Nghi B. Ha

Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil

Renal dysfunction has been reported in patients treated with adefovir dipivoxil (ADV); however, its incidence and clinical importance may be underappreciated given the lack of long‐term follow‐up and data outside of a clinical trial setting. Our goal was to examine the severity and incidence of renal dysfunction in a real‐life setting for patients treated with ADV and whose baseline estimated glomerular filtration rate (eGFR) was >50 mL/minute. We performed a cohort study of 290 chronic hepatitis B patients: 145 patients treated with 10 mg ADV and 145 patients unexposed to ADV at two community clinics, who were matched for age (±10 years), sex, and baseline eGFR. The exposed and unexposed populations were well‐matched with a similar mean age (46–47 years), proportion of male patients (76.5%), baseline serum creatinine (0.97–0.99 mg/dL), and baseline creatinine clearance (85.0–85.4 mL/minute). The incidence density for renal dysfunction defined by treatment termination and/or development of eGFR ≤50 mL/minute was five cases per 100 patient‐years in the exposed group compared with 1.36 cases per 100 patient‐years in the unexposed group (P = 0.02). The relative risk of exposed to unexposed was 3.68 (95% confidence interval 1.1–19.3). On Cox proportional hazard analysis also inclusive of sex, ADV was a significant predictor of significant renal dysfunction (hazard ratio [HR] 3.94, P = 0.03). There were also significant trends for age >50 years (HR 3.49, P = 0.087), mild renal impairment at baseline (HR 4.49, P = 0.073), and hypertension and/or diabetes mellitus (HR 2.36, P = 0.074). Conclusion: ADV is an independent predictor for significant deterioration of renal function. Patients on ADV should be monitored, especially patients who are older, have baseline renal insufficiency, or have hypertension and/or diabetes mellitus. (HEPATOLOGY 2009.)

Tu1018 Chronic Hepatitis B (CHB) Management Based on Standard Guidelines: Primary Care Physicians (Pcp) and Specialist Care Examined

Purpose: Prior studies have underlined the need for increased hepatitis B screening and awareness, especially in certain high-risk populations, but few examine the prevalence of adequate evaluation and management of CHB between PCP and specialists according to standard guidelines. Our goal was to examine adherence to current guidelines on the management of CHB between primary care physicians (PCP) and specialists. Methods: We retrospectively studied 253 CHB patients who were evaluated by PCP only (n=63) or by specialist (n=190) for CHB at a community multispecialty medical center between March 2007 and June 2009. Criteria for CHB management and treatment eligibility were based on AASLD 2009 guideline and US Panel 2008 algorithm. Adequate evaluation for CHB was defined as having done testing for hepatitis B e antigen (HBeAg), HBV DNA PCR and alanine aminotransferase (ALT) six months from initial presentation. First-line antiviral agents for CHB include pegylated interferon, entecavir and tenofovir. Due to high rates of antiviral resistance, lamivudine is not a recommended first-line therapy for CHB. Results: The majority of patients were Asians (90%) and male (54%) with a mean age of 43±11.6 years. As shown in Figure 1, more patients underwent more thorough laboratory testing for CB evaluation by specialists than those seen by their PCP only. Adequate laboratory evaluation (≥3 tests) was significantly higher among specialists (62% vs. 33%, p<0.0001) (Figure 1). Compared to PCPs, specialist were more likely to order laboratory testing for ALT (94% vs. 86%, p= 0.05), HBeAg (67% vs. 41%, p<0.0001) and HBV DNA (83% vs. 52%, p<0.0001). Of those who were started on treatment by specialists (n=56, 30%) and PCPs (n=8, 13%), lamivudine was prescribed much more often by PCPs compared to specialists (33% vs. 2%, p=0.05). Conclusion: Patients evaluated by specialists for CHB are more likely to undergo more complete laboratory evaluation and if eligible, they were also more likely to be treated with newer first-line agents for CHB than those evaluated by PCP only. Long-term clinical significance of this lack of adequate evaluation in patients not evaluated by specialists should be further studied.

High Rate of Recurrent Hepatitis B Viremia Following Treatment-Induced Hepatitis B E Antigen (HBeAg) Seroconversion

Purpose: In patients with HBeAgpositive chronic hepatitis B (CHB), one of the primary endpoints of therapy is HBeAg seroconversion; however, there is inconsistent data on the durability of HBeAg seroconversion following consolidation therapy. Our goal is to investigate the rate of recurrent HBV viremia in CHB patients after HBeAg seroconversion. Methods: We retrospectively studied 88 consecutive CHB patients who achieved treatment-induced HBeAg seroconversion among the 458 HBeAg-positive patients treated with various antiviral regimens at 3 GI and liver clinics in the U.S. between 3/1998 and 9/2010. HBeAg seroconversion was defined as loss of HBeAg and development of hepatitis B e antibody (anti-HBe). Recurrent HBV viremia was defined as reappearance of detectable HBV DNA (>100 IU/mL) from nadir in two consecutive laboratory tests. Results: Patients were stratified into two groups: Group I 49 patients who remained on therapy, and Group II 39 patients who discontinued therapy following HBeAg seroconversion. In both groups, the majority of patients were Asian (94-95%) and male (62-69%). Antiviral medications in which patients achieved HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), adefovir+lamivudine (1%), and entecavir+tenofovir (2%). Median treatment duration before HBeAg seroconversion was similar in Group I and Group II (18 [1-86] vs. 21 [5-63] months, p=0.99). At the time of HBeAg seroconversion, compared to Group I, Group II was younger (37±10 vs. 41±12 years), had lower mean HBV DNA levels (0.27±0.78 vs. 0.95±1.69 log10 IU/mL), and median ALT levels (24 [8-60] vs. 30 [593] U/L). In Group II, the median duration of consolidation therapy before treatment discontinuation was 12 months (range, 1-55), in which 10 completed <6 months, 10 completed 6-11 months, and 19 completed ≥12 months. At time of treatment discontinuation, all patients in Group II had undetectable HBV DNA. The rate of recurrent HBV viremia was significantly higher in Group II compared to Group I (90% vs. 0%, p<0.0001). After a median of 3 (1-42) months off therapy, the mean HBV DNA level detected at time of recurrent HBV viremia was 4.11±1.92 log10 IU/mL. Conclusion: The majority of patients (90%) who discontinued therapy after achieving HBeAg seroconversion with undetectable HBV DNA by PCR experienced recurrent HBV viremia. Patients who remained on therapy achieved and maintained undetectable level of HBV DNA. Patients should be monitored closely for recurrent HBVwhen therapy is discontinued, despite achieving HBeAg seroconversion.

M1903 Long-Term Outcome of Treatment-NaïVE Chronic Hepatitis B (CHB) E Antigen-Negative Treated With Entecavir 0.5 Mg (ETV) or Adefovir 10 Mg (ADV) in a Real-Life Community Setting

PURPOSE:Data from registration trials have shown that CHB patients response well to antiviral therapy with antiviral resistance as the primary reason for treatment failure. However, patients seen in these settings may differ from real-life settings as they are generally carefully selected and followed closely with rigid study protocols. Our goal is to examine long-term outcomes of CHB treated with ETV or ADV in a real-life setting. METHOD:We performed a retrospective cohort study of 190 consecutive eAgpatients started on either ETV(n= 108) or ADV(n=82) between 1/02-1/09 at 2 community U.S.GI clinics. Annual/cumulative outcome variables were analyzed and reported in both cohorts. Patients were excluded from analysis if they developed resistance(n=11), started on alternate treatment(n=24), increased ETV dose(n=4), noncompliant(n=15), and/or lost to F/U(n=11). RESULTS:All patients were Asians; the majority being male.Both cohorts had similar age(52±11), median baseline ALT(62 vs.77 U/L,p=0.94) and mean baseline HBV DNA (5.6±1.3vs.5.±1.7 IU/mL,p=0.10). Table 1&2 summarized treatment outcome of both groups.By year 4, similar proportion of ETVA however, more patients in the ADV cohort failed monotherapy treatment (27%vs.5%).No patient in ETV cohort developed resistance while 18% of the ADV cohort did by year 4. Cumulative noncompliance rates were 12-13% for both cohorts. CONCLUSION:In our cohorts, monotherapy failure rate was due to both viral resistance(ADV) and noncompliance (ADV&ETV). Attention to medical compliance in addition to antiviral resistant surveillance is needed in a real-life setting.