- Email: [email protected]
M1002 Treatment of Alcoholic Hepatitis (AH) in Clinical Practice
is product of anaerobic bacterial glycolysis produced by Bacillus spp. and several Enterobacteriacae. The volatile substances identified will easily cross the blood-brain barrier and are thus candidates for a better mechanistic understanding and therapy of HE.
M1000 Completion of Hepatitis C Virus (HCV) Treatment in Community Based Practice—An Insight Into the Effectiveness of Treatment Fasiha Kanwal, Hashem B. El-Serag, Mark Schnitzler, Paula Buchanan, Bruce R. Bacon
S1851
Background: Clinical trials show that treatment with interferon (IFN) and ribavirin is efficacious in patients with HCV. Although most of the patients enrolled in clinical trials complete the recommended treatment course, the extent to which HCV patients managed in community based practice settings meet this standard—and hence the effectiveness of HCV treatment—is largely unknown. We sought to determine the rate and determinants of treatment completion in a demographically diverse group of privately insured patients with HCV. Methods: Using a national healthcare claims database from 1/1/2003-12/30/2006, we identified HCV patients with active viremia who were dispensed ≥1 IFN prescription and had ≥1 year follow-up after treatment initiation. We estimated length of treatment (LOT) by summing up days of IFN supply, and defined treatment completion as dispension of ≥48 weeks of INF in genotype 1, and 24 weeks in genotype 2/3 patients. Using logistic regression analyses, we identified patient demographic (age, gender, year), clinical (baseline lab values, cirrhosis, HIV, psychiatric illness, drug or alcohol use, comorbidity, IFN type, ribavirin dose, and HCV RNA at 12 and 24 weeks), and provider factors (primary care [PCP], specialists) associated with treatment completion. Results: We identified 1090 patients with HCV (age 47±7yr, 64% men). Of these, 539 (49%) completed the recommended treatment course. Treatment completion rates were 39.5% in genotype 1 (median LOT=40 wks) and 69.5% in genotype 2/3 patients (median LOT=24 wks). Approximately 40% of genotype 1 patients with undetectable RNA by week 24 did not complete treatment. Diagnosis of drug use (OR=0.67, p=0.04), platelet count <75K/mm3 (OR=0.19, p=0.03), detectable HCV RNA at week 12 (OR=0.32, p=0.0004), or at 24 weeks (OR=0.23, p<0.0001), and care by PCP alone (OR=0.51, p=0.02) were associated with low treatment completion in genotype 1 patients. For genotype 2/3 patients, low neutrophil count and a switch between the 2 IFN types were the only significant predictors of not completing treatment. However, these patient factors explained only 18% of variation in the treatment completion rates. Conclusions: Only half of the HCV patients who receive treatment in community based practice complete the recommended treatment course. These data suggest that the effectiveness of HCV treatment is likely to be considerably lower in clinical practice compared to the efficacy reported in clinical trials. Although patients' characteristics are important determinants of treatment completion rates, other system-level factors may play an important role, and need to be further examined and corrected.
AASLD Abstracts
The Risk Factors for Mortality of the Cirrhotic Patients Hospitalized in Intensive Care Units Sehmus Olmez, Yuksel Gumurdulu, Burcak E. Tasdogan, Banu Kara, Macit Sandikci, Hikmet Akkiz It is very important to determine the prognosis of cirrhotic patients in the intensive care units. Prognosis of cirrhotic patients depends on the degree of hepatic failure, complications of cirrhosis and concominant other extrahepatic reasons. Several scoring systems are used to evaluate the cirrhotic patients' prognosis objectively. In this study, we aimed to show and compare the effectiveness of Child-Turcotte-Pugh (CTP) and Model of End-stage Liver Disease (MELD) scores which are being used for cirrhotic patients and the other scoring systems Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assesment (SOFA). 201 cirrhotic patients, 130 (64.7 %) male and 71 (35.3%) female, are included in this study who are admitted to the internal medicine intensive care unit between January 2004 and December 2006. As risk factors for mortality; age, sex, ChildTurcotte-Pugh score, Model of End-stage Liver Disease score, Sequential Organ Failure Assesment score, Acute Physiology and Chronic Health Evaluation II score, serum lactate, blood urea nitrogen, creatinine, total bilirubin, prothrombin time levels, protein electrophoresis, ethyology of cirrhosis, patient's need for mechanical ventilation, duration of hospitalization in the intensive care unit, complications of cirrhosis such as hepatocellular carcinoma, gastrointestinal bleeding, hepatorenal syndrome, spontaneus bacterial peritonitis and concominant infections were defined and their influences on prognosis are investigated. As a result, since cirrhotic patients hospitalized in intensive care unit have advanced disease and the reasons for hospitalization here are cirrhotic complications, the mortality rate is found quite high (41.8%). Child-Turcotte-Pugh, Model of End-stage Liver Disease, Sequential Organ Failure Assesment, Acute Physiology and Chronic Health Evaluation II scores can be used to predict the mortality. Sequential Organ Failure Assesment and Acute Physiology and Chronic Health Evaluation II scores are found more powerful than Model of End-stage Liver Disease and Child-Turcotte-Pugh scores in this prediction (AUROC values respectively 0.847, 0.821, 0.790 and 0.7249). Sequential Organ Failure Assesment score can be performed easily and is found to be the best scoring system. Although Child-Turcotte-Pugh score is the one most used in cirrhotic patients, it's power to determine the prognosis is found low. Also higher lactate levels are found assosiated with worse prognosis, so lactate values can be used as a prognostic parameter.
M1001 Quality of Diagnosis and Evaluation-Related Care in Patients with Chronic Hepatitis C Virus Infection Fasiha Kanwal, Jennifer R. Kramer, Tuyen Hoang, Hashem B. El-Serag, Seth Eisen, Steven M. Asch
S1852 Induction of Glutamine Synthetase By Exercise in Healthy Volunteers: Exploring An Alternative Proposal for Nonhepatic Ammonia Metabolism Andres Duarte-Rojo, Miguel A. Torres-Vega, Jose Estradas, Aaron Dominguez, Fausto Sanchez-Munoz, Arturo Orea-Tejeda, Lilia Castillo-Martinez, Angel Miliar-Garcia, Aldo Torre
Background: Chronic hepatitis C virus infection (HCV) is a prevalent, burdensome, and expensive condition. With the advent of Medicare's pay for performance initiative, it is critical to understand the current process of care in HCV. We sought to determine the level and determinants of the initial evaluation process in patients diagnosed with HCV. Methods: Using a national Veterans Administration HCV Registry from 1/1/2000 to 12/30/2006, we evaluated 7 modified Delphi-panel derived quality indicators (QIs): confirmation of HCV viremia, specialty evaluation after confirmation, testing for HCV genotype, liver function testing, excluding hepatitis B virus infection, autoimmune hepatitis, and iron overload conditions. We derived the aggregate score as the proportion of QIs satisfied among those for which patients were eligible. Using logistic regression multivariable analysis, we evaluated patient demographic, clinical, and comorbidity related factors potentially associated with the receipt of evaluation-related care in HCV. Results: Of 165,599 patients with positive HCV antibody (age 52±9 y, 43% White, 21% African American), 66% received a confirmatory PCR test within a year follow-up after HCV diagnosis. Of those with confirmed infection, 56.6% were evaluated by a specialist, and 66% received a genotype test. The rates for the remaining QIs were 96% for liver function, 89% for hepatitis B, 70% for iron overload, and 53% for autoimmune liver disease testing. On average, patients received 66% of the recommended care. Fewer than 25% patients received all indicated QIs. In the multivariable analysis, older age (>65 y vs. <65 y, RR=0.63) African American race (RR=0.90), alcohol or drug use (RR=0.86), psychiatric illness (RR=0.85), and severe heart failure (RR=0.85) were associated with poor adherence to aggregate measure of quality. In contrast, patients with a diagnosis of cirrhosis (RR=1.3), depression (RR=1.2), diabetes (RR=1.06), and those with HIV (RR=1.06) were more likely to receive higher quality care. All p-values <0.001. Conclusions: Among patients with HCV, we found low overall adherence to the evidencebased indicators measuring the initial evaluation process. Our data show that several demographic, clinical, and comorbidity related factors are associated with receipt of quality care. Future research will attempt to measure the role of system factors in explaining the difference between expected and observed care. These data may ultimately assist researchers and policymakers in focusing quality improvement efforts in HCV
BACKGROUND: Glutamine synthetase (GS) enzyme plays a central role in ammonia metabolism, and skeletal muscle constitutes its major pool. Ammonia metabolism in muscle has been shown to occur in patients with hepatic encephalopathy. An exploratory study was designed to disclose an inducing-effect of exercise on GS in healthy volunteers. METHODS: Peripheral blood mononuclear cells (PBMC) were used as a surrogate of skeletal muscle (Zeibig 2005). A treadmill test was performed by 29 healthy volunteers, and blood was drawn before the test; and 15 min, 60 min, 2 h, 6 h and 24 h after this test (Treadmill Group). A Control Group of 13 healthy volunteers had blood drawn at the same time intervals, without any inducing maneuver. GS was identified in lymphocytes by indirect immunoflourescence and Western blot. Total RNA was isolated from PBMC, and GS mRNA expression was assessed by real time RT-PCR. BMI and whole-body bioimpedance were evaluated only in the treadmill subjects. Statistics were performed by means of Friedman and Student t tests, and Spearman correlation. RESULTS: GS was distributed in the cytoplasm of lymphocytes (molecular weight: 44 KDa). Medians (interquartile ranges) of GS mRNA measurements from PBMC are shown in Table 1. Significant differences among serial measurements were only found in the treadmill group (p=0.004). Peak of induction was observed at 2 hours, returning to basal after 6 hours. AUC were constructed at these time intervals (AUC2h and AUC6h, Table 1 [mean±SD]), and a higher expression of GS was observed when the treadmill group was compared to controls (AUC2h, p=0.021; AUC6h, p=0.037). Considering only the treadmill group, no differences were observed between genders, and there was a negative association between GS expression (AUC2h) and increasing age (r=0.368, p<0.05). Regarding anthropometry and bioimpedance, AUC2h was only correlated with fat free mass (r=0.412, p<0.05). CONCLUSION: We could characterize the presence of GS enzyme in lymphocytes. GS mRNA was acutely induced by a bout of exercise at a transcriptional level in PMNC. The correlation with fat free mass presumes a parallel induction in skeletal muscle (Zeibig 2005). These results establish the basis for considering exercise as a maneuver for increasing ammonia metabolism within skeletal muscle. Pending research could support its use for the treatment of low-grade hepatic encephalopathy if a sustained effect is found within a chronic exercising program.
M1002 Treatment of Alcoholic Hepatitis (AH) in Clinical Practice Robert O'Shea, Margaret F. Kinnard, Nadia Umar, Achuthan Sourianarayanane, Mitchell D. Schraider, Arthur J. McCullough Controversy exists regarding the optimal treatment of patients with AH, a disease with high morbidity and mortality. Steroids have been recommended for severe AH, based on 13 trials and several meta-analyses. However the most recent systematic review advises against their use (Aliment Pharm & Therap 2008; 27:1167). Two single center studies have evaluated the rates of treatment in patients and shown that only a third of patients were treated with steroids, even in patients with severe disease and no contra-indications. One study of pentoxifylline (Px) showed a 22% decrease in mortality; the use of Px however has not been studied subsequently. This retrospective cohort study was designed to examine the rates of
mRNA expression is shown as fold inductions over basal.
AASLD Abstracts
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steroid and Px use in 4 teaching hospitals in a single city over a 10 yr period. This report presents a preliminary analysis of data abstracted to date. Methods: Records from all patients discharged from 4 teaching hospitals in Cleveland from 1992-2005 were searched to identify patients with a primary diagnosis of AH (ICD-9 571.1): the Cleveland Clinic (n = 85), the Cleveland VAMC (n = 138), Metrohealth Medical Center (n = 273), and University Hospitals (n=793). Patient records were then reviewed. Results: A total of 890 charts have been reviewed to date. Demographics of the cohort are shown in Table 1. The number of those with an elevated Maddrey discriminant score (MDF ≥ 32) or MELD score > 18 and their treatments are listed in Table 2. Discussion: Multiple clinical trials have suggested a decrease in mortality in patients with severe AH treated with prednisone. However, physicians remain reluctant to prescribe them: only 25% of patients with an MDF ≥ 32 (the usual treatment threshold) were given steroids. Px was used in 28.7% of the cohort. Almost 40% went untreated, despite severe disease. Further research is needed regarding the determinants of physician prescribing, and to define the optimal medical treatments in AH. Table 1
visited the methadone center for one 3 hourly session, every 4-6 weeks. There were four stages: firstly, all the HCV positive clients were invited to a group meeting regarding treatment,(50/114 attended) . Secondly 25 of the 50 clients had further testing. The third stage included standard HCV treatment with coordination between the hepatologist and methadone physician and open access telephone consultation. Fourthly, the methadone physician aided the clients' medical compliance. The diagnosis of HCV was made by standard means. 20 patients were treated. 10 were genotype 3, 9 genotype 1 and one genotype 2. There were 19 males and one female. The average age was 43.8+ 2.8 years. On an intentionto-treat analysis the overall SVR was 8/20 (40%). Three patients are still receiving treatment. Reasons for non-successful treatment included medical reasons in two, social reasons in 4, one relapse and one treatment failure (6months HCV RNA+). In summary, HCV patients with a drug addiction problem can be successfully treated in Israel. In many professions, pro bono work is an accepted practice and could be extended to physicians. We suggest that a similar model could enable patients treated with methadone to receive successful eradication of HCV . M1005
Residents and medical students at the University of Arizona, Emory University, and the University of Virginia recently organized a new national health education campaign called Music Inspires Health aimed at teaching adults about Hepatitis C and HIV Prevention. Our goals were to reduce Hepatitis C and HIV transmission by educating communities about the dangers of IV drug use, tattoos, and unprotected sex through innovative multimedia projects. We sought to create cost-effective Hepatitis C programs that would resonate with communities through the use of multimedia messages delivered by hip-hop and rock music stars. We conducted paper surveys at inner city hospitals, universities, movie theatres, and bars to identify which music celebrities adults trust to present accurate health information about Hepatitis C and HIV prevention. We determined the most preferred multimedia education methods for our target audiences. In addition, a national online survey was created and administered on www.surveymonkey.com between 2006-2008. Survey items were written by medical students, physicians, and public health experts on our national medical advisory board. Recruitment of survey responders occurred via inner city posters and emails to entire university student bodies. All paper and online survey responders in the study agreed to an informed consent form and filled out demographic info. Survey response options were jumbled at random to prevent order bias. A sampling of the college campuses that participated included: University of Georgia, Georgia State, Morehouse College, University of Florida, Howard University, Virginia Commonwealth University, University of Virginia, NYU, University of Arizona, and UC Berkeley. Inner cities targeted by paper surveys and posters included Atlanta, Washington DC, NYC, Boston, and Chicago. Dave Matthews, Mario, Trey Songz, and Will Smith were selected as the most trusted rock and hip-hop musicians to teach the public about the dangers of IV drug use and the importance of condoms. Innovative short films and flash animation were selected as the two most preferred multimedia strategies that should be utilized to educate our two target audiences (innercity communities and young adults) about Hepatitis C and HIV Prevention. Survey responders also suggested compelling storylines about Hepatitis C prevention for us to film. Seventyeight percent of responders believed that entertaining short films should be used to empower adults to avoid IV drug use and to find safe tattoo parlors. This research study fine-tuned plans for a cost-effective national health education concert tour and a multimedia based health education website.
Patients with MDF ≥ 32 and MELD > 18 (n=254)
M1003 Use of a Patient Registry Database to Improve Hepatocellular Carcinoma Screening, Vaccination Rates, and Esophageal Varices Screening in Patients with Cirrhosis James T. Kwiatt, Parin N. Desai, Samer Gawrieh, Kia Saeian Managing patients with complicated chronic illnesses requires innovations in health care delivery. Previous studies on managing diabetics have shown improvement in quality indicators through the use of provider performance feedback. The AGA and the AASLD have established guidelines regarding health maintenance for patients with cirrhosis in regards to vaccination, management of esophageal varices, and screening for hepatocellular carcinoma. Little has been reported in the literature regarding adherence to recommendations. Addressing standards of care and ensuring they are met is one method to improve health care quality in cirrhosis. The purpose of our study is to assess adherence to cirrhosis guidelines in an academic hepatology practice as an indicator of quality of care. We propose that making our performance data available to the providers in our clinic will also result in improved health care delivery to patients with cirrhosis. METHODS A registry database of 2311 patients with cirrhosis was generated. All patients were managed by a hepatology clinic at a large academic medical center. From a random sample of medical records, data regarding dates of hepatocellcular carcinoma screening, esophageal varices screening, and immunization to hepatitis A and hepatitis B was obtained. A report was generated and given to the clinic providers detailing the percentage of patients in the clinic who have undergone preventive care. Performance in these measures was then tracked after distribution of the feedback. RESULTS 138 charts were reviewed (95% CI). 96% of patients had been evaluated for hepatocellular carcinoma at least once. 68% of the patients had undergone endoscopy for esophageal varices screening. Immunization to hepatitis A and hepatitis B was addressed in 51% and 47% of the patients respectively. Data regarding performance improvement following the providers' review of the registry reports is still pending. CONCLUSIONS The results illustrate that established standards of care are not always met in patients with cirrhosis, thus creating a need for quality improvement. This provides opportunities to examine why gaps in care exist and standards of care are not being met. Physician awareness of performance should lead to better means of addressing deficiencies in care on individual and system-based levels. Direct provider feedback may be one way to facilitate adherence to practice recommendations.
M1006 Copy Number Variation: A Potential Susceptibility Factor for Biliary Atresia Melissa Leyva-Vega, Brian Thiel, Elizabeth B. Rand, Hakon Hakonarson, Nancy B. Spinner, Barbara Haber Biliary atresia (BA) is a progressive, idiopathic obliteration of the extrahepatic biliary system occurring in infancy and leading to liver transplantation in the majority of cases. While the etiology of BA is unknown, an underlying genetic susceptibility has been hypothesized. In this study we will test the hypothesis that genomic copy number variation (CNV) underlies susceptibility to BA. The genetic susceptibility could be caused by common CNV's that are more frequent in patients with BA or by rare variants that can pinpoint the location of BA susceptibility genes. Aim: Identify copy number variation in subjects with BA and compare these variants to those seen in a control population. Methods: DNA from 35 BA patients was genotyped on the Illumina Quad550 platform, which includes 550,000 SNP's. Areas of increased and decreased copy number were compared to known variants using the UCSC Genome Browser and Database of Genomic Variants to identify possible candidate regions. Control data was obtained from 2026 healthy individuals. Results: We identified two potential rare variants. The first is a deletion found in two different patients. One patient with BA and no other congenital anomalies had a 280 single nucleotide polymorphism (SNP), 1.75 Mb deletion within chromosome 2q37. This region contains over 20 genes, some of which have functions potentially important to BA pathogenesis. One gene in this region is the alanine-gloxylate aminotransferase (AGXT) gene, which is expressed only in the liver. AGXT is found in peroxisomes, which play a role in the metabolism of toxins. Potentially the deletion of a detoxifying gene may lincrease susceptibility to hepatotoxins, which may be involved in the development of BA. A second patient with BA and multiple congenital anomalies had a similar deletion on chromosome 2q37. None of the 2026 normal controls had the deletion found in these two patients. The second interesting finding is a 55 SNP, 282 kb duplication on chromosome 11p15.5 in a patient with BA and malrotation. This finding has been validated by quantitative PCR. None of the controls had this duplication. This region includes the insulin-like growth factor 2 (IGF2) gene. IGF2 is a polypeptide growth factor involved in development and growth. IGF2 has been found to be up-regulated in patients with the embryonic form of biliary atresia. Conclusions: Our findings point to 2q37.3 and 11p15.5 as regions that may be important in the pathogenesis of BA. We plan to validate our findings in a larger cohort of patients.
M1004 A Model for Treating HCV Hepatitis in Patients Receiving Methadone Maintenance Therapy Stephen D. Malnick, Victoria Sheidvasser, Alon Basevitz, Shabtay Levit Hepatitis C is commonly transmitted by intravenous drug use but treatment of addicts is not successful.. Methadone Maintenance Treatment (MMT) including pharmacologic and psycho-social treatment can reduce high-risk behavior but there is scarce data on HCV treatment. We report here the results of a pilot scheme for treatment in a MMT center. The program included recruitment of a supervising hepatologist volunteer working with a multidisciplinary staff. This offered a solution treatment to uptake barriers. The hepatologist
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AASLD Abstracts
AASLD Abstracts
Cost-Effectiveness of Designing Hepatitis C Prevention Programs and Innovative Multimedia Strategies That Empower the Public Benjamin H. Levy
M1000 Completion of Hepatitis C Virus (HCV) Treatment in Community Based Practice—An Insight Into the Effectiveness of Treatment Fasiha Kanwal, Hashem B. El-Serag, Mark Schnitzler, Paula Buchanan, Bruce R. Bacon
S1851
Background: Clinical trials show that treatment with interferon (IFN) and ribavirin is efficacious in patients with HCV. Although most of the patients enrolled in clinical trials complete the recommended treatment course, the extent to which HCV patients managed in community based practice settings meet this standard—and hence the effectiveness of HCV treatment—is largely unknown. We sought to determine the rate and determinants of treatment completion in a demographically diverse group of privately insured patients with HCV. Methods: Using a national healthcare claims database from 1/1/2003-12/30/2006, we identified HCV patients with active viremia who were dispensed ≥1 IFN prescription and had ≥1 year follow-up after treatment initiation. We estimated length of treatment (LOT) by summing up days of IFN supply, and defined treatment completion as dispension of ≥48 weeks of INF in genotype 1, and 24 weeks in genotype 2/3 patients. Using logistic regression analyses, we identified patient demographic (age, gender, year), clinical (baseline lab values, cirrhosis, HIV, psychiatric illness, drug or alcohol use, comorbidity, IFN type, ribavirin dose, and HCV RNA at 12 and 24 weeks), and provider factors (primary care [PCP], specialists) associated with treatment completion. Results: We identified 1090 patients with HCV (age 47±7yr, 64% men). Of these, 539 (49%) completed the recommended treatment course. Treatment completion rates were 39.5% in genotype 1 (median LOT=40 wks) and 69.5% in genotype 2/3 patients (median LOT=24 wks). Approximately 40% of genotype 1 patients with undetectable RNA by week 24 did not complete treatment. Diagnosis of drug use (OR=0.67, p=0.04), platelet count <75K/mm3 (OR=0.19, p=0.03), detectable HCV RNA at week 12 (OR=0.32, p=0.0004), or at 24 weeks (OR=0.23, p<0.0001), and care by PCP alone (OR=0.51, p=0.02) were associated with low treatment completion in genotype 1 patients. For genotype 2/3 patients, low neutrophil count and a switch between the 2 IFN types were the only significant predictors of not completing treatment. However, these patient factors explained only 18% of variation in the treatment completion rates. Conclusions: Only half of the HCV patients who receive treatment in community based practice complete the recommended treatment course. These data suggest that the effectiveness of HCV treatment is likely to be considerably lower in clinical practice compared to the efficacy reported in clinical trials. Although patients' characteristics are important determinants of treatment completion rates, other system-level factors may play an important role, and need to be further examined and corrected.
AASLD Abstracts
The Risk Factors for Mortality of the Cirrhotic Patients Hospitalized in Intensive Care Units Sehmus Olmez, Yuksel Gumurdulu, Burcak E. Tasdogan, Banu Kara, Macit Sandikci, Hikmet Akkiz It is very important to determine the prognosis of cirrhotic patients in the intensive care units. Prognosis of cirrhotic patients depends on the degree of hepatic failure, complications of cirrhosis and concominant other extrahepatic reasons. Several scoring systems are used to evaluate the cirrhotic patients' prognosis objectively. In this study, we aimed to show and compare the effectiveness of Child-Turcotte-Pugh (CTP) and Model of End-stage Liver Disease (MELD) scores which are being used for cirrhotic patients and the other scoring systems Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assesment (SOFA). 201 cirrhotic patients, 130 (64.7 %) male and 71 (35.3%) female, are included in this study who are admitted to the internal medicine intensive care unit between January 2004 and December 2006. As risk factors for mortality; age, sex, ChildTurcotte-Pugh score, Model of End-stage Liver Disease score, Sequential Organ Failure Assesment score, Acute Physiology and Chronic Health Evaluation II score, serum lactate, blood urea nitrogen, creatinine, total bilirubin, prothrombin time levels, protein electrophoresis, ethyology of cirrhosis, patient's need for mechanical ventilation, duration of hospitalization in the intensive care unit, complications of cirrhosis such as hepatocellular carcinoma, gastrointestinal bleeding, hepatorenal syndrome, spontaneus bacterial peritonitis and concominant infections were defined and their influences on prognosis are investigated. As a result, since cirrhotic patients hospitalized in intensive care unit have advanced disease and the reasons for hospitalization here are cirrhotic complications, the mortality rate is found quite high (41.8%). Child-Turcotte-Pugh, Model of End-stage Liver Disease, Sequential Organ Failure Assesment, Acute Physiology and Chronic Health Evaluation II scores can be used to predict the mortality. Sequential Organ Failure Assesment and Acute Physiology and Chronic Health Evaluation II scores are found more powerful than Model of End-stage Liver Disease and Child-Turcotte-Pugh scores in this prediction (AUROC values respectively 0.847, 0.821, 0.790 and 0.7249). Sequential Organ Failure Assesment score can be performed easily and is found to be the best scoring system. Although Child-Turcotte-Pugh score is the one most used in cirrhotic patients, it's power to determine the prognosis is found low. Also higher lactate levels are found assosiated with worse prognosis, so lactate values can be used as a prognostic parameter.
M1001 Quality of Diagnosis and Evaluation-Related Care in Patients with Chronic Hepatitis C Virus Infection Fasiha Kanwal, Jennifer R. Kramer, Tuyen Hoang, Hashem B. El-Serag, Seth Eisen, Steven M. Asch
S1852 Induction of Glutamine Synthetase By Exercise in Healthy Volunteers: Exploring An Alternative Proposal for Nonhepatic Ammonia Metabolism Andres Duarte-Rojo, Miguel A. Torres-Vega, Jose Estradas, Aaron Dominguez, Fausto Sanchez-Munoz, Arturo Orea-Tejeda, Lilia Castillo-Martinez, Angel Miliar-Garcia, Aldo Torre
Background: Chronic hepatitis C virus infection (HCV) is a prevalent, burdensome, and expensive condition. With the advent of Medicare's pay for performance initiative, it is critical to understand the current process of care in HCV. We sought to determine the level and determinants of the initial evaluation process in patients diagnosed with HCV. Methods: Using a national Veterans Administration HCV Registry from 1/1/2000 to 12/30/2006, we evaluated 7 modified Delphi-panel derived quality indicators (QIs): confirmation of HCV viremia, specialty evaluation after confirmation, testing for HCV genotype, liver function testing, excluding hepatitis B virus infection, autoimmune hepatitis, and iron overload conditions. We derived the aggregate score as the proportion of QIs satisfied among those for which patients were eligible. Using logistic regression multivariable analysis, we evaluated patient demographic, clinical, and comorbidity related factors potentially associated with the receipt of evaluation-related care in HCV. Results: Of 165,599 patients with positive HCV antibody (age 52±9 y, 43% White, 21% African American), 66% received a confirmatory PCR test within a year follow-up after HCV diagnosis. Of those with confirmed infection, 56.6% were evaluated by a specialist, and 66% received a genotype test. The rates for the remaining QIs were 96% for liver function, 89% for hepatitis B, 70% for iron overload, and 53% for autoimmune liver disease testing. On average, patients received 66% of the recommended care. Fewer than 25% patients received all indicated QIs. In the multivariable analysis, older age (>65 y vs. <65 y, RR=0.63) African American race (RR=0.90), alcohol or drug use (RR=0.86), psychiatric illness (RR=0.85), and severe heart failure (RR=0.85) were associated with poor adherence to aggregate measure of quality. In contrast, patients with a diagnosis of cirrhosis (RR=1.3), depression (RR=1.2), diabetes (RR=1.06), and those with HIV (RR=1.06) were more likely to receive higher quality care. All p-values <0.001. Conclusions: Among patients with HCV, we found low overall adherence to the evidencebased indicators measuring the initial evaluation process. Our data show that several demographic, clinical, and comorbidity related factors are associated with receipt of quality care. Future research will attempt to measure the role of system factors in explaining the difference between expected and observed care. These data may ultimately assist researchers and policymakers in focusing quality improvement efforts in HCV
BACKGROUND: Glutamine synthetase (GS) enzyme plays a central role in ammonia metabolism, and skeletal muscle constitutes its major pool. Ammonia metabolism in muscle has been shown to occur in patients with hepatic encephalopathy. An exploratory study was designed to disclose an inducing-effect of exercise on GS in healthy volunteers. METHODS: Peripheral blood mononuclear cells (PBMC) were used as a surrogate of skeletal muscle (Zeibig 2005). A treadmill test was performed by 29 healthy volunteers, and blood was drawn before the test; and 15 min, 60 min, 2 h, 6 h and 24 h after this test (Treadmill Group). A Control Group of 13 healthy volunteers had blood drawn at the same time intervals, without any inducing maneuver. GS was identified in lymphocytes by indirect immunoflourescence and Western blot. Total RNA was isolated from PBMC, and GS mRNA expression was assessed by real time RT-PCR. BMI and whole-body bioimpedance were evaluated only in the treadmill subjects. Statistics were performed by means of Friedman and Student t tests, and Spearman correlation. RESULTS: GS was distributed in the cytoplasm of lymphocytes (molecular weight: 44 KDa). Medians (interquartile ranges) of GS mRNA measurements from PBMC are shown in Table 1. Significant differences among serial measurements were only found in the treadmill group (p=0.004). Peak of induction was observed at 2 hours, returning to basal after 6 hours. AUC were constructed at these time intervals (AUC2h and AUC6h, Table 1 [mean±SD]), and a higher expression of GS was observed when the treadmill group was compared to controls (AUC2h, p=0.021; AUC6h, p=0.037). Considering only the treadmill group, no differences were observed between genders, and there was a negative association between GS expression (AUC2h) and increasing age (r=0.368, p<0.05). Regarding anthropometry and bioimpedance, AUC2h was only correlated with fat free mass (r=0.412, p<0.05). CONCLUSION: We could characterize the presence of GS enzyme in lymphocytes. GS mRNA was acutely induced by a bout of exercise at a transcriptional level in PMNC. The correlation with fat free mass presumes a parallel induction in skeletal muscle (Zeibig 2005). These results establish the basis for considering exercise as a maneuver for increasing ammonia metabolism within skeletal muscle. Pending research could support its use for the treatment of low-grade hepatic encephalopathy if a sustained effect is found within a chronic exercising program.
M1002 Treatment of Alcoholic Hepatitis (AH) in Clinical Practice Robert O'Shea, Margaret F. Kinnard, Nadia Umar, Achuthan Sourianarayanane, Mitchell D. Schraider, Arthur J. McCullough Controversy exists regarding the optimal treatment of patients with AH, a disease with high morbidity and mortality. Steroids have been recommended for severe AH, based on 13 trials and several meta-analyses. However the most recent systematic review advises against their use (Aliment Pharm & Therap 2008; 27:1167). Two single center studies have evaluated the rates of treatment in patients and shown that only a third of patients were treated with steroids, even in patients with severe disease and no contra-indications. One study of pentoxifylline (Px) showed a 22% decrease in mortality; the use of Px however has not been studied subsequently. This retrospective cohort study was designed to examine the rates of
mRNA expression is shown as fold inductions over basal.
AASLD Abstracts
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steroid and Px use in 4 teaching hospitals in a single city over a 10 yr period. This report presents a preliminary analysis of data abstracted to date. Methods: Records from all patients discharged from 4 teaching hospitals in Cleveland from 1992-2005 were searched to identify patients with a primary diagnosis of AH (ICD-9 571.1): the Cleveland Clinic (n = 85), the Cleveland VAMC (n = 138), Metrohealth Medical Center (n = 273), and University Hospitals (n=793). Patient records were then reviewed. Results: A total of 890 charts have been reviewed to date. Demographics of the cohort are shown in Table 1. The number of those with an elevated Maddrey discriminant score (MDF ≥ 32) or MELD score > 18 and their treatments are listed in Table 2. Discussion: Multiple clinical trials have suggested a decrease in mortality in patients with severe AH treated with prednisone. However, physicians remain reluctant to prescribe them: only 25% of patients with an MDF ≥ 32 (the usual treatment threshold) were given steroids. Px was used in 28.7% of the cohort. Almost 40% went untreated, despite severe disease. Further research is needed regarding the determinants of physician prescribing, and to define the optimal medical treatments in AH. Table 1
visited the methadone center for one 3 hourly session, every 4-6 weeks. There were four stages: firstly, all the HCV positive clients were invited to a group meeting regarding treatment,(50/114 attended) . Secondly 25 of the 50 clients had further testing. The third stage included standard HCV treatment with coordination between the hepatologist and methadone physician and open access telephone consultation. Fourthly, the methadone physician aided the clients' medical compliance. The diagnosis of HCV was made by standard means. 20 patients were treated. 10 were genotype 3, 9 genotype 1 and one genotype 2. There were 19 males and one female. The average age was 43.8+ 2.8 years. On an intentionto-treat analysis the overall SVR was 8/20 (40%). Three patients are still receiving treatment. Reasons for non-successful treatment included medical reasons in two, social reasons in 4, one relapse and one treatment failure (6months HCV RNA+). In summary, HCV patients with a drug addiction problem can be successfully treated in Israel. In many professions, pro bono work is an accepted practice and could be extended to physicians. We suggest that a similar model could enable patients treated with methadone to receive successful eradication of HCV . M1005
Residents and medical students at the University of Arizona, Emory University, and the University of Virginia recently organized a new national health education campaign called Music Inspires Health aimed at teaching adults about Hepatitis C and HIV Prevention. Our goals were to reduce Hepatitis C and HIV transmission by educating communities about the dangers of IV drug use, tattoos, and unprotected sex through innovative multimedia projects. We sought to create cost-effective Hepatitis C programs that would resonate with communities through the use of multimedia messages delivered by hip-hop and rock music stars. We conducted paper surveys at inner city hospitals, universities, movie theatres, and bars to identify which music celebrities adults trust to present accurate health information about Hepatitis C and HIV prevention. We determined the most preferred multimedia education methods for our target audiences. In addition, a national online survey was created and administered on www.surveymonkey.com between 2006-2008. Survey items were written by medical students, physicians, and public health experts on our national medical advisory board. Recruitment of survey responders occurred via inner city posters and emails to entire university student bodies. All paper and online survey responders in the study agreed to an informed consent form and filled out demographic info. Survey response options were jumbled at random to prevent order bias. A sampling of the college campuses that participated included: University of Georgia, Georgia State, Morehouse College, University of Florida, Howard University, Virginia Commonwealth University, University of Virginia, NYU, University of Arizona, and UC Berkeley. Inner cities targeted by paper surveys and posters included Atlanta, Washington DC, NYC, Boston, and Chicago. Dave Matthews, Mario, Trey Songz, and Will Smith were selected as the most trusted rock and hip-hop musicians to teach the public about the dangers of IV drug use and the importance of condoms. Innovative short films and flash animation were selected as the two most preferred multimedia strategies that should be utilized to educate our two target audiences (innercity communities and young adults) about Hepatitis C and HIV Prevention. Survey responders also suggested compelling storylines about Hepatitis C prevention for us to film. Seventyeight percent of responders believed that entertaining short films should be used to empower adults to avoid IV drug use and to find safe tattoo parlors. This research study fine-tuned plans for a cost-effective national health education concert tour and a multimedia based health education website.
Patients with MDF ≥ 32 and MELD > 18 (n=254)
M1003 Use of a Patient Registry Database to Improve Hepatocellular Carcinoma Screening, Vaccination Rates, and Esophageal Varices Screening in Patients with Cirrhosis James T. Kwiatt, Parin N. Desai, Samer Gawrieh, Kia Saeian Managing patients with complicated chronic illnesses requires innovations in health care delivery. Previous studies on managing diabetics have shown improvement in quality indicators through the use of provider performance feedback. The AGA and the AASLD have established guidelines regarding health maintenance for patients with cirrhosis in regards to vaccination, management of esophageal varices, and screening for hepatocellular carcinoma. Little has been reported in the literature regarding adherence to recommendations. Addressing standards of care and ensuring they are met is one method to improve health care quality in cirrhosis. The purpose of our study is to assess adherence to cirrhosis guidelines in an academic hepatology practice as an indicator of quality of care. We propose that making our performance data available to the providers in our clinic will also result in improved health care delivery to patients with cirrhosis. METHODS A registry database of 2311 patients with cirrhosis was generated. All patients were managed by a hepatology clinic at a large academic medical center. From a random sample of medical records, data regarding dates of hepatocellcular carcinoma screening, esophageal varices screening, and immunization to hepatitis A and hepatitis B was obtained. A report was generated and given to the clinic providers detailing the percentage of patients in the clinic who have undergone preventive care. Performance in these measures was then tracked after distribution of the feedback. RESULTS 138 charts were reviewed (95% CI). 96% of patients had been evaluated for hepatocellular carcinoma at least once. 68% of the patients had undergone endoscopy for esophageal varices screening. Immunization to hepatitis A and hepatitis B was addressed in 51% and 47% of the patients respectively. Data regarding performance improvement following the providers' review of the registry reports is still pending. CONCLUSIONS The results illustrate that established standards of care are not always met in patients with cirrhosis, thus creating a need for quality improvement. This provides opportunities to examine why gaps in care exist and standards of care are not being met. Physician awareness of performance should lead to better means of addressing deficiencies in care on individual and system-based levels. Direct provider feedback may be one way to facilitate adherence to practice recommendations.
M1006 Copy Number Variation: A Potential Susceptibility Factor for Biliary Atresia Melissa Leyva-Vega, Brian Thiel, Elizabeth B. Rand, Hakon Hakonarson, Nancy B. Spinner, Barbara Haber Biliary atresia (BA) is a progressive, idiopathic obliteration of the extrahepatic biliary system occurring in infancy and leading to liver transplantation in the majority of cases. While the etiology of BA is unknown, an underlying genetic susceptibility has been hypothesized. In this study we will test the hypothesis that genomic copy number variation (CNV) underlies susceptibility to BA. The genetic susceptibility could be caused by common CNV's that are more frequent in patients with BA or by rare variants that can pinpoint the location of BA susceptibility genes. Aim: Identify copy number variation in subjects with BA and compare these variants to those seen in a control population. Methods: DNA from 35 BA patients was genotyped on the Illumina Quad550 platform, which includes 550,000 SNP's. Areas of increased and decreased copy number were compared to known variants using the UCSC Genome Browser and Database of Genomic Variants to identify possible candidate regions. Control data was obtained from 2026 healthy individuals. Results: We identified two potential rare variants. The first is a deletion found in two different patients. One patient with BA and no other congenital anomalies had a 280 single nucleotide polymorphism (SNP), 1.75 Mb deletion within chromosome 2q37. This region contains over 20 genes, some of which have functions potentially important to BA pathogenesis. One gene in this region is the alanine-gloxylate aminotransferase (AGXT) gene, which is expressed only in the liver. AGXT is found in peroxisomes, which play a role in the metabolism of toxins. Potentially the deletion of a detoxifying gene may lincrease susceptibility to hepatotoxins, which may be involved in the development of BA. A second patient with BA and multiple congenital anomalies had a similar deletion on chromosome 2q37. None of the 2026 normal controls had the deletion found in these two patients. The second interesting finding is a 55 SNP, 282 kb duplication on chromosome 11p15.5 in a patient with BA and malrotation. This finding has been validated by quantitative PCR. None of the controls had this duplication. This region includes the insulin-like growth factor 2 (IGF2) gene. IGF2 is a polypeptide growth factor involved in development and growth. IGF2 has been found to be up-regulated in patients with the embryonic form of biliary atresia. Conclusions: Our findings point to 2q37.3 and 11p15.5 as regions that may be important in the pathogenesis of BA. We plan to validate our findings in a larger cohort of patients.
M1004 A Model for Treating HCV Hepatitis in Patients Receiving Methadone Maintenance Therapy Stephen D. Malnick, Victoria Sheidvasser, Alon Basevitz, Shabtay Levit Hepatitis C is commonly transmitted by intravenous drug use but treatment of addicts is not successful.. Methadone Maintenance Treatment (MMT) including pharmacologic and psycho-social treatment can reduce high-risk behavior but there is scarce data on HCV treatment. We report here the results of a pilot scheme for treatment in a MMT center. The program included recruitment of a supervising hepatologist volunteer working with a multidisciplinary staff. This offered a solution treatment to uptake barriers. The hepatologist
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AASLD Abstracts
AASLD Abstracts
Cost-Effectiveness of Designing Hepatitis C Prevention Programs and Innovative Multimedia Strategies That Empower the Public Benjamin H. Levy