For RA patients, the reported difference of the HBV infection rates may associate with the alteration of HBV infection status after suffering from RA. To elucidate this issue, the current case-control study was performed. Compared to the age-and gender-matched general CHB patients, low proportions of positivity for HBeAg and HBV DNA were observed for the CHB patients with RA.
The HBeAg positivity often represents a high replicative phase of the chronic HBV infection, and HBeAg loss is considered as a partial immune control of the chronic HBV infection[15]. In this study, the CHB patients with RA exhibited lower positive rates of HBeAg and titers of HBeAg when comparing with the matched CHB patients. HBV DNA directly indicates HBV replication. The positive rate of HBV DNA in the CHB patients with RA was less than that of the matched CHB patients, as well the HBV DNA load. It demonstrated that CHB patients with RA had more probability of HBeAg seroconversion and HBV DNA load decline, which may associate with immune control after suffering from RA.
Immune dysregulation is the characteristics of RA. It plays a complicated role in HBV infection for abnormal innate and adaptive immune activation of RA patients. First, the type I interferons (IFNs) play a critical role in defending against HBV, and the type I interferon signature is detectable in the peripheral blood of RA patients[16]. Second, CD8+ T cells are capable to control HBV infection and eliminate HBV infected cells[17]. For RA patients, CD8+ T cells are abundant and associated with disease activity, due to pro-inflammatory cytokines production[18] and self-antigens response upon cross-presentation[19]. Third, the humoral immune response has protective role against pathogens[20]. Abnormalities in B cells not only participates in pathogenesis of RA[21] (including production of autoantibody, presentation of autoantigens and secretion of proinflammatory cytokines)[22], but also affects HBV elimination.
The elevated ALT is an important characteristic of immune clearance[23], and inactive HBsAg carrying status can be obtained after immune clearance. Compared to the matched CHB patients, low proportion of ALT > 40U/L and low ALT levels were found for the CHB patients with RA. This suggested that CHB patients with RA were more prone to obtain immune control for HBV after immune clearance.
HBsAg positivity is a definite HBV infection marker. In the present work, low HBsAg(+) rate of 3.0% was found in the RA patients, which was consistent with the previous study[9]. Then, survey outcomes also indicated that RA patients exhibited low HBsAg(+) rate according to the second Chinese National Hepatitis Seroepidemiological Survey[8] and the estimated China prevalence of HBsAg[12, 13]. Hepatitis B core antigen (HBcAg) is an inner nucleocapsid component, the production of anti-HBc is induced by a cellular and humoral immune response to HBcAg during natural HBV infection. Anti-HBc positivity mostly occurs in chronic HBV infection or resolved infection[14]. We found that the positive rate of anti-HBc was 44.6% in the RA patients, higher than the rate of Chinese general population from the China national data[8]. Consistent with the previous studies[10, 11], the RA patients may have higher risk of HBV infection in comparison with the general population, due to receiving disease modifying antirheumatic drugs and complicated immunity related to the disease itself[4, 5]. During the natural history of HBV, HBsAg seroclearance can emerge in 0.5 – 1.0% patients per year after immune clearance phase[24]. It was expected that low positive rate of HBsAg suggested HBsAg seroclearance was more common in the RA patients. The susceptible ages were different for RA and CHB patients. The mother-to-infant transmission was the main route of HBV infection in China. HBV infected early in life, and conferred a high risk of chronicity[25]. In contrast, RA occurred much frequently in the elderly women. Hence, RA was supposed to be later than HBV infection for most patients. We speculated that HBV infection status altered after suffering from RA. Among the 27 patients in this study, 62.9% of them had the HBV duration more than 10 years, and 96.3% of them had the RA duration less than 10 years. This indicates that the majority suffered from RA after HBV infection. After suffering from RA, HBV DNA declines, HBeAg and even HBsAg lose as consequent.
Here, some limitations of the study were as follows: the numbers of patients were limited, a prospective cohort study with large sample size is necessary to evaluate the difference in the natural history of chronic HBV infection between RA and general CHB patients.
In conclusion, HBV infection status altered after suffering from RA. Compared to the matched CHB patients, variations were significant, including low positive proportions of HBeAg and HBV DNA, due to immune dysregulation of RA patients.