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Leptospirosis- Is Cirrhosis a Predisposing Factor?
AGA Abstracts
liver biopsy or evaluated for liver transplantation at our center from 2005-2010 were analyzed. Data regarding disease severity, biopsy findings, nephrolithiasis (defined as presence of renal stones on imaging), symptoms, medical procedures and UTI were collected. To minimize detection bias, we included only patients who had an abdominal CT current within the previous 3 years. Patients without cirrhosis on biopsy were age-matched to those who had cirrhosis on biopsy (compensated cirrhosis) and those with cirrhosis on the transplant list (decompensated cirrhosis) during the same time span. We excluded patients with gout, hyperparathyroidism, inflammatory bowel disease, myeloproliferative disorders and those on calcium supplements. Chi-square test was used to compare categorical variables and ttest to compare continuous variables. Results: 340 non-cirrhotic and 256 cirrhotic [194 diagnosed by biopsy (early) and 62 on transplant list(advanced)] HCV patients were included. There was no difference in the age, BMI, serum calcium, or renal size between the two groups. There was a significantly higher prevalence of nephrolithiasis in cirrhotic patients compared to non-cirrhotics (13% vs. 4%, p=0.0001). A trend was noted toward greater prevalence of nephrolithiasis with more advanced cirrhosis, but did not achieve statistical significance (cirrhosis compensated 9% vs. decompensated 15%, p=0.293). There was a significantly higher rate of symptomatic renal stones in the cirrhosis group compared to non-cirrhosis group (6.3% vs. 2.9%, p=0.04). Similarly a history of nephrolithiasis-associated UTI was found more often in cirrhotics than noncirrhotics (7% vs 2.1%, p=0.01). Conclusion: In patients with hepatitis C, nephrolithiasis is significantly more common in cirrhotics than non-cirrhotics, and frequently is symptomatic.
Child-Pugh score class C (OR 3.45, 95% CI 1.36- 8.7, p= 0.009) were independent predictors of death. AUROC values of DM, CP and MELD were 0.62, 0.69 and 0.63, respectively (p >0.05) Conclusions: DM was associated with a significant reduction in 18-months survival of patients with compensated LC. Serum creatinine > 1.5 mg/dL and Child-Pugh score class C were independent predictors of death. Finally, DM was a predictor of death with similar efficacy to that of CP and MELD scores. Su1333 Incidence of Malignancies in Liver Transplant Patients: A Single Center Analysis Anand Gupta, Aby Philip, Tarun Rustagi, Vinay Ranga, Martin Hoffman Introduction: Malignancies after liver transplantation (LT) are becoming an increasingly recognized entity especially with better post transplant survival with improvements in surgical techniques and immunosuppressive medications. This is a descriptive epidemiologic study of liver transplant patients in a tertiary care center and the incidence of malignancies post transplant. Methods: All patients who had liver transplant at our institution were included in a retrospective review of a prospectively collected database. Data obtained was analyzed for indications for transplant, occurrence of malignancy during post-transplant follow-up, and recurrence of HCC in patients who had liver transplant for HCC itself. Results: 350 patients were identified who had LT at our institution. The most common indication for LT was Hepatitis C (152/350), followed by alcoholic liver disease (44/350). 51 patients out of 350 went on to develop some form of malignancy. The mean duration between transplant and detection of malignancy was 1700 days. HCC was noted to have the shortest mean duration (667 days) and majority of these cases were of recurrence of hepatocellular cancer. The most common malignancy observed was skin cancer, in 24% of patients followed by HCC in 18% of patients. Squamous cell carcinoma of the skin (16% of all malignancies, 2/ 3rd of all skin malignancies) was seen to be more common than basal cell cancer (8% of all malignancies). There was also a significant difference noted in mean interval between detection of SCC (2624 days) and BCC (1502 days). Lymphoreticular malignancies were next in frequency (12%). Other tumors included colon cancer (10%), lung cancers (10%), pancreatic and bladder cancers. Conclusions: Data on incidence of malignancies in post liver transplant patients is sparse. Variable prevalence and incidence rates have been documented in different studies. Various factors contribute to the predisposition to developing cancers in post translplant patients with chronic immunosupression and viral agents playing the most significant roles. More studies are needed to investigate if particular immunosuppressive regimes are associated with a higher incidence of malignancies. Strict cancer surveillance needs to be an integral part of post translplant therapy. Setting up of such guidelines needs more multi center studies investigating the cohort of liver transplant patients and the malignancies developing in them.
Su1331 Leptospirosis- Is Cirrhosis a Predisposing Factor? Rajoo S. Chhina, Deepinder Chhina, Omesh Goyal, Prerna Goyal, Rajdeep S. Chhina Background & aim: Epidemics of leptospirosis have been reported from all over the world. However, there is no data regarding the incidence, clinical profile and outcome of patients of chronic liver disease (CLD) who get leptospira infection. Hence, this study was undertaken. Methods: Data of serologically confirmed cases of leptospirosis (positive IgM anti-leptospira antibody by ELISA), admitted from January 2008 to December 2008 in a tertiary care institute of northern India was analysed. Patients were diagnosed to have CLD on the basis of clinical, radiological or biochemical criteria. ‘Good outcome’ was defined as recovery and discharge from hospital; while ‘poor outcome’ was defined as non-survival or leaving against medical advice in a sick condition. Statistical analysis was done using Fisher's exact test and Student's unpaired t test. Results: Leptospirosis was diagnosed in 216 patients, of which 124 (57.4%) had underlying CLD (male: female = 4.2:1). Alcohol was the most common etiology of CLD, followed by HCV. The mean age in CLD and non-CLD groups was 46.7 ± 11.3 years and 45.3 ± 16.8 years respectively (p > 0.05). Significantly more number of patients in CLD group presented with jaundice (95.2% v/s 71.7%; p= 0.0001), while significantly fewer patients had history of fever (72.8% v/s 50.8%; p = 0.0001). The number of patients with renal involvement (62.1% v/s 65.2%), pulmonary involvement (30.6% v/s 43.5%), and haemorrhagic manifestations (27.4% vs 16.3%) were not significantly different in the CLD and non-CLD groups. However, the mean creatinine value was significantly higher in the non-CLD group (3.0 ± 2.7 v/s 2.3 ± 2.0; p= 0.029). The mean values of serum bilirubin, albumin and INR were significantly higher, while that of AST, ALT, ALP and platelets were significantly lower in the CLD group. More number of patients in the CLDgroup had poor outcome (33.9 % v/s 21.7 %, p =0.06). Factors predicting poor outcome in the CLD group were - presence of renal failure, pulmonary involvement, requirement of dialysis and artificial ventilation, leucocytosis and high bilirubin levels at admission. Conclusions: CLD appears to be a risk factor for acquiring leptospira infection. Patients with CLD and leptospirosis present more commonly with jaundice, rather than fever, and have a poorer outcome as compared to patients without CLD. Factors which predict poor outcome are - renal failure, pulmonary involvement, requirement of dialysis and artificial ventilation, leucocytosis, and high bilirubin levels at admission.
Su1334 The Effect of Concomitant Lactulose on Gastrointestinal Adverse Events in Cirrhotic Patients Treated With Rifaximin Todd Frederick, Robert S. McFadden, jOSEPH Galati, Sardar D. Khan, Shirley Huang, Kunal Merchant, Enoch Bortey, William P. Forbes Purpose: Lactulose is frequently used to treat hepatic encephalopathy (HE) is commonly associated with gastrointestinal (GI) side effects. Recently, rifaximin 550 mg BID was shown to significantly reduce the risk of overt HE in patients with cirrhosis over 6 months when compared with placebo (p<0.0001) in a randomized, double-blind, placebo-controlled trial (RCT). Long-term safety and efficacy of rifaximin 550 mg BID were further demonstrated in new and rollover patients in an open-label trial (OLM). Concomitant lactulose was optional in both the RCT and OLM. This analysis compares the incidence and rates of GI-related adverse events (AEs) between patients treated with rifaximin + lactulose and patients treated with rifaximin alone. Methods: Patients with cirrhosis who had ≥2 episodes of overt HE (Conn score [CS] ≥2) within 6 months of screening and who were currently in remission (CS 0 or 1) were enrolled into the RCT and randomized to either rifaximin 550 mg BID or placebo for 6 months. Patients either rolled over from RCT or were newly enrolled in the OLM if they met eligibility requirements. Adverse event data were pooled from both studies to compare GI-related AEs between rifaximin-treated patients who also used lactulose, and those who did not. Results: There were 264 patients treated with rifaximin + lactulose; the daily lactulose doses ranged from approximately 15-300mL/day. 84 patients received rifaximin alone. The overall incidence of GI-related AEs was higher in patients treated with lactulose: 69% (183/264) of rifaximin patients treated with lactulose experienced at least one GI-related AE versus 49% (41/84) of patients treated with rifaximin alone. Person years of rifaximin exposure (PEY) were 252.7 in the rifaximin + lactulose group and 94.1 in the rifaximin group. Conclusions: These results suggest that concomitant lactulose use contributed to higher incidences and event rates of GI-related AEs in rifaximin-treated patients. Normalized Rate Of Most Frequent GI-Related AEs (events/100 PEY)
Su1332 Diabetes Mellitus (DM) Reduces Survival in Patients With Compensated Liver Cirrhosis (Lc) - A Prospective Study Diego Garcia-Compean, Joel O. Jaquez Quintana, Jose A Gonzalez, Jesus Z. Villarreal, Linda Muñoz, Pedro A. Lopez Hernandez, Fernando J. Lavalle Gonzalez, Erick A. Reyes Cabello, Edgar R. Redondo, Alma I. Cano, Hector J. Maldonado Background: It has been suggested that DM may reduce survival of patients with liver cirrhosis (LC). Nevertheless only few prospective studies assessing the impact of DM on mortality of cirrhotic patients have been published, none in compensated LC. Aims: (a) to study the impact of DM on survival; (b) to identify predictors of death; and (c) to compare the prognostic capacity of death of DM with the ones of the Child-Pugh classification (CP) and MELD in patients with compensated LC. Methods: Patients who were admitted to our hospital from August 2007 to March 2010 with compensated LC with and without DM were prospectively studied. Diagnosis of DM was defined based on the criteria of the American Diabetes Association. Compensated cirrhosis was defined as the absence of: visible GI hemorrhage, clinical hepatic encephalopathy, severe ascites, spontaneous bacterial peritonitis, infection, hepatorenal syndrome, alcoholic hepatitis, and hepatocellular carcinoma. Patients were followed-up every 3 months by outpatient department. Survival was analyzed by the Kaplan-Meier Method. Univariate and multivariate analysis was performed to determine independent predictors of mortality and the performance of DM, CP and MELD scores for predicting mortality was evaluated by AUROC curves. Results: 110 patients were included: 60 without DM and 50 with DM. Diabetic patients had significantly higher frequency of cryptogenic cirrhosis, anemia, hypoalbuminemia, and hypercreatininemia. They also had significantly higher BMI and Child-Pugh score. The 18-months cumulative survival was significantly lower in patients with DM than those without (48% vs. 69%, p <0.03). By univariate analysis: DM ( OR 3.3, 95% CI 1.34-8.3, p= 0.007), female gender (OR 0.03, 95% CI 0.01-0.09, p=0.025), serum creatinine > 1.5 mg/dL (OR 5.1, 95% CI 1.69-16.5, p=0.01) , Child-Pugh score class C (OR 5, 95% CI 1.4-17.3, p= 0.012) and cryptogenic cirrhosis (OR 4.8, 95% CI 2 -9.8, p =0.004 ) were significant. However, by multivariate analysis only serum creatinine > 1.5 mg/dL (OR 3.39, 95% CI 1.69-8.21, p= 0.046) and
AGA Abstracts
S-460
liver biopsy or evaluated for liver transplantation at our center from 2005-2010 were analyzed. Data regarding disease severity, biopsy findings, nephrolithiasis (defined as presence of renal stones on imaging), symptoms, medical procedures and UTI were collected. To minimize detection bias, we included only patients who had an abdominal CT current within the previous 3 years. Patients without cirrhosis on biopsy were age-matched to those who had cirrhosis on biopsy (compensated cirrhosis) and those with cirrhosis on the transplant list (decompensated cirrhosis) during the same time span. We excluded patients with gout, hyperparathyroidism, inflammatory bowel disease, myeloproliferative disorders and those on calcium supplements. Chi-square test was used to compare categorical variables and ttest to compare continuous variables. Results: 340 non-cirrhotic and 256 cirrhotic [194 diagnosed by biopsy (early) and 62 on transplant list(advanced)] HCV patients were included. There was no difference in the age, BMI, serum calcium, or renal size between the two groups. There was a significantly higher prevalence of nephrolithiasis in cirrhotic patients compared to non-cirrhotics (13% vs. 4%, p=0.0001). A trend was noted toward greater prevalence of nephrolithiasis with more advanced cirrhosis, but did not achieve statistical significance (cirrhosis compensated 9% vs. decompensated 15%, p=0.293). There was a significantly higher rate of symptomatic renal stones in the cirrhosis group compared to non-cirrhosis group (6.3% vs. 2.9%, p=0.04). Similarly a history of nephrolithiasis-associated UTI was found more often in cirrhotics than noncirrhotics (7% vs 2.1%, p=0.01). Conclusion: In patients with hepatitis C, nephrolithiasis is significantly more common in cirrhotics than non-cirrhotics, and frequently is symptomatic.
Child-Pugh score class C (OR 3.45, 95% CI 1.36- 8.7, p= 0.009) were independent predictors of death. AUROC values of DM, CP and MELD were 0.62, 0.69 and 0.63, respectively (p >0.05) Conclusions: DM was associated with a significant reduction in 18-months survival of patients with compensated LC. Serum creatinine > 1.5 mg/dL and Child-Pugh score class C were independent predictors of death. Finally, DM was a predictor of death with similar efficacy to that of CP and MELD scores. Su1333 Incidence of Malignancies in Liver Transplant Patients: A Single Center Analysis Anand Gupta, Aby Philip, Tarun Rustagi, Vinay Ranga, Martin Hoffman Introduction: Malignancies after liver transplantation (LT) are becoming an increasingly recognized entity especially with better post transplant survival with improvements in surgical techniques and immunosuppressive medications. This is a descriptive epidemiologic study of liver transplant patients in a tertiary care center and the incidence of malignancies post transplant. Methods: All patients who had liver transplant at our institution were included in a retrospective review of a prospectively collected database. Data obtained was analyzed for indications for transplant, occurrence of malignancy during post-transplant follow-up, and recurrence of HCC in patients who had liver transplant for HCC itself. Results: 350 patients were identified who had LT at our institution. The most common indication for LT was Hepatitis C (152/350), followed by alcoholic liver disease (44/350). 51 patients out of 350 went on to develop some form of malignancy. The mean duration between transplant and detection of malignancy was 1700 days. HCC was noted to have the shortest mean duration (667 days) and majority of these cases were of recurrence of hepatocellular cancer. The most common malignancy observed was skin cancer, in 24% of patients followed by HCC in 18% of patients. Squamous cell carcinoma of the skin (16% of all malignancies, 2/ 3rd of all skin malignancies) was seen to be more common than basal cell cancer (8% of all malignancies). There was also a significant difference noted in mean interval between detection of SCC (2624 days) and BCC (1502 days). Lymphoreticular malignancies were next in frequency (12%). Other tumors included colon cancer (10%), lung cancers (10%), pancreatic and bladder cancers. Conclusions: Data on incidence of malignancies in post liver transplant patients is sparse. Variable prevalence and incidence rates have been documented in different studies. Various factors contribute to the predisposition to developing cancers in post translplant patients with chronic immunosupression and viral agents playing the most significant roles. More studies are needed to investigate if particular immunosuppressive regimes are associated with a higher incidence of malignancies. Strict cancer surveillance needs to be an integral part of post translplant therapy. Setting up of such guidelines needs more multi center studies investigating the cohort of liver transplant patients and the malignancies developing in them.
Su1331 Leptospirosis- Is Cirrhosis a Predisposing Factor? Rajoo S. Chhina, Deepinder Chhina, Omesh Goyal, Prerna Goyal, Rajdeep S. Chhina Background & aim: Epidemics of leptospirosis have been reported from all over the world. However, there is no data regarding the incidence, clinical profile and outcome of patients of chronic liver disease (CLD) who get leptospira infection. Hence, this study was undertaken. Methods: Data of serologically confirmed cases of leptospirosis (positive IgM anti-leptospira antibody by ELISA), admitted from January 2008 to December 2008 in a tertiary care institute of northern India was analysed. Patients were diagnosed to have CLD on the basis of clinical, radiological or biochemical criteria. ‘Good outcome’ was defined as recovery and discharge from hospital; while ‘poor outcome’ was defined as non-survival or leaving against medical advice in a sick condition. Statistical analysis was done using Fisher's exact test and Student's unpaired t test. Results: Leptospirosis was diagnosed in 216 patients, of which 124 (57.4%) had underlying CLD (male: female = 4.2:1). Alcohol was the most common etiology of CLD, followed by HCV. The mean age in CLD and non-CLD groups was 46.7 ± 11.3 years and 45.3 ± 16.8 years respectively (p > 0.05). Significantly more number of patients in CLD group presented with jaundice (95.2% v/s 71.7%; p= 0.0001), while significantly fewer patients had history of fever (72.8% v/s 50.8%; p = 0.0001). The number of patients with renal involvement (62.1% v/s 65.2%), pulmonary involvement (30.6% v/s 43.5%), and haemorrhagic manifestations (27.4% vs 16.3%) were not significantly different in the CLD and non-CLD groups. However, the mean creatinine value was significantly higher in the non-CLD group (3.0 ± 2.7 v/s 2.3 ± 2.0; p= 0.029). The mean values of serum bilirubin, albumin and INR were significantly higher, while that of AST, ALT, ALP and platelets were significantly lower in the CLD group. More number of patients in the CLDgroup had poor outcome (33.9 % v/s 21.7 %, p =0.06). Factors predicting poor outcome in the CLD group were - presence of renal failure, pulmonary involvement, requirement of dialysis and artificial ventilation, leucocytosis and high bilirubin levels at admission. Conclusions: CLD appears to be a risk factor for acquiring leptospira infection. Patients with CLD and leptospirosis present more commonly with jaundice, rather than fever, and have a poorer outcome as compared to patients without CLD. Factors which predict poor outcome are - renal failure, pulmonary involvement, requirement of dialysis and artificial ventilation, leucocytosis, and high bilirubin levels at admission.
Su1334 The Effect of Concomitant Lactulose on Gastrointestinal Adverse Events in Cirrhotic Patients Treated With Rifaximin Todd Frederick, Robert S. McFadden, jOSEPH Galati, Sardar D. Khan, Shirley Huang, Kunal Merchant, Enoch Bortey, William P. Forbes Purpose: Lactulose is frequently used to treat hepatic encephalopathy (HE) is commonly associated with gastrointestinal (GI) side effects. Recently, rifaximin 550 mg BID was shown to significantly reduce the risk of overt HE in patients with cirrhosis over 6 months when compared with placebo (p<0.0001) in a randomized, double-blind, placebo-controlled trial (RCT). Long-term safety and efficacy of rifaximin 550 mg BID were further demonstrated in new and rollover patients in an open-label trial (OLM). Concomitant lactulose was optional in both the RCT and OLM. This analysis compares the incidence and rates of GI-related adverse events (AEs) between patients treated with rifaximin + lactulose and patients treated with rifaximin alone. Methods: Patients with cirrhosis who had ≥2 episodes of overt HE (Conn score [CS] ≥2) within 6 months of screening and who were currently in remission (CS 0 or 1) were enrolled into the RCT and randomized to either rifaximin 550 mg BID or placebo for 6 months. Patients either rolled over from RCT or were newly enrolled in the OLM if they met eligibility requirements. Adverse event data were pooled from both studies to compare GI-related AEs between rifaximin-treated patients who also used lactulose, and those who did not. Results: There were 264 patients treated with rifaximin + lactulose; the daily lactulose doses ranged from approximately 15-300mL/day. 84 patients received rifaximin alone. The overall incidence of GI-related AEs was higher in patients treated with lactulose: 69% (183/264) of rifaximin patients treated with lactulose experienced at least one GI-related AE versus 49% (41/84) of patients treated with rifaximin alone. Person years of rifaximin exposure (PEY) were 252.7 in the rifaximin + lactulose group and 94.1 in the rifaximin group. Conclusions: These results suggest that concomitant lactulose use contributed to higher incidences and event rates of GI-related AEs in rifaximin-treated patients. Normalized Rate Of Most Frequent GI-Related AEs (events/100 PEY)
Su1332 Diabetes Mellitus (DM) Reduces Survival in Patients With Compensated Liver Cirrhosis (Lc) - A Prospective Study Diego Garcia-Compean, Joel O. Jaquez Quintana, Jose A Gonzalez, Jesus Z. Villarreal, Linda Muñoz, Pedro A. Lopez Hernandez, Fernando J. Lavalle Gonzalez, Erick A. Reyes Cabello, Edgar R. Redondo, Alma I. Cano, Hector J. Maldonado Background: It has been suggested that DM may reduce survival of patients with liver cirrhosis (LC). Nevertheless only few prospective studies assessing the impact of DM on mortality of cirrhotic patients have been published, none in compensated LC. Aims: (a) to study the impact of DM on survival; (b) to identify predictors of death; and (c) to compare the prognostic capacity of death of DM with the ones of the Child-Pugh classification (CP) and MELD in patients with compensated LC. Methods: Patients who were admitted to our hospital from August 2007 to March 2010 with compensated LC with and without DM were prospectively studied. Diagnosis of DM was defined based on the criteria of the American Diabetes Association. Compensated cirrhosis was defined as the absence of: visible GI hemorrhage, clinical hepatic encephalopathy, severe ascites, spontaneous bacterial peritonitis, infection, hepatorenal syndrome, alcoholic hepatitis, and hepatocellular carcinoma. Patients were followed-up every 3 months by outpatient department. Survival was analyzed by the Kaplan-Meier Method. Univariate and multivariate analysis was performed to determine independent predictors of mortality and the performance of DM, CP and MELD scores for predicting mortality was evaluated by AUROC curves. Results: 110 patients were included: 60 without DM and 50 with DM. Diabetic patients had significantly higher frequency of cryptogenic cirrhosis, anemia, hypoalbuminemia, and hypercreatininemia. They also had significantly higher BMI and Child-Pugh score. The 18-months cumulative survival was significantly lower in patients with DM than those without (48% vs. 69%, p <0.03). By univariate analysis: DM ( OR 3.3, 95% CI 1.34-8.3, p= 0.007), female gender (OR 0.03, 95% CI 0.01-0.09, p=0.025), serum creatinine > 1.5 mg/dL (OR 5.1, 95% CI 1.69-16.5, p=0.01) , Child-Pugh score class C (OR 5, 95% CI 1.4-17.3, p= 0.012) and cryptogenic cirrhosis (OR 4.8, 95% CI 2 -9.8, p =0.004 ) were significant. However, by multivariate analysis only serum creatinine > 1.5 mg/dL (OR 3.39, 95% CI 1.69-8.21, p= 0.046) and
AGA Abstracts
S-460