Overview】 Hepatitis B virus-associated glomerulonephritis is a disease of glomerulonephritis secondary to hepatitis B virus infection and confirmed by serum immunology and renal pathology biopsy, while excluding other etiologies such as systemic lupus erythematosus caused by liver and kidney lesions. Epidemiology】 China is a high prevalence area of hepatitis B virus (HBV) infection. Epidemiological survey shows that: the rate of HBsAg positivity in China is 9.8%; the incidence of hepatitis B virus infection with glomerulonephritis is 15.6% among patients with hospitalized glomerulonephritis. The incidence of hepatitis B virus infection with glomerulonephritis is 15.6% in hospitalized patients with glomerulonephritis. The age of onset is mostly children and adolescents, and the incidence is significantly higher in males than females, with a male to female ratio of about 2.9:1. [Pathogenesis] The deposition of hepatitis B virus antigen-antibody complexes in renal tissue is the main pathogenesis, and direct invasion of renal tissue by hepatitis B virus is also an important pathogenic route. The clinical manifestations of hepatitis B virus-associated nephritis are varied and can be manifested as nephrotic syndrome, simple hematuria, chronic nephritis syndrome, and acute nephritis syndrome. Some patients have a history of hepatitis and liver function abnormalities before the onset of nephritis, and the rate of positive serum e antigen is significantly higher in hepatitis B virus-positive patients than in negative patients, while the rate of positive e antibody is significantly lower than in the negative group, suggesting that active hepatitis B virus replication is an important link in the development of hepatitis B virus-associated nephritis. In addition, some patients showed accelerated blood sedimentation, decreased serum immunoglobulin level and complement level, etc. Ancillary tests] Except for some patients who are consistent with nephrotic syndrome changes, proteinuria, hematuria and abnormal urine sedimentation are mostly seen. Serum immunological examination shows: HBsAg and anti-HBs are mostly positive, HBeAg is mostly positive; IgG and IgA may be increased, hypocomplementemia, and some patients may have decreased serum C3 level is considered an important indicator of hepatitis B virus-related nephritis. Renal pathology】 Hepatitis B virus-associated nephritis includes almost all types of renal pathology: membranous nephropathy (membranous nephropathy), membranoproliferative nephritis (MsPGN), membranoproliferative nephritis (MPGN), intracapillary proliferative glomerulonephritis (EPGN), IgA nephropathy, microscopic lesion nephropathy (MCD) and focal segmental glomerulosclerosis (FSGS), etc. . Pathologically, hepatitis B virus-associated nephritis is similar to the corresponding type of primary nephritis, but viral particles and tubuloreticular inclusions are seen on electron microscopy, indicating that the disease is associated with viral infection. The natural course of hepatitis B virus-associated nephritis remains unclear, with 30% to 60% of patients with hepatitis B virus-membranous nephropathy resolving spontaneously within 12 months or more of onset, while the rest have persistent proteinuria and sodium retention. The majority of patients have a benign course, and Glibert et al. 1994 reported that of 71 patients with hepatitis B virus-associated nephritis, 37 (52.1%) achieved spontaneous remission after 90 months of follow-up, and 33 (89.2%) of them achieved seroconversion of HBeAg. The mean interval from HBeAg clearance to nephrotic remission was 5 months. In children with hepatitis B virus-associated nephrotic syndrome without antiviral therapy, the course of the disease was continuously progressive, with 1.4% to 2.8% progressing to ESRD; in contrast, 1/3 of adults with hepatitis B virus-membranous nephropathy without antiviral therapy progressed to ESRD. in children, the mean duration of proteinuria was 30 months, and the rate of involvement in remission was 64% within 4 years and 84 percent, and remission of the nephrotic syndrome parallels negative hepatitis B virus antigen, especially HBeAg. In the majority of patients, proteinuria also subsided 6 months after HBeAg negative regression. However, the spontaneous clearance of hepatitis B virus was extremely low. In a follow-up of 46 South African children who were double positive for HBeAg and HBsAg, only 22% achieved spontaneous clearance of HBsAg and HBeAg with remission of the nephrotic syndrome. Diagnosis and differential diagnosis] (a) Western medicine diagnosis The current diagnosis is mostly based on the diagnostic criteria established at the symposium on hepatitis B virus-associated nephritis held in Beijing in October 1989: 1. Positive serum hepatitis B virus markers; 2. Glomerulonephritis with the exception of secondary glomerular diseases such as lupus nephritis; 3. Hepatitis B virus antigen or hepatitis B virus-DNA found in renal tissue sections; 4. Pathology of membranous nephropathy. (Note: 1. Diagnosis can be confirmed by meeting 1, 2 and 3, regardless of renal histopathology; 2. When 1 and 2 diagnostic criteria are met and renal histopathology is confirmed as membranous nephropathy, although hepatitis B virus antigen or hepatitis B virus-DNA is not found in renal tissue sections, it can be considered as a proposed diagnosis; 3. (Hemoglobinemia is not yet sufficient as a basis for the diagnosis of hepatitis B virus-associated nephritis). (ii) Differential diagnosis: Hepatitis B virus-associated nephritis is differentiated from primary membranous nephropathy: membranous nephropathy and membranoproliferative glomerulonephritis are the most common forms of hepatitis B virus-associated nephritis, and the pathomorphology of membranous nephropathy is slightly different from that of primary membranous nephropathy. Immunocomplexes and electron-dense material can be found in different parts of the glomerulus, varying in size and even appearing as giant fastidious deposits. Immunopathological examination often shows the phenomenon of “full brightness”. The majority of studies to date have not advocated glucocorticoids for the treatment of hepatitis B virus-associated nephritis, although some have used glucocorticoids based on the consideration of reducing proteinuria, but more and more scholars have found that glucocorticoids do not alleviate the nephrotic syndrome or lead to viral clearance. In a prospective study of the therapeutic role of glucocorticoids in hepatitis B virus-associated nephritis, Lai et al. showed that after six months of glucocorticoid treatment in eight patients with hepatitis B virus-membranous nephropathy, the hormone-treated group showed active transient viral replication and elevated serum HBeAg and hepatitis B virus-DNA. Two of the patients treated with diuretics only achieved spontaneous remission, which was significantly delayed compared with the hormone-treated group. Repeat renal biopsy was performed in one patient and did not reveal a renal protective effect of hormones. In addition, the finding of virus-like particles in the glomeruli after hormone treatment confirmed that hormones can lead to active viral replication. However, small doses of hormone have been given orally for two weeks at 1 mg/Kg.d prior to treatment with IFN-α, followed by abrupt discontinuation of the drug and administration of IFN-α at 1 million units intramuscularly every other day. It is believed that the hormone induces an immunosuppressive response. An immune rebound against the infected cells occurred right after discontinuation of the drug, and IFN-α treatment was given at this time to promote synergistic effects. Therefore, hormones should be used with caution in hepatitis B virus-associated nephritis. Only when the kidney disease cannot be controlled, under the close supervision of the doctor, IFN-α treatment should be given simultaneously or sequentially in small doses, and the maximum dose should be controlled at 0.6 mg/kg.d, and the course of treatment should be within six months. 2, interferon-α general authors use a dose of 5 million iu each time (3 million to 8 million) 3 times a week or every other day, the course of treatment varies from 8 to 12 months, generally 16 weeks. Lin et al. reported that treatment with IFN-α at 5 to 8 million iu (3 million to 8 million iu) 3 times a week for 12 months resulted in a complete conversion of urine protein after 3 months, with 80% achieving HBeAg seroconversion at 12 months and 60% negative conversion of HBsAg, which may be related to the high dose and long duration of treatment. Currently, it is believed that the serological response to IFN-α treatment does not appear until after 8-12 weeks of treatment, so it is recommended that the course of treatment should be at least 3 months. The overall effective rate for hepatitis B virus-membranous nephropathy is 20%-62.5%, as reported by various authors. Adverse effects: fever, chills, hypotension, nausea, diarrhea, headache, malaria, myalgia, and uncommon cachexia, alopecia, and psychoneurological disorders. Generally, no special treatment is needed, and they disappear within 7-10 days of continued use. However, it is expensive and requires subcutaneous injection. It should also be noted that patients who have responded to TNF-α treatment for 6 to 8 weeks often show an increase in ALT, and some patients show phase fluctuations in ALT. This indicates that the patient’s immune system is activated and the organism is clearing the virus. The prognosis is usually better for those with elevated ALT, and enzyme lowering is not advocated, but should be discontinued and symptomatic treatment given if jaundice develops. ALT elevation after the end of treatment may be due to the delayed antiviral effect of TNF-α, which can continue to be applied and suggests a good prognosis. 3.Lamivudine Dose: Lamivudine is an oral preparation with a recommended adult dose of 100mg/d. In children, the blood concentration and degree of inhibition of hepatitis B virus achieved at a dose of 3mg/kg.d is similar to the effect of 100mg/d in adults and can be increased to 100mg/d. Patients with ALT levels 2-5 times higher than normal before treatment, active viral replication and compensated liver function Lamivudine has the best efficacy. For HBeAg-positive patients with complete response at 1 year of treatment, it is recommended to continue the drug for at least 6 months, with a review at 3 months interval, and those who still maintain complete response can be discontinued for observation; for HBeAg-positive patients before treatment, those with partial response at 1 year of treatment are recommended to continue the drug until complete response, then continue the drug for 6 months, with a review at 3 months interval, and those who still maintain complete response can be discontinued for observation; HBeAg-negative HBeAg-negative patients with active hepatitis B virus-DNA replication who are in complete response should be discontinued for at least 2 years, regardless of whether they were HBeAg-negative or positive before treatment. Clinical studies on the use of lamivudine in pregnant women and children are inconclusive, therefore, for the time being, China does not provide treatment with lamivudine for pregnant women and children under 12 years of age with hepatitis B virus infection. Adverse reactions and side effects: The biggest problem with lamivudine is drug resistance mutation. In general, YMDD mutation of hepatitis B virus often occurs after 6 months of lamivudine treatment, and the incidence increases gradually with longer treatment time. Other adverse reactions of lamivudine include: (1) allergic reactions, manifested as angioneurotic edema and urticaria; (2) nail infection, effective with antibiotics; (3) psychiatric disorders; (4) bone marrow suppression; (5) sexual dysfunction; (6) edema; (7) sinus tachycardia; (8) hypokalemia; (9) other disorders such as lipid metabolism and frozen shoulder syndrome, which are rare clinically. 4.Enzyme phenolate Enzyme phenolate (MMF) is a new microbial product purified from cyanase group of bacteria. 1992 was first used in renal transplant rejection, since then, MMF began to be widely used in the prevention and treatment of organ transplant rejection, and in recent years began to expand to immune glomerulonephritis, especially autoimmune diseases, hepatitis B virus-associated nephritis and vasculitis, etc. 5.Other Angiotensin-converting enzyme inhibitors (ACEI) have been shown to reduce proteinuria, and statin lipid-lowering drugs can reduce the hypermetabolic state of tubular interstitium and slow down the progression of renal disease. The combination of these drugs along with the above mentioned drugs has an important role in improving the long-term prognosis of patients. The main symptoms are: distension and pain in the liver and ribs, stuffiness and distension in the abdomen, poor appetite and bitterness, fatigue, swelling of the limbs, loose stools, yellow urine, foamy, red tongue, yellow greasy coating and smooth pulse. Treatment: Diversify the liver and strengthen the spleen. Main formula: Xiao Chai Hu Tang with Wu Ling San plus reduction. Herbs: Ginseng 10g, Radix et Rhizoma tigrinum 15g, Atractylodes Macrocephala 10g, Glycyrrhiza glabra 10g, Radix zedoaria 20g, Poria 15g, Poria 15g, Radix chaihu 15g, Rhizoma chuanxiong 20g, Rhizoma dioscorea 20g, Plantago lanceolata 30g. Addition and subtraction: If the mouth is bitter, add Patchouli and Pelargonium. Scutellaria baicalensis to strengthen the spleen and resolve dampness; if the limbs are swollen with little urination, add Zedoary, Che Qian Zi to diuretic and reduce swelling; or jaundice, add Yin Chen, Chicken Bone Cao, Feng Wei Cao to promote dampness and reduce yellow. 2, spleen and kidney deficiency evidence: less abdominal distension, especially after meals, waist and knee weakness, tinnitus and forgetfulness, loose stools, weakness and drowsiness, edema of the limbs, pale tongue with white fur, sunken pulse. Treatment: Tonifying the spleen and kidney, inducing diuresis and removing dampness. Main formula: Fangji Huangqi Tang with reduction. Chinese herbs: 10g of Radix Angelicae Sinensis, 30g of Radix Astragali, 10g of Atractylodes Macrocephala, 10g of Glycyrrhiza Uralensis, 30g of Plantago Major, 10g of Jujube, 30g of Yam, 10g of Angelicae Sinensis, 30g of Cornus Officinalis. Addition and subtraction: for nausea and vomiting, add Chen Pi, Radix et Rhizoma Pinelliae, Bamboo Roo to harmonize the stomach and stop vomiting; if abdominal distension is obvious, add Citrus Aurantium, Fructus Foetida to regulate Qi and reduce swelling. 3, damp-heat internalized evidence Main symptoms: pain in the ribs, irritability, bitterness, fatigue, short, red urine, dry stools or sticky stools, yellow, greasy tongue coating, slippery pulse. Treatment: Clearing dampness and heat Main formula: Artemisia Inchi Tang Herbs: Inchi 30g, Gardenia 12g, Rhubarb 9g. Add and subtract: If edema is obvious, add Poria, Zeligia, Big Belly Skin, Plantago; if irritable and easily irritated, add Fragrant Rhizoma, Yujin; if the bowels are loose, add Atractylodes Macrocephalae, Jiao Sanxian, Chicken Neijin. 4.Qi stagnation and blood stasis evidence Main symptoms: prolonged illness, stabbing pain in the ribs, sallow face, emaciated body, short urine, dark red tongue or petechiae, thin and astringent pulse. Treatment: Promote blood circulation, resolve blood stasis, promote Qi flow and promote water circulation. Main formula: Blood Mansion and Eliminating Blood Stasis Tang Herbs: Peach kernel 12g, safflower 12g, angelica 12g, raw groundnut 12g, Chuanxiong 12g, red peony 12g, hyssop 12g, orris 9g, bupleurum 12g, heliotrope 12g, licorice 6g. Add and subtract: if edema is obvious, add poria, zedoary, dagger skin; if chest is distended and painful, add aromatic herb, yujin; if mouth is dry and tongue is red, add raw groundnut, danpi. The higher the rate of hepatitis B virus infection, the higher the incidence of glomerulonephritis. Since the 1990s, China’s universal implementation of the hepatitis B vaccine program immunization, hepatitis B virus infection rate and HBsAg carrier rate has been significantly reduced. The survey showed that the decline in both rates was over 95.0% in the 3-8 year old group, and the HBsAg positivity rate also decreased by 82.2% in the 1-2 year old group, which is of great significance in controlling the hepatitis B epidemic in China. The rate of hepatitis B virus infection in children has now dropped to less than 0.5%. Hepatitis B virus-associated nephritis in children has decreased significantly. The prevalence of membranous nephropathy in children has also gradually decreased. However, mother-to-child transmission and vaccination failure still occur at a certain rate. Further control of the incidence of hepatitis B virus infection should focus on interruption of mother-to-child transmission of hepatitis B virus (including prenatal screening of pregnant women, prenatal hepatitis B immunoglobulin injections for high-risk pregnant women, and combined HBIG and vaccine prophylaxis for high-risk newborns) and strengthening serological follow-up of high-risk patients.