Clinical effects of HBV infection on patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus

Objective: To investigate the clinical effects of HBV infection on patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods: This is a prospective study. Thirty patients with RA and 30 patients with SLE admitted to Affiliated Hospital of Hebei University from January 2020 to December 2021 with co-infection of HBV were randomly selected and divided into two groups. Both groups were given anti-HBV treatment. An additional 60 patients with a healthy physical examination during the same period were also selected as a control group. The disease activity, immune function and serum inflammatory factor levels were compared between the RA group and the SLE group before and after treatment. Results: After anti-HBV treatment, DAS scores in the RA group and SLEDAI scores in the SLE group were significantly lower than before treatment(P<0.05). The levels of IgG, IgA, IgM and CD8+ in the RA group and the SLE group after treatment were significantly lower than those before treatment. The levels of CCP, RF, ESR and CRP in the RA group before and after treatment were higher than those in the control group(P<0.05). The levels of ESR and CRP in the SLE group before and after treatment were higher than those in the control group, with statistically significant differences(P<0.05). Conclusion: Patients in the RA and SLE groups after HBV infection have an increased degree of inflammatory response in their organism, an altered normal state of immunoglobulin and T-lymphocyte subsets, and a loss of organism immune function, leading to an increase in disease activity.


INTRODUCTION
Hepatitis B Virus (HBV), as a common clinical hepatotropic DNA virus, may cause chronic hepatitis B once infected. 1,2Most of the patients are in a decompensated stage when they are treated, and some severe cases have already suffered from liver cancer. 3The occurrence and progression of HBV have a close bearing on the immune tolerance of the body.Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as autoimmune diseases, are closely related to the immune system of the body.
According to a clinical study, 4 patients usually suffer from RA and SLE after viral infection, which is attributed to the destruction of the immune system and the aggravation of immune dysfunction in such patients after co-infection with HBV. 5 Additionally, various immunosuppressive agents, such as glucocorticoids and biologics, are clinically applied in the treatment of RA and SLE, which may increase the risk of HBV infection or contribute to the reactivation of HBV in the latent phase. 6or the clarification of the effect of HBV infection on patients with RA and SLE, anti-HBV was used in this study to treat patients with RA and SLE co-infected with HBV in order to provide guidance for clinical treatment.The effects of HBV infection on disease activity, immune function and serum inflammatory factors in RA and SLE were observed to provide a theoretical basis for guiding the clinical selection of a reasonable treatment regimen.

METHODS
This is a prospective study, which included 120 participants in total in this study, thirty patients with RA and 30 patients with SLE admitted to Affiliated Hospital of Hebei University from January 2020 to December 2021 with co-infection of HBV were randomly selected and divided into two groups: the RA group and SLE group.An additional 60 patients with a healthy physical examination during the same period were also selected as a control group.

Statistical methods:
All data in this study were statistically analyzed using SPSS22.0software.Measurement data were expressed as mean ± standard deviation ( ), and t test was used for comparison among the groups.Enumeration data were expressed as n (%), and c² test was used for comparison among the groups.P<0.05 indicates a statistically significant difference.

RESULTS
No statistically significant difference was observed between the RA and SLE groups and the control group in terms of gender, age, weight and BMI (P>0.05), which was comparable.See Table-I.The levels of five items of hepatitis B and HBV-DNA in the RA group and the SLE group were significantly different from those in the control group (P<0.05).Table - The DAS score of the RA group after treatment was significantly lower than that before treatment, with a The levels of CCP, RF, ESR and CRP in the RA group before and after treatment were higher than those in the control group, with statistically significant differences (P<0.05).The intra-group comparison showed that the levels of CCP, RF, ESR and CRP in the RA group after treatment were significantly lower than those before treatment, with statistically significant differences (P<0.05).Table-V.
The levels of ESR and CRP in the SLE group before and after treatment were higher than those in the control group, with statistically significant differences (P<0.05).The intra-group comparison showed that the levels of ESR and CRP in the SLE group after treatment were significantly lower than those before treatment, with a statistically significant difference (P<0.05).Table-VII.

DISCUSSION
It was found in this study that the DAS28 scores of RA patients with HBV infection decreased after treatment, and that of SLE patients also decreased after treatment, indicating that HBV infection can aggravate the disease activity of RA and SLE patients; Not only that, the disease activity of RA and SLE patients was reduced after anti-HBV treatment, indicating that anti-HBV treatment of RA and SLE patients with HBV infection has obvious clinical efficacy in controlling RA and SLE.These are consistent HBV Infection on Patients with Rheumatoid Arthritis with the results of several clinical studies. 7To explain the reason, HBV aggravates the inflammatory response in patients with RA and SLE, supplemented by biologics for the treatment of RA and SLE, which can lead to aggravation or even worsening of hepatitis B disease.The interaction of these factors resulted in increased disease activity in RA and SLE patients during HBV decompensation.In response to this, entecavir clears HBV and contributes to a decrease in disease activity. 8gM, IgA and IgG are important players in humoral immunity. 9CD3+ responds to the overall cellular immune status of the body, and CD4+ T lymphocytes direct the body against HBV.In contrast, CD8+ T lymphocytes are able to recognize HBV-infected target cells and kill them, ultimately clearing HBV. 10 Meanwhile, CD8+ stimulates B cells and T cells to secrete inflammatory factors and destroy bones.CD4+/CD8+ responds to the immune status of the body, and when HBV infection occurs, it suffers from a lower ratio, decreased immune function of the patient, and impaired anti-HBV ability of the body. 11BV infection is a serious public health problem currently spreading in China. 12,13Most patients with HBV infection are only clinically diagnosed when they have obvious clinical manifestations, such as spider nevus and hepatosplenomegaly, and some of them are already in the decompensated stage of HBV infection. 14RA and SLE, which are autoimmune diseases, both require the application of immunosuppressive drugs in their treatment, combined with glucocorticoids if necessary.
To date, there are few clinical studies on the effects of HBV infection on disease activity, immune function and inflammatory response in RA and SLE, let alone any clinical reports on the effects before and after treatment.
It was shown in this study that for RA and SLE patients with co-infection with HBV, the levels of IgG, IgA, IgM and CD8+ were significantly lower after treatment, while CD3+, CD4+ and CD4+/CD8+ were significantly higher, indicating that in RA and SLE patients with co-infection with HBV, their immunoglobulin and T lymphocyte subsets recovered with the improvement of their disease.For this reason, clinical monitoring of the levels of immunoglobulin and T lymphocyte subsets is a good indicator of the patient's disease activity.
CCP is a highly specific autoantibody secreted by B cells, which can be used to predict the severity of RA disease.It is positive in the early stage of RA and shows good sensitivity and specificity for the diagnosis of RA.It can also be used to predict the severity of RA disease. 15,16F is an autoantibody that uses IgG as a target antigen, and its secretion increases in the presence of RA, which binds to IgG to produce a reaction. 17In this study, both CCP and RF levels were higher in RA patients than in the normal population before and after treatment.
It has been shown in related studies 18 that the occurrence of cirrhosis in HBV infection has a close bearing on the release of inflammatory factors such as serum ESR and CRP.CRP is an acute temporal protein 19 involved in the non-specific immune response of the body.It has been pointed out that the level of CRP concentration is positively correlated with the severity of inflammation in the body. 20n this study, RA and SLE patients with co-infection with HBV had significantly higher ESR and CRP levels than the normal population.After treatment, these patients showed disease improvement, lower levels of the organismal inflammatory response, and correspondingly lower ESR and CRP levels, but still higher than the normal population.The conclusion of this study provides a new clinical reference for the clinical impact of HBV infection on patients with SLE and RA.
Limitations: It includes small sample size, short followup time, and failure to combine the study content with the final patient regression.

CONCLUSION
HBV infection significantly aggravates the disease in patients with RA and SLE.RA and SLE patients with HBV co-infection suffer from an increased disease activity, a loss of body immune status, an altered normal state of immunoglobulin and T-lymphocyte subsets, and a loss of organism immune function, and an increased degree of inflammatory response.
Ethical Approval:The study was approved by the Institutional Ethics Committee of Affiliated Hospital of Hebei University (No.:2022020; date: December 30, 2022), and written informed consent was obtained from all participants.

Table - I
: Comparison of general information [n (%), ( )].Note: * Indicates P>0.05 compared with the RA group; Δ indicates P>0.05 compared with the SLE group.Table-II: Comparison of the levels of five items of hepatitis B and HBV-DNA among the three groups [()].Table-III.The levels of IgG, IgA, IgM and CD8+ in the RA group and the SLE group after treatment were significantly lower than those before treatment, and the levels of CD3+, CD4+ and CD4+/CD8+ were significantly higher than those before treatment, with statistically significant differences (P<0.05).Table-IV.Table-VI.
Note: * Indicates P>0.05 compared with the RA group; Δ indicates P>0.05 compared with the RA group and the SLE group.statistically significant difference (P<0.05).The SLEDAI score of the SLE group after treatment was significantly lower than that before treatment, with a statistically significant difference (P<0.05).
Note: * Indicates P<0.05 compared with the control group; Δ indicates P<0.05 compared with before treatment.Note: * Indicates P<0.05 compared with a control group; Δ indicates P<0.05 compared with before treatment.

Table -
VI: Comparison of immune indicators between the SLE group and the control group before and after treatment [n (%), ( )]. * Indicates P<0.05 compared with the control group; Δ indicates P<0.05 compared with before treatment.
Note: * Indicates P<0.05 compared with the control group; Δ indicates P<0.05 compared with before treatment.