Anti-HCVAg positive
Introduction
Anti-HCVAg positive introduction Anti-HCVAg positivity is one of the symptoms of the diagnosis of non-cold globulinic glomerulonephritis (noncryoglobulinemic MPGN) and membranous nephropathy. Hepatitis C virus (HCV) is a single-stranded RNA virus first discovered in 1989. It is estimated that there are about 100×106 infected people in the world, mainly through blood products and the use of intravenous drugs. In the past 10 years, the relationship between HCV infection and glomerular diseases has gradually increased. It is believed that HCV-related renal damage mainly includes: cryoglobulin-induced proliferative glomerulonephritis (cryoglobulinemicMPGN), non-cold globulin blood. Synovial proliferative glomerulonephritis (noncryoglobulinemicMPGN) and membranous nephropathy (MN). Clinically diagnosed should have: 1. have proteinuria or hematuria; 2. serum hepatitis C virus RNA (HCV-RNA) positive, anti-HCVAg positive. 3. Cold globulin and immune complexes are present, including HCV-RNA viral core antigen and IgG anti-HCV antibody. 4. Renal biopsy showed severe mononuclear cell infiltration and deposition of a large number of glomerular immune complexes. basic knowledge The proportion of sickness: 0.004% - 0.009% Susceptible people: no specific population Mode of transmission: mother-to-child transmission, iatrogenic infection, blood transfusion, close contact with life, sexual transmission Complications: glomerulonephritis, arthritis, diabetes, fatty liver, aplastic anemia, pleurisy, myocarditis, pericarditis
Cause
Anti-HCVAg positive cause
(1) Causes of the disease
The association between HCV and cryoglobulinemia was first reported in 1990. Recent studies have found evidence of HCV infection in 95% of patients with type II cryoglobulinemia and 50% of patients with type III cryoglobulinemia, including: serum There is a circulating anti-HCV antibody, a cryoprecipitate containing a polyclonal IgG anti-HCV antibody, and HCV-RNA present in plasma and cryoprecipitate. HCV-associated cryoglobulinemia MPGN was first reported in 1994, and HCV-associated proteins were detected in renal tissue sections of patients with cryoglobulinous MPGN using monoclonal antibodies against specific HCV antigens, in 12 HCV-like cases. Eight of the patients with positive cryoglobulinemia MPGN were tested for glomerular capillary wall and mesangial area and HCV antigen deposition, while HCV was not detected in 8 patients with HCV-negative cryoglobulinemia MPGN. antigen. It is believed that cryoglobulinemia MPGN of HCV is mediated by HCV immune complexes, and HCV antigen-antibody immune complexes are deposited under the endothelium and mesentery, activating complement and secondary cell proliferation and inflammatory cell infiltration. However, it is unclear whether HCV antigen mediates glomerular damage independent of cryoglobulin. HCV infectious glomerulonephritis is classified as follows
1. cryoglobulinemia proliferative glomerulonephritis cryoglobulinemia refers to the presence of reversible precipitation of -globulin in serum at 4 ° C, divided into 3 types due to different components: type I cold Globulin is a monoclonal immunoglobulin produced secondary to monoclonal gamma globulin lesions such as multiple myeloma. Type II cryoglobulin is a mixed cryoglobulin composed of polyclonal IgG and monoclonal IgM directed against the IgG Fc segment, wherein IgM has rheumatoid factor activity. Type III cold globulin is a mixed polyclonal immunoglobulin, which is more common in inflammation and autoimmune diseases such as systemic lupus erythematosus. About 50% of patients with type II cryoglobulinemia develop kidney disease, but rarely in patients with type III cryoglobulinemia.
2. Non-cold globulinemia membranous hyperplasia glomerulonephritis Non-cold globulinemia MPGN pathology, clinical course and cryoglobulinemia MPGN similar. The role of HCV in the pathogenesis of non-cold globulinemia MPGN is still controversial.
3. Membrane nephropathy A small number of HCV patients with renal damage is MN, the patient's clinical manifestations are nephrotic syndrome, serum complement is normal, cold globulin and rheumatoid factor negative. HCV-associated proteins were also detected on the kidney tissue sections of patients.
(two) pathogenesis
The association between HCV and cryoglobulinemia was first reported in 1990. Recent studies have found evidence of HCV infection in 95% of patients with type II cryoglobulinemia and 50% of patients with type III cryoglobulinemia, including: serum There is a circulating anti-HCV antibody, a cryoprecipitate containing a polyclonal IgG anti-HCV antibody, and HCV-RNA present in plasma and cryoprecipitate. HCV-associated cryoglobulinemia MPGN was first reported in 1994, and HCV-associated proteins were detected in renal tissue sections of patients with cryoglobulinous MPGN using monoclonal antibodies against specific HCV antigens, in 12 HCV-like cases. Eight of the patients with positive cryoglobulinemia MPGN were tested for glomerular capillary wall and mesangial area and HCV antigen deposition, while HCV was not detected in 8 patients with HCV-negative cryoglobulinemia MPGN. antigen. It is believed that cryoglobulinemia MPGN of HCV is mediated by HCV immune complexes, and HCV antigen-antibody immune complexes are deposited under the endothelium and mesentery, activating complement and secondary cell proliferation and inflammatory cell infiltration. However, it is unclear whether HCV antigen mediates glomerular damage independent of cryoglobulin. HCV infectious glomerulonephritis is classified as follows:
1. cryoglobulinemia proliferative glomerulonephritis cryoglobulinemia refers to the presence of reversible precipitation of -globulin in serum at 4 ° C, divided into 3 types due to different components: type I cold Globulin is a monoclonal immunoglobulin produced secondary to monoclonal gamma globulin lesions such as multiple myeloma. Type II cryoglobulin is a mixed cryoglobulin composed of polyclonal IgG and monoclonal IgM directed against the IgG Fc segment, wherein IgM has rheumatoid factor activity. Type III cold globulin is a mixed polyclonal immunoglobulin, which is more common in inflammation and autoimmune diseases such as systemic lupus erythematosus. About 50% of patients with type II cryoglobulinemia develop kidney disease, but rarely in patients with type III cryoglobulinemia.
2. Non-cold globulinemia membranous hyperplasia glomerulonephritis Non-cold globulinemia MPGN pathology, clinical course and cryoglobulinemia MPGN similar. The role of HCV in the pathogenesis of non-cold globulinemia MPGN is still controversial.
3. Membrane nephropathy A small number of HCV patients with renal damage is MN, the patient's clinical manifestations are nephrotic syndrome, serum complement is normal, cold globulin and rheumatoid factor negative. HCV-associated proteins were also detected on the kidney tissue sections of patients.
Prevention
anti-HCVAg positive prevention
The main source of HCV infection is blood transfusion and application of blood products, so anti-HCV screening of blood donors is currently the main measure to prevent HCV infection. Contamination of HCV in blood products is also an important source of HCV infection. In addition to strict screening of blood donors, how to effectively inactivate HCV and maintain the activity of biological products in the production process of blood products remains to be further studied.
The ultimate control of the disease will depend on the application of the vaccine. The successful cloning of HCV molecules has opened up possibilities for the development of hepatitis C vaccines. However, due to the different types of HCV and variability, the current development of HCV vaccines is still very arduous. The prevention of HCV renal damage depends on the prevention and effective treatment of hepatitis C.
Complication
anti-HCVAg positive complications Complications glomerulonephritis arthritis diabetes fatty liver aplastic anemia pleurisy myocarditis pericarditis
Common complications include arthritis (12% to 27%), glomerulonephritis (26.5%), nodular polyarteritis, etc., using direct immunofluorescence and electron microscopy, found that there are HBV particles on the synovial membrane, serum In patients with membranous glomerulonephritis with persistent HBsAg, HBcAg deposition was found in renal biopsy glomerular tissue. In this hospital, 180 patients with glomerulonephritis were examined by renal biopsy, and 33 patients with HBcAg deposition in the kidney were found. 18.3%), the complex of HBcAg, IgG, IgM, C3 and other immune complexes can be seen on the wall of the diseased tuberculosis. The rare complications are diabetes, fatty liver, aplastic anemia, multiple Neuritis, pleurisy, myocarditis and pericarditis, among which diabetes and fatty liver are worthy of attention, and a small number of patients may have hyperbilirubinemia after hepatitis.
Symptom
Anti-HCVAg positive symptoms Common symptoms Hemoglobinuria proteinuria hematuria
1. Latency: The incubation period of this disease is 2 to 26 weeks, with an average of 7.4 weeks. The incubation period of hepatitis C caused by blood products is short, generally 7 to 33 days, with an average of 19 days.
2. Clinical experience: clinical manifestations are generally lighter than hepatitis B, mostly subclinical without jaundice, common single ALT is elevated, long-term persistence does not drop or repeated fluctuations, patients with lower mean ALT and serum bilirubin, jaundice The duration is shorter, but it is also more serious, and the clinical difficulty is different from hepatitis B.
Hepatitis C virus infection is more chronic than hepatitis B virus infection. It is observed that about 40% to 50% develop chronic hepatitis, 25% develop cirrhosis, and the rest is self-limiting. Acute hepatitis C develops into chronic Most of them are jaundice-free, ALT long-term fluctuations do not fall, serum anti-HCV continues to be high titer positive, therefore, clinical attention should be paid to observe changes in ALT and anti-HCV.
Although the clinical manifestations of hepatitis C are mild, but severe hepatitis can also occur, HAV, HBV, HCV, HDV and HEV can cause severe hepatitis, but the background and frequency of occurrence are different. The causes of acute, subacute severe hepatitis are: HBV is mostly, and most cases are HCV in Japan. It is speculated that the reason may be that the HCV infection rate in Japanese population is much higher than that in Europe and America, and the HCV genotype in Europe and America is different from that in Japan. Most of the reports were mostly HBV. HCV-induced severe hepatitis was mostly caused by chronic hepatitis B with HCV infection. 3. Viral model. Follow-up study of patients with hepatitis C after transfusion showed that HCV was as follows. Mode:
(1) Acute self-limiting hepatitis with transient viremia.
(2) Acute self-limiting hepatitis with persistent viremia.
(3) persistent viremia but no hepatitis, as a symptomatic carrier of HCV.
(4) Chronic hepatitis C with intermittent viremia.
(5) Chronic hepatitis C with persistent viremia.
4. Overlap infection of HBV and HCV Because HCV has a similar transmission route to HBV, the possibility of infecting both viruses is present, but it is more common to infect HCV on the basis of persistent HBV infection. The 302 Hospital of the People's Liberation Army found that the anti-HCV positive rate in the serum of patients with HBsAg-positive chronic liver disease was 0 (0/14) in mild chronic hepatitis (slow-moving liver); 24.24% (8/33) in chronic active hepatitis; chronic heavy Hepatitis was 33.33% (3/9), indicating an increase in the positive rate with the progression and evolution of hepatitis B. It is speculated that this may be due to the increased chance of receiving iatrogenic infections such as blood transfusion during the progression of chronic hepatitis B. On the other hand, there are reports that HBV/HCV overlap infection with severe hepatitis and severe HBV-infected severe hepatitis, two groups of bilirubin, AST/ALT and mortality, there are significant differences, indicating overlapping infection group Hepatocyte necrosis is much more severe than severe hepatitis with HBV infection alone.
It has been observed that HBV DNA and HCV RNA in HBV and HCV overlap cases are only 19% positive, and most of them are HCV RNA or HBV DNA single positive. In addition, almost all HCV RNA positive patients are e antigen negative cases, suggesting that the virus overlaps. The proliferation of infection occurs.
5. HCV infection and hepatocellular carcinoma (HCC) The relationship between HCV infection and HCC is receiving more and more attention. From HCV infection to HCC, the average is about 25 years. It can also be directly developed from chronic hepatitis without cirrhosis. The detection rate of anti-HCV was different. The preliminary report in China was 10.96%-59%. Due to the wide heterogeneity of HCV, the occurrence of HCC has a certain relationship with HCV infection of different genotypes. The prevalence of HCV in Japan and the United States Basically similar, but there are more HCCs related to HCV in Japan, but less in the United States. The results show that type II HCV has the characteristics of high level of replication and poor response to interferon therapy, leading to progressive development of liver disease and carcinogenesis. It may play an important role and provide a molecular epidemiological basis for studying HCV-induced HCC mechanisms.
The mechanism of HCV carcinogenesis is different from that of HBV. It has been shown that HCV is not integrated into the DNA of liver cells like HBV. It is reported that the double infection of HBV and HCV seems to increase the incidence of hepatocellular carcinoma, so HCV should be noted. The role of HBV in carcinogenesis.
6. HCV infection and autoimmune hepatitis (AIH) Generally, autoimmune hepatitis is classified into four types according to different autoantibodies. Among them, type II AIH refers to anti-nuclear antibody negative and anti-LKM-I positive, recently studied type II AIH is divided into two subtypes: Type IIa AIH: younger-looking, female-dominated, familial autoimmune disease, immunosuppressive therapy, not related to HCV infection, type IIb AIH: mostly elderly, male , no familial autoimmune disease, antiviral therapy is superior to immunosuppressive agents, associated with HCV infection, anti-HCV positive, anti-GOR positive, such patients should check HCV RNA when necessary.
Examine
anti-HCVAg positive test
Urinary bilirubin (BIL)
Serum 1 antitrypsin assay (1-AT)
Serum -glutamyltranspeptidase (-GTP)
Serum lactate dehydrogenase
Serum alpha-fetoprotein (AFP)
Blood ammonia
Erythrocyte acetylcholinesterase
Prothrombin time (PT)
Diagnosis
Anti-HCVAg positive diagnosis
1. Clinical manifestations of hepatitis C: The incubation period of this disease is 2 to 26 weeks, with an average of 7.4 weeks. Hepatitis C caused by blood products has a short incubation period of 7 to 33 days, with an average of 19 days. The clinical manifestations are generally lighter than hepatitis B, mostly subclinical and no jaundice. Common single ALT is elevated, long-term continuous decline or repeated fluctuations, the average ALT and serum bilirubin are lower, and the duration of jaundice is shorter. However, there are also serious illnesses, and the clinical difficulty is different from hepatitis B.
Hepatitis C virus infection is more chronic than hepatitis B virus infection. It is observed that 40% to 50% develop into chronic hepatitis, 25% develop into cirrhosis, and the rest is self-limiting. Most patients with acute hepatitis C develop chronically without jaundice. The long-term fluctuation of ALT does not decrease, and serum anti-HCV continues to be high titer positive. Therefore, clinical attention should be paid to the observation of changes in ALT and anti-HCV. Although the clinical manifestations of hepatitis C are mild, the incidence of severe hepatitis can also be seen. HCV-induced severe hepatitis is associated with chronic hepatitis B with HCV infection.
2. The manifestations of HCV cryoglobulinemia nephritis: cryoglobulinemia is a systemic vasculitis lesion, HCV cryoglobulinemia MPGN patients can have a variety of non-specific clinical manifestations, such as purpura, joint pain, surrounding Neuropathy, hypocomplementemia, etc. Renal manifestations include: hematuria, proteinuria (more in the range of nephrotic syndrome), significant hypertension, and varying degrees of renal insufficiency, with approximately 25% of patients with nephrotic syndrome being the initial manifestation. There is often a mild elevation of transaminase, some patients with normal transaminase, and no history of acute hepatitis.
Serological tests for hepatitis C have only recently improved, but hepatitis C is associated with cryoglobulinemia glomerulonephritis. In addition to autoimmune active hepatitis, cryoglobulin and circulating immune complexes can occur in a variety of acute and chronic liver diseases, except for common purpura, weakness, joint pain, hepatitis, nephritis, and vasculitis. In addition to cryoglobulinemia, hepatitis C antigenemia is also common. In mixed cryoglobulinemia, patients with renal impairment were positive for serum hepatitis C virus RNA (HCV-RNA), positive for anti-HCVAg, and positive for cryoprecipitate. The cryoprecipitate includes the HCV-RNA viral core antigen and the IgG anti-HCV antibody, however, HCV-RNA is not localized to immunodeposition in the glomerulus. A 39-year-old hepatitis C antibody-positive woman with a history of drug abuse, manifested as weakness, purpura, joint pain, facial and lower extremity edema, the patient has renal proteinuria, loss of renal function, mixed cryoglobulin blood disease. Therefore, the clinical manifestations of this disease are not specific.
There is currently no uniform diagnostic criteria for nephritis associated with hepatitis C. The diagnosis of the disease, in addition to the diagnosis of hepatitis C, should have the following four clinically diagnosed:
1. There are proteinuria or hematuria.
2. Serum hepatitis C virus RNA (HCV-RNA) positive, anti-HCVAg positive.
3. There must be a presence of cryoglobulin and immune complexes, ie, cryoprecipitate positive, with HCV-RNA viral core antigen and IgG anti-HCV antibodies in the cryoprecipitate.
4. Renal biopsy showed severe mononuclear cell infiltration and a large number of glomerular immune complex deposition, because the HCV-RNA immune deposits are not necessarily located in the glomerulus, so renal biopsy can also be negative. Renal biopsy confirmed glomerulonephritis and may exclude other secondary glomerular diseases.
In view of the high prevalence of liver disease in China, and HBV and HCV often overlap infection. Since HCV has a similar transmission route to HBV, the possibility of infecting both viruses is present, but it is more common to infect HCV based on persistent HBV infection. In order to avoid missed diagnosis, in patients with glomerulonephritis, HBV and HCV antigens should be routinely examined.
1. Urine examination: hematuria and proteinuria, tubular urine can occur, and urine protein is mainly albumin. Mostly proteinuria in the range of nephrotic syndrome. Patients with acute jaundice hepatitis can be positive for urinary bilirubin and urobilinogen before the onset of jaundice.
2. Blood test: The total number of white blood cells is normal or slightly lower, the neutrophils can be reduced in the classification count, and the lymphocytes are relatively increased. When accompanied by renal insufficiency, elevated blood urea nitrogen, creatinine and hypo-complementemia can be seen.
3. Liver function test: For those with acute hepatitis symptoms, the following tests can be performed:
(1) Serum bilirubin: The patient's serum bilirubin increased day by day in the jaundice stage, and reached a peak in 1 to 2 weeks.
(2) Serum enzyme assay: serum alanine aminotransferase (ALT) began to rise before the onset of jaundice, peaking at the extreme stage of the disease, acute hepatitis can have very high enzyme activity, and the recovery period slowly decreases with serum bilirubin. In chronic hepatitis, ALT can fluctuate repeatedly. In severe hepatitis, ALT decreases when bilirubin rises sharply. It is called separation of enzymes and sputum, which is a sign of serious illness.
About 4/5 of aspartate aminotransferase (AST) is present in mitochondria (ASTm) and 1/5 in cytosol (ASTs). When mitochondria is damaged, serum AST is significantly increased, reflecting the severity of hepatic lesions.
In the case of acute viral hepatitis, the ALT value is higher than the AST value, and the ALT/AST ratio is close to 1 when the chronic viral hepatitis lesion continues to be active. The AST increase in cirrhosis is often more significant than ALT.
ALT and AST can be increased in the active period of viral hepatitis, other liver diseases (such as liver cancer, poison, drugs or alcoholic liver damage), biliary tract disease, pancreatitis, myocardial disease, heart failure and other diseases. Raise, should pay attention to identification.
Serum lactate dehydrogenase (LDH), cholinesterase (ChE), and r-glutamyltranspeptidase (rGT) may be altered in acute and chronic liver damage, but the sensitivity and extent of change are far less than that of transaminase. Serum alkaline phosphatase (ALP) can be significantly elevated in intrahepatic and extrahepatic bile duct obstruction and hepatic space-occupying lesions. rGT can be increased in cholestasis and hepatocyte damage, and can be used to identify whether ALP elevation is associated with hepatobiliary disease. Alcohol abuse can also cause an increase in rGT. Chronic hepatitis after excluding biliary tract disease, increased rGT indicates that the lesion is still active, liver cell microsomes are severely damaged during liver failure, rGT synthesis is reduced, and blood rGT is also decreased.
(3) Protein metabolism test: Low protein (A1b) is an important indicator of liver disease. Low A1bemia and hyperglobulinemia are characteristic serological indicators for diagnosing cirrhosis. Pre-serum A1b has a half-life of only 1.9 days, so the change is more sensitive in the liver parenchymal damage, and the extent of the decline is consistent with the degree of hepatocyte damage, and the mechanism of change is similar to that of Alb.
1 alpha-fetoprotein (AFP): short-term low and moderate elevation in acute viral hepatitis, chronic hepatitis and cirrhosis (activity), increased AFP marks the regeneration of hepatocytes, extensive hepatocyte necrosis Among patients, an increase in AFP may have a better prognosis. Patients with extremely high serum AFP levels are most likely to have hepatocellular carcinoma.
2 Determination of blood ammonia: ammonia can not be synthesized into urea excretion in severe hepatitis liver failure; blood ammonia can be increased in patients with good cirrhosis and collateral circulation. Ammonia poisoning is one of the main causes of hepatic coma, but the level of blood ammonia and the incidence and severity of encephalopathy can also be inconsistent.
(4) Prothrombin time (Pt) and activity (PTA): Reduced synthesis of coagulation factors in liver disease, which may cause prolongation of Pt. The prolongation of Pt marks the degree of hepatocyte necrosis and liver failure, and its related coagulation factors. The half-life is very short, such as VII (4 ~ 6h), X (48 ~ 60h), II (72 ~ 96h), so it can reflect liver failure more quickly. Severe hepatitis PTA is more than 40%, PTA is below 20%, often indicating a poor prognosis. Pt prolongation can also be seen in patients with congenital coagulation factor deficiency, diffuse intravascular coagulation and vitamin K deficiency, etc., should be noted. (5) Lipid metabolism related tests: Serum total cholesterol (TC) was significantly reduced in severe hepatitis, and it was considered that the prognosis was poor when TC < 2.6 mmol/L. Serum triacylglycerol (TG) can be increased in hepatocyte injury and intrahepatic obstructive jaundice.
4. Serological diagnosis of liver fibrosis: In the case of chronic liver disease, the formation of extracellular matrix (ECM) is unbalanced with the degradation of the matrix, resulting in excessive deposition of ECM to form fibrosis. Detection of matrix components in serum, degradation products and enzymes involved in metabolism can be used as serum markers for the diagnosis of liver fibrosis.
The pathology of patients with cryoglobulinemia MPGN is similar to that of primary type I MPGN, but dense macrophage infiltration can be seen. Transparent thrombus can be seen in the glomerular capillary lumen. The dense deposits are fingerprint-like structures under electron microscope. A small number of patients may have a primary type III MPGN-like alteration. Renal biopsy showed mononuclear cell infiltration and glomerular massive immune complex deposition.
