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

• Published in: Arthritis research & therapy Vol. 19; no. 1; p. 214
• Main Authors: Chiu, Ying-Ming, Lai, Mei-Shu, Chan, K Arnold
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.11.2017; BioMed Central; BMC
• Subjects: Anti-TNF; Antigens; Antiviral drugs; Arthritis; Care and treatment; Development and progression; Drugs; Enzymes; Genetic aspects; HBsAg; HBsAg–/HBcAb; Health aspects; Hepatitis; Hepatitis B; Hepatitis B virus; Hepatology; Infections; Liver cirrhosis; Liver diseases; Liver enzyme elevation; Patient outcomes; Psoriasis; Rheumatoid arthritis; TNF inhibitors; Transaminases; Tumor necrosis factor inhibitors; Tumor necrosis factor-TNF; Taiwan; Anti-TNF; HBsAg; HBsAg–/HBcAb; Hepatitis B virus; Liver enzyme elevation
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-017-1413-y

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. 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 ≤ 12 months 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. 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). 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.