 + 0.8 mil IU/ml respectively and 52.5 + 1.6 years and 3.3 + 0.7 mil IU/ml in the extended treatment. There were 42 males and 9 females. ETR was achieved in 13/30 (43%) and SVR in 8/30 (27%) patients treated for 48 weeks. Extended treatment achieved ETR in 4/21 (19%) additional patients and SVR enhanced in 3/21 (14%) more patients. Treatment interruption with either PEG-IFN, RBV or both was required in 8/30 (27%) patients treated for 48 weeks and in 9/21 (43%) patients treated for extended duration. Of the 3/21 (14%) patients in the extended treatment who achieved SVR, 2 had no treatment interruptions and the other had a near 2-log drop at 12 weeks of therapy. Conclusion: Our study indicates that extension of treatment with PEG-IFN and RBV in post-transplant HCV genotype 1 only mildly enhances the SVR in patients who fail 48wks of standard treatment. It is likely that the high rate of treatment interruptions (27% to 43%) in post OLT HCV impacts treatment outcome. Our study suggests that extended treatment for post-OLT HCV may be of value in select individuals with favorable viral kinetics who experience treatment interruptions due to their post OLT co-morbid conditions. More studies are needed to evaluate such an intervention in the post transplant population.
The Presence of Cryptogenic Cirrhosis is Significantly Increased in Patients With Idiopathic Pulmonary Fibrosis but is Not Dependent on Telomerase Mutations Natasha J. Schneider, Lisa H. Lancaster, Joy D. Cogan, Roman Perri Introduction: Cryptogenic cirrhosis is a common clinical problem, but the etiology of this condition remains unclear. The coexistence of cryptogenic cirrhosis with idiopathic pulmonary fibrosis (IPF) has been reported but the overall prevalence of this association has not been fully described. Familial IPF has been linked to mutations in a specific telomerase subunit; thus a unifying mechanism of fibrosis in the lung and liver may provide a framework to understand the pathogenesis of cryptogenic cirrhosis. Aim: To determine the prevalence of idiopathic cirrhosis in a large population of patients with IPF and to assess for telomerase mutations in patients with both IPF and cirrhosis. Methods: We reviewed the medical records of all the patients in a large IPF database at an academic medical center. Information collected included: age, gender, BMI, alcohol use, and laboratory results. Imaging studies reviewed included high resolution CT scans of the chest and, when available, imaging studies of the abdomen and liver biopsies. Genomic DNA harvested from peripheral blood leukocytes isolated from patients identified with both IPF and cirrhosis was examined for mutations in the telomerase complex. Results: 427 patients were included. 84 patients were eliminated because they did not have a definitive diagnosis of IPF. The remaining 343 patients had a mean age of 67 (range 31-85) and all had documented IPF based on classic findings of high resolution CT, open lung biopsy, or both. The majority of the patients were male (71%). Ten patients (2.9%) had cirrhosis as determined by laboratory data, clinical examination and imaging studies, which was nearly ten-fold higher than would be expected in the general population (estimated 0.25-0.8%). One patient without obvious cirrhosis had hepatocellular carcinoma. Only two patients with IPF and cirrhosis had a documented history of heavy alcohol use and one patient had evidence of exposure to hepatitis B and C. Eight patients in the database had a family history significant for a first degree relative with cirrhosis. One patient with IPF and cryptogenic cirrhosis had a sister with cryptogenic cirrhosis and a brother with IPF. Seven of the 10 patients with concomitant IPF and cirrhosis were deceased and one patient had undergone orthotopic liver transplantation. Eight of 10 patients (80%) with IPF and cirrhosis had blood available for telomerase sequencing; 6 patients have been sequenced and no mutations have been identified in the telomerase complex. Conclusions: Our data reveals a strikingly high prevalence of cirrhosis in patients with IPF, suggesting that a common mechanism may underlie the pathogenesis of these fibrotic conditions. However, telomerase mutations were not identified in these patients, implying that an undiscovered mechanism underlies the development of fibrosis in these two organ systems.
Su1329 “Human Babesiosis” an Emerging Transfusion Dilemma: Acridine Orange as a Feasible Diagnostic Technology Helieh S. Oz, Willem J. de Villiers
Su1327
Babesiosis, a common disease of animals, can infect humans via vector “tick bite”, particularly in endemic areas, New England, Northwest, Midwest and California. Recent reports from non-endemic area including fatal cases in Hepatitis C and postliver transplant patients resulting from contaminated blood transfusion should alert the Hepatology and Gastroenterology community regarding this emerging dilemma, and an urgent need for accurate blood screening technology. Here we present the progression of babesiosis in an immunocompromised hamster model and a feasible florescent technique to detect the parasitemia. Methods: Male golden hamsters were immunosuppressed with depomedrol injection followed by addition of dexamethasone in daily drinking water. Animals were bled via tail vein every 3 days until the full progression of disease on day 12. Blood smears stained with different florescent and non-florescent techniques were compared. In addition, infected blood cells were processed for scanning and transmission electron microscopy. Results: Animals developed parasitemia (8%) detected on day 4 post-infection and progressed (90% day 12) in a time dependent manner. Pathology revealed, enlarged internal organs (25-30%), splenomegaly, glomerulonephritis, hematuria, and hemolytic anemia. Animals has moderate to severe hepatitis with hepatocytes degeneration and necrosis, periportal infiltration of inflammatory cells, lymphocytes and macrophages, and bile stasis. In addition, animals demonstrated severe edematous pneumonitis and myocarditis with hemocidrin deposits. Blood smears stained with florescent Acridine orange were superior to Wright, Giemsa or Rodamine Red in detecting parasitemia. Scanning and transmission electron micrographs revealed different stages of the parasite lifecycle. In conclusion, this study alerts the profession of the Babesial transfusion dilemma and offers a simple and feasible staining technique to screen the blood. This study was supported in part by a grant from NIH NIDCRDE19177 (HO).
Gastrointestinal Symptoms Are Associated With Reduced Energy Intake as Well as Psychological Distress and Hormonal Abnormalities in Patients With Liver Cirrhosis Evangelos Kalaitzakis, Axel Josefsson, Maria Castedal, Pia Henfridsson, Irene Hugosson, Maria Bengtsson, Einar Bjornsson Gastrointestinal (GI) symptoms are common in patients with liver cirrhosis (LC). Diabetes mellitus and abnormalities in thyroid and adrenal hormones are common in LC but their relation to GI symptoms is unexplored. Also it is unknown if GI symptoms are related to energy intake and if they improve after liver transplantation. Methods A total of 108 LC patients (mean age 53(SD9); 36F; 25 viral, 24 alcoholic, and 21 cholestatic LC; Child score 9(2); MELD 15(6); 20 HCC) under pretransplant evaluation were prospectively enrolled. Two validated questionnaires were used to measure GI symptoms (GI Symptom Rating Scale-GSRS) and anxiety and depression (Hospital Anxiety and Depression-HAD). Results were compared with reference values from the general population. Fasting serum glucose, insulin, thyrotropin, free T3 and T4, and cortisol were measured. Insulin resistance was defined as homeostasis model assessment index >2.29 (Exp Clin Endocrinol Diabetes 2006). Transplant recipients (n=66) were followed up one year post-transplant. Forty LC patients (age 58(10); 17F) underwent a high-caloric satiety drinking test(ST) where a caloric drink (1.5kcal/ml) was ingested at a constant rate, 15ml/min, until maximal satiety. Ten healthy subjects also underwent ST and served as controls. Results LC patients had more severe GI symptoms than controls (mean total GSRS score 2.27, 95%CI 2.09-2.47 vs 1.53, 95%CI 1.50-1.55, respectively). In all, 50% of patients had moderate to severe GI symptoms (total GSRS score >2), 15% significant depression and 13% anxiety according to HAD, 30% diabetes, 69% insulin resistance, 33% low T3, 5% increased thyrotropin, and 17% low cortisol at baseline. All patients were euthyroid and had normal T4. All GSRS domain scores improved significantly one year post-transplant (p<0.05 vs pre-transplant, p>0.05 vs controls). In multivariate analysis moderate to severe GI symptoms were related to anxiety according to HAD (b=4.1, p=0.003), lower T3 (b=0.42, p=0.028) and lower cortisol (b= 0.99, p=0.029) but not to diabetes or insulin resistance. At ST, patients ingested similar amounts of kcal as controls (1405(607) vs 1505(525), p>0.05). However, patients with moderate to severe GI symptoms (16/40) ingested fewer kcal at ST compared to other LC patients and controls (1123kcal (389) vs 1594kcal (659), p=0.02 and 1505kcal (525), p= 0.04 respectively). The amount of kcal ingested was negatively related to cirrhosis severity, assessed as the Child score (r=-0.35,p=0.03), and recent weight loss (r=-0.31,p=0.06). Conclusion GI symptoms are common in cirrhosis. Psychological distress, low T3 (sick euthyroid syndrome) and low cortisol but not insulin resistance are important determinants
Su1330 Prevalence of Nephrolithiasis is Significantly Higher in Hepatitis C Cirrhosis Compared to Patients Without Cirrhosis Imran S. Farooq, Douglas M. Heuman, Jasmohan S. Bajaj Background: Nephrolithiasis predisposes to urinary tract infections (UTI) that, in cirrhosis, may precipitate acute-on-chronic renal failure. Renal failure is a common accompaniment of end stage liver disease, but subtle changes in renal function may occur early in cirrhosis. It is not known whether cirrhosis can predispose to development of urinary tract calculi. Aim: We undertook a case control study in a homogeneous population of men with HCV to determine whether prevalence of nephrolithiasis (asymptomatic and symptomatic) is associated with presence of cirrhosis. Methods: Records of all male HCV patients undergoing
S-459
AGA Abstracts
AGA Abstracts
Su1328