Investigate The Clinical, Pathological And Immunotherapy Of HBV-associated Glomerulonephritis

Background:HBV infection is becoming a global public health problem. In China, the number of chronic HBV infection over130million. In addition to causing hepatitis, cirrhosis, liver cancer, HBV can also involve kidney, leading to hepatitis B virus associated glomerulonephritis (HBV-GN). HBV-GN has become one of the common secondary renal disease. However, the pathogenesis of HBV-GN is still not very clear currently. And there is no a clear and unified program to follow to treatment HBV-GN. Additionally, the trend of the disease into end-stage renal failure increases every year, the corresponding treatment costs are also rising year by year. Therefore, improving the study of the pathogenesis and clinical characteristics of HBV-GN further, exploring the factors that may affect the treatment of HBV-GN and possible treatment options, not just a clinical problem, but also has important significance in sociology and economics.Objective:(1) This study summarizes the clinical, pathological and laboratory data of HBV-GN patients in our department, analysis the pathology, clinical characteristics of HBV-GN, and explore the relationship between HBV replication and the clinical and pathological manifestations of HBV-GN. The results of this study may provide a theoretical basis for the diagnosis and treatment of HBV-GN.(2) Discussion the therapeutic effect and safety of alone mycophenolate mofetil, and mycophenolate mofetil combined with small dose of hormone therapy for HBV-GN. Screening the optimal treatment for HBV-GN preliminary.Method:(1) Collect124cases retrospectively, who admitted to the First Affiliated Hospital of Nanchang University hospital during January2006to December2013, with biopsy diagnosis of HBV-GN. Analyzing the general information, clinical manifestations, laboratory tests, serum virology, biopsy pathology of this124patients with HBV-GN retrospectively. And do interrelated statistical comparison.(2) Collected date of patients with HBV-GN, who admitted to our department during January2006to December2012, with complete information of inpatient and outpatient, and receive mycophenolate mofetil therapy. In a total, there are46cases. Depending on the treatment plan, we divided into32cases of mycophenolate mofetil combined small dose of the hormone group (hereinafter referred to as the treatment group), and14cases of a single treatment with mycophenolate mofetil group (hereinafter referred to as the control group). Observed12months, compare and evaluate the clinical manifestations the main laboratory parameters, treatment remission rates, adverse reactions, and remission rate of different pathological types, remission rate of different serum virological of this two groups.Results:I. General:1.1In124patients of HBV-GN, there are more males than females in various pathological types, male to female ratio is2.26:1. The average age is27.5years, most common in youth. There are37.9%of patients have clear history of hepatitis B before onset.1.2In HBV-GN, the most common is nephrotic syndrome (accounting for55.65%). Other are followed by the proteinuria and hematuria (20.07%), proteinuria alone (17.74%), microscopic hematuria (4.03%), gross hematuria (1.61%) in turn. There are62.1%of the patients associated with edema;16.94%associated with anemia;20.97%with hypertension when the onset of HBV-GN.1.3HBV-GN with membranous nephropathy most common, accounting for65.32%. Second are followed by IgAN (14.52%), MsPGN (7.26%), MPGN(6.45%). Other types are rare, such as MCD (2.42%), ENPGN (2.42%), FSGS (1.61%).1.4In HBV-GN patients, there are15.32%of patients with renal dysfunction. FSGS occurs most frequently.20.16%of patients exist abnormal liver function, the highest incidence of MPGN. Most patients with serum complement decreased, the rate decline of C3(51.19%) is higher than the C4(28.23%).1.5Immunofluorescence detection show that a variety of immune complex deposit in the kidney. IgG deposition rate is the highest, accounting for94.35%, followed by IgM (87.1%), C3(86.29%), IgA (83.6%), Clq (69.35%), FRA (67.74%), C4(50%). And visible a variety of immune complex deposition at the same time, 44.35%presented "full house". HBVAb can be detected in almost, HBsAg positive rate is94.35%, HBcAg detection rate of91.13%, the detection rate of HBsAg and HBcAg both positive is87.9%. Deposition of immune complexes is not only found in the glomerular capillary wall (in the basement, under epithelial cells, under endothelial cells), also seen in the mesangial area. And found that the deposition site and distribution of hepatitis B antigen agreement with deposition of immunoglobulin and complement.2. The relationship among HBV replication status and nephritis2.1There is no difference in the pathological type and clinical manifestations between serological HBeAg positive and negative groups.2.2The incidence of renal dysfunction (24%), renal failure (8%), abnormal liver function (28%), hypocomplementemia (68%) in HBeAg-positive group is higher than in HBeAg-negative group. HBV-DNA mean titers of HBeAg-positive group is higher than HBeAg-negative group, P<0.05. Hypertension incidence of HBeAg-negative group is higher than HBeAg-positive group.2.3The incidence of "Full house" in HBeAg-positive group (58%) is higher than HBeAg-negative group (33.33%),P<0.05.2.4There is no difference in pathological type among HBV-DNA titer negative group, high load group, and low load group. The incidence of nephrotic syndrome in High load group (71.874%) is higher than the other two groups,P<0.05.2.5The incidence of macroalbuminuria (75%), hypoalbuminemia (71.88%) in low load group is higher than the other two groups,P<0.05.2.6There is no difference in the renal tissue deposition of immune globulin, complement, HBV markers among HBV-DNA titer negative, high load group and low load group. The incidence of "Full house" in high load group is higher than other groups, P<0.05.3. Evaluation of mycophenolate mofetil3.1There are54.35%complete remission,30.43%partial remission,15.22%ineffective. The total efficiency is82.61%(38cases in46patients).The efficiency of MN (85.71%) is higher than MsPGN (83.33%), higher than MPGN (75%). But the difference is not statistically significant. With prolonged treatment, complete remission rate, partial remission rate and total efficiency are significant increased, P <0.05. The total efficiency of treatment group is higher than control group,P<0.05.3.2The complete remission rate and tatal efficiency of treatment group is higher in MN and MsPGN.3.3For HBV markers of HBsAg, HBeAg, HBcAb are positive, there is no significant difference in the efficiency between the control group and the treatment group. For markers of HBsAg, HBeAb, HBcAb are positive, the complete remission rate and total efficiency of the treatment group is higher. But the difference is not statistically significant.3.4The treatment group and control group compared with before therapy, urinary protein significantly reduced, and serum albumin significantly increased, P<0.05. Treatment for3months, serum lipid levels in the treatment group is significantly lower than the control group,P<0.05. The changes in liver and kidney function, blood cell count, HBV-DNA titers are no significant difference.3.5During the treatment, there are four cases appear nausea, vomiting, two cases appear diarrhea, one case appear leukopenia. They relieved after symptomatic treatment, the original treatment plan has not changed.2patients with HBV-DNA titers increased progressively, after change lamivudine to adefovir or entecavir, the titer decreased to the same level or lower.3patients serum creatinine mildly elevated.2patient serum creatinine elevated more than50%, one patient disabled immunosuppressant.2patients with mild liver dysfunction, after lowering liver enzymes treatment, liver function returned to normal. No case of fulminant hepatitis. No other immunosuppressive side effects occurs, such as bone marrow suppression. No significant difference in adverse reactions between treatment group and control group.Conclusion:1. The patients with HBV-GN is given priority to with young and middle-aged, male more than female. The clinical manifestations of nephrotic syndrome is the most common. The main pathology type is membranous nephropathy, and is atypical membranous nephropathy. 2. HBV antigen-antibody complex deposite in the kidney may be one of the main pathogenesis of HBV-GN.3. Diagnosis of HBV-GN depends on renal biopsy.4. Serum HBeAg-positive and HBeAg-negative patients did not differ in the type of renal pathology, but also no differences in clinical manifestations, nephrotic syndrome are more common. However, there are slight differences in terms of the severity of kidney disease.5. There is no difference in the type of renal pathology among HBV-DNA titer negative group, high-load group, and low-load group. The incidence of macroalbuminuria, hypoalbuminemia in high-load group is higher than the other two groups.6. Single-use MMF or combined hormone have the exact effect on therapy HBV-GN both. With prolonged treatment, efficiency increased. And adverse reactions are fewer and light during treatment. MMF combined hormone therapy HBV-GN are more efficient than single-use MMF.7. In MN and MsPGN, MMF combined hormone are more efficient than single-use MMF.8. Both "HBsAg, HBeAg, and HBcAb test positive" and "HBsAg, HBeAb, and HBcAb test positive", there are no significant differences in the efficacy of single-use MMF and combined hormone of HBV-GN treatment.