Pacific Health Foundation

Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates. We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion-loss of HBeAg and antibody to HBeAg (anti-HBe) development. The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26-52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA < 7.5 log10 IU/mL (hazard ratio [HR] = 2.59 [1.04-6.44]), P = 0.041) and alanine transaminase (ALT) > 1.5 × upper normal limit (HR = 2.86 [1.05-7.81], P = 0.040), but not the choice of nucleos(t)ides. The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.

Purpose: Two of the most recent and frequently used treatment guidelines for CHB in the U.S. were the 2007 AASLD practice guideline and the 2008 U.S. panel algorithm. Our goal was to examine a random population of CHB patients to determine the proportion of patients who were eligible (recommended) for antiviral therapy and of those who were ineligible (not recommended) for therapy, and the reasons for treatment ineligibility. Methods: We performed a retrospective study of 164 randomly queried patients with CHB at 2 U.S. GI clinics during 1999-2008. CHB treatment recommendations were based on the 2007 AASLD guideline and the 2008 U.S. panel treatment algorithm. In patients with unconfirmed hepatitis B e antigen (HBeAg) status, patients were considered treatment-eligible if hepatitis B virus (HBV) DNA was >20,000 IU/mL. If HBeAg status was unknown and HBV DNA <20,000 IU/mL, treatment eligibility would be considered unknown. In both cases, if ALT<2x ULN (2007AASLD) or <ULN (2008 U.S. Panel), patients would be considered treatment ineligible. Results: The majority of patients was male (59%) and Asian (92%). Median age=43 (16-81). Of the 134 patients with known HBeAg status, 22% were HBeAg+ and 78% were HBeAg-. Median ALT =31 (10-1105) U/L and median HBV DNA= 10,000 (95-500,000,000) IU/mL. Table 1 described the distribution of patients by treatment eligibility. Figure 1 described the reasons for treatment ineligibility based on the applied guidelines.Table: Table. Proportion of patients who would be treatment-eligible according to 2007 AASLD and 2006/2008 US panel guidelinesFigureConclusion: Almost half of all patients would be recommended for antiviral therapy by the U.S. panel algorithm compared to about one-third by the 2007 AASLD guideline. The largest group of patients not recommended for therapy had low HBV DNA/ low ALT levels by the U.S. panel algorithm and high HBV DNA /low ALT levels by the 2007 AASLD guideline. Larger studies are needed to examine treatment eligibility rate, reasons for treatment ineligibility and their evolution during long-term follow-up, and the rate of actual therapy initiation in those who are currently recommended for therapy.

Purpose: Registration trials have shown that ETV had high efficacy, with 67% of HBeAg-positive patient achieving virogical response and 21% of patients achieving seroconversion at year 1. However, clinical study patients are generally highly selected and followed closely with rigid study protocols and may differ from the general patient population seen in a real-life clinical setting. We propose a study to examine the efficacy and proportion of seroconversion in patients in a real-life clinical setting. Methods: We performed a retrospective cohort study of 77 treatment-naive HBeAg(+) CHB patients treated with ETV by 5 gastroenterologists from 2 GI clinics between 06/05 and 06/08. Results: All patients were Asian. Mean age was 39±10 years. Sixty-five percent were male. Mean treatment duration was 23±9 months. Mean baseline HBVDNA (log IU/L) was 7.40±1.15 and median baseline ALT was 51 (19-588) IU/L. Table 1 summarizes treatment outcome through year 3. Proportions of patients with seroconversion at year 1, 2, and 3 were 4%, 8%, and 10%, respectively. Complete viral suppression (HBV DNA < 100 IU/mL) was seen in 39%, 53%, and 62% of patients at year 1, 2, and 3, respectively. No incidence of virologic breakthrough due to resistance was observed. Failure to achieve sustained viral suppression was primarily due to suboptimal response, followed by non-compliance. Incidence density for noncompliance was 8.3 cases per 100 patient-years.Table 1: Treatment outcome for HBeAg+ CHB patients treated with ETV through 3 yearsConclusion: Patients treated with ETV in a real-life clinical setting achieved lower incidences of sustained viral suppression and lower proportion of seroconversion when compared to registration trial data. Patients on long-term therapy should be monitored closely for non-compliance. Disclosure: Dr Huy Trinh - Consultant, Advises, Stockholder, Speaker's Bureau, Grant/Research Support: Gilead Sciences, Inc., Consultant, Advises, Speakers' Bureau, Grant/Research Support: Bristol-Myers Squibb; Dr Ruel Garcia - Consultant, Advises, Grant/Research Support: Bristol-Myers Squibb; Consultant, Advises, Speaker's Bureau, Grant/Research Support: Gilead Sciences, Inc., Grant/ Research Support: Novartis; Dr Huy Nguyen - Advises: Bristol-Myers Squibb, Advises, Speaker's Bureau: Gilead Sciences, Inc. Dr Mindie Nguyen - Consultant, Advises, Grant/Research Support: Bristol-Myers Squibb, Gilead Sciences, Inc., Grant/Research Support: Novartis and Roche.

To determine the yield of colonoscopy in a predominantly Asian American gastroenterology practice in California from 8/2003 to 2/2005. A total 2,723 subjects were included: 87% were Asian and 13% were non-Asian. Advanced neoplasia prevalence was 12% in Asian men and 9% in non-Asian men (P = 0.21), and 8% and 7% in women (P = 0.62). Similar results were found in asymptomatic patients (13% and 13%, P = 0.99, for men; 8% and 6%, P = 0.46, for women). Factors associated with presence of advanced neoplasia were total number of polyps and presence of right-sided lesions. Asian men were more likely to have neoplasia overall compared with non-Asian men with odds ratio (OR) of 2.14 (1.23-3.72); however, there were no significant differences in the prevalences of advanced neoplasia in the two groups. Colorectal neoplasia is as prevalent in Asian Americans and preventive guidelines for colorectal cancer should also be advocated for this ethnic group.