BackgroundRecent studies showed that positive rate of HBsAg was 19–24% in Chinese spondyloarthritis (SpA) patients. Since biosimilar of TNF-α antagonists such as TNF-α recptor II: IgG Fc fusion protein (TNFR: Fc) can be paid partly by Chinese medical insurance and is much cheaper than other TNF-α antagonists, TNFR: Fc is the most widely used in Chinese SpA patients. However, little is known about the influence of TNFR: Fc on HBV infection status in SpA patients with different HBV infection status.ObjectivesTo investigate the influence of TNFR: Fc on HBV reactivation and liver function in SpA patients with chronic or past HBV infection.MethodsPatients with active SpA were enrolled from Dec 2013 to Aug 2014. HBV infection was screened at baseline. All patients were treated with TNFR: FC (50mg/w, at least 12 weeks) plus Salazosulfadimidine (SSZ), thalidomine, and/or methotrexate (MTX). Antiviral prophylaxis was recommended for HBsAg+ patients. Clinical inflammatory indexs, HBV biomarkers, HBV-DNA load and liver function were evaluated at 4th, 12th, 24th week. HBV reactivation was defined as a 10-fold rise of HBV-DNA compared to baseline or switch from undetectable to detectable or HBsAg/HBeAg seroconversion from negative to positive.Results(1) Among 81 patients enrolled, 85% (69/81) were male, age (median and IQR, similarly hereinafter) was 27 (21–33) years, disease duration was 36 (8–84) months, ESR was 42 (17–68) mm/H, CRP was 21 (9–35) mg/L, and SAA was 51 (10–158) mg/L at baseline. 21% (17/81) received TNFR: FC monotherapy. (2) Patients with active SpA were divided into chronic HBV infection group (HBsAg and/or HBV-DNA +, n=21), past HBV exposure group (HBcAb or HBeAb + but HBsAg or HBV-DNA -, n=25), and free of HBV infection group (only HBsAb + or all the serum HBV biomarkers -, n=35). There was no significant difference of the change of ESR, CRP, SAA and transaminases before and 4, 12, 24 weeks after therapy (all P>0.05). Each group has 1 case of transaminases elevated to more than 2-times upper limit of normal (ULN) at 12th week. And 2 patients' transaminases elevated to more than 2-times ULN at 24th week in free of HBV infection group.(3) Chronic HBV infection group (n=21) were divided into negative HBV-DNA subgroup (HBV-DNA load less than 500 copies/ml, n=8) and positive HBV-DNA subgroup (n=13) according to HBV-DNA load. In negative HBV-DNA subgroup, 3 patients developed HBV reactivation with normal aminotransferases, and one of them received antiviral prophylaxis. In positive HBV-DNA subgroup, the baseline HBV-DNA load was 2.95×103–5.07×108copies/mL, 5 patients received antiviral prophylaxis and one of them developed HBV reactivation with normal aminotransferases. The patient received antival drug lamivudine (LMF) in baseline, and the HBV-DNA load reduced to normal but reparidly elevated to 1.6×106copies/mL at 24th week with resistance to LMF, the HBV-DNA load returned to normal 20 weeks after combination with LMF and adefovir.ConclusionsLiver function should be monitored during TNFR: FC therapy regardless ...
Background Hepatitis B virus (HBV) reactivation, which refers to the abrupt rise in HBV replication in patients with inactive or resolved hepatitis B and is triggered typically by immunosuppressive chemotherapy in patients with cancer, can also occur in patients with RA undergoing DMARDs therapy, especially in endemic areas of HBV infection such as China. However, most related publications until now are based on case reports or case series. Objectives To investigate the clinical features of HBV reactivation associated with non-biological DMARDs therapy in a cohort of Chinese RA patients. Methods The follow-up records of 18 Chinese RA patients with positive serum HBsAg treated with non-biological DMARDs from March 2006 to September 2011 were analyzed. A multiple regression model was developed by stepwise method to screen the risk factor(s) for HBV reactivation from gender, age, non-biological DMARDs including glucocorticoid, MTX, leflunomide (LEF), HCQ, SSZ,and preventive antiviral therapy. Results 1. Among 18 patients, 15 (83%) were females and mean age was (47±12) years, with 2 to 61 months’ follow-up. Baseline load of HBV-DNA was determined in 11 patients and four (36%) was positive (≥103 copies/mL). Transaminases and bilirubins were normal before DMARDs therapy in all patients. All patients took combination therapy of non-biological DMARDs without biologic agents during follow-up. Glucocorticoid (equivalent to prednisone 10mg/d, except one overlapped with lupus and one complicated with rheumatoid vasculitis) was taken in 13 patients, and MTX 10∼20mg/week in sixteen, LEF 10∼20mg/d in ten, HCQ 0.2∼0.4g/d in five and SSZ 1.5∼2g/d in four. 2. Seven of 18 patients (39%) developed HBV reactivation 4 to 38 months after non-biological DMARDs therapy, of whom six cases showed more than 10-fold rise than baseline HBV-DNA and the other one showed reversion from negative to positive HBsAg. Five of 7 patients (71%) with HBV reactivation developed active hepatitis, of whom three (43%) with jaundice (one died of acute hepatic failure, one developed decompensated cirrhosis and one recovered), the other two (29%) without jaundice who recovered after therapy. 3. The multiple regression analysis showed LEF (p<0.001) and glucocorticoid (p=0.002) were risk factors for HBV reactivation in RA patients, in which LEF alone could explain 48% risk of HBV reactivation and the combination of LEF and glucocorticoid explain 70%. HBV reactivation occurred in all six patients with combination therapy of LEF and glucocorticoid. 4. Two patients with baseline HBV-DNA ≥105 copies/mL received preventive antiviral drug before DMARDs therapy, and the load of HBV-DNA decreased to 103∼104 copies/mL with normal liver function for more than one year. Conclusions Chinese RA patients should screen HBV infection including the load of HBV-DNA before non-biological DMARDs therapy. LEF, especially with glucocorticoid, should be used cautiously or even be avoided for RA patients with positive HBsAg and/or positive HBV-DNA. HBV reactivation and liver functio...
BackgroundThe hepatitis B surface antigen (HBsAg) carrying rate of rheumatoid arthritis (RA) was 11.2% in China according to recent studies. HBV infection is a major issue in RA patients undergoing disease-modifying anti-rheumatic drugs (DMARDs) therapy. Iguratimod was a newer effective conventional DMARD, which was small molecular and approved in China in Augest, 2011. However, little was known about the influence of iguratimod to liver injury and HBV reactivation.ObjectivesTo explore the influence of iguratimod on HBV reactivation in HBsAg/HBcAb+ RA patients and the influence on HBsAb titer in HBsAb+ RA patients.MethodsPatients with active RA were enrolled from October 2013 to September 2014. All were treated with iguratimod (25mg Bid) alone or in combination with other conventional DMARDs for 24 weeks, such as methotrexate (MTX), leflunomide (LEF), etc. Adding with non-steroidal anti-inflammatory drugs (NSAIDs) or small doses of corticosteroids was permitted if constant pain observed. HBsAg+ RA patients were suggested to be treated with anti-virus therapy preventively. Liver function, HBsAg or HBsAb titer, and HBV-DNA load were evaluated at baseline, 12th and 24th week. HBV reactivation was defined as a 10-fold rise in HBV-DNA compared to baseline or HBsAg/HBeAg switch from undetectable to detectable.Results1) Thirty-six patients with active RA were enrolled and 74% (29/36) were female, age (median and IQR, similarly hereinafter) was 49 (39–58) years, disease duration was 59 (23–81) months, and DAS28-CRP was 4.44 (3.96–5.75). Twelve patients received iguratimod monotherapy. 2) Patients with active RA were grouped according to serum HBV biomarkers, including chronic or past HBV infection group (HBsAg or HBcAb +, N=20) and free of HBV infection group (HBsAg and HBcAb -, N=16).There was no significance difference of transaminases (AST 18 (14–24) vs 17 (12–25), ALT 14 (12–30) vs 13 (8–22)) and DAS28 (4.82 (4.03–5.85)vs 4.28 (3.81–5.65)) of baseline (all P>0.05). 3) The chronic or past HBV infection group was divided into chronic HBV infection subgroup (HBsAg or HBV-DNA +, n=3) and past HBV exposed subgroup (HBcAb + but HBsAg-,n=17). In the chronic HBV infection subgroup, all refused antiviral prophylaxis, and 2 developed HBV reactivation without aminotransferases elevation in 10th and 24th weeks. In pass HBV exposed subgroup, 2 patients developed transient 3-times elevation of aminotransferases in 24th weeks. 4) In free of HBV infection group, none developed transaminases elevation. The changes of HBsAg and HBsAb has no statistical significance among baseline,12th and 24th weeks according to repeated measures analysis of variance (F=0.795, P=0.472) and Wilcoxon Matched-Pairs Signed-Ranks Test (all P>0.05).ConclusionsActive RA patients should be screened for liver function and HBV biomarker before iguratimod therapy. RA patients with HBV infection, especially with positive baseline HBV-DNA,were recommended to be treated with antiviral prophylaxis and monitor liver function and HBV-DNA load regularly.Acknowledgements...
Background Rheumatoid arthritis (RA) is a common chronic inflammatory disease which could lead to joint destruction and disability. Osteoclasts are essential for bone resorption and play key roles in joint destruction in RA. A recent research on mice suggested that B cell lymphoma 6 (Bcl6) is a negative regulator of osteoclastogenesis, and Bcl6 deficiency facilitates osteoclast formation. B lymphocyte–induced maturation protein-1 (Blimp1) regulates Bcl6 expression and osteoclastogenesis. However, the effect of Bcl6 and Blimp1 on osteoclastogenesis in RA patients is unknown. Objectives To investigate the expression of Bcl6 in peripheral blood monocytes (PBMs, osteoclast precursors) and its correlation with disease activity and radiographic joint destruction in RA. Methods PBMs were isolated from 24 RA patients and 16 healthy controls matched with age and gender, and identified by flow cytometry with CD14 and CD3 markers. The expression of Bcl6 protein was detected by immunofluorescence. Bcl6 and Blimp1 mRNA expression in PBMs was determined by real-time PCR and correlated with clinical parameters which reflect disease activity and radiographic joint destruction (Sharp score). Results (1) Immunofluorescence staining showed significantly decreased expression of Bcl6 in PBMs from RA patients than healthy controls (1.76±0.08 vs 1.88±0.03 AU/mm2, p=0.009). (2) Bcl6 and Blimp1 mRNA expression in PBMs was decreased significantly in RA patients than in healthy controls (χ2 =9.733, p=0.002; χ2 =9.334, p=0.001, respectively). (3) To exclude the influence of medication, 12 treatment-naïve RA patients who had never been treated with disease-modifying antirheumatic drugs or glucocorticoids were analyzed. Bcl6 and Blimp1 mRNA expression in PBMs was decreased significantly in treatment-naïve RA patients, compared with that in healthy controls (χ2 =12.452, p<0.001; χ2 =8.077, p=0.003, respectively). (4) Spearman’s rank order correlation showed that Bcl6 mRNA expression in PBMs from RA patients was positively correlated with joint space narrowing subscore and Blimp1 mRNA expression (r=0.488, p=0.021; r=0.639, p=0.001, respectively), but not significantly correlated with clinical parameters including rheumatoid factor, C-reactive protein, anti-cyclic citrullinated peptide antibody, erythrocyte sedimentation rate, the 28-joint tender and swollen joint count and the disease activity score in 28 joints (DAS28) with three variables including CRP (DAS28(3)-CRP) (all p>0.05). Conclusions Our results showed that Bcl6 expression was decreased in PBMs in RA patients, which implied that Bcl6 may be involved in osteoclastogenesis in RA. Further studies are needed to establish the mechanisms of Bcl6 in osteoclatogenesis and joint destruction in RA. Acknowledgements This work was supported by the Chinese National Natural Science Research Grant (grant no.30972742 and 81001334) and the Natural Science Research Grant of Guangdong Province, China (grant no. 9151008901000130 and 10451008901004542). Disclosure of Interest None Declared
BackgroundUrolithiasis greatly impact urate lowering therapy in Chinese gout patients. Benzbromarone is contraindicated and Chinese is high risk of allopurinol hypersensitivity syndrome. Febuxostat is too expensive for many patients. Few study about urolithiasis in Chinese gout patients are presented.ObjectivesTo investigate the prevalence and risk factors of urolithiasis in south Chinese gout patients.MethodsPatients with primary gout were recruited in the present cross-section study. Urolithiasis was defined as positive stone history and/or ultrasonography. All inpatients with estimated glomerular filtration rate (eGFR) over 30 ml/min/1.73 m2 underwent 24 hours urinary chemistry assay including uric acid (UA), UA concentration, clearance of UA, Cr, calcium, phosphorus, potassium, sodium and chloride. Logistic regression were performed to examine association of urolithiasis with independent variables including age, gender, duration of gout, sUA, previous urate lowering therapy, serum creatinine, eGFR, body mass index, urine pH and 24 hours urinary chemistry assay.Results(1) Two hundred and nighty-four patients were recruited. Mean age of male (N=255) and female (N=39) were 54.4±16.4 and 67.2±15.3, respectively. Average serum UA was 9.0±2.5mg/dl and 25.9% of patients presented tophi. Allopurinol, benzbromarone, or a combination of these two drugs had been prescribed in 97 patients (33.0%), 18 patients (6.1%) and 36 patients (12.2%), respectively. The rest 143 patients (48.6%) had not received urate lowering therapy before. (2) One hundred and eleven gout patients (37.8%) complicated with urolithiasis and urolithiasis was observed in 69 of them (62.1%) on ultrasonography. Compared with non urolithiasis group, urolithiasis group had significant higher serum creatinine (1.6±0.6 VS 1.3±0.3 mg/dl], lower eGFR (56.3±18.0 VS 64.1±18.4 ml/min/1.73m2) and higher alcohol overuse (38.7% VS 26.2%) (P<0.05). (3) Among 102 patients performed 24 hours urinary chemical assay, 45 patients complicated with urolithiasis. Urolithiasis group had significantly higher 24 hours urine UA concentration than non-urolithiasis group (30.4±13.1 VS 23.9±11.9 mg/dl, P=0.01). There were no significant difference of other variables between two groups. Prevalence of urolithiasis increased significantly across increasing quartiles of urinary UA concentration (P=0.012, Table 1). (4) Logistic regression suggested that risk factors of urolithiasis were urinary UA concentration grouped by quartile (P=0.05) and urinary calcium excretion [OR 1.26 (1.01, 1.57), P=0.04]. Urinary UA concentration over 24.4mg/dl was associated with increasing risk of urolithiasis (Table 1).Table 1.Prevalence of urolithiasis among quartiles of urinary UA concentrationQuartiles of urinary UA concentration (mg/dl)I (<17.6)II (17.6–24.3)III (24.4–34.9)IV (≥35.0)Median (mg/dl)12.820.830.042.5Prevalence*13.3% (6)22.2% (10)33.3% (15)31.1% (14)Adjusted OR#12.47 (0.66, 9.24)5.5 (1.50, 20.72)4.58 (1.24, 16.92)P#–0.180.010.02*Test for a linear trend P=0.012. #By logistic regression.Conc...
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