- Email: [email protected]
Factors Associated With Immunoprophylaxis Failure in Infants Born to HBsAg Positive Mothers: A Retrospective Study
562
fixed factor such as race and virus genotype, the drop in effectiveness is due to low antiviral treatment initiation and treatment completion.
Performance Feedback Impacts Quality Measures in the Management of Cirrhosis James T. Kwiatt, Parin N. Desai, Samer Gawrieh, Kia Saeian
564
Introduction: Quality improvement (QI) is an emerging area of importance in health care. The Medicare Physician Quality Reporting Initiative, AASLD, and AGA recommend tracking, reporting, and training in QI measures for gastroenterologists and hepatologists (1,2). Vaccination for viral hepatitis, management of esophageal varices (EV), and screening for hepatocellular carcinoma (HCC) are areas of potential QI that have been identified in the management of cirrhosis (3). Our group previously reported baseline deficiencies in vaccination for hepatitis A & B, EV screening, and HCC screening at DDW 2008. Performance feedback is one approach to possibly increase adherence to these measures. Aim: Assess if performance feedback improved adherence to guidelines and if so, see if adherence sustained over one year. Methods: Design- Retrospective and prospective chart review at a tertiary academic medical center. Participants- Health care providers in an outpatient hepatology clinic caring for 2311 cirrhotics. Data regarding appropriate HCC screening, EV screening/surveillance, and documented immunity to hepatitis A and hepatitis B was obtained utilizing chart review and a database. At the start of the study, providers were given retrospective data on previous 3 years of performance on addressing health maintenance. After having providers review past performance, prospective adherence to health maintenance measures was tracked and assessed at 60 days and 365 days in all patients seen in clinic by chart review. Results: Retrospective assessment revealed baseline deficiencies in recommended health maintenance (See Table). After giving performance feedback, medical records of all cirrhotics seen in clinic were assessed for recommended health maintenance compliance. 60 days after performance feedback, documentation of immunity to hepatitis A improved to 81%, immunity to hepatitis B to 91 %, screening for HCC 100%, and EV management to 98% (p<0.001 compared to retrospective data). Performance improvement was sustained after 1 year (p=NS comparing 60 day and 365 day data). At one year, documentation of immunity to hepatitis A was 85%, immunity to hepatitis B 85%, screening for HCC 100%, and EV management 97%. Discussion: Performance feedback to health care providers can improve adherence to health maintenance guidelines in managing cirrhotics. When providers are aware that performance is being tracked, improvement is sustained over 1 year. Systems to provide performance feedback can be an important part of QI initiatives. References 1. AGA Institute Press. PQRI Updates. GI Quality and Practice Management News 2008; 9:12 2. AASLD, ACG, AGA Institute, ASGE. The Gastroenterology Core Curriculum. May 2007 3. Kanwal,F. et.al. An Explicit Quality Indicator Set for Measurement of Quality of Care in Patients With Cirrhosis. Clin Gastro Hep.2010;8:709-717 Quality Improvement in Cirrhosis Health Mainanence
BACKGROUND & AIMS: Shorter courses of treatment with pegylated interferon and ribavirin for patients with hepatitis C who achieve rapid virologic response (RVR) have been shown to be effective in appropriately selected patients. However, truncated therapy may result in a higher rate of relapse than standard therapy and necessitate retreatment. The aim of this study was to evaluate the cost effectiveness of truncated therapy as compared to the standard of care. METHODS: We developed a decision model for chronic hepatitis C that combined a decision tree and Markov cohort model. In the decision tree, we modeled two treatment strategies; the first modeled the standard of care which included 48 weeks of therapy with pegylated interferon and ribavirin for individuals with genotypes 1 and 4 and 24 weeks of therapy for individuals with genotypes 2 and 3; the second strategy consisted of shortening therapy by 50% in individuals with RVR. Individuals who failed to achieve SVR with truncated therapy were retreated with the standard of care. Lifetime costs and qualityadjusted life-years (QALYs) were estimated using a Markov cohort model and compared between the two treatment strategies. We performed a probabilistic sensitivity analysis to assess parameter uncertainty and multiple univariate and bivariate sensitivity analyses to test model assumptions. All costs and benefits were discounted at a rate of 3% per year as recommended by the US Panel on Cost-Effectiveness in Health and Medicine. RESULTS: In the base case, the average lifetime cost was $43,950 (± 1,906) in the standard arm and $39,717 (±1,914) in the truncated therapy arm resulting in a savings of $4,233 (± 325) in favor of truncated therapy. Average lifetime QALYs were similar with 17.04 (± 0.69) in the standard arm as compared to 17.09 (± 0.69) in the truncated therapy arm; thus, truncated therapy dominated standard therapy. In a probabilistic sensitivity analysis using a Monte Carlo simulation of 10,000 trials, the probability of truncated therapy being dominant (i.e. cost-saving and QALY increasing) was 78%. When stratified by genotype, truncated therapy remained cost effective (i.e. dominant or cost per QALY < $5000) as compared to standard therapy. One-way sensitivity analyses revealed that the results were insensitive to variations in costs, utilities, transition probabilities and baseline characteristics of the study cohort, including age, genotype distribution and baseline fibrosis. CONCLUSIONS: Truncated therapy based on RVR is likely to be cost effective when compared to standard of care for individuals with chronic hepatitis C. These findings are applicable to populations of individuals with hepatitis C as well as those stratified by genotype. Decision analysis may be helpful in optimizing resource allocation in the era of personalized therapy for chronic hepatitis C. 565
Performance feedback resulted in sustained improvement in adherence to QI indicators.
Factors Associated With Immunoprophylaxis Failure in Infants Born to HBsAg Positive Mothers: A Retrospective Study Huaibin Zou, Yu Chen, Zhongping Duan, Hua Zhang, Calvin Pan
563
Background and Aim Despite the active-passive immunization, immunoprophylaxis failure occurs in infants born to mothers with hepatitis B virus (HBV). Prior studies showed HBeAg(+) and DNA > 1×108 c/ml are the major risk for immunoprophlaxi failure, but the lower DNA level or other risk factors have not been fully explored, we evaluate the risk factors associated with the immunoprophylaxis failure. Methods Infants born to HBsAg+ mothers with >7 month follow up in 1/2007-3/2010 at our center were eligible. Infants from mothers with co-infection, antiviral use, missed immunoprophylasix were excluded. Maternal and infants clinical and laboratory data was collected by chart review. HBV serology of all infant was assessed by microparticle enzyme immunoassy technique (Abbott kits,USA),HBV DNA at birth was measure by RT-PCR. HBV immunoprophylaxis failure was defined as infant with HBsAg(+) and anti-HBs (-) at 7-12 months of age. Results Among 3536 infants born to 3521 HBsAg+ mother, 1045 infants were eligible. 8 infants were excluded (1 co-infection, 4 anti-HBV drug use, 3 missed vaccines). 1037 infants from 1031 mothers were analyzed. All infants received HBIG 200 IU and HBV vaccine 10 mcg within 6 hours of birth, and a second injection of HBIG at week 2, the vaccine were given again at 1 and 6 months. Among 1031 mothers, HBeAg(+) in 573(55.6%), detectable HBV DNA in 689 (66.8%), maternal DNA levels at 3.0-5.9 logs, 6-7.9 logs and >or = 8 logs were 151, 457 and 81 respectively; The correspondent infant prophylaxis failure rates were 0%, 5.3% and 7.4%, respectively. The trend test chi-square = 15.785 (P<0.001). Among 1037 infants, 30 failed immunoprophylaxis were selected as cases and the rest as controls. The rate of immunoprophylaxis failure was 2.9% vs 5.8% in the infants born to HBeAg-negative vs HBeAg positive mothers, respectively. Clinical presentation and possible related factors of cases and controls were listed on Table 1. The factors with statistically significant differences between two groups on univariate analysis were: maternal HBeAg+, maternal HBV DNA > 6×log10 c/ml, HBV DNA detectable in core blood. Conclusions Our study showed infants' HBV immunoprophylaxis failure was associated with maternal DNA level > 6 log10 c/ml, HBeAg+, and HBV DNA detectable in core blood. Further prospective studies needed to verify the finding and provide more aggressive intervention in patients with the above risk factors. Characteristics of the patients
Effectiveness of Hepatitis C Virus (HCV) Antiviral Treatment in Veterans With HIV-HCV Coinfection Jennifer R. Kramer, Fasiha Kanwal, Minghua Mei, Thomas P. Giordano, Hashem El-Serag Background: Efficacy of antiviral treatment for hepatitis C virus (HCV) in patients with HCV and HIV coinfection in achieving sustained viral response (SVR) rates has been shown to be between 28% and 44% in randomized controlled trials. However, effectiveness in a community-based practice setting can be much lower and is influenced by other factors related to access, adherence, and representation of low response groups (e.g. blacks, HCV genotype, and drug and alcohol use). We determined the effectiveness of HCV treatment in veterans with HCV-HIV coinfection in the United States. Methods: We conducted a retrospective cohort study of veterans with HCV viremia and HIV (positive antibody or viral load test) from the nationwide Veterans Affairs HCV Clinical Case Registry during 2000 to 2006. We identified patients who had at least one prescription for pegylated-interferon and ribavirin and calculated the duration of treatment and the proportions of patients completing treatment (at least 44 for genotypes 1 or 4 or 22 weeks for 2 or 3). The effectiveness of treatment was measured as the proportions of patients who achieved an SVR (negative test for HCV RNA at least 12 weeks after the end of treatment) in the overall coinfected cohort and among both patients who initiated and completed treatment. We also stratified by genotype and race/ethnicity. Results: We identified 6,137 patients coinfected with HCV and HIV. Of those, 896 (14.6%) had at least one released prescription for any antiviral treatment and 638 (10.4%) received pegylated-interferon with ribavirin. Of the 638 patients on combination therapy, 72.3% had genotype 1, 22.1% had genotype 2 or 3, and 5.6% were not tested for genotype. One-third completed at least 44 weeks of treatment for genotype 1 while almost three-fourths completed at least 22 weeks of treatment for genotype 2 or 3. Absolute or relative contraindications were documented in only 61.5% of patients who did not receive treatment. SVR was documented in 33.6% and 65.7% of those who completed treatment, 18.7% and 56.0% of those who initiated treatment, and 2.6% and 15.6% of the entire coinfected cohort for genotype 1 and 2 or 3, respectively. Black and Hispanic patients were significantly less likely to achieve an SVR compared to whites for both genotypes (1: 10.2% and 5.9% vs. 24.7%; 2 or 3: 46.7% and 45.5% vs. 58.3%). Overall, only 2.8% of the entire coinfected cohort had documented SVR. Conclusions: Treatment effectiveness for HCV in HIV coinfected veterans is low. Compared to previously published VA data in an HCV cohort (with and without HIV), treatment effectiveness is lower for coinfected veterans for HCV genotype 1, but higher for coinfected veterans with genotype 2 or 3. Other than
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AASLD Abstracts
AASLD Abstracts
Truncated Therapy Based on Rapid Virologic Response is a Cost Effective Treatment Paradigm for Chronic Hepatitis C Ziad F. Gellad, Shelby Reed, Andrew J. Muir, John McHutchison, William Sievert, Ala I. Sharara, Kimberly Ann A. Brown, Robert Flisiak, Ira M. Jacobson, David Kershenobich, Michael P. Manns, Kevin A. Schulman
567 Proportion of Patients Who Were Previously Ineligible for Anti-HBV Therapy Who Became Eligible After 12 Months of Follow-up: Application of U.S. Panel and AASLD Guidelines Jessica T. Ristau, Shu Zhang, Huy N. Trinh, Ruel T. Garcia, Huy A. Nguyen, Khanh K. Nguyen, Mindie H. Nguyen
AASLD Abstracts
PURPOSE: Given the dynamic nature of chronic hepatitis B (CHB) and the fluctuation of certain clinical parameters used to determine patient treatment eligibility by treatment guidelines (U.S. Panel 2008 and AASLD 2009), many patients who were initially ineligible may become treatment eligible during follow up. Our goal was to study such patient populations and examine the reasons and timeline for future treatment eligibility. METHODS: We performed a retrospective cohort study with 190 consecutive treatment-naïve CHB patients who were treatment ineligible when they first presented between 3/07-1/09 and had ≥ 12 months of follow up with laboratory testing every 6-12 months at 2 U.S. community GI clinics. US Panel 2008 eligibility requirements are as follows; ALT >30 IU/mL for males, >19 IU/mL for females and HBV DNA >2,000 IU/mL for HBeAg negative patients and >20,000 IU/mL for HBeAg positive patients. AASLD 2009 eligibility included ALT >60 IU/ mL for males, >38 IU/mL for females and HBV DNA >20,000 IU/mL regardless of HBeAg status. RESULTS: The majority of patients were over 35 years old (74%) and Asian (97%). The proportion of patients who became eligible was described in the table. Of those who became eligible according to US Panel 2008 guidelines, 33% became eligible by 12 months, 47% by 24 months and the remaining 20% by 36 months. Accounting for variance in total follow-up time, the proportions of patients becoming eligible were as follows; 9% with 12 months of follow up, 5% of patients with 18 months of follow up and 12% of patients with 24 months of follow up. Corresponding data for AASLD 2009 guidelines were: 2%, 2% and 3% at 12, 18 and 24 months of follow-up, respectively. On multivariate analysis also inclusive of age, gender, and HBeAg status, significant predictors of later eligibility by AASLD guidelines at follow-up were higher ALT at baseline (0.5-1.0 xULN) (OR=5.01, p=0.031) and serum HBV DNA at baseline (>20,000 IU) (OR=4.6, p=0.05). No significant predictors were found for later eligibility by US Panel guidelines. CONCLUSION: While the majority of patients who were initially ineligible for anti-HBV therapy continued to require no therapy, approximately one-fifth may meet treatment criteria on even short to medium term follow-up (median 23 months). This data suggests that all CHB patients should continue to have regular followup with periodic review of their disease status and potential need for antiviral therapy.
* lowest detectable limit. 566 Liver Biochemical Course, Serum HBV DNA and Liver Stiffness Measurement for Therapeutic Decisions in HBeAg-Negative Chronic Hepatitis B Infection Phunchai Charatcharoenwitthaya, Pochamana Phisalprapa, Pimpattana Rungkaew, Sorrayut Kajornvuthidej, Wimolrak Bandidniyamanon, Siwaporn P. Chainuvati, Nonthalee Pausawasdi, Supot Nimanong, Watcharasak Chotiyaputta, Somchai Leelakusolvong, Kanit Atisook, Tawesak Tanwandee
568 Tenofovir Disoproxil Fumarate (TDF) Shows Similar Virologic Suppression and Safety Between Asians and Non-Asians With Chronic Hepatitis B (CHB) Calvin Pan, Sing Chan, Huy N. Trinh, Alan Yao, Ho Bae, Patrick Marcellin, E. Jenny Heathcote, Betty Chiang, Lillian Lou
Background & Aims: Assessment of liver histology in patients with HBeAg-negative chronic hepatitis B virus (HBV) infection allows clinicians to determine the extent of hepatic inflammation and fibrosis and consequently to assess suitability for treatment. It is, however, poorly accepted by patients due to procedure-related complications. Thus, we evaluated the ability of various noninvasive methods in determining the presence of histological indication for treatment (at least grade A2 or stage F2 by METAVIR scoring) in this population. Methods: Consecutive HBeAg-negative patients with serum HBV DNA levels >2,000 IU/ml and serial measurement of alanine aminotransferase (ALT) were enrolled to perform liver stiffness measurement using Fibroscan followed by liver biopsy on the same day. Individual liver specimens were evaluated independently by 2 pathologists without knowledge of the clinical data. Differences in interpretation were settled by consensus of the pathologists. Results: A total of 399 patients had a mean age of 47.5±9.6 years and 42% were female. Mean body mass index at baseline was 23.9±3.8 kg/m2. Using the normal range of serum ALT <40 IU/ L, 142 patients (36%) had persistently normal ALT levels (PNALT) whereas 257 patients had persistently or intermittent elevated ALT (PIEALT) in previous 1 year prior to liver biopsy. The proportion of PIEALT patients with moderate to severe necroinflammation (48% vs. 13%, p<.0001) and significant fibrosis (43% vs. 13%, p<.0001) was higher than those of PNALT patients. Histological indication for treatment was present in 57% of PIEALT patients and 22% of PNALT patients (p<.0001). In PNALT patients defined by criteria of normal ALT; 30 IU/L for men and 19 IU/L for women on the day of liver biopsy, HBV carriers with ALT levels less than updated cut-off values had no difference in the frequency of histological indication for treatment compared to those with ALT levels higher than updated cut-off values (18% vs. 28%, p=.2). Among patients with HBV DNA of 2,00019,999, 20,000-199,999, and ≥200,000 IU/mL, histological indication for treatment was present in 40%, 45%, and 71% of PIEALT patients and 15%, 31%, and 36% of PNALT patients, respectively. In PNALT patients with HBV DNA <20,000 IU/L, the use of liver stiffness value <7 pKa in determining nonsignificant histology can avoid liver biopsy in 89% of patients and miss only 13% of patients who indeed had histological indication for treatment. In PIEALT patients with HBV DNA >200,000 IU/L, the measurement of liver stiffness ≥7 pKa can predict histological indication for treatment reducing the need for liver biopsy in 56% of patients with a false-positive of 17%. Conclusions: The combination of serial measurement of liver enzymes, serum HBV DNA, and liver stiffness is a noninvasive approach that may be useful for therapeutic decision in HBeAg-negative patients.
AASLD Abstracts
Background: TDF has demonstrated potent antiviral activity upon initiation of treatment in CHB patients. Two TDF registration trials in CHB (127 Asian and 299 non-Asian patients) and an open-label trial (90 Asians) were analyzed in a cross sectional study to compare efficacy and safety of TDF in Asians versus non-Asians during the first 48 weeks (W) of treatment. Methods: Eligibility criteria were similar between registration vs. open-label trials except for HBV DNA >=10^5 vs. >=10^4 copies(c)/mL and ALT >2x vs. >1x ULN [HBeAg(+) patients], respectively. All three trials were analyzed independently and compared side-byside. Subsequently, 217 Asians were combined, and compared with 299 non-Asians stratified for HBeAg status. Results: 288 HBeAg(-) and 228 HBeAg(+) CHB patients were available for the analysis. Baseline characteristics were similar between Asians vs. non-Asians except for mean weight, height and BMI (65.6 vs. 79.3 kg, 165 vs. 173 cm^2, and 24.1 vs. 26.4 kg/m^2, respectively). HBeAg(-) Asians (n=102) and non-Asians (n=186) patients had median (quartiles Q1, Q3) baseline HBV DNA of 6.4 (5.5, 7.7) and 7.0 (5.9, 7.8) log10 c/mL, which decreased by 3.1 log10 (both) at 4W; 96% and 98% patients achieved <400 c/mL HBV DNA at 48W, respectively. HBeAg(-) patients grouped by baseline HBV DNA ranges (from <10^6 to >10^9 c/mL at intervals of 10) showed median HBV DNA declined from baseline to 4W by similar levels upon TDF treatment (2.8 to 3.2 log10 c/mL). In HBeAg(+) patients, Asian (n=115) and non-Asians (n=113), showed median (Q1, Q3) baseline HBV DNA of 8.7 (8.0, 9.2) and 9.1 (8.6, 9.5) log10 c/mL, which decreased by 3.1 log10 (both) at 4W; 83% and 79% patients reached <400 c/mL HBV DNA at 48W, respectively. HBeAg(+) patients by the same grouping of baseline HBV DNA (ranges of 10) showed decline from baseline to 4W of 2.9 to 3.4 log10 c/mL in patients with baseline HBV DNA ranges from 10^7 to >10^9 c/mL, and 2.0 or 2.4 in those with <10^6 or 10^6-10^7 c/mL. Percentage of normal ALT at baseline was 17/9% vs. 6/4% (HBeAg-/+) for Asians vs. non-Asians, and increased to 78/71% vs. 81/74%, respectively, at 48W. Loss/seroconversion for HBeAg and HBsAg at 48W were lower for Asians vs. non-Asians; 15/14% vs. 26/24%, and 0/0% vs. 4.5/1.8%, respectively. No patient developed resistance to TDF. Mean creatinine clearances were stable and maintained within the normal range. No patient had a confirmed >=0.5 mg/dL increase in serum creatinine or decrease to <50 mL/min in creatinine clearance from baseline. Conclusion: TDF demonstrated similar ALT normalization, rapid virologic suppression, and good safety profile in Asian and non-Asian CHB patients. No resistance to TDF developed in 48W.
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fixed factor such as race and virus genotype, the drop in effectiveness is due to low antiviral treatment initiation and treatment completion.
Performance Feedback Impacts Quality Measures in the Management of Cirrhosis James T. Kwiatt, Parin N. Desai, Samer Gawrieh, Kia Saeian
564
Introduction: Quality improvement (QI) is an emerging area of importance in health care. The Medicare Physician Quality Reporting Initiative, AASLD, and AGA recommend tracking, reporting, and training in QI measures for gastroenterologists and hepatologists (1,2). Vaccination for viral hepatitis, management of esophageal varices (EV), and screening for hepatocellular carcinoma (HCC) are areas of potential QI that have been identified in the management of cirrhosis (3). Our group previously reported baseline deficiencies in vaccination for hepatitis A & B, EV screening, and HCC screening at DDW 2008. Performance feedback is one approach to possibly increase adherence to these measures. Aim: Assess if performance feedback improved adherence to guidelines and if so, see if adherence sustained over one year. Methods: Design- Retrospective and prospective chart review at a tertiary academic medical center. Participants- Health care providers in an outpatient hepatology clinic caring for 2311 cirrhotics. Data regarding appropriate HCC screening, EV screening/surveillance, and documented immunity to hepatitis A and hepatitis B was obtained utilizing chart review and a database. At the start of the study, providers were given retrospective data on previous 3 years of performance on addressing health maintenance. After having providers review past performance, prospective adherence to health maintenance measures was tracked and assessed at 60 days and 365 days in all patients seen in clinic by chart review. Results: Retrospective assessment revealed baseline deficiencies in recommended health maintenance (See Table). After giving performance feedback, medical records of all cirrhotics seen in clinic were assessed for recommended health maintenance compliance. 60 days after performance feedback, documentation of immunity to hepatitis A improved to 81%, immunity to hepatitis B to 91 %, screening for HCC 100%, and EV management to 98% (p<0.001 compared to retrospective data). Performance improvement was sustained after 1 year (p=NS comparing 60 day and 365 day data). At one year, documentation of immunity to hepatitis A was 85%, immunity to hepatitis B 85%, screening for HCC 100%, and EV management 97%. Discussion: Performance feedback to health care providers can improve adherence to health maintenance guidelines in managing cirrhotics. When providers are aware that performance is being tracked, improvement is sustained over 1 year. Systems to provide performance feedback can be an important part of QI initiatives. References 1. AGA Institute Press. PQRI Updates. GI Quality and Practice Management News 2008; 9:12 2. AASLD, ACG, AGA Institute, ASGE. The Gastroenterology Core Curriculum. May 2007 3. Kanwal,F. et.al. An Explicit Quality Indicator Set for Measurement of Quality of Care in Patients With Cirrhosis. Clin Gastro Hep.2010;8:709-717 Quality Improvement in Cirrhosis Health Mainanence
BACKGROUND & AIMS: Shorter courses of treatment with pegylated interferon and ribavirin for patients with hepatitis C who achieve rapid virologic response (RVR) have been shown to be effective in appropriately selected patients. However, truncated therapy may result in a higher rate of relapse than standard therapy and necessitate retreatment. The aim of this study was to evaluate the cost effectiveness of truncated therapy as compared to the standard of care. METHODS: We developed a decision model for chronic hepatitis C that combined a decision tree and Markov cohort model. In the decision tree, we modeled two treatment strategies; the first modeled the standard of care which included 48 weeks of therapy with pegylated interferon and ribavirin for individuals with genotypes 1 and 4 and 24 weeks of therapy for individuals with genotypes 2 and 3; the second strategy consisted of shortening therapy by 50% in individuals with RVR. Individuals who failed to achieve SVR with truncated therapy were retreated with the standard of care. Lifetime costs and qualityadjusted life-years (QALYs) were estimated using a Markov cohort model and compared between the two treatment strategies. We performed a probabilistic sensitivity analysis to assess parameter uncertainty and multiple univariate and bivariate sensitivity analyses to test model assumptions. All costs and benefits were discounted at a rate of 3% per year as recommended by the US Panel on Cost-Effectiveness in Health and Medicine. RESULTS: In the base case, the average lifetime cost was $43,950 (± 1,906) in the standard arm and $39,717 (±1,914) in the truncated therapy arm resulting in a savings of $4,233 (± 325) in favor of truncated therapy. Average lifetime QALYs were similar with 17.04 (± 0.69) in the standard arm as compared to 17.09 (± 0.69) in the truncated therapy arm; thus, truncated therapy dominated standard therapy. In a probabilistic sensitivity analysis using a Monte Carlo simulation of 10,000 trials, the probability of truncated therapy being dominant (i.e. cost-saving and QALY increasing) was 78%. When stratified by genotype, truncated therapy remained cost effective (i.e. dominant or cost per QALY < $5000) as compared to standard therapy. One-way sensitivity analyses revealed that the results were insensitive to variations in costs, utilities, transition probabilities and baseline characteristics of the study cohort, including age, genotype distribution and baseline fibrosis. CONCLUSIONS: Truncated therapy based on RVR is likely to be cost effective when compared to standard of care for individuals with chronic hepatitis C. These findings are applicable to populations of individuals with hepatitis C as well as those stratified by genotype. Decision analysis may be helpful in optimizing resource allocation in the era of personalized therapy for chronic hepatitis C. 565
Performance feedback resulted in sustained improvement in adherence to QI indicators.
Factors Associated With Immunoprophylaxis Failure in Infants Born to HBsAg Positive Mothers: A Retrospective Study Huaibin Zou, Yu Chen, Zhongping Duan, Hua Zhang, Calvin Pan
563
Background and Aim Despite the active-passive immunization, immunoprophylaxis failure occurs in infants born to mothers with hepatitis B virus (HBV). Prior studies showed HBeAg(+) and DNA > 1×108 c/ml are the major risk for immunoprophlaxi failure, but the lower DNA level or other risk factors have not been fully explored, we evaluate the risk factors associated with the immunoprophylaxis failure. Methods Infants born to HBsAg+ mothers with >7 month follow up in 1/2007-3/2010 at our center were eligible. Infants from mothers with co-infection, antiviral use, missed immunoprophylasix were excluded. Maternal and infants clinical and laboratory data was collected by chart review. HBV serology of all infant was assessed by microparticle enzyme immunoassy technique (Abbott kits,USA),HBV DNA at birth was measure by RT-PCR. HBV immunoprophylaxis failure was defined as infant with HBsAg(+) and anti-HBs (-) at 7-12 months of age. Results Among 3536 infants born to 3521 HBsAg+ mother, 1045 infants were eligible. 8 infants were excluded (1 co-infection, 4 anti-HBV drug use, 3 missed vaccines). 1037 infants from 1031 mothers were analyzed. All infants received HBIG 200 IU and HBV vaccine 10 mcg within 6 hours of birth, and a second injection of HBIG at week 2, the vaccine were given again at 1 and 6 months. Among 1031 mothers, HBeAg(+) in 573(55.6%), detectable HBV DNA in 689 (66.8%), maternal DNA levels at 3.0-5.9 logs, 6-7.9 logs and >or = 8 logs were 151, 457 and 81 respectively; The correspondent infant prophylaxis failure rates were 0%, 5.3% and 7.4%, respectively. The trend test chi-square = 15.785 (P<0.001). Among 1037 infants, 30 failed immunoprophylaxis were selected as cases and the rest as controls. The rate of immunoprophylaxis failure was 2.9% vs 5.8% in the infants born to HBeAg-negative vs HBeAg positive mothers, respectively. Clinical presentation and possible related factors of cases and controls were listed on Table 1. The factors with statistically significant differences between two groups on univariate analysis were: maternal HBeAg+, maternal HBV DNA > 6×log10 c/ml, HBV DNA detectable in core blood. Conclusions Our study showed infants' HBV immunoprophylaxis failure was associated with maternal DNA level > 6 log10 c/ml, HBeAg+, and HBV DNA detectable in core blood. Further prospective studies needed to verify the finding and provide more aggressive intervention in patients with the above risk factors. Characteristics of the patients
Effectiveness of Hepatitis C Virus (HCV) Antiviral Treatment in Veterans With HIV-HCV Coinfection Jennifer R. Kramer, Fasiha Kanwal, Minghua Mei, Thomas P. Giordano, Hashem El-Serag Background: Efficacy of antiviral treatment for hepatitis C virus (HCV) in patients with HCV and HIV coinfection in achieving sustained viral response (SVR) rates has been shown to be between 28% and 44% in randomized controlled trials. However, effectiveness in a community-based practice setting can be much lower and is influenced by other factors related to access, adherence, and representation of low response groups (e.g. blacks, HCV genotype, and drug and alcohol use). We determined the effectiveness of HCV treatment in veterans with HCV-HIV coinfection in the United States. Methods: We conducted a retrospective cohort study of veterans with HCV viremia and HIV (positive antibody or viral load test) from the nationwide Veterans Affairs HCV Clinical Case Registry during 2000 to 2006. We identified patients who had at least one prescription for pegylated-interferon and ribavirin and calculated the duration of treatment and the proportions of patients completing treatment (at least 44 for genotypes 1 or 4 or 22 weeks for 2 or 3). The effectiveness of treatment was measured as the proportions of patients who achieved an SVR (negative test for HCV RNA at least 12 weeks after the end of treatment) in the overall coinfected cohort and among both patients who initiated and completed treatment. We also stratified by genotype and race/ethnicity. Results: We identified 6,137 patients coinfected with HCV and HIV. Of those, 896 (14.6%) had at least one released prescription for any antiviral treatment and 638 (10.4%) received pegylated-interferon with ribavirin. Of the 638 patients on combination therapy, 72.3% had genotype 1, 22.1% had genotype 2 or 3, and 5.6% were not tested for genotype. One-third completed at least 44 weeks of treatment for genotype 1 while almost three-fourths completed at least 22 weeks of treatment for genotype 2 or 3. Absolute or relative contraindications were documented in only 61.5% of patients who did not receive treatment. SVR was documented in 33.6% and 65.7% of those who completed treatment, 18.7% and 56.0% of those who initiated treatment, and 2.6% and 15.6% of the entire coinfected cohort for genotype 1 and 2 or 3, respectively. Black and Hispanic patients were significantly less likely to achieve an SVR compared to whites for both genotypes (1: 10.2% and 5.9% vs. 24.7%; 2 or 3: 46.7% and 45.5% vs. 58.3%). Overall, only 2.8% of the entire coinfected cohort had documented SVR. Conclusions: Treatment effectiveness for HCV in HIV coinfected veterans is low. Compared to previously published VA data in an HCV cohort (with and without HIV), treatment effectiveness is lower for coinfected veterans for HCV genotype 1, but higher for coinfected veterans with genotype 2 or 3. Other than
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AASLD Abstracts
AASLD Abstracts
Truncated Therapy Based on Rapid Virologic Response is a Cost Effective Treatment Paradigm for Chronic Hepatitis C Ziad F. Gellad, Shelby Reed, Andrew J. Muir, John McHutchison, William Sievert, Ala I. Sharara, Kimberly Ann A. Brown, Robert Flisiak, Ira M. Jacobson, David Kershenobich, Michael P. Manns, Kevin A. Schulman
567 Proportion of Patients Who Were Previously Ineligible for Anti-HBV Therapy Who Became Eligible After 12 Months of Follow-up: Application of U.S. Panel and AASLD Guidelines Jessica T. Ristau, Shu Zhang, Huy N. Trinh, Ruel T. Garcia, Huy A. Nguyen, Khanh K. Nguyen, Mindie H. Nguyen
AASLD Abstracts
PURPOSE: Given the dynamic nature of chronic hepatitis B (CHB) and the fluctuation of certain clinical parameters used to determine patient treatment eligibility by treatment guidelines (U.S. Panel 2008 and AASLD 2009), many patients who were initially ineligible may become treatment eligible during follow up. Our goal was to study such patient populations and examine the reasons and timeline for future treatment eligibility. METHODS: We performed a retrospective cohort study with 190 consecutive treatment-naïve CHB patients who were treatment ineligible when they first presented between 3/07-1/09 and had ≥ 12 months of follow up with laboratory testing every 6-12 months at 2 U.S. community GI clinics. US Panel 2008 eligibility requirements are as follows; ALT >30 IU/mL for males, >19 IU/mL for females and HBV DNA >2,000 IU/mL for HBeAg negative patients and >20,000 IU/mL for HBeAg positive patients. AASLD 2009 eligibility included ALT >60 IU/ mL for males, >38 IU/mL for females and HBV DNA >20,000 IU/mL regardless of HBeAg status. RESULTS: The majority of patients were over 35 years old (74%) and Asian (97%). The proportion of patients who became eligible was described in the table. Of those who became eligible according to US Panel 2008 guidelines, 33% became eligible by 12 months, 47% by 24 months and the remaining 20% by 36 months. Accounting for variance in total follow-up time, the proportions of patients becoming eligible were as follows; 9% with 12 months of follow up, 5% of patients with 18 months of follow up and 12% of patients with 24 months of follow up. Corresponding data for AASLD 2009 guidelines were: 2%, 2% and 3% at 12, 18 and 24 months of follow-up, respectively. On multivariate analysis also inclusive of age, gender, and HBeAg status, significant predictors of later eligibility by AASLD guidelines at follow-up were higher ALT at baseline (0.5-1.0 xULN) (OR=5.01, p=0.031) and serum HBV DNA at baseline (>20,000 IU) (OR=4.6, p=0.05). No significant predictors were found for later eligibility by US Panel guidelines. CONCLUSION: While the majority of patients who were initially ineligible for anti-HBV therapy continued to require no therapy, approximately one-fifth may meet treatment criteria on even short to medium term follow-up (median 23 months). This data suggests that all CHB patients should continue to have regular followup with periodic review of their disease status and potential need for antiviral therapy.
* lowest detectable limit. 566 Liver Biochemical Course, Serum HBV DNA and Liver Stiffness Measurement for Therapeutic Decisions in HBeAg-Negative Chronic Hepatitis B Infection Phunchai Charatcharoenwitthaya, Pochamana Phisalprapa, Pimpattana Rungkaew, Sorrayut Kajornvuthidej, Wimolrak Bandidniyamanon, Siwaporn P. Chainuvati, Nonthalee Pausawasdi, Supot Nimanong, Watcharasak Chotiyaputta, Somchai Leelakusolvong, Kanit Atisook, Tawesak Tanwandee
568 Tenofovir Disoproxil Fumarate (TDF) Shows Similar Virologic Suppression and Safety Between Asians and Non-Asians With Chronic Hepatitis B (CHB) Calvin Pan, Sing Chan, Huy N. Trinh, Alan Yao, Ho Bae, Patrick Marcellin, E. Jenny Heathcote, Betty Chiang, Lillian Lou
Background & Aims: Assessment of liver histology in patients with HBeAg-negative chronic hepatitis B virus (HBV) infection allows clinicians to determine the extent of hepatic inflammation and fibrosis and consequently to assess suitability for treatment. It is, however, poorly accepted by patients due to procedure-related complications. Thus, we evaluated the ability of various noninvasive methods in determining the presence of histological indication for treatment (at least grade A2 or stage F2 by METAVIR scoring) in this population. Methods: Consecutive HBeAg-negative patients with serum HBV DNA levels >2,000 IU/ml and serial measurement of alanine aminotransferase (ALT) were enrolled to perform liver stiffness measurement using Fibroscan followed by liver biopsy on the same day. Individual liver specimens were evaluated independently by 2 pathologists without knowledge of the clinical data. Differences in interpretation were settled by consensus of the pathologists. Results: A total of 399 patients had a mean age of 47.5±9.6 years and 42% were female. Mean body mass index at baseline was 23.9±3.8 kg/m2. Using the normal range of serum ALT <40 IU/ L, 142 patients (36%) had persistently normal ALT levels (PNALT) whereas 257 patients had persistently or intermittent elevated ALT (PIEALT) in previous 1 year prior to liver biopsy. The proportion of PIEALT patients with moderate to severe necroinflammation (48% vs. 13%, p<.0001) and significant fibrosis (43% vs. 13%, p<.0001) was higher than those of PNALT patients. Histological indication for treatment was present in 57% of PIEALT patients and 22% of PNALT patients (p<.0001). In PNALT patients defined by criteria of normal ALT; 30 IU/L for men and 19 IU/L for women on the day of liver biopsy, HBV carriers with ALT levels less than updated cut-off values had no difference in the frequency of histological indication for treatment compared to those with ALT levels higher than updated cut-off values (18% vs. 28%, p=.2). Among patients with HBV DNA of 2,00019,999, 20,000-199,999, and ≥200,000 IU/mL, histological indication for treatment was present in 40%, 45%, and 71% of PIEALT patients and 15%, 31%, and 36% of PNALT patients, respectively. In PNALT patients with HBV DNA <20,000 IU/L, the use of liver stiffness value <7 pKa in determining nonsignificant histology can avoid liver biopsy in 89% of patients and miss only 13% of patients who indeed had histological indication for treatment. In PIEALT patients with HBV DNA >200,000 IU/L, the measurement of liver stiffness ≥7 pKa can predict histological indication for treatment reducing the need for liver biopsy in 56% of patients with a false-positive of 17%. Conclusions: The combination of serial measurement of liver enzymes, serum HBV DNA, and liver stiffness is a noninvasive approach that may be useful for therapeutic decision in HBeAg-negative patients.
AASLD Abstracts
Background: TDF has demonstrated potent antiviral activity upon initiation of treatment in CHB patients. Two TDF registration trials in CHB (127 Asian and 299 non-Asian patients) and an open-label trial (90 Asians) were analyzed in a cross sectional study to compare efficacy and safety of TDF in Asians versus non-Asians during the first 48 weeks (W) of treatment. Methods: Eligibility criteria were similar between registration vs. open-label trials except for HBV DNA >=10^5 vs. >=10^4 copies(c)/mL and ALT >2x vs. >1x ULN [HBeAg(+) patients], respectively. All three trials were analyzed independently and compared side-byside. Subsequently, 217 Asians were combined, and compared with 299 non-Asians stratified for HBeAg status. Results: 288 HBeAg(-) and 228 HBeAg(+) CHB patients were available for the analysis. Baseline characteristics were similar between Asians vs. non-Asians except for mean weight, height and BMI (65.6 vs. 79.3 kg, 165 vs. 173 cm^2, and 24.1 vs. 26.4 kg/m^2, respectively). HBeAg(-) Asians (n=102) and non-Asians (n=186) patients had median (quartiles Q1, Q3) baseline HBV DNA of 6.4 (5.5, 7.7) and 7.0 (5.9, 7.8) log10 c/mL, which decreased by 3.1 log10 (both) at 4W; 96% and 98% patients achieved <400 c/mL HBV DNA at 48W, respectively. HBeAg(-) patients grouped by baseline HBV DNA ranges (from <10^6 to >10^9 c/mL at intervals of 10) showed median HBV DNA declined from baseline to 4W by similar levels upon TDF treatment (2.8 to 3.2 log10 c/mL). In HBeAg(+) patients, Asian (n=115) and non-Asians (n=113), showed median (Q1, Q3) baseline HBV DNA of 8.7 (8.0, 9.2) and 9.1 (8.6, 9.5) log10 c/mL, which decreased by 3.1 log10 (both) at 4W; 83% and 79% patients reached <400 c/mL HBV DNA at 48W, respectively. HBeAg(+) patients by the same grouping of baseline HBV DNA (ranges of 10) showed decline from baseline to 4W of 2.9 to 3.4 log10 c/mL in patients with baseline HBV DNA ranges from 10^7 to >10^9 c/mL, and 2.0 or 2.4 in those with <10^6 or 10^6-10^7 c/mL. Percentage of normal ALT at baseline was 17/9% vs. 6/4% (HBeAg-/+) for Asians vs. non-Asians, and increased to 78/71% vs. 81/74%, respectively, at 48W. Loss/seroconversion for HBeAg and HBsAg at 48W were lower for Asians vs. non-Asians; 15/14% vs. 26/24%, and 0/0% vs. 4.5/1.8%, respectively. No patient developed resistance to TDF. Mean creatinine clearances were stable and maintained within the normal range. No patient had a confirmed >=0.5 mg/dL increase in serum creatinine or decrease to <50 mL/min in creatinine clearance from baseline. Conclusion: TDF demonstrated similar ALT normalization, rapid virologic suppression, and good safety profile in Asian and non-Asian CHB patients. No resistance to TDF developed in 48W.
S-896