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M1000 Completion of Hepatitis C Virus (HCV) Treatment in Community Based Practice—An Insight Into the Effectiveness of Treatment
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
A-830
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
A-830