Efficacy and safety of prolonged 3-year telbivudine treatment in patients with chronic hepatitis B.

BACKGROUND: In the GLOBE trial, telbivudine demonstrated superior efficacy to lamivudine at 2 years in patients with chronic hepatitis B (CHB). AIMS: To investigate the long-term efficacy and safety of telbivudine in the telbivudine-treated cohort from the GLOBE trial. METHODS: Virological and biochemical responses were assessed in 213 HBeAg-positive and 186 HBeAg-negative CHB patients who continued telbivudine treatment for 3 years. RESULTS: Undetectable hepatitis B virus DNA and HBeAg seroconversions were achieved by 77 and 37% of HBeAg-positive patients respectively. Cumulative HBeAg seroconversion rate was 46%. HBeAg seroconversion was sustained at 52 weeks off therapy in 84% of the patients enrolled in the off-treatment follow-up arm of the study. Undetectable viraemia and normal alanine aminotransferase (ALT) levels at 3 years were achieved by 85 and 83% of HBeAg-negative patients respectively. Genotypic resistance rates for the study population who continued therapy during the third year were 11.3 in HBeAg-positive and 6.5% in HBeAg-negative patients. Patients with undetectable viraemia at treatment week 24 had optimal outcomes at 3 years. In the HBeAg-positive population, cumulative HBeAg seroconversion occurred in 58%. Resistance rates for HBeAg-positive and HBeAg-negative patients were 3.6 and 6.2% respectively. The telbivudine safety profile during prolonged therapy was similar to that in the GLOBE trial. CONCLUSIONS: Three years of telbivudine treatment yielded high rates of viral suppression and ALT normalization with a favourable safety profile. High rates of HBeAg seroconversion were achieved with prolonged telbivudine therapy and were sustained in the majority of patients over 52 weeks off therapy.

Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial.

BACKGROUND: The efficacy of nucleoside and nucleotide analogues for hepatitis B has been linked to the magnitude and durability of hepatitis B virus (HBV) suppression. OBJECTIVE: To compare the antiviral efficacy of telbivudine and adefovir dipivoxil, and the effects of switching from adefovir to telbivudine, in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B. DESIGN: Randomized, controlled, open-label trial. SETTING: 16 outpatient clinics. PATIENTS: 135 treatment-naive, HBeAg-positive adults with chronic hepatitis B. INTERVENTION: Patients were randomly assigned in a 1:1:1 ratio to 52 weeks of telbivudine (group A) or adefovir (group B), or 24 weeks of adefovir and then telbivudine for the remaining 28 weeks (group C). One hundred thirty-one patients completed 52 weeks of treatment. MEASUREMENTS: The primary efficacy comparison was serum HBV DNA reduction at week 24, with a secondary comparison at week 52. RESULTS: At week 24, mean HBV DNA reduction was greater in group A than in pooled groups B and C (-6.30 vs. -4.97 log10 copies/mL; difference, -1.33 log10 copies/mL [95% CI, -1.99 to -0.66 log(10) copies/mL]; P < 0.001), and more patients in group A were polymerase chain reaction-negative (39% vs. 12%; odds ratio, 4.46 [CI, 1.86 to 10.72]; P = 0.001). At week 52, the mean residual HBV DNA level was lower in group A and group C than in group B (3.01 log10 copies/mL [group A] and 3.02 log10 copies/mL [group C] vs. 4.00 log10 copies/mL [group B]; difference, -0.99 log10 copies/mL [CI, -1.67 to -0.32 log10 copies/mL] and -0.98 log10 copies/mL [CI, -1.64 to -0.32 log10 copies/mL]; P = 0.004). Adverse events were similar across groups; the most common were upper respiratory symptoms, headache, back pain, and diarrhea. LIMITATIONS: The trial was open-label and was not of sufficient size or duration to compare clinical outcomes and long-term efficacy. CONCLUSION: Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment. After 52 weeks, HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir.

Poor Sleep Quality Predicts Hypogonadal Symptoms and Sexual Dysfunction in Male Nonstandard Shift Workers.

OBJECTIVE: To investigate the impact of sleep quality in hypogonadal symptoms and sexual function in men working nonstandard shifts. MATERIALS AND METHODS: Men treated at a single andrology clinic between July and October 2014 completed questionnaires assessing sleep quality, hypogonadal symptoms (Androgen Deficiency in the Aging Male [ADAM/qADAM]), and sexual function (International Index of Erectile Function [IIEF]). Serum hormone levels were assessed at the time of survey completion. RESULTS: One hundred eighty-two men were identified as working nonstandard shifts (work that starts before 7 a.m. or after 2 p.m., rotates, or regularly includes hours outside of the standard 7 a.m. to 6 p.m. workday) with a mean ± SD age of 41.1 ± 10.8 years. Of men working nonstandard shifts, those with better sleep quality had fewer hypogonadal symptoms and better sexual function. Multivariate regression analysis revealed significant linear associations between sleep quality and qADAM score (P = .008), positive ADAM responses (P = .003), and IIEF score (P = .0004). When comparing individual groups, men who were "very satisfied" (n = 60) with sleep quality had higher qADAM scores than men who were "somewhat dissatisfied" (P = .02), and men who were "very dissatisfied" had significantly lower IIEF scores than men who were "very satisfied" (P = .001) and "somewhat satisfied" (P = .005). No associations between sleep quality and mean serum testosterone, free testosterone, estrogen, dehydroepiandrosterone, follicle-stimulating hormone, and luteinizing hormone levels were observed. CONCLUSION: Men who work nonstandard shifts and have poor sleep quality are at increased risk for hypogonadal symptoms and sexual dysfunction.