Assessing risk of liver enzyme elevation in patients with immune-mediated diseases and different hepatitis B virus serostatus receiving anti-TNF agents: A nested case-control study
Journal
Arthritis Research and Therapy
Journal Volume
19
Journal Issue
1
Date Issued
2017
Author(s)
Abstract
Background: Liver enzyme elevation is an important and common adverse effect among patients with immune-mediated diseases who receive tumour necrosis factor inhibitors (anti-TNF), and has various causes. Hence, we evaluated the relative risks of developing liver enzyme elevation in anti-TNF users with differing hepatitis B virus (HBV) infection status. Methods: At a hospital in central Taiwan, 407 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis received anti-TNF therapy between 1 January 2004 and 30 June 2012. We performed a nested case-control study (n=368) of cases with serum alanine aminotransferase (ALT)>40 international units/L?12months after starting anti-TNF therapy, and corresponding controls without liver enzyme elevation. Conditional logistic regression was used to evaluate associations between liver enzyme elevation and HBV serostatus, as well as other risk factors. Results: Thirty cases were compared to 338 controls. After adjustment for potential confounders, HBV surface antigen-positive (HBsAg+) serostatus was associated with substantially higher likelihood of developing elevated ALT (adjusted odds ratio 7.91, 95% confidence interval (CI) 2.16-31.31) relative to those with an uninfected HBV status; no such association was observed among HBsAg-negative/HBV core antibody-positive (HBsAg-/HBcAb+) patients (adjusted odds ratio 1.00, 95% CI 0.33-3.25). Increased risk of ALT elevation was associated with methotrexate used alone, without folic acid (adjusted odds ratio 11.60, 95% CI 2.52-56.46), and history of ALT elevation (adjusted odds ratio 13.71, 95% CI 4.32-45.75). Conclusions: HBsAg+ patients with immune-mediated diseases who received anti-TNF therapy had an approximately eight-fold higher likelihood of liver enzyme elevation than those without HBV infection, whereas patients with HBsAg-/HBcAb+ serostatus had a risk similar to that of uninfected patients. ? 2017 The Author(s).
Subjects
Anti-TNF; HBsAg+; HBsAg-/HBcAb+; Hepatitis B virus; Liver enzyme elevation
SDGs
Other Subjects
adalimumab; alanine aminotransferase; azathioprine; cyclophosphamide; cyclosporin; disease modifying antirheumatic drug; etanercept; folic acid; golimumab; hepatitis B core antibody; hepatitis B surface antigen; hydroxychloroquine; leflunomide; liver enzyme; methotrexate; prednisolone; salazosulfapyridine; tumor necrosis factor antibody; alanine aminotransferase; antirheumatic agent; hepatitis B surface antigen; tumor necrosis factor; adult; alanine aminotransferase blood level; ankylosing spondylitis; Article; case control study; cohort analysis; controlled study; disease association; enzyme analysis; female; hepatitis B; high risk patient; hospital based case control study; hospital patient; human; immunopathology; major clinical study; male; medical history; psoriasis; psoriatic arthritis; reference value; retrospective study; rheumatoid arthritis; risk assessment; risk factor; Taiwan; aged; antagonists and inhibitors; blood; complication; hepatitis B; Hepatitis B virus; immunology; metabolism; middle aged; multivariate analysis; physiology; statistical model; virology; Adult; Aged; Alanine Transaminase; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan; Tumor Necrosis Factor-alpha
Publisher
BioMed Central Ltd.
Type
journal article