Dataset Information

Changes in hepatitis B virus surface antibody titer and risk of hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients undergoing biologic therapy for rheumatic diseases: a prospective cohort study.

ABSTRACT:

Background

Our aim was to investigate dynamic changes in hepatitis B virus (HBV) surface antibody (HBsAb) titer and the associated risk of HBV reactivation and clinical course in patients with HBV surface antigen negative/core antibody positive (HBsAg^-/HBcAb⁺) serostatus during antirheumatic therapy with biologic agents.

Methods

In a prospective study from January 2013 to June 2017, we monitored the HBV serostatus of HBsAg^-/HBcAb⁺ patients undergoing biologic therapy for rheumatic diseases. From HBsAb titers at baseline and subsequent time points, we calculated the person-years (PY) contributed by patients with different HBsAb levels: ?100 mIU/mL (high). We analyzed the incidence of detectable HBV DNA and HBV reactivation in each group, and documented the clinical courses of patients.

Results

Among 380 participants, 83 (21.8%) had baseline HBsAb ?100 mIU/mL. Total PY at study end were 169.3 PY from the HBsAb-negative group, 362.7 PY from the low-titer group, and 285.8 PY from the high-titer group. Seventeen patients had detectable HBV DNA, with respective incidence rates in negative, low- and high-titer groups of 4.7/100 PY, 2.5/100 PY, and 0/100 PY. Two HBsAb-negative patients subsequently developed HBV reactivation, an incidence of 1.2/100 PY.

Conclusions

The risk of HBV reactivation varied with HBsAb titer, which changed during biologic therapy. Neither HBV DNA nor reactivation were detected in patients with HBsAb >?100 mIU/mL, whereas HBV DNA without reactivation occurred periodically in patients with HBsAb 10-100 mIU/mL; HBsAb-negative serostatus was associated with a risk of HBV reactivation.

SUBMITTER: Tien YC

PROVIDER: S-EPMC6235201 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Changes in hepatitis B virus surface antibody titer and risk of hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients undergoing biologic therapy for rheumatic diseases: a prospective cohort study.

Tien Ya-Chih YC Yen Hsu-Heng HH Li Ching-Fang CF Liu Mei-Ping MP Hsue Yin-Tzu YT Hung Ming-Hui MH Chiu Ying-Ming YM

Arthritis research & therapy 20181101 1

<h4>Background</h4>Our aim was to investigate dynamic changes in hepatitis B virus (HBV) surface antibody (HBsAb) titer and the associated risk of HBV reactivation and clinical course in patients with HBV surface antigen negative/core antibody positive (HBsAg<sup>-</sup>/HBcAb<sup>+</sup>) serostatus during antirheumatic therapy with biologic agents.<h4>Methods</h4>In a prospective study from January 2013 to June 2017, we monitored the HBV serostatus of HBsAg<sup>-</sup>/HBcAb<sup>+</sup> patien ...[more]

PMID: 30382902

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Project description:Abstract Background The risk of hepatitis B virus (HBV) reactivation after biologic and targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs) therapy in patients with rheumatoid arthritis (RA) combined with HBsAg–/HBcAb+ is still inconsistent. Methods We conducted a systematic review of existing databases from 1977 to August 22, 2021. Studies of RA patients combined with HBsAg−/HBcAb +, treated with b/tsDMARDs and the reported number of HBV reactivation were included. Results We included 26 studies of 2252 HBsAg−/HBcAb+ RA patients treated with b/tsDMARDs. The pooled HBV reactivation rate was 2.0% (95% confidence interval [CI]: 0.01−0.04; I2 = 66%, p < .01). In the subgroup analysis, the HBV reactivation rate of rituximab (RTX), abatacept, and inhibitors of Janus kinase (JAK), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) were 9.0% (95% CI: 0.04−0.15; I2 = 61%, p = .03), 6.0% (95% CI: 0.01−0.13; I2 = 40%, p = .19), 1.0% (95% CI: 0.00−0.03; I2 = 41%, p = .19), 0.0% (95% CI: 0.00−0.02; I2 = 0%, p = .43), 0.0% (95% CI: 0.00−0.01; I2 = 0%, p = .87), respectively. While HBsAb‐ patients have a significant risk of reactivation (odds ratio [OR] = 4.56, 95% CI = 2.45−8.48; I2 = 7%, p = .37), low HBsAb+ group also display a significant risk of reactivation (OR = 5.45, 95% CI: 1.35−21.94; I2 = 0%, p = .46). Conclusions This meta‐analysis demonstrates the highest potential risk of HBV reactivation in HBsAg−/HBcAb+ RA patients receiving RTX treatment, especially HBsAb− patients. Our study furthers the understanding of the prophylactic use of anti‐HBV drugs in such patients. However, it is relative safety to use the inhibitors of IL‐6, TNF‐α, and JAK in these patients. Abatacept is second to rituximab (RTX) at high risk of HBV reactivation in RA patients combined with HBsAg−/HBcAb + . Prophylactic use of anti‐HBV drugs should also be considered in HBsAg−/HBcAb+ RA patients treated with abatacept if they have multiple risk factors.

Project description:Background & aimsHBsAg proteins are useful to identify HBV inactive carriers (ICs), but data on chronic hepatitis D (CHD) are scarce. This study aimed to describe HBsAg composition in CHD, its changes during the evolution, and the potential association with clinical outcomes. In addition, we assess the composition of HBsAg across different HBV genotypes and validate previous results on HBsAg proteins in an independent HBV cohort.MethodsQuantitative HBsAg, medium HBsAg proteins (MHBs), and large HBsAg proteins (LHBs) were measured in two cohorts. The first cohort consisted of patients with CHD. A cross-sectional study of samples from two European institutions (N = 46) was conducted. Outcomes were assessed in a retrospective-prospective study of those patients with a follow-up of >1 year (n = 36), and the longitudinal evolution of HBsAg proteins in those with samples >5 years apart (n = 12) was analysed. The second cohort consisted of patients with HBeAg-negative HBV, and a cross-sectional study was performed (N = 141).ResultsForty-one (89%) patients with CHD had detectable HDV-RNA, and the presence of HDV-RNA was associated with higher LHBs proportion (p = 0.010). Baseline MHBs (p = 0.051) and MHBs proportion (p = 0.086) tended to be higher in those developing clinical outcomes (9/36, 25%) after a median follow-up of 5.9 years. Patients in which HDV-RNA became spontaneously undetectable during follow-up (5/31, 16.1%) tended to present lower MHBs proportion (p = 0.085). In the longitudinal study, changes in LHBs proportion were observed (p = 0.041), whereas MHBs proportion remained stable (p = 0.209). Regarding HBV, ICs showed lower LHBs proportion (p = 0.027). LHBs and MHBs differed significantly according to HBV genotype, regardless of the HBV phase.ConclusionsPatients with CHD with detectable HDV-RNA presented higher LHBs proportion than those with undetectable HDV-RNA. A trend toward having higher baseline MHBs proportion was observed in patients who developed clinical outcomes or remained with detectable HDV-RNA. This study validates the different HBsAg composition in HBV ICs and reveals the HBV-genotype influence in HBsAg composition.Impact and implicationsThe composition of HBsAg in chronic hepatitis D differs in patients with detectable and undetectable HDV viral load and may help predict the likelihood of achieving undetectable HDV viraemia and the development of clinical events such as decompensation. The composition of the surface antigen is also useful to distinguish inactive carriers of HBV, and it varies according to HBV genotype.

Dataset Information

Changes in hepatitis B virus surface antibody titer and risk of hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients undergoing biologic therapy for rheumatic diseases: a prospective cohort study.

Background

Methods

Results

Conclusions

Publications

Changes in hepatitis B virus surface antibody titer and risk of hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients undergoing biologic therapy for rheumatic diseases: a prospective cohort study.

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