Commensurate incidence and outcomes of liver enzyme elevation between anti-tumor necrosis factor users with or without prior hepatitis B virus infections

<div><p>Background and objective</p><p>Potential hepatoxicity is an important clinical concern when administering immunosuppressive therapies to patients infected by hepatitis B virus (HBV). Tumor necrosis factor inhibitors (anti-TNF) increase the likelihood of hepatitis consequent to HBV reactivation, but reported risks and outcomes vary. We determined the risks of liver enzyme elevation in anti-rheumatic drug users from an HBV-endemic region with differing HBV serostatus.</p><p>Methods</p><p>We established retrospective cohorts with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis who: 1) received anti-TNF agents from 1 January 2004 to 30 June 2013; 2) received care from 1 June 2011 to 30 June 2013 but only ever used conventional disease-modifying anti-rheumatic drugs (DMARDs). Serology results defined three subgroups: HBV surface antigen positive (HBsAg+), HBsAg negative/HBV core antibody positive (HBsAg−/HBcAb+), or uninfected. We compared incidences of serum alanine aminotransferase (ALT) exceeding twice the upper reference limit between HBV serostatus subgroups in each treatment cohort.</p><p>Results</p><p>Among 783 patients treated with anti-TNF (n = 472) or DMARDs only (n = 311), HBsAg−/HBcAb+ anti-TNF users had incidence of ALT elevation commensurate with uninfected counterparts (6.1 vs. 6.0/100 person-years), compared to 19.6/100 person-years in HBsAg+ patients (standardized rate ratio 3.3, 95% CI 1.3–8.2); none effected had severe or fatal hepatitis and ALT levels in all HBsAg−/HBcAb+ patients remained stable, mostly normalizing spontaneously, or after moderating treatment. Patterns of of ALT elevation associated with differing HBV serostatus in the DMARD cohort, resembled those in anti-TNF users.</p><p>Conclusions</p><p>In this large HBV-endemic cohort, the absolute incidence of ALT elevation in anti-TNF users was more than three-fold higher in HBsAg+ patients than in uninfected counterparts; however, no such association was evident in patients with HBsAg−/HBcAb+ serotype, whose risk and outcomes of liver enzyme elevation were similar to uninfected patients, suggesting that anti-TNF use by HBsAg−/HBcAb+ patients is probably safe.</p></div

Clinical status of patients with abnormal liver function during anti-TNF therapy.

<p>Clinical status of patients with abnormal liver function during anti-TNF therapy.</p

Selection and disposition of anti-TNF and DMARD cohorts.

<p>TNF, tumor necrosis factor; DMARD, disease-modifying anti-rheumatic drug; RA, rheumatoid arthritis; AS, ankylosing spondylitis; PsO/PsA, psoriasis/psoriatic arthritis; CCH, Changhua Christian Hospital; HCV, hepatitis C virus; HBV, hepatitis B virus; HBsAg+, HBV surface antigen positive; HBsAg−/HBcAb+, HBV surface antigen negative/HBV core antibody positive; ULN, upper limit of normal.</p

Characteristics of the DMARD cohort.

<p>Characteristics of the DMARD cohort.</p

Incidence of liver enzyme elevation in anti-TNF cohort patients with different HBV serostatus.

<p>Incidence of liver enzyme elevation in anti-TNF cohort patients with different HBV serostatus.</p

Incidence of liver enzyme elevation in DMARD cohort patients with different HBV serostatus.

<p>Incidence of liver enzyme elevation in DMARD cohort patients with different HBV serostatus.</p

Distribution of patient characteristics: Patients who received a drug-eluting stent or bare-metal stent.

<p>Distribution of patient characteristics: Patients who received a drug-eluting stent or bare-metal stent.</p

Characteristics of the anti-TNF cohort.

<p>Characteristics of the anti-TNF cohort.</p

Proportion of patients received DES, by income.

<p>Proportion of patients received DES, by income.</p

Discretionary decisions and disparities in receiving drug-eluting stents under a universal healthcare system: A population-based study

<div><p>Objectives</p><p>One of the main objectives behind the expansion of insurance coverage is to eliminate disparities in health and healthcare. However, researchers have not yet fully elucidated the reasons for disparities in the use of high-cost treatments among patients of different occupations. Furthermore, it remains unknown whether discretionary decisions made at the hospital level have an impact on the administration of high-cost interventions in a universal healthcare system. This study investigated the adoption of drug-eluting stents (DES) versus bare metal-stents (BMS) among patients in different occupations and income levels, with the aim of gauging the degree to which the inclination of health providers toward treatment options could affect treatment choices at the patient-level within a universal healthcare system.</p><p>Design and participants</p><p>We adopted a cross-sectional observational study design using hierarchical modeling in conjunction with the population-based National Health Insurance database of Taiwan. Patients who received either a BMS or a DES between 2007 and 2010 were included in the study.</p><p>Results</p><p>During the period of study, 42,124 patients received a BMS (65.3%) and 22,376 received DES (34.7%). Patients who were physicians or the family members of physicians were far more likely to receive DES (OR: 3.18, CI: 2.38–4.23) than were patients who were neither physicians nor in other high-status jobs (employers, other medical professions, or public service). Similarly, patients in the top 5% income bracket had a higher probability of receiving a DES (OR: 2.23, CI: 2.06–2.47, p < .001), than were patients in the lowest income bracket. After controlling for patient-level factors, the inclination of hospitals (proportion of DES>50% or between 25% and 50%) was shown to be strongly associated with the selection of DESs (OR: 3.64 CI: 3.24–4.09 and OR: 2.16, CI: 2.01–2.33, respectively).</p><p>Conclusions</p><p>Even under the universal healthcare system in Taiwan, socioeconomic disparities in the use of high-cost services remain widespread. Differences in the care received by patients of lower socioeconomic status may be due to the discretionary decisions of healthcare providers.</p></div