Hepatitis B Virus Reactivation Research Articles

A Hyper-Glycosylation of HBV Surface Antigen Correlates with HBsAg-Negativity at Immunosuppression-Driven HBV Reactivation in Vivo and Hinders HBsAg Recognition in Vitro.

Immune-suppression driven Hepatitis B Virus (HBV)-reactivation poses serious concerns since it occurs in several clinical settings and can result in severe forms of hepatitis. Previous studies showed that HBV strains, circulating in patients with HBV-reactivation, are characterized by an enrichment of immune-escape mutations in HBV surface antigen (HBsAg). Here, we focused on specific immune-escape mutations associated with the acquisition of N-linked glycosylation sites in HBsAg (NLGSs). In particular, we investigated profiles of NLGSs in 47 patients with immunosuppression-driven HBV-reactivation and we evaluated their impact on HBsAg-antigenicity and HBV-replication in vitro. At HBV-reactivation, despite a median serum HBV-DNA of 6.7 [5.3–8.0] logIU/mL, 23.4% of patients remained HBsAg-negative. HBsAg-negativity at HBV-reactivation correlated with the presence of >1 additional NLGSs (p < 0.001). These NLGSs are located in the major hydrophilic region of HBsAg (known to be the target of antibodies) and resulted from the single mutation T115N, T117N, T123N, N114ins, and from the triple mutant S113N+T131N+M133T. In vitro, NLGSs strongly alter HBsAg antigenic properties and recognition by antibodies used in assays for HBsAg-quantification without affecting HBsAg-secretion and other parameters of HBV-replication. In conclusion, additional NLGSs correlate with HBsAg-negativity despite HBV-reactivation, and hamper HBsAg-antigenicity in vitro, supporting the role of NGSs in immune-escape and the importance of HBV-DNA for a proper diagnosis of HBV-reactivation.

An electronic alert system increases screening for hepatitis B and C and improves management of patients with haematological disorders

Treatment of haematological disorders in patients with chronic hepatitis B or resolved infection (anti-HBc-positive) is associated with a risk of hepatitis B reactivation. Moreover, patients with chronic hepatitis C have a higher risk of haematological malignancies than general population. An electronic alert system was developed to promote screening of hepatitis B (HBV) and C (HCV) in patients starting haematological therapies. The system included screening and linkage to care and a request for testing in those without data. From March, 2017 to March, 2018 data from 420 consecutive patients with haematological diseases were included. At first prescription before the alerts, the HCV and HBV screening rate was 60.5%. Following the alerts, an additional 115 were screened, increasing the overall screening rate to 87.9%. Anti-HBc alone was detected in 57, anti-HCV in 13, and HBsAg in 2 patients. Overall, 68% of patients with any viral hepatitis markers were previously not know, and the impact was particularly important for anti-HBc detection (47/57 unknown). Nucleoside analogues were prescribed in 28 (49.1%) anti-HBc-positive and the 2 HBsAg-positive patients. Prospective follow-up with HBV DNA and HBsAg testing showed no cases of HBV reactivation. An estimated 1.2 HBV reactivations were avoided as consequence of the alert system. In summary, an electronic alert system increased viral hepatitis screening in patients receiving haematological treatment and led to improvements in the management of these patients, including avoided HBV reactivation.

Safety and Efficacy of CAR-T Cell Targeting BCMA in Patients with Multiple Myeloma Co-Infected with Chronic Hepatitis B Virus

Background: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in patients with chronic or resolved HBV infection undergoing anticancer therapy. There is a risk of HBV reactivation after infusion of chimeric antigen receptor (CAR) T cells for patients with refractory/relapsed (R/R) multiple myeloma (MM). Methods: We administered B cell maturation antigen (BCMA) CAR-T cells by infusion to nine R/R MM patients with chronic or resolved HBV infection. Patient serum was analyzed to determine the expression of five components of HBV and the copy number of HBV DNA. HBV reactivation was defined if a patient re-exhibited hepatitis B surface antigen (HBsAg) or HBV DNA regrowth after CAR-T therapy. Findings: In one HBsAg-positive patient, no HBV reactivation was observed during the follow-up period of 9.8 months after administration of anti-HBV drugs before and after CAR-T therapy. Among eight patients with MM who had resolved HBV infection, two patients administered prophylactic anti-HBV drugs did not exhibit HBV reactivation. Of the six patients who did not use prophylactic antiviral drugs, five did not exhibit HBV reactivation, while one showed recurrence of HBsAg without detection of HBV DNA or damage to liver function. The best objective response rate was 100%, and the progression-free survival (PFS) at 12 months was of 88.89% (median PFS was not observed). Interpretation: These findings showed that BCMA CAR-T cell therapy could be used in R/R MM patients with chronic or resolved HBV infection and that antiviral drugs should be administered in these patients during CAR-T cell therapy. Trial Registration: This study was conducted at the Affiliated Cancer Hospital of Zhengzhou University and was registered with clinicaltrials.gov (registration number: NCT03664661). Funding Statement: This study was supported by grants from Henan Medical Science and Technique Foundation (grant number 2018020484; SBGJ2018085); Henan Provincial Scientific and technological project (grant number 162300410095); Natural Science Foundation of Henan (grant number 182300410344); Henan province industry-university-research cooperation project (grant number 182107000027). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by the Ethics Committee of the Affiliated Cancer Hospital of Zhengzhou University. Informed consent was obtained from all patients.

A prospective trial of vaccine to prevent hepatitis B virus reactivation after hematopoietic stem cell transplantation

Hepatitis B virus (HBV) reactivation reportedly occurs frequently after hematopoietic stem cell transplantation (HSCT) in resolved HBV-infected patients. Here, 50 patients with resolved HBV infections and scheduled to undergo HSCT were enrolled; all subjects were vaccinated with three doses of hepatitis B vaccine 12 months after HSCT and the incidence of HBV reactivation was monitored. The patients’ characteristics were: median age, 61 (34–72) years; male/female, 27/19; allogeneic/autologous, 40/6; bone marrow/peripheral blood stem cells/cord blood, 26/16/4. Of the 46 patients who underwent HSCT, 19 were excluded and did not make it to vaccination due to relapse of underlying disease, HBV reactivation within 12 months of HSCT, or transfer of patients. The remaining 27 were vaccinated 12 months after HSCT and monitored for 2 years. Six showed HBV reactivation, with a 2-year cumulative reactivation incidence of 22.2%; the same incidence was 27.3% only in allogeneic HSCT patients. Factors associated with HBV reactivation included the discontinuation of immunosuppressants (P = 0.0379) and baseline titers of antibody against hepatitis B surface antigen (P = 0.004). HBV reactivation with vaccination following HSCT could occur despite maintenance of serum anti-HBs at more than protective levels.

Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection

The outcome of HBV infection, including the dynamics of HBsAg and HBV virological reactivation, among patients coinfected with HCV receiving direct-acting antivirals (DAAs) remains unclear. Thus, we aimed to analyze HBV-related outcomes in these patients. Serial HBsAg and HBV DNA levels were measured in 79 HBV/HCV-coinfected patients receiving DAAs (13 receiving anti-HBV nucleot(s)ide analog [NUC] therapy simultaneously). The endpoints included HBsAg dynamics and seroclearance, HBV reactivation (HBV DNA >1 log increase or >100 IU/ml if undetectable at baseline) and HBV-related clinical reactivation. HBsAg levels declined from a median of 73.3 IU/ml at baseline to 16.2 IU/ml at the end-of-DAA treatment and increased to 94.1 IU/ml at 12 months post-treatment. During a mean 11.1-months of follow-up, 8 (10.1%) patients experienced HBsAg seroclearance and 30 (38.0%) HBV reactivation (12-month cumulative incidence, 10.3% and 40.4%, respectively). Patients with pre-treatment HBsAg ≤10 IU/ml had a significantly higher rate of HBsAg seroclearance (hazard ratio [HR] 8.52; 95% CI 1.048-69.312) and lower risk of HBV reactivation than those with pre-treatment HBsAg >10 IU/ml (HR 2.88; 95% CI 1.057-7.844) in multivariate analyses. Six patients (4 cirrhotics) not receiving NUC therapy experienced HBV-related clinical reactivation; 3 of the 4 cirrhotics developed liver failure and 2 died despite immediate NUC therapy. Compared to untreated HBV-monoinfected patients, HBV/HCV-coinfected patients without NUC prophylaxis had a similar rate of HBsAg seroclearance, but a significantly higher risk of HBV reactivation following DAA therapy (HR 6.59; 95% CI 2.488-17.432). DAA-treated HBV/HCV-coinfected patients had significantly higher rates of HBV seroclearance, particularly among those with low pre-treatment HBsAg titer, but were at higher risk of HBV reactivation, particularly among those with higher pre-treatment HBsAg titer. Prophylactic anti-HBV therapy is essential for cirrhotic patients, irrespective of baseline HBV DNA levels. We studied outcomes relating to hepatitis B virus (HBV) in patients coinfected with both hepatitis B and C. Patients receiving direct-acting antiviral treatment for hepatitis C were more likely to experience seroclearance (or functional cure of HBV), but were also more likely to experience HBV reactivation, which can lead to hepatitis, liver failure and death. In coinfected cirrhotic patients being treated for HCV, prophylactic treatment for HBV is mandatory.

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg\u2212/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis

To investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)−/ HBV core antibody (HBcAb)+ patients who underwent rituximab (RTX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg−/HBcAb+ patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg−/HBcAb+ RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1–4 years after the first dose of RTX and 0.5–1.5 years after the last one. In HBsAg−/HBcAb+ patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)− at baseline than in those who were HBsAb+ (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg−/HBcAb+ RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.

Hepatitis B virus reactivation in kidney transplant patients with resolved hepatitis B virus infection: Risk factors and the safety and efficacy of preemptive therapy.

Hepatitis B virus (HBV) reactivation is associated with complications and adverse outcomes in patients with clinically resolved HBV infection who are seronegative for hepatitis B surface antigen (HBs Ag), and seropositive for hepatitis B core antibody (HBc Ab) and/or hepatitis B surface antibody (HBs Ab) before kidney transplantation (KT). We retrospectively analyzed 52 patients with resolved HBV infection who were HBV-DNA negative. HBV-DNA after KT was evaluated, and the occurrence of HBV reactivation and outcomes were monitored. We defined HBV reactivation as seropositivity for HBV-DNA at or above the minimal detection level of 1.0log IU/mL and treated preemptively (using entecavir) when the HBV-DNA level was at or above 1.3log IU/mL, in accordance with the Japanese Guidelines for HBV treatment. Among the 52 patients, the mean age was 57.2±10.8years. The median HBc Ab titer was 12.8 (interquartile range, 4.6-42.6) cutoff index, and five (9.6%) cases of HBV reactivation occurred. No patients developed graft loss and died due to HBV reactivation. Statistical analysis showed that age and HBc Ab titer were significant risk factors for HBV reactivation (P=.037 and P=.042, respectively). No significant differences were found between graft survival and the presence or absence of HBV reactivation. These results suggest that HBc Ab titer and age could be significant risk factors for HBV reactivation. Resolution of HBV infection did not appear to be associated with patient or graft survival, regardless of whether HBV reactivation occurred, when following our preemptive strategy.

Anti-HBc impacts on the risk of hepatitis B reactivation but not on survival of solid-organ transplant recipients.

Immunosuppression can lead to hepatitis B virus (HBV) reactivation in hepatitis B core antigen antibodies (anti-HBc) positive patients, especially those undergoing chemotherapy, although there is limited data on solid organ recipients, especially lung transplantation. Our aim was to analyze the risk of HBV reactivation and the potential impact of anti-HBc-positive status (both donors and recipients) on prognosis in a lung, kidney, and liver transplantation cohort.Retrospective analysis including data from all transplants in adults (2011–2012) in a tertiary hospital, with prospective HBV serology study to assess the risk of reactivation and its possible impact on survival.In total, 392 transplant recipients were included (196 kidney, 113 lung, 83 liver). Pre-transplantation anti-HBc screening was more frequent in liver recipients (P < .001) and donors (P < .001) than in kidney or lung. Fifty-five (14%) recipients were anti-HBc-positive and were not undergoing antiviral prophylaxis. Three (5.4%) cases of HBV reactivation occurred: 2 in pre-transplant anti-HBc-positive recipients and 1 with prior unknown anti-HBc status. All were HBeAg+ with HBV deoxyribonucleic acid (DNA) >10E8 IU/mL and only mild fibrosis. Baseline recipient anti-HBc positive status was the only factor associated with HBV reactivation. No reactivation cases occurred in lung or kidney recipients of anti-HBc positive grafts. Survival was lower in lung transplants, especially in human immunodeficiency virus-infected patients and those with prior immunosuppression.Anti-HBc positive status is a risk factor for HBV reactivation in solid organ recipients. Anti-HBc testing is highly recommended in solid-organ transplant recipients in order to identify those anti-HBc positive and therefore candidates for periodical hepatitis B surface antigen (HBsAg) and HBV DNA screening after transplant.

Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis

BackgroundReactivation of hepatitis B virus (HBV) replication is a well-recognised complication in patients receiving disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA). Limited data exist on HBV reactivation among patients...

The combined usage of accurate virological and serological HBV markers can help to identify HBsAg-negative/anti-HBc-positive patients at higher risk of HBV-reactivation and to optimize prophylaxis duration in oncohematological setting

Introduction: Prevention of HBV-reactivation (HBV-R) in patients undergoing immunosuppressive therapy is still challenging. We investigate the role of HBV markers in predicting HBV-R in HBsAg-negative/anti-HBc-positive oncohematological patients.

Impact of HBV infection in HCV/HBV coinfected patients treated with DAAs IN Northern Italy

Background and AIMS: Several small series have described the incidence of HBV reactivation during direct -acting antivirals (DAAS), so far. However, many key issues remain unresolved. Aims of the present study was to evaluate both the incidence and the clinical impact of HBV reactivation in a large cohort of HCVHBV co-infected- patients treated in North Italy Methods: Between January-2015 and December-2018 data from a common web based program (NAVIGATORE), 16.161 patients treated with DAAs in Veneto and Lombardia were collected.

Hepatitis B Reactivation: A Potentially Serious Complication of Chemotherapy for Solid Tumors

We present a case of hepatitis B reactivation in a patient receiving adjuvant chemotherapy for early breast cancer. This is a 49-year-old post-menopausal, Chinese female with history of chronic hepatitis B with inactive carrier state, and right invasive ductal carcinoma staged as cT2N1M0, pT2N1aM0, anatomic stage IIB, prognostic stage IIA, estrogen and progesterone receptor positive, and human epidermal growth factor 2 negative. The patient underwent bilateral mastectomy with implant reconstruction and right axillary lymph node dissection followed by adjuvant chemotherapy planned as dose dense doxorubicin and cyclophosphamide (ddAC), followed by dose dense paclitaxel (ddT). Two weeks after her first cycle of dose dense paclitaxel, she developed grade III HBV reactivation with hepatitis. This report highlights HBV reactivation as a potential complication of chemotherapy for solid tumors, and reviews recommended HBV screening, prevention and management of HBV reactivation in this patient population.

Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway

Mechanisms of hepatitis B virus (HBV) reactivation after hepatitis C virus (HCV) elimination by direct-acting antiviral (DAA) treatment in HBV/HCV-co-infected patients remain unclear. We examined RIG-I-like helicase (RLH) pathway activation by HBV mono-infection, HCV mono-infection or HBV/HCV co-infection and interference between HBV and HCV in primary human hepatocytes. Interference between HBV and HCV and HBV reactivation after DAA treatment in humanized-liver mice were assessed. HCV infection activated RLH pathway, as evidenced by RIG-I, ISG15 and ISG56 expression induction; HBV caused only RIG-I induction in vitro. RLH activation was also found in HBV/HCV-co-infected cells, and HBV replication were suppressed in HBV/HCV-co-infected than in HBV-mono-infected cells. siRNA-mediated double knockdown of ISG15 and ISG56 increased HBV replication in HBV/HCV-co-infected cells. HCV infection activated RLH pathway and suppressed HBV replication in humanized-liver mice. Subsequent elimination of HCV by DAA administration downregulated RLH pathway and upregulated HBV replication in mice. RLH pathway was activated in livers of chronic hepatitis C patients compared to those of chronic hepatitis B or non-B, non-C patients. The RLH pathway activation was downregulated by HCV elimination. In conclusion, HCV infection activated RLH pathway and suppressed HBV replication in human hepatocytes. HCV elimination upregulated HBV replication, probably through RLH pathway downregulation.

Determining Whether Prophylactic Antiviral Treatment Is Necessary in HBsAg-Negative/HBcAb-Positive Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation.

The incidence of hepatitis B virus (HBV) infection is high in the Asian population. Increasing attention is being given to the risk of HBV reactivation in hepatitis B core antibody-positive [HBcAb(+)] patients during immunosuppressive therapy. Knowledge of HBV reactivation in hematopoietic stem cell transplantation (HSCT) is limited. Moreover, the effect of hepatitis B surface antibody (HBsAb) on HBV reactivation in HBcAb(+) patients during HSCT remains uncertain. We sought to investigate the role of HBsAb and the need for prophylactic antiviral treatment in hepatitis B surface antigen-negative [HBsAg(-)]/HBcAb(+) patients during HSCT. We classified 665 HBsAg(-) HSCT recipients into 4 groups: HBcAb(-)HBsAb(-) (n=189), HBcAb(-)HBsAb(+) (n=176), HBcAb(+)HBsAb(-) (n=49), and HBcAb(+)HBsAb(+) (n=251). HBV reactivation was identified in 16 patients after HSCT. The median time to HBV reactivation was 645 days (range, 455 to 1957 days) after transplantation. The cumulative HBV reactivation rate was significantly higher in the HBcAb(+)HBsAb(-) group compared with the HBcAb(+)HBsAb(+), HBcAb(-)HBsAb(-), and HBcAb(-)HBsAb(+) groups, respectively (P< .001). Notably, the risk of HBV reactivation was significantly higher in the HBcAb(+)HBsAb(-) group compared with the HBcAb(+)HBsAb(+) group (P= .007; hazard ratio, 4.750; 95% confidence interval, 1.531 to 14.737). Our results point to a protective role of HBsAb in HBV-resolved patients undergoing HSCT and indicate that prophylactic anti-HBV treatment might not be mandatory for HBsAg(-), HBcAb(+)HBsAb(+) patients following HSCT. The surveillance protocol of intense follow-up early (HBV DNA and HBsAg monthly) might not be necessary.

Isolated Anti-HBc: Significance and Management.

Hepatitis B virus (HBV) infection is prevalent worldwide and is associated with dramatic levels of morbidity and mortality. Isolated anti-HBc (IAHBc) is a particular serological pattern that is commonly found in immunocompromised patients. There is ongoing debate regarding the management of patients with IAHBc. Herein, we summarize the current guidelines and the newest evidence. The frequency of IAHBc is variable, with a higher prevalence in some populations, such as persons living with HIV and others immunocompromised patients. The risk of HBV reactivation depends on host factors (including immunosuppression) and viral factors. It is now well established that immunocompromised patients can be classified into three groups for risk according to the type of immunosuppression and/or treatment. In patients at high risk, HBV therapy has to be considered systematically. In patients at moderate risk, the decision is based on the level of HBV DNA (preemptive treatment or monitoring and vaccination). In patients with low risk, HBV vaccination is another possible approach, although further studies are needed to assess the type of preemptive strategy.

Optimal timing of antiviral therapy for patients with malignant tumor who presented with hepatitis B reactivation during chemotherapy and/or immunosuppressive therapy.

Background: Hepatitis B virus (HBV) reactivation may occur with chemotherapy and/or immunotherapy. Antiviral prophylaxis is recommended for all patients who are hepatitis B surface antigen (HBsAg)-positive during chemotherapy and/or immunosuppressive therapy. However, the optimal timing of antiviral therapy before chemotherapy and/or immunosuppressive therapy is not fully elucidated.Patients and methods: We retrospectively evaluated 446 HBsAg-positive patients who underwent chemotherapy and/or immunosuppressive therapy. The cumulative rates of HBV reactivation were evaluated using the Kaplan-Meier method and were compared using the log-rank test. The risk factors of HBV reactivation were examined via univariate and multivariate analyses using the Cox proportional hazards model.Results: The cumulative HBV reactivation rates of patients who received antiviral therapy before chemotherapy and/or immunosuppressive therapy were significantly lower than those of patients who received antiviral therapy after chemotherapy and/or immunosuppressive therapy (P = 0.002). The incidence of HBV reactivation was significantly different between patients who received antiviral therapy at least 1 day before chemotherapy and/or immunosuppressive therapy and those who did not (P = 0.006). No significant difference was observed in the HBV reactivation rates between patients who received antiviral therapy at least 2 days (P = 0.310), 3 days (P = 0.494), and 1 week (P = 0.655) before chemotherapy and/or immunosuppressive therapy and those who did not. The multivariate Cox proportional hazards model showed that women had a lower risk of developing HBV reactivation than men (P = 0.025). The use of the prophylactic antiviral agent entecavir, compared with lamivudine and telbivudine, was associated with the decreased risk of developing HBV reactivation (P = 0.002).Conclusion: HBsAg-positive patients who received preemptive antiviral therapy after chemotherapy and/or immunosuppressive therapy had a high risk of developing HBV reactivation. However, it is not necessary for patients to receive antiviral therapy at least 1 week before chemotherapy and/or immunosuppressive therapy.

Hepatitis B Virus Reactivation in Patients with Psoriasis on Biologic Therapies: A Retrospective Study

Background: There are limited data on the safety of biological therapies in psoriasis patients with hepatitis B virus (HBV) infection in the literature, and are still ongoing controversies about HBV reactivation in patients treated with biologics for psoriasis. Aims: This was aimed to investigate the demographic, clinical, and laboratory characteristics of the patients with HBV seropositive receiving biological treatment for psoriasis. Study Design: This was a retrospective observational study. Materials and Methods: Ninety-seven patients with psoriasis treated with biologics in the outpatient clinic were evaluated retrospectively. Of these, 16 patients with HBV seropositive were included in the study. Patients with positive HBV serology were divided into three groups as chronic HBV infection, past HBV infection, and isolated core antibody positivity (HBV core-specific antibody [HBcAb]). The demographic, clinical, and laboratory characteristics of the patients were obtained from the records. Results: Of the patients, 5 patients were female (31.2%), and 11 were male (68.8%). The mean age of the patients was 55.81 ± 11.05. Thirteen of the patients had past HBV infection, three had isolated HBcAb positive. Infliximab (n = 13) was the most common biologic agent used, followed by adalimumab (n = 6), secukinumab (n = 4), ustekinumab (n = 2), and etanercept (n = 2). The mean duration of treatment was 3.59 ± 2.76 years. The HBV reactivation occurred in only one patient with past HBV infection receiving infliximab (6.2%). Conclusion: It remains unclear how exactly the biologic drugs for psoriasis impact viral reactivation. For the safe use of biological agents in psoriasis patients with HBV seropositive, screening tests must be performed with a triple serology, including HBV surface antigen, HBV surface-specific antibody, and HBcAb. The patients who have positive HBV serology must be monitored closely with reactivation markers and receive antiviral prophylaxis if they are at moderate-to-high risk of HBV reactivation.

Reactivation of hepatitis B virus infection in rheumatic diseases: risk and management considerations.

In patients with rheumatic diseases undergoing immunosuppressive treatment, hepatitis B virus reactivation (HBVr) has been long recognized as a major treatment-related adverse event with substantial morbidity and mortality. Because HBVr is easily preventable with appropriate screening and monitoring strategies, and, when indicated, prophylactic antiviral treatment, awareness of this complication is of the utmost importance, especially in the era of biologic treatments. As a condition, it continues to be topical, in view of the emergence of novel classes of immunosuppressive drugs (i.e. Janus kinase inhibitors) acquiring licenses for a variety of rheumatic diseases. The class-specific risk of these agents for HBVr has not yet been determined. Moreover, ambiguity still exists for the management of patients planned to be treated with traditional agents, such as cyclophosphamide and glucocorticoids, particularly in the setting of resolved HBV infection. Clinicians in the field of rheumatic diseases should be tailoring their practice according to the host’s profile and treatment-specific risk for HBVr. In this review, the authors attempt to critically review the existing literature and provide practical advice on these issues.

Multidisciplinary Approach to Prevent de novo Hepatitis B in Patients with Rheumatoid Arthritis.

The reactivation of hepatitis B virus (HBV) in patients with rheumatoid arthritis (RA) is currently a social problem. Our hospital has established a project team, which consisted of medical staff including doctors, nurses, pharmacists, and technicians, to prevent HBV reactivation and subsequent de novo hepatitis B in 2015. To verify the usefulness of the team, we aimed to examine the implementation rate of HBV screening tests in patients with RA in 2011, 2015, and 2018. We also examined the rate of HBV infection, as well as the rate of HBV reactivation during the course. In this study, medical records of patients who visited our hospital in 2011, 2015, and 2018 were retrospectively reviewed. HBV screening was completed when hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb) were all examined. The prevalence of patients who completed HBV screening dramatically increased from 2.4% in 2011 to 79.1% in 2015 and 86.9% in 2018. Patients who completed the screening had significantly higher rates of liver dysfunction, methotrexate use, and use of biological disease-modifying antirheumatic drugs than those who did not. Of the 767 patients who completed HBV screening in 2018, 157 patients (20.5%) had previously resolved HBV infection (HBsAg-negative but HBsAb- and/or HBcAb-positive). During a mean follow-up of 41.0 months, reactivation of HBV was observed in 10 out of the 157 patients (6.4%); however, none developed de novo hepatitis B. In conclusion, our multidisciplinary approach to prevent de novo hepatitis B is considered useful.

Atypical presentation of Good syndrome: acute hepatitis from hepatitis B virus reactivation

Good syndrome (GS) is a primary immunodeficiency (PID) that presents in middle aged to older adults with features of thymoma, hypogammaglobulinemia, CD4 T lymphopenia, inverted CD4/CD8+ ratio, and impaired T-cell mitogen proliferative responses. We present a patient, a 62-year-old female, who first presented with disease manifestation of acute hepatitis from hepatitis B virus (HBV) reactivation, which was subsequently complicated by recurrent hospitalizations for recurrent pneumonia and concomitant Helicobacter pylori and cytomegalovirus enteritis. She was later found to have thymoma and hypogammaglobulinemia and was diagnosed with GS. Although the well-known importance of T cell is in directing B-cell responses in the immunopathology of thymoma, low levels of natural killer and CD4+ γδ T cells may also be the cause of both low immune surveillance of tumor development and weak clearance of viral infection. Hence, the temporal sequence of opportunistic infections following HBV reactivation and thymoma discovery may reflect a loss of immune surveillance as the first manifestation of PID.