scholarly journals SAT0140 SAFETY OF TOFACITINIB THERAPY IN HBSAG CARRIERS WITH RHEUMATOID ARTHRITIS: A PROSPECTIVE STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1008.2-1008
Author(s):  
L. Fang ◽  
Z. Lin ◽  
Z. Liao ◽  
O. Jin ◽  
Y. Pan ◽  
...  

Background:Targeted synthetic DMARDs (ts-DMARDs) are becoming more available and affordable in developing countries, where the prevalence of hepatitis B virus (HBV) infection is still an important public health issue. The safety of ts-DMARDs therapy in terms of the reactivation of hepatitis B virus (HBV) infection need more concern. Rare data from a prospective study focus on the use of ts-DMARDs in patients with concurrent rheumatoid arthritis (RA) and HBV infection were available by now.Objectives:To evaluate the influence of tofacitinib on reactivation of HBV infection in HBsAg carriers with RA.Methods:In this 52 weeks observation, HBsAg carriers with active RA (DAS28>5.1) despite failed combined treatment with MTX and other non-biological DMARDs were enrolled. Patients must have normal liver function prior to study. All patients received therapy with tofacitinib (5mg twice daily) and concomitant MTX (10-12.5mg/w). Entecavir was prescribed preventively for patients who had a baseline HBV load >2000 copy/ml (group 1), and Lamivudin for patients with HBV load ≤ 2000 copy/ml (group 2). Liver enzymes (AST/ALT) and HBV viral load were monitored every 4 weeks. Increased viral load and abnormal liver function were managed according to expert opinion.Results:Thirteen patients (10 female) were recruited. Nine patients had a baseline viral load >2000 copy/ml (group 1, with preventive Entecavir), and the other 4 patients had a viral load ≤ 2000 copy/ml (group 2, with preventive Lamivudin). Two patients from group 1 discontinued tofacitinib at week 12 due to ineffectiveness, and both continued taking Entecavir for another 3 months after the discontinuation of tofacitinib.No reactivation of hepatitis B was observed in patients from group 1. One patients (female, 54 years old) from group 2 underwent a mild increase of both ALT and AST (67 and 56 IU/L, respectively) at week 16. An elevated viral load (4.9e6 copies/ml, baseline 1.4e3) and a HBV YMDD mutant was also found. The tofacitinib treatment continued. After prescription of Adefovir (combined with the pre-existing Lamivudin), both liver enzyme and viral load decreased to normal range in 8 weeks and remained normal throughout the study.Conclusion:An aggressive Tofacitinib + MTX therapy may be a safe option for HBsAg carriers with cs-DMARDs refractory RA. More active and effective prophylaxis strategy may be recommended to reduce the risk of HBV reactivation during the treatment.References:[1]Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis 2018; 77:780-2.Disclosure of Interests: :None declared

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 427.2-427
Author(s):  
L. Fang ◽  
Z. Lin ◽  
Z. Liao ◽  
O. Jin ◽  
J. Gu

Background:Targeted synthetic DMARDs (ts-DMARDs) are becoming more available and affordable in developing countries, where the prevalence of hepatitis B virus (HBV) infection is still an important public health issue. The safety of ts-DMARDs therapy in terms of the reactivation of hepatitis B virus (HBV) infection need more concern. Rare data from a prospective study focus on the use of ts-DMARDs in patients with concurrent ankylosing spondylitis (AS) and HBV infection were available by now.Objectives:To evaluate the influence of tofacitinib on reactivation of HBV infection in HBsAg carriers with AS.Methods:In this 52 weeks observation, HBsAg carriers with active AS (BASDAI ≥ 4) despite failed treatment with at least two NSAIDs and sulfasalazine (for patients with persistent peripheral arthritis) were studied. Patients must be positive for HBsAg and have a normal liver function prior to study.All patients received therapy with tofacitinib (5mg twice daily). Entecavir were prescribed preventively regardless of individual viral load. Pre-existing NSAIDs and sulfasalazine were allowed. Liver enzymes (AST/ALT) and HBV viral load were monitored every 4 weeks. Increased viral load and abnormal liver function were managed according to expert opinion.Results:Eleven patients (9 male) were recruited. Eight patients had a baseline viral load >2000 copy/ml (group 1), and the other 3 patients had a viral load ≤ 2000 copy/ml (group 2). Two patients from group 1 discontinued tofacitinib at week 12 due to ineffectiveness, and both continued taking Entecavir for another 3 months after the discontinuation of tofacitinib.One patients (male, 26 years old) from group 1 underwent a mild increase of both ALT and AST (67 and 56 IU/L, respectively) at week 16, but no elevated viral load (2.1e3 copies/ml, baseline 2.8e3) or a HBV YMDD mutant was found. The tofacitinib treatment continued. After prescription of polyene phosphatidyl choline, the liver enzyme of this patient decreased to normal range in 4 weeks and remained normal throughout the study.No reactivation of hepatitis B was observed in patients from group 2.Conclusion:Tofacitinib treatment may be a safe and effective option for HBsAg carriers with AS refractory to traditional treatment. Prophylaxis strategy with effective anti-viral drugs is recommended.References:[1]Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis 2018; 77:780-2.Disclosure of Interests:None declared


2016 ◽  
Vol 43 (5) ◽  
pp. 869-874 ◽  
Author(s):  
Valentina Varisco ◽  
Mauro Viganò ◽  
Alberto Batticciotto ◽  
Pietro Lampertico ◽  
Antonio Marchesoni ◽  
...  

Objective.Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc–positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis.Methods.Thirty-three HBsAg-negative/anti-HBc–positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1–8) over 34 months (range 0–80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated.Results.None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs–negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0–70) after RTX discontinuation, no HBV reactivation was observed.Conclusion.The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.


1978 ◽  
Vol 8 (3) ◽  
pp. 302-305
Author(s):  
A Tzukert ◽  
S G Sandler

Sera from 576 healthy adults were tested for the hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) to evaluate the role of routine dental care as a factor in the spread of hepatitis B virus (HBV) infection. Serological evidence of prior HBV infection, manifested by acquisition of anti-HBs, was detected in 97 (16.8%) individuals, and 6 (1.0%) were identified to be asymptomatic HBsAg carriers. The anticipated correlations of HBsAg and anti-HBs with age, country of birth, and socioeconomic status were observed in the study population. However, prevalences of both HBsAg and anti-HBs were inversely related to the lifetime total of dental care visits. These findings indicated that, in a region in which the HBsAg carrier state and hepatitis B are prevalent, routine dental care is not identified as an important factor in the spread of HBV infection. While the results do not exclude the obvious possibility that cross-infections with HBV may occur during dental care in specific situations, they indicate that this mode of infection is exceptional.


Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 430
Author(s):  
Asgeir Johannessen ◽  
Bitsatab Mekasha ◽  
Hailemichael Desalegn ◽  
Hanna Aberra ◽  
Kathrine Stene-Johansen ◽  
...  

High viral load and positive hepatitis B e-antigen (HBeAg) results are risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV). In sub-Saharan Africa, little is known about the distribution of these risk factors, as well as early childhood HBV transmission. In this study, Ethiopian women aged 18–45 years with chronic hepatitis B were assessed for the presence of HBeAg and high viral load. Their children below 4 years of age were invited for assessment of viral markers, defining active HBV infection as a positive hepatitis B s-antigen (HBsAg) and/or detectable HBV DNA. In total, 61 of 428 HBV-infected women (14.3%) had a positive HBeAg result and/or a high viral load. Of note, 26 of 49 women (53.1%) with viral load above 200,000 IU/mL were HBeAg negative. Among 89 children born of HBV-infected mothers (median age 20 months), 9 (10.1%) had evidence of active HBV infection. In conclusion, one in seven women with chronic hepatitis B had risk factors for MTCT, and HBeAg was a poor predictor of high viral load. One in ten children born of HBV-infected women acquired HBV-infection despite completing their scheduled HBV vaccination at 6, 10 and 14 weeks of age.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3882-3882
Author(s):  
Dawn Mya ◽  
Shuting Han ◽  
Yeow Tee Goh ◽  
Daryl Tan

Abstract Abstract 3882 Poster Board III-818 Introduction Patients with hepatitis B virus (HBV) infection, defined by the presence of HBV surface antigen (HBsAg), have an increased risk of HBV reactivation when they are on immunosuppressive treatment for multiple myeloma (MM). Although there is no guideline for MM patients with HBV infection, current lymphoma guidelines do recommend that these patients should receive antiviral prophylaxis during and after chemotherapy. Of late, the advent of bortezomib in the management of MM has resulted in a high reported incidence of variecella-zoster reactivation. The risk of HBV reactivation in MM patients with HBV infection undergoing treatment has not been previously studied. As HBV infection is endemic in Asia, we sought to evaluate the prevalence of HBV infection in our patients, the incidence of its reactivation especially in patients receiving bortezomib and the role of anti-viral prophylaxis. Methods Previously untreated MM patients diagnosed from 2000-2008 who were tested for HBsAg in our institution were included. Hepatitis attributable to HBV reactivation was defined as an increase in HBV DNA levels of tenfold, or an absolute increase greater than105 copies/ml in the HBV DNA level. HBV infected patients were prospectively followed. 33% of all patients have been exposed to bortezomib, while 26% received high dose therapy with autologous stem cell transplantation (HDT/ASCT). Results 243 untreated MM patients were identified. The prevalence of HBV infection is 5.8% (14/243). 6 (43%) HBV infected patients had detectable HBV DNA viral load (>3 log) at baseline. All 6 patients had normal baseline liver function tests and received lamivudine prophylaxis. All 14 HBV infected patients went on to receive systemic therapy for MM, with continual monitoring of HBV DNA viral load and liver enzymes for viral reactivation. 4 patients with undetectable HBV DNA load did not receive anti-viral prophylaxis. Of these 14 patients, 3 (21%) who had been on lamivudine prophylaxis had reactivation of the virus, with 1 dying from it, and 1 having emergence of a mutant viral strain. Two of them had no detectable viral load at presentation. Two patients reactivated 3 and 5 months after HDT/ASCT, while 1 reactivated immediately after a bortezomib/ doxil salvage regimen. Conclusion The risk of HBV reactivation appeared to be commonest during the immune reconstitution phase after HDT/ASCT. Although the majority of patients with HBV infection and not receiving HDT/ASCT do not reactivate, the risk may not negligible when bortezomib is used (7%). Undetectable HBV DNA and the use of anti-viral prophylaxis do not appear to preclude reactivation. The optimal use of anti-viral prophylaxis, particularly if bortezomib is given, should be further evaluated. This is particularly relevant in the current era where bortezomib plays a dominant role in the treatment of MM, and especially in endemic regions where the incidence of HBV infection is high. Disclosures: No relevant conflicts of interest to declare.


2001 ◽  
Vol 45 (1) ◽  
pp. 229-235 ◽  
Author(s):  
Martin L. Bryant ◽  
Edward G. Bridges ◽  
Laurent Placidi ◽  
Abdesslem Faraj ◽  
Anna-Giulia Loi ◽  
...  

ABSTRACT A unique series of simple “unnatural” nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3′-OH group of the β-l-2′-deoxyribose of the β-l-2′-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides β-l-2′-deoxycytidine, β-l-thymidine, and β-l-2′-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (α, β, and γ) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 108 genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.


2009 ◽  
Vol 36 (4) ◽  
pp. 712-716 ◽  
Author(s):  
MI-KYOUNG LIM ◽  
DONG-HYUK SHEEN ◽  
YUN JUNG LEE ◽  
YOU RI MUN ◽  
MIRA PARK ◽  
...  

Objective.To determine whether anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are a highly specific test for rheumatoid arthritis (RA), could differentiate between hepatitis B virus (HBV)-associated arthropathy and concomitant RA in Korean patients with chronic HBV infection.Methods.We investigated 240 patients with HBV infection. Anti-CCP antibodies were measured by ELISA and rheumatoid factor (RF) by the latex fixation test. Patient records were reviewed, and a standard form was used to record all demographic, clinical, and laboratory characteristics. Patients were divided into 4 groups according to joint symptoms: asymptomatic, arthralgia, oligoarthritis, and RA. We categorized liver disease into 3 groups: carrier, chronic hepatitis, and cirrhosis.Results.Anti-CCP antibodies and RF were detected in 11 and 28 of 240 patients, respectively. Anti-CCP antibodies were detected in 9 of 10 RA (90%) and 2 of 230 non-RA patients (0.86%). The positive rate for RF was 90% in RA and 8.3% in non-RA. Eight of 10 RA patients were positive for both RF and anti-CCP antibodies. RF was detected in 11 patients without joint symptoms, 4 with arthralgia, and 4 with oligoarthritis, whereas anti-CCP antibodies were found in 1 patient without joint symptoms and 1 with oligoarthritis. Specificity of anti-CCP antibody for RA was 99.1%, whereas RF showed 91.7% specificity (p < 0.0002). We compared the titers and positive detection rates of anti-CCP antibodies and RF among liver disease subgroups. There was no significant between–subgroup difference.Conclusion.Measurement of anti-CCP antibodies is better than RF detection to discriminate HBV-associated arthropathy from concomitant RA in patients with chronic HBV infection.


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