Time-varying serum gradient of hepatitis B surface antigen predicts risk of relapses after off-NA therapy.

BACKGROUND: The serum gradient of hepatitis B surface antigen (HBsAg) varies over time after cessation of nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB). The association between the time-varying HBsAg serum gradient and risk of relapse has not been elucidated. METHODS: This multicenter cohort study prospectively enrolled CHB patients who discontinued 3 year-NA treatment. Eligible patients were serologically negative for HBeAg and viral DNA at NA cessation. The participants (n = 140) were followed every 3 months through HBsAg quantification. Virological and clinical relapses were defined as viral DNA levels >2000 IU/mL and alanine aminotransferase (ALT) levels >80 U/mL, respectively. The association of time-varying HBsAg levels with relapses was assessed through a time-dependent Cox analysis. RESULTS: During a median follow-up of 19.9 (interquartile range [IQR], 10.6-25.3) months, virological and clinical relapses occurred in 94 and 49 patients, with a 2-year cumulative incidence of 79.2% (95% confidence interval [CI], 70.9%-86.4%) and 42.9% (95% CI, 34.1%-52.8%), respectively. The serum level of HBsAg was associated with virological (P < 0.001) and clinical (P = 0.01) relapses in a dose-response manner, with adjusted hazard ratios of 2.10 (95% CI, 1.45-3.04) and 2.32 (95% CI, 1.28-4.21). Among the patients (n = 19) whose HBsAg levels ever dropped below 10 IU/mL, only one and three patients subsequently developed clinical and virological relapses. CONCLUSION: The serum gradient of HBsAg measured throughout the off-therapy observation is associated with the subsequent occurrence of virological and clinical relapses in CHB patients who discontinue NA treatment.

Comparison of 10-day sequential therapy with 7-day standard triple therapy for Helicobacter pylori eradication in inactive peptic ulcer disease and the efficiency of sequential therapy in inactive peptic ulcer disease and non-ulcer dyspepsia.

BACKGROUND: Eradication rates of standard triple therapy for Helicobacter pylori infections have decreased in recent years due to a worldwide increase in bacterial resistance. Sequential therapy has the advantage of a two-phase treatment regimen and achieves a superior result for H. pylori eradication in peptic ulcer disease. However, no study has yet compared the efficacy of sequential therapy for H. pylori eradication exclusively in inactive duodenal ulcer (iDU) or non-ulcer dyspepsia (NUD). METHOD: We retrospectively recruited 408 patients with endoscopic proven iDU (170 patients) or NUD (238 patients) infected with H. pylori. Patients with iDU were assigned into two groups: iDU triple therapy group, 44 patients treated with 40 mg pantoprazole, 1000 mg amoxicillin and 500 mg clarithromycin, twice daily for 7 days; iDU sequential therapy group, 126 patients treated with 40 mg pantoprazole and 1000 mg amoxicillin, twice daily for the first 5 days, followed by 40 mg pantoprazole, 500 mg clarithromycin and 500 mg tinidazole, twice daily for the next 5 days. All patients with NUD were treated with sequential therapy and assigned as the NUD sequential group. Post-treatment H. pylori status was confirmed by a (13)C-urea breath test. RESULT: The eradication rates of intention-to-treat (ITT) and per-protocol (PP) analysis were 77.3 % (95 % CI 64.9-89.7 %) and 85.0 % (95 % CI 73.9-96.1 %) in the iDU triple therapy group and 87.3 % (95 % CI 81.5-93.1 %) and 92.4 % (95 % CI 87.6-97.2 %) in the iDU sequential therapy group. The overall eradication efficacy was superior in the sequential group than in the triple group, both with ITT analysis (83.5 % vs. 77.3 %, P = 0.29) and PP analysis (88.1 % vs. 85.0 %, P = 0.57). Eradication rates for ITT and PP analysis were 81.5 % (95 % CI 76.6-86.4 %) and 85.8 % (95 % CI 83.5-88.2 %) in the NUD sequential therapy group. Eradication rate was statistically better in the iDU sequential therapy group than the NUD sequential therapy group according to per protocol analysis (P = 0.04). Eradication rate was not significantly different between the iDU sequential- and iDU triple therapy groups according to protocol analysis (P = 0.14). CONCLUSION: The sequential regimen has a better eradiation rate in the iDU group than in the NUD group. There is no statistically difference between 10-day sequential therapy and 7-day standard triple in iDU group.