Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV study.

BACKGROUND: Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long-term virological and adherence outcomes to antiviral treatment in CHB patients. METHODS: A prospective 183 Brazilian CHB patient cohort treated with monotherapy or combination adefovir dipivoxil, entecavir, lamivudine and/or tenofovir disoproxil fumarate was studied in a reference tertiary centre. Treatment adherence was evaluated by a validated questionnaire named 'Assessment of Adherence to Antiviral Therapy Questionnaire' (CEAT-HBV) within three yearly periods (2010/2011, 2013/2014 and 2014/2015). RESULTS: CEAT-HBV identified 43% (79/183) patients with non-adherence to antiviral treatment and among them, 67% (53/79) were viral load positive. The main causes associated with non-response to antiviral treatment were drug resistance variants followed by non-adherence, insufficient treatment duration and other causes. Single-dose pharmacokinetics demonstrated 35% (23/65) antiviral non-adherence. 2 years after the first assessment, the CEAT-HBV indicated that 71% (101/143) of subjects adhered to treatment (per-protocol population). However, 21% (40/183) of the patients could not be evaluated and were excluded. The main reasons for exclusion were death (20/183), 11 out 20 deaths due to hepatocellular carcinoma. HBV booklet was used for medical education. The third CEAT-HBV assessment (2014/2015) showed that 83% (112/135) patients were compliant with treatment adherence (per-protocol population). Long-term evaluation showed that adherence rate based on CEAT-HBV continue to increase after 4-years (P<0.001). CONCLUSIONS: The results highlight the importance of CHB therapy adherence assessment monitoring. Long-term adherence outcomes were dynamic and it is possible to increase the migration rate to adherence/HBV-DNA-negative group.

Aerobic exercise attenuates pulmonary inflammation induced by Streptococcus pneumoniae.

Aerobic exercise has been recognized as a stimulator of the immune system, but its effect on bacterial infection has not been extensively evaluated. We studied whether moderate aerobic exercise training prior to Streptococcus pneumoniae infection influences pulmonary inflammatory responses. BALB/c mice were divided into four groups: Sedentary Untreated (sedentary without infection); Sedentary Infected (sedentary with infection); Trained Untreated (aerobic training without infection); and Trained Infected (aerobic training with infection). Animals underwent aerobic training for 4 wk, and 72 h after last exercise training, animals received a challenge with S. pneumoniae and were evaluated either 12 h or 10 days after instillation. In acute phase, Sedentary Infected group had an increase in respiratory system resistance and elastance; number of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BAL); polymorphonuclear cells in lung parenchyma; and levels of keratinocyte-derived chemokine (KC), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1ß (IL-1ß) in lung homogenates. Exercise training significantly attenuated the increase in all of these parameters and induced an increase in expression of antioxidant enzymes (CuZnSOD and MnSOD) in lungs. Trained Infected mice had a significant decrease in the number of colony-forming units of pneumococci in the lungs compared with Sedentary Infected animals. Ten days after infection, Trained Infected group exhibited lower numbers of macrophages in BAL, polymorphonuclear cells in lung parenchyma and IL-6 in lung homogenates compared with Sedentary Infected group. Our results suggest a protective effect of moderate exercise training against respiratory infection with S. pneumoniae. This effect is most likely secondary to an effect of exercise on oxidant-antioxidant balance.