Study of the role of hepatitis B virus on liver function abnormality in patients with autoimmune disease using anti-tumor necrosis factor agents
Date Issued
2014
Date
2014
Author(s)
Chiu, Ying-Ming
Abstract
Background and objective: Anti-tumor necrosis factor (anti-TNF) agents are new drugs for the treatment of autoimmune disease, such as rheumatoid arthritis, ankylosing spondylitis and psoriasis/psoriatic arthritis. Although anti-TNF agents have good efficacy, this class of drugs could suppress tumor necrosis factor which results in the duplication of hepatitis B virus (HBV) in patients with prior HBV infection, increasing the possibility of acute viral hepatitis. This happens not only in HBsAg-positive patients, but can also occur in HBsAg-negtive/anti-HBc-positive patients. As Taiwan is an endemic area for HBV infection, this study will focus on the analysis of autoimmune patients treated by anti-TNF agents to (1) compare the incidence of liver function abnormality in different HBV infection status, (2) understand the clinical characteristics of case with liver function abnormality, and (3) analyze the risk of liver function abnormality of each HBV infection status.
Method: The first part of the study was a retrospective cohort study which collected all autoimmune patients who were treated by anti-TNF agents in Department of Rheumatology of Changhua Christian Hospital from 2004 to 2013. The incidence of liver function abnormality was compared between patients tested HBsAg-positive, HBsAg-negtive/anti-HBc-positive, and uninfected, and the onset time of liver function abnormality were analyzed. In addition, chart review of those patients who developed liver function abnormality was performed. Autoimmune patients who only used traditional immunosuppressant were also collected, and the incidence of liver function abnormality of different HBV infection status was analyzed in these patients. Standardized rate ratio (SPR) and 95% confidence interval (95% CI) were used to test the statistically significant difference of liver function abnormality incidence between different HBV infection status groups.
The second part of the study was a retrospective cohort using the study population from the first part but excluding patients who were followed less than one year or lacked liver function data in the first year of treatment. The incidence of liver function abnormality in first year was calculated. Furthermore, HBV infection status and immunosuppressant use in the cases of liver function abnormality was analyzed to explore the possible risk factors of liver function abnormality.
The third part of the study was a nested case-control study which controlled all potential confounders to estimate the risk of liver function abnormality of each HBV infection status. Study group from the second part of the study was used. Patients were categorized in the same subgroup if they had the same underlying autoimmune disease and started anti-TNF agent therapy in the same calendar year. In each subgroup, those patients developed liver function abnormality in the first year of anti-TNF treatment were defined as case group, and those who did not were defined as control group. "1-to-all" matching was used to select the controls. With subgroup as the stratum variable in model analysis, conditional logistic regression was used to estimate the odds ratio for liver function abnormality of each HBV infection status after gender, age, past history of liver function abnormality, and immunosuppressant use were adjusted.
Result: (1) When the liver function abnormality was defined as >2-fold the upper limit of normal, HBsAg-positive patients (n=35) had significantly higher incidence of liver function abnormality than uninfected (n=155). The gender- and age-adjusted incidence rate were 19.6 per 100 person-year (PY) and 6.5 per 100 PY respectively, (SRR=3.02, 95% CI=1.23-7.46) and they were statistically different. On the other hand, incidence for HBsAg-negtive/anti-HBc-positive patients and uninfected were not significantly different from each other (6.8 per 100 PY and 6.5 per 100 PY respectively; SRR=1.05, 95% CI=0.49-2.25). 79% of the patients developed first incident of liver function abnormality during the first year of anti-TNF treatment.
(2) Among the 390 anti-TNF users who were included for the analysis, 31 developed liver function abnormality in the first year of anti-TNF treatment, an incidence rate of 7.9%. Among those cases with liver function abnormality, 64.5% were female (n=14), mean age was 45.5 years. Furthermore, 25.8% were HBsAg positive (n=8), 45.2% were HBsAg-negtive/anti-HBc-positive (n=14), and uninfected were 29.0% (n=9). 61.3% of the cases were rheumatoid arthritis (n=19), 45.2% of the cases started using anti-TNF agents in 2010~2012 (n=14). 25.8% of the cases had past history of liver function abnormality (n=8). 67.7% of the cases used methotrexate (n=21); of those, 36.7% of the cases combined with folic acid (n=12) and 29.0% of the cases did not combine with folic acid (n=9).
(3) A total of 368 patients were included for analysis. The HBsAg-positive patients had significantly higher risk of liver function abnormality than the uninfected (OR=6.33, 95% CI=1.79-23.52). However, the association of liver function abnormality between HBsAg-negtive/anti-HBc-positive and uninfected was statistically insignificant (OR=0.88, 95% CI=0.29-2.87). Past history of liver function abnormality and treatment with methotrexate alone without folic acid were the two major risk factors for liver function abnormality in those patients.
Conclusion: In this hospital-based retrospective cohort study of autoimmune patients treated by anti-TNF agents, the risk for liver function abnormality in HBsAg-positive patients was about 6-fold higher than uninfected, and HBsAg-negtive/anti-HBc-positive patients was not associated with higher risk of liver function abnormality. Past history of liver function abnormality and methotrexate only treatment without folic acid were the major risk factors for liver function abnormality.
Subjects
抗腫瘤壞死因子藥物
B型肝炎病毒
自體免疫疾病
回溯性世代研究
鑲嵌式病例對照研究
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-103-F93842009-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):4e8d94ccfb21aa637d683809a0091e94