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M1745 Morbidity and Mortality of TIPS Placement in the Elderly Is No Different Than in Younger Age Groups
AGA Abstracts
of PPI+ patients were on therapy due to acid-peptic disease, 28% had PPI started after banding but 36% had no discernable reason for PPI use. No rebleeding from post-banding ulcers was evident in PPI+ or PPI- groups. Outcomes of VB were similar between PPI+ and PPI- groups. Conclusions: PPI use does not affect outcomes after VB. PPI+ patients had similar outcomes to PPI- VB patients despite a lower CTP score. Given the adverse effects associated with PPI use, careful consideration must be given to the indication before prescribing PPI to cirrhotics. Subgroup analysis of patients with variceal bleeding
scores. This analysis showed no differences in mortality or morbidity, including HE, between these patients. Pre-TIPS MELD scores were statistically correlated with morbidity and mortality at 12 months across all age groups (p=0.001.) Conclusions: There is no significant difference between age groups in regards to 3 and 12-month mortality after TIPS. In addition, there is no significant difference in overall morbidity after TIPS between age groups. Advanced age alone should not be an exclusion criterion for TIPS. M1746 Toll-Like Receptor 4-Mediated Immune Response Is Required for In Vivo Eradication of C. Parvum Infection of the Biliary Tract Pamela S. Bogert, Steven P. O'Hara, Christy E. Trussoni, Angela J. Stroope, Jason T. Lewis, XianMing Chen, Nicholas F. LaRusso Toll-like receptors (TLRs) are a conserved family of cell surface pattern recognition receptors key to innate immunity through detection of invading pathogens. Upon pathogen recognition, TLRs initiate host defense responses to mobilize immune effector cells and activate adaptive immunity. We previously showed that Cryptosporidium parvum (C. parvum), a parasite that infects both intestinal and biliary epithelia, induces a TLR4-dependent antimicrobial response in cholangiocytes (epithelial cells lining the bile ducts) using an In Vitro model of biliary cryptosporidiosis. Disruption of the TLR4 signal pathway in cultured cholangiocytes results in a reduced capacity to clear C. parvum infection. Here we tested the role of TLR4 against C. parvum biliary infection using an In Vivo model of biliary cryptosporidiosis in both wild type (WT) and TLR4 knock-out mice. Mice were infected via direct injection of C. parvum (200,000 oocysts) into the gallbladder and sacrificed at 1,2,3 and 4 weeks post infection; control animals received injections of saline. Serum chemistries (ALT, AST, alkaline phosphatase and bilirubin) were performed and oocyst clearance rates quantitated in specimens of bile and stool by light and fluorescence microscopy. Liver specimens were assessed histologically for severity of inflammation and presence of parasites, and tumor necrosis factor (TNF-α) and interferon-Υ levels measured by ELISA. WT mice displayed a transient biliary tract infection; their serum ALT, AST levels, liver inflammation and TNF-α and interferon-Υ levels, and stool and bile oocyte burden peaked at two weeks and normalized by four weeks. In contrast, the TLR4 knock-out mice displayed a persistent biliary tract infection. All serum makers, all liver measurements and histology, and oocyte burden remained abnormal at four weeks. These data suggest that a TLR4-mediated response is required for In Vivo eradication of biliary C. parvum infection and the lack of this pattern recognition receptor contributes to persistent inflammation.
*CTP score was significantly lower in PPI+ group but all other comparisons were not significant. M1744 Health-Related Quality of Life in Men with Liver Cirrhosis: the Impact of Low Testosterone Evangelos Kalaitzakis, Axel Josefsson, Einar Bjornsson Liver cirrhosis (LC) has a negative impact quality of life (QoL). In elderly non-cirrhotic men low testosterone levels are related to impaired QoL (Moncada et al, Aging Male 2006). Low testosterone levels are common in male cirrhotics but their relation to QoL in these patients is unexplored. Methods: 74 men with LC (median age 54yr (IQR48-58), Child-Pugh score 8(7-10), MELD 14(11-18), 34 alcoholic LC, 25 hepatitis C, 15 with HCC, 34 with ascites) under pretransplantation evaluation were prospectively enrolled. A validated questionnaire was used to measure QoL(SF-36). Results were compared with reference values from the general population. Serum testosterone was measured at 7-10am(ref >15nmol/l). Patients were assessed for the presence of hepatic encephalopathy(HE) clinically and with number connection tests A & B(NCT-A/B). Patients with HE grade >2 were excluded. Demographic variables(marital, employment and educational status) were also analyzed. Results: Cirrhotics, compared to the general population, had profound reduction in QoL(mean physical composite score(PCS) and mental composite score(MCS) in the general population 50.0, 95% CI 49.8-50.2(for both) vs 37.1, 95% CI 34.6-39.6 and 41.8, 95% CI 38.9-44.7, respectively in LC). 14 patients(19%) had overt and 5(7%) had minimal HE. Median testosterone was 13nmol/l (5.3-14) and 19 patients(26%) had low (<8nmol/l) testosterone. Patients with low serum testosterone scored significantly(p<0.05) lower in 7/8 SF-36 domains compared to those with normal testosterone. Marital, employment and educational status did not influence any SF-36 domain. In univariate analysis, PCS was related to the ChildPugh (r=-0.45, p<0.05) and MELD score (r=-0.28, p<0.05) as well as to ascites (p<0.05), overt or minimal HE(p<0.05), presence HCC (p<0.05) and serum testosterone levels (r= 0.53, p<0.05) but not to other complications or etiology of LC. MCS was related to the Child-Pugh (r=-0.48, p<0.05) and MELD score (r=-0.28, p<0.05) as well as to previous variceal bleeding (p<0.05) and serum testosterone (r=0.48, p<0.05). Also, MCS tended to be related to overt or minimal HE (p=0.06) but not to other complications or etiology of LC. Serum testosterone was related cirrhosis severity indices (Child-Pugh (r=-0.69, p<0.05) and MELD score (r=-0.6, p<0.05). In multivariate analysis, PCS and MCS were independently related solely to testosterone levels (r=0.49 and r=0.39 respectively, p<0.05 for both). Conclusions: Low testosterone levels seem to be related to impaired health-related QoL in men with cirrhosis. Clinical trials testing the value of testosterone supplementation in order to improve QoL in these patients seem to be warranted.
M1747 IGF-1 Vs Rifaximine for Hepatic Encephalopathy Treatment in Ascitic Cirrhotic Rats with Total Portal Vein Ligation Mireia Miquel, Gemma Odena, Ramon Bartoli, Anna Serafin, Amparo Galan, Ramon Planas Introduction: Hepatic encephalopathy (HE) in cirrhosis is due to hepatic failure and/or the presence of portosystemic shunting that leads the passage of nitrogenate compounds from intestine to bloodstream. Rifaximine is an established treatment for HE in human cirrhosis. IGF-1 could be useful for this purpose for its antifibrogenic and anabolic effects. Aim: To compare the effectiveness of Rifaximine and IGF-1 in the treatment of hepatic encephalopathy in an experimental model of ascitic cirrhotic rats with total portal vein ligation (TPL). Methods: 55 Sprague-Dawley rats were distributed in 6 groups: A: 10 Control rats; B: 9 Control rats+Rifaximine (50mg/kg daily for 14 days); C: 9 Control rats+IGF-1 (2µg/kg s.c. twice daily for 14 days); D: 9 Cirrhosis with TPL; E: 9 Cirrhotic rats with TPL+Rifaximine; F: 9 Cirrhotic rats with TPL+IGF-1. Cirrhosis with ascites was induced by CCl4 oral administration. Six weeks after starting cirrhosis induction (or the same period on control rats) TPL was assessed, and cirrhosis induction continued until ascites developed. At this point animals were randomized to receive; IGF-1, Rifaximine or placebo for 14 days. Afterwards, oral glutamine challenge (OGC) test was performed. Animals were laparotomized to obtain portal and peripheral blood, liver, brain and ileocecal content samples to quantify plasmatic and cerebral ammonia, presence or not of low grade cerebral edema, liver and brain histology and ileocecal cultures. Results: When compared with control rats (groups A, B and C) cirrhotic rats with TPL (group D) showed a significantly increase in plasmatic and cerebral ammonia, area under OGC curve, and low grade brain edema (brain water content). Rifaximine (group E) significantly reduced bacterial overgrowth when compared with groups D and F, and this was associated with a reduction in plasmatic an cerebral ammonia, area under OGC curve and cerebral water content, achieving similar values to those observed in control groups (A, B, C). Otherwise IGF-1 administration (group F) was unable to improve changes observed in group D. Histological alterations (astrocyte type II Alzheimer) were observed similarly in almost half of cirrhotic animals independently on their treatment. Conclusion: Rifaximine seems to be useful in the treatment of most of the alterations associated to HE in experimental cirrhosis. IGF-1 is not indicated in this pathology.
M1745 Morbidity and Mortality of TIPS Placement in the Elderly Is No Different Than in Younger Age Groups Neehar Parikh, Andres T. Blei, Steven L. Flamm ABSTRACT: Background: TIPS is widely used for treatment of refractory variceal bleeding or refractory ascites/hepatic hydrothorax (HH) in patients with chronic liver disease. There is reluctance to perform TIPS in older age groups because of perceived increased postprocedure mortality and morbidity. Aim: We sought to determine if age is an independent risk factor for mortality and morbidity in patients undergoing TIPS. Methods: A retrospective review of 89 consecutive pts undergoing de novo TIPS placement at a tertiary care center from 1/03-7/05 was performed with at least 12 months follow-up. Comparisons were made based upon age deciles: <50 yrs (13), 50-60 yrs (41), >60 yrs (35). Endpoints included 3 and 12-mos survival and numerous clinical endpoints such as HE, shunt re-stenosis, liver failure or bacteremia. Data was analyzed based upon comparisons between age deciles using a chi-square test. Significance was defined as a p value <0.05. Results: 89 consecutive pts (49M:40F) underwent the procedure. The etiologies of liver disease in these patients were: 24 (27%) alcoholic, 24 (27%) HCV, 13 (15%) cryptogenic, 10 (11%) NASH, 7 (8%) BuddChiari, and 11 (12%) other. The indications for TIPS placement were: 33 (37%) refractory ascites, 38 (43%) variceal bleed and 18 (20%) other. Age stratified mortality rates at 3 mos and 12 mos were: (P> 0.05 for all): <50 yrs: 23%/23%, 50-60 yrs: 24%/24%, >60 yrs: 17%/ 26%. Age stratified morbidity rates within one year were (P> 0.05 for all): <50 yrs: 77%, 50-60 yrs: 78%, >60: 71%. There was no difference in HE requiring hospitalization: <50 yrs 31%; 50-60 yrs: 36%; >60 yrs: 31%. A matched analysis was conducted comparing the 12 patients that were >70 yrs old with patients in younger age groups with similar MELD
AGA Abstracts
M1748 Vitamin D Deficiency in Consecutive Patients with Chronic Liver Disease Anita Narshi, Sabina S. Beg, Christine Blanshard, Anne Ballinger BACKGROUND: Vitamin D deficiency is associated with low bone density and osteoporosis. The latter is a common complication in patients with chronic liver disease (CLD). About 60% of patients with CLD are vitamin D deficient but assessment studies have mainly been restricted to patients with cholestatic liver disease, such as primary biliary cirrhosis, who may also have malabsorption of fat soluble vitamins. AGA guidelines on osteoporosis in hepatic disorders recommend 400-800IU daily of Vitamin D supplementation in patients with CLD. Higher doses are only recommended in CLD associated with malabsorption. Routine measurement of serum 25 (OH) vitamin D in all patients with CLD is not recommended, and the guidelines restrict measurements in pre-transplant liver patients or if the
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of PPI+ patients were on therapy due to acid-peptic disease, 28% had PPI started after banding but 36% had no discernable reason for PPI use. No rebleeding from post-banding ulcers was evident in PPI+ or PPI- groups. Outcomes of VB were similar between PPI+ and PPI- groups. Conclusions: PPI use does not affect outcomes after VB. PPI+ patients had similar outcomes to PPI- VB patients despite a lower CTP score. Given the adverse effects associated with PPI use, careful consideration must be given to the indication before prescribing PPI to cirrhotics. Subgroup analysis of patients with variceal bleeding
scores. This analysis showed no differences in mortality or morbidity, including HE, between these patients. Pre-TIPS MELD scores were statistically correlated with morbidity and mortality at 12 months across all age groups (p=0.001.) Conclusions: There is no significant difference between age groups in regards to 3 and 12-month mortality after TIPS. In addition, there is no significant difference in overall morbidity after TIPS between age groups. Advanced age alone should not be an exclusion criterion for TIPS. M1746 Toll-Like Receptor 4-Mediated Immune Response Is Required for In Vivo Eradication of C. Parvum Infection of the Biliary Tract Pamela S. Bogert, Steven P. O'Hara, Christy E. Trussoni, Angela J. Stroope, Jason T. Lewis, XianMing Chen, Nicholas F. LaRusso Toll-like receptors (TLRs) are a conserved family of cell surface pattern recognition receptors key to innate immunity through detection of invading pathogens. Upon pathogen recognition, TLRs initiate host defense responses to mobilize immune effector cells and activate adaptive immunity. We previously showed that Cryptosporidium parvum (C. parvum), a parasite that infects both intestinal and biliary epithelia, induces a TLR4-dependent antimicrobial response in cholangiocytes (epithelial cells lining the bile ducts) using an In Vitro model of biliary cryptosporidiosis. Disruption of the TLR4 signal pathway in cultured cholangiocytes results in a reduced capacity to clear C. parvum infection. Here we tested the role of TLR4 against C. parvum biliary infection using an In Vivo model of biliary cryptosporidiosis in both wild type (WT) and TLR4 knock-out mice. Mice were infected via direct injection of C. parvum (200,000 oocysts) into the gallbladder and sacrificed at 1,2,3 and 4 weeks post infection; control animals received injections of saline. Serum chemistries (ALT, AST, alkaline phosphatase and bilirubin) were performed and oocyst clearance rates quantitated in specimens of bile and stool by light and fluorescence microscopy. Liver specimens were assessed histologically for severity of inflammation and presence of parasites, and tumor necrosis factor (TNF-α) and interferon-Υ levels measured by ELISA. WT mice displayed a transient biliary tract infection; their serum ALT, AST levels, liver inflammation and TNF-α and interferon-Υ levels, and stool and bile oocyte burden peaked at two weeks and normalized by four weeks. In contrast, the TLR4 knock-out mice displayed a persistent biliary tract infection. All serum makers, all liver measurements and histology, and oocyte burden remained abnormal at four weeks. These data suggest that a TLR4-mediated response is required for In Vivo eradication of biliary C. parvum infection and the lack of this pattern recognition receptor contributes to persistent inflammation.
*CTP score was significantly lower in PPI+ group but all other comparisons were not significant. M1744 Health-Related Quality of Life in Men with Liver Cirrhosis: the Impact of Low Testosterone Evangelos Kalaitzakis, Axel Josefsson, Einar Bjornsson Liver cirrhosis (LC) has a negative impact quality of life (QoL). In elderly non-cirrhotic men low testosterone levels are related to impaired QoL (Moncada et al, Aging Male 2006). Low testosterone levels are common in male cirrhotics but their relation to QoL in these patients is unexplored. Methods: 74 men with LC (median age 54yr (IQR48-58), Child-Pugh score 8(7-10), MELD 14(11-18), 34 alcoholic LC, 25 hepatitis C, 15 with HCC, 34 with ascites) under pretransplantation evaluation were prospectively enrolled. A validated questionnaire was used to measure QoL(SF-36). Results were compared with reference values from the general population. Serum testosterone was measured at 7-10am(ref >15nmol/l). Patients were assessed for the presence of hepatic encephalopathy(HE) clinically and with number connection tests A & B(NCT-A/B). Patients with HE grade >2 were excluded. Demographic variables(marital, employment and educational status) were also analyzed. Results: Cirrhotics, compared to the general population, had profound reduction in QoL(mean physical composite score(PCS) and mental composite score(MCS) in the general population 50.0, 95% CI 49.8-50.2(for both) vs 37.1, 95% CI 34.6-39.6 and 41.8, 95% CI 38.9-44.7, respectively in LC). 14 patients(19%) had overt and 5(7%) had minimal HE. Median testosterone was 13nmol/l (5.3-14) and 19 patients(26%) had low (<8nmol/l) testosterone. Patients with low serum testosterone scored significantly(p<0.05) lower in 7/8 SF-36 domains compared to those with normal testosterone. Marital, employment and educational status did not influence any SF-36 domain. In univariate analysis, PCS was related to the ChildPugh (r=-0.45, p<0.05) and MELD score (r=-0.28, p<0.05) as well as to ascites (p<0.05), overt or minimal HE(p<0.05), presence HCC (p<0.05) and serum testosterone levels (r= 0.53, p<0.05) but not to other complications or etiology of LC. MCS was related to the Child-Pugh (r=-0.48, p<0.05) and MELD score (r=-0.28, p<0.05) as well as to previous variceal bleeding (p<0.05) and serum testosterone (r=0.48, p<0.05). Also, MCS tended to be related to overt or minimal HE (p=0.06) but not to other complications or etiology of LC. Serum testosterone was related cirrhosis severity indices (Child-Pugh (r=-0.69, p<0.05) and MELD score (r=-0.6, p<0.05). In multivariate analysis, PCS and MCS were independently related solely to testosterone levels (r=0.49 and r=0.39 respectively, p<0.05 for both). Conclusions: Low testosterone levels seem to be related to impaired health-related QoL in men with cirrhosis. Clinical trials testing the value of testosterone supplementation in order to improve QoL in these patients seem to be warranted.
M1747 IGF-1 Vs Rifaximine for Hepatic Encephalopathy Treatment in Ascitic Cirrhotic Rats with Total Portal Vein Ligation Mireia Miquel, Gemma Odena, Ramon Bartoli, Anna Serafin, Amparo Galan, Ramon Planas Introduction: Hepatic encephalopathy (HE) in cirrhosis is due to hepatic failure and/or the presence of portosystemic shunting that leads the passage of nitrogenate compounds from intestine to bloodstream. Rifaximine is an established treatment for HE in human cirrhosis. IGF-1 could be useful for this purpose for its antifibrogenic and anabolic effects. Aim: To compare the effectiveness of Rifaximine and IGF-1 in the treatment of hepatic encephalopathy in an experimental model of ascitic cirrhotic rats with total portal vein ligation (TPL). Methods: 55 Sprague-Dawley rats were distributed in 6 groups: A: 10 Control rats; B: 9 Control rats+Rifaximine (50mg/kg daily for 14 days); C: 9 Control rats+IGF-1 (2µg/kg s.c. twice daily for 14 days); D: 9 Cirrhosis with TPL; E: 9 Cirrhotic rats with TPL+Rifaximine; F: 9 Cirrhotic rats with TPL+IGF-1. Cirrhosis with ascites was induced by CCl4 oral administration. Six weeks after starting cirrhosis induction (or the same period on control rats) TPL was assessed, and cirrhosis induction continued until ascites developed. At this point animals were randomized to receive; IGF-1, Rifaximine or placebo for 14 days. Afterwards, oral glutamine challenge (OGC) test was performed. Animals were laparotomized to obtain portal and peripheral blood, liver, brain and ileocecal content samples to quantify plasmatic and cerebral ammonia, presence or not of low grade cerebral edema, liver and brain histology and ileocecal cultures. Results: When compared with control rats (groups A, B and C) cirrhotic rats with TPL (group D) showed a significantly increase in plasmatic and cerebral ammonia, area under OGC curve, and low grade brain edema (brain water content). Rifaximine (group E) significantly reduced bacterial overgrowth when compared with groups D and F, and this was associated with a reduction in plasmatic an cerebral ammonia, area under OGC curve and cerebral water content, achieving similar values to those observed in control groups (A, B, C). Otherwise IGF-1 administration (group F) was unable to improve changes observed in group D. Histological alterations (astrocyte type II Alzheimer) were observed similarly in almost half of cirrhotic animals independently on their treatment. Conclusion: Rifaximine seems to be useful in the treatment of most of the alterations associated to HE in experimental cirrhosis. IGF-1 is not indicated in this pathology.
M1745 Morbidity and Mortality of TIPS Placement in the Elderly Is No Different Than in Younger Age Groups Neehar Parikh, Andres T. Blei, Steven L. Flamm ABSTRACT: Background: TIPS is widely used for treatment of refractory variceal bleeding or refractory ascites/hepatic hydrothorax (HH) in patients with chronic liver disease. There is reluctance to perform TIPS in older age groups because of perceived increased postprocedure mortality and morbidity. Aim: We sought to determine if age is an independent risk factor for mortality and morbidity in patients undergoing TIPS. Methods: A retrospective review of 89 consecutive pts undergoing de novo TIPS placement at a tertiary care center from 1/03-7/05 was performed with at least 12 months follow-up. Comparisons were made based upon age deciles: <50 yrs (13), 50-60 yrs (41), >60 yrs (35). Endpoints included 3 and 12-mos survival and numerous clinical endpoints such as HE, shunt re-stenosis, liver failure or bacteremia. Data was analyzed based upon comparisons between age deciles using a chi-square test. Significance was defined as a p value <0.05. Results: 89 consecutive pts (49M:40F) underwent the procedure. The etiologies of liver disease in these patients were: 24 (27%) alcoholic, 24 (27%) HCV, 13 (15%) cryptogenic, 10 (11%) NASH, 7 (8%) BuddChiari, and 11 (12%) other. The indications for TIPS placement were: 33 (37%) refractory ascites, 38 (43%) variceal bleed and 18 (20%) other. Age stratified mortality rates at 3 mos and 12 mos were: (P> 0.05 for all): <50 yrs: 23%/23%, 50-60 yrs: 24%/24%, >60 yrs: 17%/ 26%. Age stratified morbidity rates within one year were (P> 0.05 for all): <50 yrs: 77%, 50-60 yrs: 78%, >60: 71%. There was no difference in HE requiring hospitalization: <50 yrs 31%; 50-60 yrs: 36%; >60 yrs: 31%. A matched analysis was conducted comparing the 12 patients that were >70 yrs old with patients in younger age groups with similar MELD
AGA Abstracts
M1748 Vitamin D Deficiency in Consecutive Patients with Chronic Liver Disease Anita Narshi, Sabina S. Beg, Christine Blanshard, Anne Ballinger BACKGROUND: Vitamin D deficiency is associated with low bone density and osteoporosis. The latter is a common complication in patients with chronic liver disease (CLD). About 60% of patients with CLD are vitamin D deficient but assessment studies have mainly been restricted to patients with cholestatic liver disease, such as primary biliary cirrhosis, who may also have malabsorption of fat soluble vitamins. AGA guidelines on osteoporosis in hepatic disorders recommend 400-800IU daily of Vitamin D supplementation in patients with CLD. Higher doses are only recommended in CLD associated with malabsorption. Routine measurement of serum 25 (OH) vitamin D in all patients with CLD is not recommended, and the guidelines restrict measurements in pre-transplant liver patients or if the
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