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Objective:To investigate the potential function and related mechanism of microRNA-223 (miRNA-223) in the podocyte pyroptosis of hepatitis B virus (HBV)-associated glomerulonephritis induced by HBV X protein (HBx).Methods:HBx-overexpressing lentivirus was transfected into human renal podocytes to mimic the pathogenesis of HBV-GN. Real-time fluorescence quantitative PCR and Western blotting experiments were used to detect the mRNA and protein expression of pyroptosis-related proteins [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1], and inflammatory factors (interleukin-1β and interleukin-18), respectively.TUNEL staining and flow cytometry were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression of podocytes biomarkers desmin and nephrin; Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to measure caspase-1 activity. The dual luciferase reporter gene assay was used to verify the downstream target of miRNA-223. Podocytes were divided into the following nine groups: control group (no special treatment), empty plasmid group (transfected with empty plasmid), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+miRNA-223 mimic group (transfected with HBx overexpression lentivirus and miRNA-223 mimic), HBx overexpression+miRNA-223 inhibitor group (transfected with HBx overexpression lentivirus and miRNA-223 inhibitor), HBx overexpression+miRNA-223 mimic+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 mimic+ NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 siRNA), HBx overexpression+miRNA-223 inhibitor+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 inhibitor+NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 siRNA).Results:miRNA-223 was down-regulated in HBx overexpression group compared with the control group ( P < 0.05). TUNEL and immunofluorescence staining showed that NLRP3 knockdown attenuated podocyte injury and pyroptosis induced by HBx overexpression ( P < 0.05). Dual luciferase reporter gene assay demonstrated that NLRP3 was one of the downstream targets of miRNA-223. Rescue experiments revealed that NLRP3 overexpression weakened the protective effect of miRNA-223 in podocyte injury ( P < 0.05). The addition of miRNA-223 mimic and NLRP3 siRNA decreased the expression of NLRP3 inflammasome and cytokines, and reduced the number of pyroptosis cells induced by HBx overexpression (all P < 0.05); The addition of miRNA-223 inhibitor and NLRP3 overexpression plasmid significantly increased the expression of NLRP3 inflammasome and cytokines, caspase-1 activity, and the number of pyroptosis cells (all P < 0.05). Conclusion:HBx may promote podocyte pyroptosis of HBV-GN via downregulating miRNA-223 targeting NLRP3 inflammasome, suggesting that miRNA-223 is expected to be a potential target for the treatment of HBV-GN.
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@#【Objective】To investigate the differential effects of B/C genotype hepatitis B virus on hepatitis B associat⁃ ed nephritis in different ALT states.【Methods】We retrospectively analysized 558 patients with hepatitis B virus associat⁃ ed glomerulonephritis in The First Hospital of Lanzhou University. All the selected patients have complete medical records and had undergone renal histopathology. Laboratory tests included：ALT，NAG，Cr，GFR，hepatitis B virus load and genotypes.【Results】We found genotype B and genotype C hepatitis B virus associated glomerulone nephritis was mainly diffuse membrane hypertrophic nephropathy（57.9% vs. 54.4%），followed by capillary hyperplastic glomerulonephritis （25.3% vs. 28.0%），and focal segment glomerulonephritis（9.7% vs. 9.0%）. Mesenteric hyperplastic lesions（7.1% vs. 8.6%）were rare. In the ALT normal group，B/C genotype hepatitis B virus had no differential effect on renal function （P > 0.05）. In the ALT ≥ double upper limit of normal group，blood creatinine，blood urea nitrogen，24 h urine protein quantification，urine N-acetyl- β-D-glucosidase，and urine β2 microglobulin significantly increased（P < 0.05）.Glomerular filtration rate significantly decreased（P < 0.05）in the genotype C hepatitis B-related glomerulonephritis group compared with the genotype B group. In the ALT normal group genotype B/C hepatitis B virus had no differential effect on the stage of chronic kidney disease（P > 0.05）. But in the ALT ≥ double upper limit of normal group，compared with genotype B，chronic kidney disease staging tends to be worse in the genotype C hepatitis B associated nephritis（χ 2 = 11.144，P = 0.025）.【Conclusion】Comparative analysis of the differential effects of different genotype hepatitis B virus on hepatitis B-associated nephritis will help to diagnose and treat hepatitis B-associated nephritis.
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Objective: To analyze the effects of serum hepatitis B virus covalently closed circular DNA (HBV-cccDNA) level on the liver and kidney functions, detection of HBV antigens in kidney tissue, pathological grading and staging of liver tissue in the children with hepatitis B virus associated glomerulonephritis (HBV-GN), and to evaluate the clinical value of HBV-cccDNA level detection in the diagnosis of the children with HBV-GN. Methods: A total of 39 HBV-GN children (observation group) were selected and all of them underwent the liver and kidney biopsy. A total of 40 HBV-carried children with normal liver function were selected as control group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the children were detected. Molecular beacons PCR method was used to detect the serum HBV-cccDNA level of the children. The morphology of liver and kidney tissues of the children was detected with HE staining. The detection rates of HBsAg, HBeAg and HBcAg in kidney tissue of the children were detected by immunofluorescence. Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the value of HBV-cccDNA level detection in the diagnosis of HBV-GN. The Ax fluorescence value of HBV-cccDNA > 21 was determined as positive, and the Ax fluorescence value of HBV-cc cDNA 0. 05). Membranous nephropathy (MN) was the main pathological type of kidney biopsy in the HBV-GN. HBeAg and HBcAg were the main components of HBV antigens. The detection rates of HBeAg and HBcAg of the children in HBV-cccDNA positive group were significantly higher than those in HBV-cccDNA negative group (χ2 =5. 652, P = 0. 027; =12. 523, P=0. 001). The ROC curve analysis results showed that the HBV-cccDNA level detection could effectively distinguish the HBV-GN children in observation group from those in control group, AUC=0. 804 (95% Cl 0. 709-0. 883). The levels of HBV-cccDNA of 10 cases of HBV-GN children underwent standardized treatment with complete follow-up treatment data were decreased significantly at the 2nd week after treatment. At the 12th week after treatment, in 7 cases the HBeAg turned negative, without proteinuria and hematuria symptoms, and the AST and ALT levels were normal. The HBV-cccDNA levels of 3 cases with ineffective treatment were higher than that those of the remaining 7 cases. Conclusion; The high expression of HBV-cccDNA is closely related to the liver function, proteinuria and HBV antigen detection in kindney tissue of the HBV-GN children. The detection of HBV-cccDNA level has potential clinical value for the auxiliaty diagnosis and evaluation on the curative effect of the HBV-GN.
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This article tried to discuss that spleen deficiency is the key mechanism of hepatitis B virus associated glomerulonephritis from TCM and Western medicine viewpoint. From the view of pathophysiology, energy metabolic disorder caused by mitochondrial injury and its series of damages are similar to symptoms caused by spleen deficiency appeared as yin fire and organs dystrophy, so mitochondrial injure belongs to spleen deficiency. And mitochondrial damage can further aggravate the virus replication of hepatitis B virus associated glomerulonephritis, causing damage to the kidney. Therefore, from the view of Western medicine, it can be known that spleen deficiency determines whether the liver function damage in the process of hepatitis B virus associated glomerulonephritis and lower energizer transformation. In terms of TCM, spleen deficiency plays an important role in all stages of the disease, and determines the outcome and prognosis of the disease. Therefore, this article proposed that the spleen deficiency is the mechanism of hepatitis B virus associated glomerulonephritis, which can provide references for clinic.
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Objective To investigate the expression of Notch 1 receptor in renal tissues of patients with hepatitis B virus associated-glomerulonephritis (HBV-GN) and its role in the pathogenesis of HBV-GN.Methods A total of 48 patients with HBV-GN confirmed by renal biopsy during 2008-2010 were enrolled in the study.Distribution of Notch1 receptor in renal tissue of HBV-GN was detected by immunohistochemistry and the association between the distribution of Notch1 receptor and HBsAg was examined by double-label immunofluorescence assays.Correlations of Notch1 receptor expression with renal pathology and clinical parameters of HBV-GN were analyzed.Results Notch1 receptor distributed mainly in renal tubular epithelial cells and interstitial area as brownish red granules,and a few expression in glomerulus was also found.The positive score of Notch1 receptor expression in HBV-GN patients was significantly higher as compared to primary glomerulonephritis patients with serum HBsAg positive or negative and normal renal tissue controls.Notch1 receptor expression was more obvious in membrano-proliferative glomerulonephritis (MPGN) and mesangial proliferative nephritis (MsPGN) patients,but there was no significant difference among the different pathology groups.Distribution of Notch1 receptor was consistent with the distribution of HBsAg and its intensity was positively correlated with renal interstitial fibrosis (r=0.473,P=0.001),tubular atrophy (r=0.690,P=0.000),inflammatory cell infiltration (r=0.616,P=0.000).Negative correlation was found between renal function and the intensity of Notch1 receptor (r=-0.393,P=0.006).Conclusions Notch1 receptor expression increases in the renal tissues of HBV-GN patients and distributes mainly in renal tubular epithelial cells and interstitium,which is consistent with the distribution of HBsAg.Its intensity is closely correlated with renal interstitial lesions and renal function.Abnormal expression of Notchl receptor in renal tissue of HBV-GN may be involved in the progress of HBV-GN.
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Objective To retrospectively evaluate the relevant factors for hepatitis B virus-associated glomerulonephritis (HBV-GN).Methods A total of 86 patients with pathologyproven HBV-GN and 135 HBV carriers with non-HBV-GN were included in this retrospective casecontrol study.Logistic regression analysis was used to detect the relevant factors for HBV-GN.Results On univariate analysis,the factors associated with HBV-GN were as follows: male (OR 2.79,95%CI 1.48-5.25,P=0.001),HBeAg positivity (OR 2.60,95%CI 1.49-4.53,P=0.001),HBV replication (OR 3.63,95%CI 1.80-7.33,P＜0.01),liver cirrhosis (OR 4.58,95%CI 1.41-14.91,P=0.011),and elevated alanine aminotransferase (ALT) (OR 2.53,95%CI 1.42-4.51,P=0.002).On multivariate analysis,the associations remained significant for male (OR 2.21,95%CI 1.12-4.33,P=0.022),HBV replication (OR 2.77,95%CI 1.28-5.97,P=0.01),liver cirrhosis (0R 4.55,95%CI 1.29-16.10,P=0.019) and elevated ALT (OR 1.96,95%CI 1.04-3.69,P=0.037).Compared with HBV-associated IgA nephritis (HBV-IgAN) in multivariate model,HBV-associated membranous nephropathy (HBV-MN) or membranoproliferative glomerulonephritis (HBV-MPGN) was significantly associated with male (OR 6.51,95%CI 1.76-24.11,P=0.005) and HBV replication (OR 7.22,95%CI 1.68-30.97,P=0.008).Conclusions Male,HBV replication,liver cirrhosis and elevated ALT may be predictive factors for HBV-GN.Compared with HBV-IgAN,HBV-MN or HBV-MPGN is significantly associated with male and HBV replication.
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Objective To assess the efficacy of mycophenolate mofetil (MMF) combined with low dose of hormone and lamivudine in the treatment of hepatitis B virus associated glomerulonephritis (HBV-GN).Methods The clinical data of 49 HBV-GN patients diagnosed by renal pathology was reviewed.They were treated with MMF( ≥ 12 years old,0.75 g,two times a day; ＜ 12 years old,0.4 g/m2,two times a day),low dose of hormone [0.5 mg/(kg·d) ],lamivudine( ≥ 12 years old,100 mg/d; ＜ 12 years old,3 mg/kg,two times a day).Results Among of 49 HBV-GN patients,clinical cure rate was 71.4％(35/49),the total effective rate was 81.6％(40/49),85.7％(42/49) patients' HBV DNA level decreased from 5.43 ×104 copies/ml to ＜ 1000 copies/ml.The complete remission rate was 88.0％ (22/25),the partial remission rate was 8.0％ (2/25),the inefficiency was 4.0％ (1/25) in membranous nephropathy (MN);the complete remission rate was 44.4％ (4/9),the inefficiency was 55.6％ (5/9) in mesangial proliferative glomerulone phritis (MsPGN) ; the complete remission rate was 70.0％(7/10); the partial remission rate was 30.0％(3/10)in membrane proliferative glomerulone phritis (MPGN) ;the complete remission rate was 40.0％ (2/5),the inefficiency was 60.0％(3/5) in focal segmental glomerulosclerosts (FSGS).There was significant difference among the different pathological type (P＜0.05).There were less adverse reactions.Conclusions MMF combined with low dose hormone and lamivudine is safe and effective in treating HBV-GN.The efficacy and pathological type has some relationship,MN has the best response,MPGN and MsPGN are second,FSGS is poor.
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1.0?108 co-pies/L)and the lower viral load group(HBV DNA
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Objective To investigate the significance of helper T cell 1(Th1)/Th2 cytokines unbalance in children with hepatitis B virus-associated glomerulonephritis(HBV-GN).Methods The serum levels of interferon-gamma(IFN-?),interleukin-2(IL-2) and IL-4 were determined in 22 children with HBV-GN and 18 children with HBV by enzyme-linked immunosorbent assay(ELISA),respectively,and the difference of Th1/Th2 cytokines in the 2 groups.Results Serum levels of IL-2 and IFN-? in children with HBV-GN were decreased(P
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Objective To investigate the efficacy and the adverse effect of mycophenolate mofetil(MMF)in HBV associated glomerulonephritis.Methods Twenty patients with HBV-GN diagnosed by renal biopsy were treated with MMF.The initial dosage of MMF was 1.5 g/d.The dosage was reduced to 1.0 g/d when 24 h excretion of urinary protein decreased to 0.5 g/d.Blood routine test,hepatic and renal function,plasma albumin,serum triglyceride and cholesterol,24 h urinary protein excretion,HBV DNA were performed before and after 2,3,6,9 months' treatment.Results Twenty-four-hour urinary protein excretion was significantly reduced by the treatment with mycophenolate mofetil(P
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Objective To investigate the clinicopathological features of hepatitis B virus-associated glomerulonephritis(HBV-GN) in children.Methods Clinical and pathological features were analyzed and correlated in 73 cases with renal biopsy-confirmed(HBV-GN).Sixty-six boys and 7 girls aged from 1 to 14 years old were included in this study,accounting for 14.4% in children under-(going) renal biopsy in the same period.Results Nephrotic syndrome(NS) was the prodominant clinical manifestation(53/73,72.6%),followed by glomerulonephritis(15/73,20.5%) and hematuria with proteinuria(5/73,6.9%).Serologic markers of HBV were found in all cases.Among them,55 cases(75%) were positive for hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg) and anti-hepatitis B core(anti-HBc),14 cases(19.2%)positive for HBsAg,anti-HBe and anti-HBc,2 cases positive for HBsAg and anti-HBc,1 child positive for HBsAg and HBeAg,and another only positive for anti-HBc.The most common pathological type of HBV-GN was membranous nephropathy(MN),which was found in 69 cases(94.5%),followed by membranoproliferative glomerulonephritis(MPGN) and mesangial proliferative glomerulonephritis(MsPGN),2 cases(2.7%),respectively.All cases with NS presented themselves with MN.The pathological grades were significantly correlated with clinical manifestations through double trend analysis(?~2=5.22 P=0.022).Conclusions MN is predominant in childhood HBV-GN,which mainly presented with NS.Their clinical patterns are somewhat correlated with pathological grades.
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Objective To investigate the efficacy and safety of mycophenolate mofetil combined with methylprednisolone and lamivudine on the treatment of hepatitis B virus associated glomerulonephritis(HBV-GN).Methods Twenty-four patients with hepatitis B virus associated glomerulonephritis were confirmed by renal biopsy and immunohistochemistry,these participant patients were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from Jan,1999 to Jan,2004.They were treated by MMF combined with methylprednisolone and lamivudine.The initial dosage of MMF was 1.0~1.5 g/d.Methylprednisolone at the dosage of 0.4 mg/(kg?d)was used at the beginning of the combined treatment.Lamivudine was in the dosage of 0.1 g/d.The duration of the treatment was six months.Regular test was conducted every two weeks.Results Nine cases had fully remission,11 cases had partial remission and 4 cases had no efficiency;no patient deterioration.Renal and hepatic function remained stable,blood cell didn't decrease and the reproduction of HBV didn't increase during the treatment.Conclusion MMF combined with methylprednisolone and lamivudine is an effective and safe method for HBV-GN.
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We performed a retrospective study to find out the frequency, clinical and pathological characteristics of membranoproliferative glomerulonephritis (MPGN) in Korean adults. Of the total 1,893 adults with biopsy-proven glomerulonephritis over the 13-year period from 1979 to 1991 in Seoul National University Hospital, there were 212 cases of MPGN of whom 22 had primary MPGN and 190 secondary MPGN. Secondary MPGN was composed of 64 cases of hepatitis B virus- associated glomerulonephritis(HBV-GN), 121 cases of lupus nephritis(LN) and 5 cases associated with other conditions. Age at diagnosis(median and range in years) was higher in primary MPGN(31, 16-67) and in HBV-GN (39, 16-60) than in LN(28, 16-44)(P<0.05). Male-to- female ratio was 1.2:1 in primary MPGN, 7.5:1 in HBV-GN and 1:13 in LN. At the time of diagnosis, nephrotic syndrome and azotemia were more frequent in primary MPGN(72%, 50%) and in HBV-GN (50%, 42%) than in LN(25%, 15%)(P<0.05). Decreases of C3 and CH50 were more common in LN(59%, 77%) than in primary MPGN(24%, 41%) or in HBV-GN(12%, 32%)(P<0.05). On light microscopic exams, tubular atrophy was more frequently observed in primary MPGN(96%) than in HBV-GN(57%) or in LN(69%)(P<0.05). Under immunofluorescence microscopy, mesangial deposition of IgM was more common in HBV-GN (50%) and in LN(59%) than in primary MPGN(6%) (P<0.05). The prognosis was better in LN(13 remission, 15 persistence, 1 end stage) than in primary MPGN(1 remission, 8 persistence, 4 deterioration, 6 end stage) or in HBV-GN(18 persistence, 4 deterioration, 2 end stage)(P<0.05). Conclusively, in Korea considering much higher incidence of secondary MPGN than that of primary MPGN contrary to western countries and the difference in prognosis between the primary and secondary forms, one should consider the possibility of secondary MPGN, especially hepatitis B virus- associated glomerulonephritis and lupus nephritis in adult patients diagnosed as MPGN by kidney biopsy in Korea.
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Adult , Female , Humans , Atrophy , Azotemia , Biopsy , Diagnosis , Glomerulonephritis , Glomerulonephritis, Membranoproliferative , Hepatitis B , Immunoglobulin M , Incidence , Kidney , Korea , Lupus Nephritis , Microscopy, Fluorescence , Nephrotic Syndrome , Prognosis , Retrospective Studies , SeoulABSTRACT
Objective To study the reliability of clinic diagnosis of hepatitis B virus(HBV)-associated glomerulonephritis.Met- hods Renal biopsy was carded out in 103 cases with clinically-diagnosed HBV-associated glomerulonephritis. The diagnostic consistency and clinical difference were evaluated.Results Sixty nine cases with clinically-diagnosed HBV-associated glomerulonephritis were confirmed through renal biopsy, 29 cases were excluded from HBV-associated glomerulonephritis. The pathologic diagnosis and clinical diagnosis methods were highly correlated and has significant difference(P
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Objective To observe the effect of combination treatment of lamivudine,tripterygium glycosides and ahalysantinfarctasum on hepatitis B virus associated glomerulonephritis(HBV-GN)in children.Methods Sixty cases with HBV-GN were divided into 2 groups randomly.The observation group was treated with lamivudine(100 mg/d),tripterygium glycosides [0.5 mg/(kg?d)],and ahalysantinfarctasum [0.01 U/(kg?d),3 d];the control group were treated with tripterygium glycosides 0.5 mg/(kg?d)only.The effect was judged after treatment according to clinical research guide principle of chronic nephritis treated with new Chinese materia medica and clinical research guide principle of viral hepatitis treated with new Chinese materia medica.Statistic analysis were performed with the PEMS 3.1 for windows statistic program package.Values were considered statistically significant at P
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Objective To understand the clinical and pathological features of hepatitis B virus-associated glomerulonephritis(HBV-GN).Methods Twenty children with HBV-GN were analysed including 17 cases of nephritic syndrome (4 cases of simple nephrosis, 13 cases of nephritic nephrosis),2 cases of isolated proteinuria, 1 case of nephritic syndrome according to the clinical classification.Results On the basis of pathology of kidney biopsy, there were 15 cases of membranous glomerulonephritis(MN),3 cases of manbranoproliferative glomerulonephritis(MPGN),2 cases of mesangial proliferative glomerulonephritis(MsPGN).Eight of 20 cases were treated with recombinated human alpha-interfeon. The average follow-up time was 5.7 years. As the result, complete remission clinically was on 5 cases,partial remission on 2 cases and ineffectiveness on one case. Besides, serum HBsAg, HBeAg were converted to negative on 3 cases , HBeAg disappeared and anti-HBe appeared on one case.Conclusion MN is common in childhood with HBV-GN.It also indicates the prognosis of the associated nephropathies is quite favorable.