Mo1029 Characteristics and Treatment Patterns of Chronic Hepatitis B at a Tertiary Care Academic Medical Center

by liquid chromatography-tandem mass spectrometry. Liver biopsy specimens were read by a pathologist blinded to clinical data. Results: 254 patients (52% male) with a mean age of 46±11 years were recruited. Metabolic features included central obesity (45%), elevated fasting glucose/diabetes (24%), hypertension (20%), hypertriglyceridemia (30%) and low HDL-cholesterol (31%). HBeAg-negative patients constituted 72% of the cohort with a median viral load of 5.4 log10IU/mL (range 3.3-8.5). The most common genotype was C (67%), followed by B (30%) and other genotypes coinfected with B or C (3%). According to the METAVIR score, necroinflammation was moderate to severe in 49 patients (19.3%). Significant fibrosis (F≥2) was noted in 119 patients (46.9%) with 33 patients having advanced fibrosis (F≥3). Mean 25OHD value was 25.6±8.1 ng/ml. The proportion of patients with different concentration of 25OHD (≥30, 20-30 and <20 ng/ml) were 25%, 50% and 25%, respectively. Serum 25OHD level had a positive correlation with age (r=.20, p=.001), male (r=.26, p<.001), waist-to-hip ratio (r=.27, p<.001) and number of metabolic features (r= .28, p<.001). No association was found between 25OHD level and serum viral load (p= .12), HBeAg status (p=.19), genotype (p=.48) and season (p=.33). In multivariate analysis, age <40 years (OR=3.74; 95% CI 1.49-9.38), female (OR=2.41; 95% CI 1.28-4.56) and absence of central obesity (OR=1.94; 95% CI 1.04-3.62) were independent predictors of vitamin D insufficiency (<30 ng/ml). Mean 25OHD values did not significantly differ between patients with steatosis (25.7±8.6 vs 25.6±7.8 ng/ml, p=.93), at least moderate necroinflammation (26.7±10.4 vs 25.4±7.4 ng/ml, p=.41), significant fibrosis (25.9±8.9 vs 25.4±7.3 ng/ ml, p=.67) and advanced fibrosis (25.8±8.3 vs 25.6±8.1 ng/ml, p=91) compared to those without these features. Moreover, vitamin D deficiency (<20 ng/ml) was not associated with histological features of moderate/severe necroinflammation and/or significant fibrosis (OR= 0.99; 95% CI 0.56-1.77). Conclusion: Vitamin D insufficiency is common in Thai CHB patients despite living in the area of abundant sunlight. However, low vitamin D level is not related to viral characteristics and the severity of liver damage in these patients.

HBV increased over the time from 31.95±0.84% in 1999-2004 to 40.66±0.96% in 20052008 to 46.62±1.29% in 2009-2012 (p<0.0001), synchronously with an increase in selfreported vaccination: from 24.44±0.77% to 33.91±0.83% to 39.21±1.06% (p<0.0001). The same increases in HBV QM were noted in CLD patients: 34.42±1.53% to 40.12±1.70% to 47.33±2.15% in QM in the three study cycles, respectively, and 22.76±1.31% to 31.53±1.60% to 39.25±2.15% in vaccination (all p<0.0001). However, a lower rate was noted in patients with diabetes: 25.51±1.80% in 1999-2004 to 28.80±2.08% in 2005-2008 to 33.15±2.72% in 2009-2012 (p=0.06) in QM, and 15.59±1.56% to 22.21±1.77% to 26.07±2.37% (p=0.0004), respectively, in vaccination. CONCLUSIONS: Despite uniform recommendations in the U.S., HBV vaccination rates and QM for HBV in patients with CLD and DM remain low. Better strategies to implement HBV vaccination for these high risk individuals should be undertaken. Mo1028

Background: Approximately 370 million people worldwide are infected with hepatitis B virus (HBV), a major cause of end-stage liver disease and hepatocellular carcinoma (HCC). HCC surveillance is associated with improved survival of CHB patients. Although HCC risk is higher in males than females, it is not known if there are gender differences in HCC surveillance adherence. Our goal is to examine HCC surveillance adherence in males versus females and to determine surveillance adherence predictors. Methods: We performed a retrospective cohort study of 1098 consecutive CHB patients without prior history of HCC and at least 12 months follow-up at a university medical center and 3 community gastroenterology and primary care sites in the U.S from 10/98-10/13. Patients were identified using ICD9 diagnosis codes. Adherence to HCC screening by AASLD 2010 guidelines was categorized by imaging: optimal (every 6 months), suboptimal (6-12 months), poor (> 12 months) and none. Results: The overall cohort was 51% male, 96% foreign-born, 97% medically insured, 92% Asian, and 61% from community practices. Males were slightly older (51.7 vs. 50.7, p=0.17), had longer mean follow-up time (62.5 vs. 58.9, p =0.11) but these differences were not statistically significant; however, and males were significantly more likely to receive anti-HBV treatment for CHB (57.5% vs. 45.0%, p<0.001). Males had more severe progression of CHB such as cirrhosis diagnosis (13% vs. 6.4%, p<0.0001) and HCC incidence (4.2% vs. 0.7%, p<0.001) during follow-up compared to females. Males were also more likely to have two or more clinic visits per year (20% vs. 14%, p=0.047) compared to females. According to AASLD HCC screening guidelines, males were more likely to undergo optimal or suboptimal screening (60% vs. 53%, p=0.046) compared to females. On multivariate logistic regression also inclusive of age, sex, cirrhosis status, independent predictors for optimal screening adherence were anti-HBV therapy (OR=2.3, p<0.0001) and more frequent clinical visits per year (OR=13.4, p<0.0001). Conclusions: In this large multicenter cohort study consisting of consecutive CHB patients followed at either academic or community practices, males were significantly more likely to have more severe progression of CHB, to receive antiviral treatment for CHB, to have more frequent clinic visits for CHB, and to have better HCC screening adherence relative to females. More frequent clinical visits may improve HCC screening adherence in both male and female patients with CHB, which ultimately can improve survival for HCC in patients of both genders. Further studies are needed to examine potential causes for the observed gender disparities in order to improve antiviral treatment access and HCC screening adherence.

Mo1026 Risk Factors for Liver Cirrhosis Among Chronic Hepatitis B Patients in a Regional Unites States Population Rasham Mittal, Bechien U. Wu Background Approximately 350 million people worldwide suffer from chronic hepatitis B (CHB), a vaccine preventable liver disease. In the United States, an estimated 1.4 million individuals have CHB leading to nearly 4000 deaths annually. The natural history of CHB infection is complicated and largely unknown for individuals living in the United States. Study Aim: 1. To determine risk factors for liver cirrhosis among patients with CHB in a diverse regional United States population. Methods Retrospective cohort study (2006-2013) on data from an integrated health care system in Southern California. All CHB (age≥ 18 years) patients identified using ICD codes. CHB status was further confirmed through reactive hepatitis B surface antigen (HBsAg) neutralization confirmatory antibody assay. Liver cirrhosis diagnosis established using ICD codes for cirrhosis, portal hypertension, esophageal varices or ascites. Patients were censored based upon loss of membership, date of last clinic visit, or death. Cox proportional hazard analysis was performed to assess risk factors for cirrhosis including age, gender, race (Asian versus non-Asian), reactive hepatitis Be antigen (HBeAg) at the time of HCC diagnosis, obesity (≥ 30 BMI), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection. Results The study cohort included 9811 confirmed CHB patients [median age at CHB diagnosis was 46 years, IQR 36,55 years; 5351 (54.5%) male; 8372 (85.3%) Asians and 1386 (14.1%) with BMI≥30]. Among 9811, 1644 (16.7%) developed liver cirrhosis; 443 (4.52%) and 433 (4.4%) were co-infected with HCV and HIV respectively. In regression analysis, age (HR 1.01; 95% CI, 1.010-1.018; P<0.0001) reactive HBeAg (HR 1.26; 95% CI, 1.04-1.51; P=0.014) and obesity (HR 2.06; 95% CI, 1.84-2.31; P<0.0001) were independently associated with increased risk of cirrhosis. Asian race, HCV co-infection and HIV co-infection were not independently associated with increased risk of liver cirrhosis. Female gender was associated with decreased risk (HR 0.63; 95% CI, 0.57-0.70; P<0.0001) of liver cirrhosis. Conclusion We have confirmed that established risk factors found in Asian population such as age, male gender and reactive HBeAg status were associated with development of liver cirrhosis in a large cohort of CHB patients in the United States. Obesity (BMI≥30) was an additional predictor for progression to liver cirrhosis in our CHB cohort. Mo1027 Low Rates of Vaccination Against Hepatitis B in Patients With Chronic Liver Disease and Type 2 Diabetes Zobair M. Younossi, Maria Stepanova, Stephen Clement, Sean Felix, Irfan Ali, Shirley Kalwaney, Aybike Birerdinc, Tasneem Shaikh, Keanu Lee, Manirath K. Srishord BACKGROUND: Given the severity of acute hepatitis B infection in patients with chronic liver diseases (CLD) and patients with type 2 diabetes (DM), which is likely related to underlying non-alcoholic steatohepatitis, these patients are recommended to receive vaccination against hepatitis B viruses (HBV). Despite these recommendations in the United States, Quality Measure rates for HBV (as defined by Medicare, at least one dose of vaccine or documented immunity) in these patients have been low (30-40%) (Younossi et al., Hepatology, 2011). AIM: To assess the recent changes in HBV vaccination rates in patients with CLD and DM in the U.S. using the most recent population data. METHODS: We used the National Health and Nutrition Examination Surveys (NHANES) conducted between 2009 and 2012, and compared those to previous cycles (1999-2004 and 2005-2008). In the entire U.S. population, as well as in those with CLD (HBsAg or HCV RNA positivity or elevated liver enzymes with or without excessive alcohol use) and DM (fasting blood glucose above 125 mg/dL or the use of hypoglycemics), we determined the rates of 1) self-reported history of HBV vaccination; 2) sero-prevalence of HBsAb; 3) effective vaccination against HBV (vaccination+HBsAb); 4) Quality Measure (QM) (vaccination or HBsAb). RESULTS: There were 10,897 participants from 2009-2012 NHANES cycle compared to 14,535 from 19992004, and 10,152 from 2005-2008. Of the study population, 13.52±0.38%, 13.92±0.58%, and 13.35±0.44% had CLD in the three cycles, respectively, and 7.79±0.33%, 9.34±0.46% and 10.11±0.50%, respectively, had DM. In general U.S. population, the rates of QM for

Clinical Characteristics and Screening Adherence Patterns of Cohort by Gender Mo1029 Characteristics and Treatment Patterns of Chronic Hepatitis B at a Tertiary Care Academic Medical Center Krysta M. Contino, Yize R. Wang Background: Chronic hepatitis B disproportionably affects immigrants from East Asia and Sub-Saharan Africa in the United States. The AASLD guideline recommends surveillance for hepatocellular carcinoma (HCC) in selected high-risk patients including Asian males >=40, Asian females >=50, African Americans, and those with cirrhosis. Aims: To study characteristics and treatment patterns of chronic hepatitis B at a tertiary care academic medical center. Data and Methods: Chart review was performed on a random sample of 111 patients

S-1067

AASLD Abstracts

AASLD Abstracts

Gender Differences in HCC Screening Adherence Patterns in Patients With Chronic Hepatitis B (CHB) in a Multicenter Academic and Community Cohort Study Linda Nguyen, Christina Wang, Joseph Hoang, Huy N. Trinh, Jiayi Li, Jian Q. Zhang, Mindie H. Nguyen

diagnosed with chronic hepatitis B (ICD-9-CM codes 070.2 and 070.3) at our institution during 2011-2014. In addition to patient demographics, characteristics of chronic hepatitis B and treatment patterns were examined. The chi-square test and multivariate logistic model were used in statistical analysis. Results: Our study sample of 111 chronic hepatitis B patients included 66 Asians, 18 African Americans, and 27 other races, with mean age of 46.7 (standard deviation 12.6), 61.3% female, 2.7% with family history of HCC, and 3.6% cirrhotic. Eighteen patients (16.2%) reported at least occasional alcohol use and 49 patients (44.1%) were treated with an anti-HBV medication, mainly tenofovir (n=36) followed by entecavir (n=9). Fifty two patients (46.8%) were deemed at high risk for HCC per the AASLD guideline, of which 51 patients (98.1%) underwent or were recommended to undergo an imaging study (ultrasound, CT or MRI) at their most recent visit. Use of anti-HBV medication was positively associated with age and cirrhosis (both p<0.05) but not family history of HCC, AASLD high-risk status, or other variables. In multivariate logistic regression, age was the only significant predicator of anti-HBV medication use (odds ratio 1.03, 95% confidence interval 1.002 - 1.07). Conclusions: The majority of chronic hepatitis B patients deemed at high risk for HCC underwent or were recommended to undergo imaging study. Interestingly, such high-risk status for HCC was not associated with a higher likelihood of anti-HBV treatment. Whether recent introduction of generic entecavir will lead to more antiHBV treatment is an important question for future research.

November 2014, 40 patients [males: 80%, median age: 60 (22-86) ys, duration of NA(s): 7.9 (4-14) years] were included. Virological relapse (HBV-DNA >2000IU/mL) developed in 37 (92%) patients, biochemical relapse (ALT >ULN) in 25 (62.5%) patients and both in 23 (57.5%) during a median follow-up of 22 (12-39) months (>24 months 11 patients). Nine (22.5%) patients experienced hepatitis flare (ALT >10x ULN) at a median of 3 (1-9) months after NA(s) discontinuation, without evidence of liver decompensation. Retreatment was required in 16 (40%) patients at a median of 4.5 (1-28) months. Of the 24 patients who remained untreated, 14 (58%) had persistently ALT20,000 IU/mL respectively during the follow-up period. At the last visit, 8 of the untreated patients (33%) had HBV-DNA <2,000 IU/mL [4 (16%) undetectable]. The mean levels of HBsAg at the end of NAs treatment did not differ between re-treated patients and those remained untreated (2.7±0.8 vs 2.7±0.7 log10 IU/ml respectively, p=0.60). Of the patients who remained untreated, 17 (71%) had decline in HBsAg levels (mean 0.58±1 log10 IU/mL) during the follow up period and another 2 (8%) reached levels of HBsAg <0.5 IU/mL (at 9th and 30th month). None of the patient characteristics could predict sustained off-NA response. Conclusion This prospective study suggests that the discontinuation of effective long-term NA(s) therapy in non-cirrhotic CHBe- patients is feasible and can result in off-treatment remission in a substantial proportion of patients. Future basic research studies is required to define predictors of sustained off-NAs responses.

Mo1030

AASLD Abstracts

Mo1032 Efficacy of Antiviral Therapy in Reactivation Prophylaxis in Patients With Hepatitis B (HBV) Infection Treated With Different Immunosuppressive Agents Melanie Deutsch, Spilios Manolakopoulos, Nikolaos Papadopoulos, Eftychia Tsironi, Antonia Solomou, Maria Skondra, Stavroula Giannouli, Maria Theochari, George V. Papatheodoridis, Dimitrios G. Pectasides, John Koskinas

Association Between Non-Homologous End Joining Genetic Variation and the Risk of Hepatocellular Carcinoma Li Liu Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Chronic infection with hepatitis B (HBV) is the main risk factor for HCC. Integration of the HBV genome, the process of non-homologous end joining (NHEJ) repair in both host genome and circular HBV-DNA, is usually considered as an irreversible in the progression to HCC. Host genetic variations that influence the NHEJ repair pathway may determine the outcome of HBV infection. To investigate the association between the potentially functional polymorphisms in DNA repair-related genes involved in the NHEJ pathway, HBV infection and risk of hepatocellular carcinoma in a Chinese population, we genotyped 22 polymorphisms in a case-control study of 1200 HBV-positive HCC cancer cases and 1200 HBV persistent carriers controls. We observed that XRCC6 rs2267437 GC/GG variant genotypes were associated with a significant decreased risk of HCC (adjusted OR=0.78, 95% CI= 0.65-0.94) compared with wild-type CC and XRCC5 rs1051677 CT/CC and rs6941 AC/AA variant genotypes decreased the risk of HCC (adjusted OR= 0.82, 95% CI = 0.68-0.98 for rs1051677; adjusted OR= 0.82, 95% CI = 0.68-0.98 for rs6941). However, DCLRE1C rs3814175 GA/ GG variant genotypes were associated with an increased risk of HCC (adjusted OR=1.29, 95% CI= 1.09-1.52). The results suggested that these four SNPs might contribute to the risk of HBV-related HCC.

Background/aim: International guidelines regarding reactivation prophylaxis in patients with HBV infection who receive immunosuppression vary among different specialities. The aim of the present study was to investigate the efficacy of prophylactic antiviral treatment with lamivudine (LAM), entecavir (ENT) or tenofovir (TDF) in patients receiving different immunosuppressive agents. Methods: 110 anti HBc(+), HBsAg(+/-) patients (males/females 60/50 mean age 63,19 ±13) who received immunosuppressive treatment [including monoclonal antiCD20 (rituximab, ofatumumab) or antiCD52 (alemtuzumab)] and had at least 6 months follow up (mean14,85/ range 6-156 months) were retrospectively ( from 2009 until 2012) and prospectively (>2012) included in the analysis. HBV reactivation was defined as >1 log increase in HBV DNA, or HBV DNA >2000 if no baseline value was available, or HBsAg+ when previously negative.( with or without clinical overt acute hepatitis) Results: 27/110 patients who did not receive prophylactic antiviral therapy presented with HBV reactivation. Rescue therapy (3 LAM, 12 ENT, 12 TDF) was successful in all except of two patients who died due to liver failure. 10 out of the 27 patients (37%) were initially HBsAg (-) and presented reverse seroconversion [6/10 with HBeAg(+)].The other 83 patients received antiviral prophylaxis (26 LAM, 23 ENT, 34 TDF) Their characteristics according to the type of immunosuppression are shown in the table. The 7 patients who presented virological breakthrough during LAM prophylaxis switched to ENT or TDF. One patient with lymphoma, baseline anti-HBc (+) and undetectable HBV DNA presented liver failure and died despite ENT rescue. Conclusion: TDF and ENT are effective in prophylaxis and rescue treatment of HBV reactivation in patients receiving immunosupressive therapy. LAM should not be the first choice especially in patients receiving monoclonal antibodies or corticosteroids even if they have initially negative HBsAg.

Mo1033 Adherence to nucleos(t)ide Analogue Therapy in Patients With Chronic Hepatitis B Spilios Manolakopoulos, John Goulis, Athanasia Striki, Melanie Deutsch, Nikoleta Perlepe, Christos Triantos, George V. Papatheodoridis Background: Treatment with any nucleos(t)ide analogue (NA) is given for long, perhaps for life, in chronic hepatitis B (CHB) often raising concerns about patients' long-term adherence and compliance. Aim: We determined the rates of and factors associated with adherence to NA therapy among CHB patients treated with entecavir or tenofovir. Methods: Until November 2014, 134 CHB patients followed at the outpatient clinics of 5 physicians from 4 Academic centers (Athens: 2, Thessaloniki: 1, Patras: 1) have been included. All prescriptions of these 134 patients between January 2011 and November 2014 were collected from the universal national electronic programme for prescribing medication. Adherence to NA therapy was defined as the percent of days in which a patient had medication in his/her possession during the period in which the medication was prescribed. Results: Of the 134 patients, 107 (80%) were on NA therapy before 2011 and the others initiated NA therapy after 2011. There were 88 (66%) males. Their mean age was 56±13 years, while 69% were older than 50 years. The mean adherence rate of all patients in the combined 2011-2014 cohort was 87% (SD:13%) and the median adherence rate was 90% (IQR:80-97%). The adherence rate was 100% in 62 (46%), 90-99% in 35 (26%), 80-89% in 20 (15%) and <80% in 17 (13%) patients. Two of the patients with adherence <80% had a great gap (almost 10 months each) between 2 consecutive prescriptions. Logistic regression analysis revealed that adherence <90% was associated significantly with presence of depression (use of anti-depressive drugs) (OR: 6.04, 95% CI: 1.76-20.68, p=0.004) and relatively with the period of onset of NA with patients starting NA before 2011 compared to those starting NA after 2011 having >2-fold higher probability not to be adherent (OR: 2.315, 95% CI: 0.905-5.922, p=0.080). Conclusions: The majority of CHB patients in Greece have high adherence to entecavir or tenofovir therapy, but the adherence rate drops below 80% in almost 15% and below 90% in almost 30% of cases. Depression and perhaps the period of treatment onset seem to affect the adherence to NAs therapy.

Mo1031 Discontinuation of Long-Term nucleos(t)ide Analogue(S) [Na(S)] Therapy in HBeAg-Negative Chronic Hepatitis B (CHBE-) Patients Without Cirrhosis: A Prospective Study Spilios Manolakopoulos, Anastasia Kourikou, Hariklia Kranidioti, Emilia Hadziyannis, Melanie Deutsch, Georgios A. Kontos, Alexandra Alexopoulou, Emanuel K. Manesis, George V. Papatheodoridis

Mo1034

Background/Aim The optimal duration of NA(s) therapy in CHBe- is currently unknown. This prospective study aims to investigate the outcome of CHBe- patients after NA(s) cessation. Methods Non-cirrhotic CHBe- patients with virological remission (undetectable HBV-DNA) under NA(s) for ≥4 years who could remain under close follow-up (every month for the first 3 months and every 3 months thereafter) were invited to consent to treatment discontinuation. Criteria for NA(s) retreatment were: ALT>2xULN & bilirubin>2mg/dl, ALT>10xULN, ALT>5xULN in 2 monthly determinations, ALT>3xULN and HBVDNA>100,000IU/mL, ALT>ULN & HBV-DNA>2,000IU/mL for ≥6 months. Results Until

AASLD Abstracts

Effect of Rural Residence on Surveillance for Hepatocellular Carcinoma in VA Primary Care Patients With Cirrhosis Yolanda Rodriguez Villalvazo, Jennifer McDanel, Antonio J. Sanchez, Mary VaughnSarrazin, Hafizur Rahman, Katz A. David BACKGROUND: Hepatocellular Carcinoma (HCC), a known complication of cirrhosis of the liver and non-cirrhotic Hepatitis B, is the 3rd leading cause of cancer-related mortality worldwide. Despite published guidelines, HCC surveillance is highly variable in patients

S-1068