Sa1302 Prospective Study of Withdrawal of Oral Antiviral Therapy in Chronic Hepatitis B Patients After Prolonged Virological Response

discuss anti-viral treatment with all of their patients with chronic HCV. In those providers who do not discuss treatment, the top reasons included: patients were not treatment candidates (8/ 14), patients did not want to discuss treatment (5/14), PCPs preferred that a gastroenterologist discuss treatment (4/14), and lack of time during office visits to discuss treatment (3/14). 42% of providers felt that at least 50% of patients were interested in treatment. For those not interested in treatment, 88% of providers (23/26) stated that patients had the perception that treatment side effects are intolerable and 46% reported that patients were told that comorbidities precluded treatment. Conclusion: Despite overall substantial PCP-initiated HCV screening and education and presumed patient knowledge of HCV infection and interest in treatment, few veterans have undergone HCV treatment. This study suggests that the reasons for this may be not only that patients have significant co-morbidities which prevent treatment but also that they perceive treatment side effects as intolerable. PCPs' attitudes and practices do not appear to be dissuading patients from treatment. Education about new regimens with fewer side effects and higher success rates is necessary to influence patients' beliefs and attitudes in order to increase treatment rates. Sa1304 Hepatitis B Viral Breakthrough Rates in Patients Receiving Immunosuppressive Therapy: A Retrospective Cohort Study Sonali Paul, Nana Owusu-Sarpong, Hannah Lee, Kathleen Viveiros BACKGROUND: Hepatitis B virus (HBV) reactivation (as defined by the reappearance of active necroinflammatory liver disease in a person known to have inactive or resolved HBV) after immunosuppressive therapy can lead to liver failure and death. It is well known that HBV screening and prophylaxis prior to immunosuppression can decrease HBV reactivation rates. However, it is unclear whether patients with chronic HBV on treatment exposed to immunosuppressive therapy experience greater rates of viral breakthrough (as defined by an abrupt increase in serum HBV DNA levels after a period of persistent suppression) as compared to those patients with chronic treated HBV not exposed to immunosuppression. AIM: The primary aim of the study was to compare HBV viral breakthrough rates in these two groups of patients. Viral breakthrough rates are hypothesized to be higher among the immunosuppressed group. METHODS: Study subjects were retrospectively identified using ICD 9 billing codes for hepatitis B virus from January 2005 to October 2013. Inclusion criteria included patients 18 years or older with a positive HBV surface antigen and core IgG antibody. All patients were on chronic HBV treatment with undetectable viral loads. Those with a history of underlying liver disease, liver transplantation, HIV, and exposure to long-term steroids were excluded. RESULTS: Nineteen patients exposed to immunosuppressive therapy and 40 unexposed patients with chronic HBV were identified and followed for an average of 56 months (range 6 to 152 months) and 62 months (range 6 to 156 months) respectively. HBV viral breakthrough occurred in 7 out of 19 (37%) patients with chronic HBV receiving immunosuppressive therapy and 4 out of 40 (10%) unexposed patients with chronic HBV. This difference was statistically significant (p = 0.028, odds ratio 5.3, 95% CI 1.1 to 26.7). The severity of viral breakthrough was either silent or mild and no patients experienced liver failure or death in both groups. Patients receiving immunosuppressive therapy for oncological malignancies experienced the majority of the HBV viral breakthroughs. Average time to viral breakthrough while on immunosuppressive therapy was 14.1 months (range 2 to 42 months). Patients in both groups that experienced HBV viral breakthrough had medication changes made to their regimen. All patients at last follow up were doing well with undetectable viral loads. CONCLUSIONS: Despite appropriate HBV treatment prior to immunosuppressive therapy, patients with chronic HBV are still at risk for viral breakthrough. This underscores the need for proper laboratory monitoring under the care of a hepatologist during their course of therapy. Table 1. Patient Demographics at Baseline and Viral Breakthrough

Sa1302 Prospective Study of Withdrawal of Oral Antiviral Therapy in Chronic Hepatitis B Patients After Prolonged Virological Response Naveen Gara, Michele M. Tana, Nancy Fryzek, Xiongce Zhao, Edward Doo, Theo Heller, Jake Liang, Jay Hoofnagle, Marc Ghany Background: Oral nucleoside analogue therapy for chronic hepatitis B (CHB) is highly effective but usually requires long-term use with risk of development of antiviral resistance, side effects, and high costs. Features that predict whether therapy can be safely stopped are not well defined and recommendations vary. Methods: Subjects with CHB who had received antiviral therapy for ≥4 years and who were HBeAg negative but HBsAg positive with undetectable or low levels of HBV DNA (≤100 IU/mL) were enrolled in a study of carefully monitored withdrawal of antiviral therapy. Exclusion criteria were presence of cirrhosis, previous tenofovir therapy, renal impairment, and HIV, HCV or HDV co-infection. Viral relapse after stopping treatment was defined as a rise in HBV DNA level >1000 IU/mL and biochemical relapse an ALT ≥100 U/L. Those with a clinically significant relapse were restarted on tenofovir therapy . Aim: The primary outcome measure was the proportion of patients in virologic and biochemical remission off oral antivirals at 1 year after stopping therapy. Results: 13 consenting HBsAg-positive patients were withdrawn from lamivudine (3), adefovir (4) or a combination of the two (6). 11 were men, mean age was 47 years, HBV genotype was A (3), B (3), C (3), D (1), or unknown (3). Patients had been on treatment for 5 to 13 (mean 8) years. 6 patients were HBeAg positive when first started on therapy and had lost HBeAg 2.8 to 8.1 years (mean 4.2 years) before withdrawal. Upon stopping therapy, HBV DNA levels rose transiently in all patients;11 reached a level >1000 IU/mL. ALT levels also increased in all patients, and rose above 100 U/L in 7, one of whom became jaundiced (peak bilirubin 8.7 mg/dL). 5 patients had a clinically significant relapse and were restarted on therapy. All 5 had been HBeAg positive when antiviral therapy was initiated 6 to 8 years prior but had been HBeAg negative for 5-6 years. All 5 re-developed HBeAg within 2-5 months of withdrawal, with marked elevations in ALT (peak 366-3435 U/L), HBV DNA levels (67 million to 1.5 billion IU/mL) & transient rise in hepatic stiffness (>8 kPa) by ultrasound elastography. All 5 responded to restarting therapy, 4 rapidly becoming HBeAg negative and one losing HBsAg. The other 8 patients remain in virological and biochemical remission off of antiviral therapy for 1 to 2.5 years; 1 became HBsAg negative at 2.3 years. Duration of treatment and duration of viral suppression were not associated with risk of relapse. Conclusions: Nucleoside analogue therapy was safely withdrawn in 7 of 7 patients with HBeAg-negative CHB who had long-term suppression of HBV DNA without loss of HBsAg. In contrast, most patients (83%) with HBeAg-positive CHB had clinically significant relapse when antiviral therapy was withdrawn, even after long-term improvement in ALT, loss of HBeAg and suppression of HBV DNA. Sa1303 Are Primary Care Providers' (PCPS) Beliefs and Attitudes Impacting Patients' Perceptions of Chronic Hepatitis C Virus (HCV) and Treatment Decisions? Stephanie Judd, Alyssa M. Liubakka, Fadi Antaki Introduction: The disease burden of chronic hepatitis C (HCV) and its complications in the veteran population is high, yet few have undergone treatment. The decision regarding which individuals to treat and the timing of treatment often remain unclear despite advances in therapy. Added to this complexity are provider attitudes and beliefs about HCV and treatment. The goal of this study is to understand how providers' beliefs and attitudes about HCV and its treatment may be influencing treatment decisions and patients' perceptions of HCV. Methods: This study was conducted by administration of an anonymous, 9-question multiple choice survey distributed to all PCPs at one medical center. Questions included topics about hepatitis C screening practices, discussion of complications of chronic liver disease and treatment options, referral practices to liver clinic, as well as PCPs impression of their patients' knowledge of HCV and interest in treatment. Results: Response rate was 90% (26 of 29 PCPs). 88% of providers screened at least 50% of their patients for HCV antibody. The majority of providers (88%) reported that 75%-100% of their patients are aware of their HCV diagnosis. Almost all PCPs (96%) discuss complications of chronic hepatitis C with their patients. 81% of PCPs refer their patients to liver clinic at least 50% of the time, with only one provider referring his/her patients less than 25% of the time. 35% of providers

*Age at time of immunosuppressive therapy. **Age at time of HBV treatment initiation. Table 2. Disease characteristics in patients with chronic HBV receiving immunosuppressive therapy at baseline and viral breakthrough.

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AGA Abstracts

AGA Abstracts

designed to assess causality in suspected drug-induced liver injury (DILI). We aimed to study the etiology and prognosis of these patients and determine the proportion of DILI among patients with notably high levels of ALT Methods: In a University Hospital setting with a catchment area of approximately 170, 000 inhabitants, a prospective study identified all patients with serum level of ALT >500 U/L (normal levels: <70 U/L in men, <45 U/L in women). All patients signed an informed consent and underwent thorough diagnostic workup by hepatologists. The RUCAM causality assessment method was used to assess causality of patients with suspected idiosyncratic DILI. Results: During the first 11 months of the study a total of 135 cases fulfilled the predefined criteria: 67/135 (56%) males, median age 50 (IQR 32-67, range 1-89 years). The most common causes were choledocholithiasis (CDL) 41/135 (30%), ischemic hepatitis (IH) 27/135 (20%), viral hepatitis 19 (14%): Epstein-Barr (n=9), hepatitis C (n=5), hepatitis B (n=4) and cytomegalovirus. Overall 17/135 (13%) fulfilled the RUCAM criteria for idiosyncratic DILI with at least probable relationship, with the following drug etiologies: methotrexate (n=3 children), dietary supplements (n=3; Diet fuel®, Herbalife Roseox®, Femmenessence ®), vincristine (n=2), ciprofloxacin, amiodarone, infliximab, amoxicillin-clavulanate, ibuprofen (n=1) and multiple drugs (n=4). Moreover, hepatobiliary cancer (n=5), post hepatic resection (n=3) autoimmune hepatitis (n=2), postERCP (n=2), intrahepatic cholestasis of pregnancy (n=2), acetaminophen (n=2), unknown (n=6) and other etiologies (n=15). In the total study cohort 68/135 (50%) had jaundice, 14/27 (52%) in IH and 30/41 (73%) CDL. Overall 13/135 (9.6%) patients died: ischemic hepatitis, 8/27 (30%), cancer (n=4), DILI (n=1). Median time from raised ALT to death was 11 (IQR 3-33) days. Conclusions: The most common cause of notably high ALT was rather unexpectedly choledocholithiasis. Ischemic hepatitis was a common etiology with approximately 30% mortality. Viral hepatitis and DILI were respectively the third and fourth most common causes and are important etiologies among these patients.