Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Hepatitis B

BACKGROUND: Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (e.g., anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with cardiovascular diseases, but its role in persistent viral infection has not been well-defined. The present study was designed to investigate the association between RDW values and different disease states in hepatitis B virus (HBV)-infected patients. In addition, we analyzed whether RDW is associated with mortality in the HBV-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and twenty-three patients, including 16 with acute hepatitis B (AHB), 61 with chronic hepatitis B (CHB), and 46 with chronic severe hepatitis B (CSHB), and 48 healthy controls were enrolled. In all subjects, a blood sample was collected at admission to examine liver function, renal function, international normalized ratio and routine hematological testing. All patients were followed up for at least 4 months. A total of 10 clinical chemistry, hematology, and biochemical variables were analyzed for possible association with outcomes by using Cox proportional hazards and multiple regression models. RDW values at admission in patients with CSHB (18.30±3.11%, P<0.001), CHB (16.37±2.43%, P<0.001) and AHB (14.38±1.72%, P<0.05) were significantly higher than those in healthy controls (13.03±1.33%). Increased RDW values were clinically associated with severe liver disease and increased 3-month mortality rate. Multivariate analysis demonstrated that RDW values and the model for end-stage liver disease score were independent predictors for mortality (both P<0.001). CONCLUSION: RDW values are significantly increased in patients with hepatitis B and associated with its severity. Moreover, RDW values are an independent predicting factor for the 3-month mortality rate in patients with hepatitis B

Placebo-controlled trial of antibody to connective tissue growth factor (CTGF) in HBV liver fibrosis

Poster presentation: P-0415This journal suppl. entitled: Conference Abstracts: 25th Annual Conference of APASL, February 20–24, 2016, Tokyo, JapanINTRODUCTION: CTGF is a matricellular glycoprotein and central mediator of tissue remodeling and fibrosis. CTGF levels are elevated in viral hepatitis and NASH liver tissue. Inhibition of CTGF-expression prevents liver fibrosis in mouse models. FG-3019 is a human mAb to CTGF that is being developed to treat advanced liver fibrosis. METHODS: 114 subjects with chronic hepatitisB (HBV) in Asia, naı¨ve to antiviral therapy with Ishak C2 (amended to C3), were randomized 2:1 to entecavir+FG-3019 (15 and 45 mg/kg IV, Q3 W, for 45 weeks) or entecavir+placebo. The primary endpoint was the proportion of subjects with C1 point improvement in Ishak fibrosis score at 48 weeks (response rate) versus baseline. ClinicalTrials.gov: NCT01217632. RESULTS: Although the study is closed, data are not yet unblinded. FG-3019/placebo with entecavir showed excellent safety and tolerability at both dose levels: Neither local nor systemic allergic reactions were reported. At end of treatment,[95 % of subjects had undetectable viral load, and the majority normalized ALTs. No abnormal laboratory trends and no evidence of liver decompensation were noted. Ishak score change is available in 76 subjects: 21 had decrease of 1 point, 18 of 2 points, 5 of C3 points, 26 were stable and 6 had increased score for an aggregate response rate of 57.9 %. Unblinded data will be presented at a subsequent congress. CONCLUSIONS: FG-3019+ entecavir was well-tolerated in subjects with advanced HBV fibrosis and FG-3019 did not appear to impair entecavir’s antiviral efficacy