Forced vital capacity paired with Framingham Risk Score for prediction of all-cause mortality.

Forced vital capacity (FVC) measures lung function and predicts coronary heart disease (CHD); whether it provides additive prediction over CHD risk factors has not been established. We examined whether FVC adds to the prediction of all-cause mortality provided by Framingham Risk Score (FRS) alone. We examined 5,485 (61.1 million projected) nonsmoking adults from the USA who were aged 20-79 yrs. Subjects were from the Third National Health and Nutrition Examination Survey, were without obstructive lung disease, had FVC measurements and had ≤ 12 yrs (mean 8.8 yrs) mortality follow-up. We performed Cox regression analysis to examine whether FVC and forced expiratory volume in 1 s (FEV(1)) (categorised as low ≤ 85% predicted, borderline 86-94% predicted and normal ≥ 95% predicted) within FRS groups (10-yr risk of cardiovascular disease low <10%, intermediate 10-20%, high 20%) predict mortality. Receiver operator characteristic analysis examined whether FVC and FEV(1) added to the prediction provided by FRS. Low-, intermediate- and high-risk FRS groups had 79.5% (n = 4,361), 10.1% (n = 555) and 10.4% (n = 569) persons, respectively. Only the intermediate FRS group showed a graded increase in mortality (10.7, 18.2 and 42.8% per 1,000 person-yrs from highest to lowest FVC categories, respectively); those with low FVC had an almost three-fold greater risk of mortality (hazard ratio 2.64; p<0.01) than those with normal FVC. FVC provided incremental additive value for predicting mortality in addition to FRS for only this group (area under curve 0.65 versus 0.58; p<0.05). Similar results were obtained for FEV(1). Evaluation of lung function may be useful to improve risk stratification in persons with intermediate CHD risk where it adds to prediction of mortality over global risk assessment.

Quantitative analysis of HBV cccDNA from clinical specimens: correlation with clinical and virological response during antiviral therapy.

Attempts to investigate changes in various forms of intrahepatic hepatitis B virus (HBV) DNA during antiviral therapy have been hampered by limitations in technologies and scarcity of adequate tissue for analysis. We used a sensitive, specific assay to detect and quantitate covalently closed circular DNA (cccDNA) from total intrahepatic HBV DNA in clinical liver specimens. Total HBV DNA and cccDNA from 21 needle-biopsy specimens were quantified, with levels ranging from 0.1 to 9.8 copies/cell and 0.3 to 491.0 copies/cell, respectively. Then, we performed the same determinations on baseline and week-52 liver needle-biopsy specimens from eight patients enrolled in a clinical trial and evaluated the association between intrahepatic HBV DNA levels and serological and virological endpoints. In most patients, levels of intrahepatic HBV DNA, including cccDNA, decreased over the 52-week study, regardless of therapy or serological outcome. Higher ratios of cccDNA to total HBV DNA were detected at week 52 than at baseline indicating a shift in predominance of nonreplicating virus in posttreatment specimens. In patients who achieved treatment-related or spontaneous hepatitis B e antigen (HBeAg) responses, including those harbouring tyrosine-methionine-aspartate-aspartate-mutant HBV, levels of intrahepatic and serum HBV DNA suppression were greater than those in patients without HBeAg responses. In conclusion, this pilot study of intrahepatic HBV replicative forms in patients with chronic hepatitis B indicated that total intrahepatic and, specifically, cccDNA levels are not static but change as a reflection of serological and virological events.