Ping-I Hsu

Nucleos(t)ide analogues reduce the incidence of hepatitis B virus (HBV) reactivation in cancer patients undergoing systemic cytotoxic chemotherapy but the experience of solid tumors remains limited. Aims. The aim of this study was to compare the efficacy of entecavir and lamivudine in the prophylaxis of HBV reactivation in solid tumor patients undergoing systemic cytotoxic chemotherapy. HBsAg seropositive patients undergoing systemic cytotoxic chemotherapy for solid tumors with prophylactic entecavir and lamivudine between January 2006 and June 2013 were retrospectively investigated. The incidence of HBV reactivation and outcome of the patients were analyzed. The risk factors of HBV reactivation were examined. A total of 213 patients (entecavir group, 70 patients; lamivudine group, 143 patients) were evaluated. Less incidence of HBV reactivation was noticed in entecavir group than in lamivudine group (0% vs. 7.0%, P = 0.02). No HBV reactivation was noticed in the patients with a baseline HBV DNA level < 2000 IU/mL. A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were significantly associated with HBV reactivation. Subgroup analysis of the patients with a baseline HBV DNA level ≥ 2000 IU/mL found that lamivudine was significantly associated with HBV reactivation. Most of the reactivation events were properly managed by using tenofovir disoproxil fumarate. The incidence of hepatitis during chemotherapy and disruption of chemotherapy was similar between patients using entecavir and lamivudine with a baseline HBV DNA level ≥ or < 2000 IU/mL. A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were the risk factors of HBV reactivation during systemic cytotoxic chemotherapy in solid tumor patients. Entecavir was superior to lamivudine in terms of less incidence of reactivation in the patients with a baseline HBV DNA level ≥ 2000 IU/mL. Both agents were equally efficacious in the patients with HBV DNA levels < 2000 IU/mL.

A previous study found that lamivudine, if started early enough, may improve the chance of survival in chronic hepatitis B virus (HBV) with severe acute exacerbation (SAE). The aim of this study was to investigate the effect of early entecavir treatment before the bilirubin level exceeds 20 mg/dl for chronic HBV with SAE. Consecutive patients with chronic HBV with SAE and a serum bilirubin level of P = 1.000). If only patients who started antiviral treatment before serum bilirubin level rose to more than 15 mg/dl were included, 3 patients (8.3%) in the entecavir group and 3 patients (3.0%) in the lamivudine group died ( P = 0.189). If only patients with an HBV DNA level higher than 10 ⁵ copies/ml and a bilirubin level lower than 15 mg/dl were included, 5 out of 40 patients (12.5%) in the entecavir group died and 1 out of 59 patients (1.7%) in the lamivudine group died. Multivariate analysis found that entecavir treatment was associated with more mortality than lamivudine ( P = 0.035). Early entecavir treatment in patients with high viral load is associated with more short-term mortality than lamivudine for chronic HBV with severe acute exacerbation.

Patients taking antiplatelet agents for the prevention of cardiovascular diseases who develop gastrointestinal bleeding represent a serious challenge in clinical practice. The initial step in reducing gastrointestinal risk of antiplatelet therapy is to assess whether the patient has a continued need for antiplatelet therapy. The next step is to eliminate the risk factors that may place the patient at increased gastrointestinal risk. In the management of bleeding ulcer patients with high‐risk stigmata of recent hemorrhage, resuming antiplatelet agents at 3–5 days after the last dosing is a reasonable strategy. However, patients with low‐risk stigmata can keep taking antiplatelet agents immediately following endoscopy. In the management of aspirin‐related uncomplicated peptic ulcers in patients requiring antiplatelet therapies, continuing aspirin plus a powerful proton pump inhibitor is the choice of treatment. Patients who require antiplatelet agents for the prevention of cardiovascular diseases should be tested and treated forHelicobacter pyloriinfection before starting antiplatelet therapy. Additionally, those with high risks for upper gastrointestinal bleeding should receive co‐therapy with a gastroprotective drug, preferably a proton pump inhibitor at standard dose. H2‐receptor antagonist can significantly reduce upper gastrointestinal bleeding risk in patients taking low‐dose aspirin but it is ineffective in the prevention of upper gastrointestinal bleeding in clopidogrel users. Although several retrospective studies reported that patients prescribed clopidogrel who also took proton pump inhibitors had significant increases in cardiovascular events, the current evidence from a prospective randomized trial does not justify a conclusion that proton pump inhibitors are associated with cardiovascular events among clopidgrel users.

Background: Baseline low platelet count (< 150,000/μL) increases the risk of on-treatment severe thrombocytopenia (platelet count < 50,000/μL) in patients with chronic hepatitis C (CHC) undergoing antiviral therapy, which may interrupt treatment. The purpose of this study was to identify risk factors for severe thrombocytopenia during treatment for CHC in patients with baseline thrombocytopenia. Methods: Medical records were reviewed for 125 patients with CHC treated with antiviral therapy according to the standard of care, with regular follow-up examinations. Early platelet decline was defined as platelet decrease during the first 2 weeks of therapy. Results: Severe thrombocytopenia developed in 12.8% of patients with baseline thrombocytopenia, and predicted a higher therapeutic dropout rate. Multivariate analysis revealed baseline platelet count < 100,000/μL and rapid early platelet decline (> 30% decline in the first 2 weeks) were significantly associated with severe thrombocytopenia (P < 0.001 and 0.003, odds ratios, 179.22 and 45.74, respectively). In these patients, baseline PLT ≥ 100,000/μL and lack of rapid early platelet decline predicted absence of severe thrombocytopenia (negative predictive values were 95.1% and 96.6%, respectively). In contrast, baseline platelet count < 100,000/μL combined with rapid early platelet decline predicted severe thrombocytopenia (positive predictive value was 100%). Conclusions: For patients with CHC on antiviral therapy, baseline platelet counts < 100,000/μL and rapid early platelet decline can identify patients at high risk of developing on-treatment severe thrombocytopenia.

Tumorigenesis is a multistep process that begins with the abrogation of normal controls of apoptosis and cell proliferation, and the FAS receptor-ligand system is a key regulator of apoptosis. The aim of this study was to investigate whether functional polymorphisms of death pathway genes (FAS and FASL) are associated with the development of gastric atrophy and intestinal metaplasia. Genotypes in the promoter regions of the FAS (-1377G/A and -670A/G) and FASL (-844T/C) genes of 101 healthy individuals and 86 gastric cancer patients were determined by PCR-RFLP. Additionally, gastric histological changes were examined according to the updated Sydney System. The carriage of FASL -844C allele significantly increased the risk of atrophy in the gastric corpus, with an adjusted odds ratio (OR) of 5.0 [95% confidence interval (CI), 1.5-6.8]. There were no gene-gene interactions among FASL -844T/C, FAS -1377G/A and FAS -670A/G polymorphisms in developing premalignant gastric lesions. In the 109 individuals with Helicobacterpylori infection, carrying the FAS -1377A allele was a protective factor for developing intestinal metaplasia in the antrum (OR, 0.3; 95% CI, 0.1-0.9), while carrying the FASL -844C allele was a risk factor for developing gastric atrophy in the corpus (OR, 9.4; 95% CI, 1.7-53.4). FAS and FASL genotypes of the hosts are important determinants in the pathogenesis of gastric atrophy and intestinal metaplasia in H. pylori-infected individuals.