Hepatitis C virus infection and glomerulonephritis
Introduction
Introduction to hepatitis C virus infection and glomerulonephritis 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). basic knowledge The proportion of illness: the incidence rate is 0.0002%--0.0005% Susceptible people: no specific people Mode of transmission: transmission of blood products Complications: glomerulonephritis chronic hepatitis
Cause
Hepatitis C virus infection and the cause of glomerulonephritis
(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 are circulating anti-HCV antibodies, cryoprecipitate containing polyclonal IgG anti-HCV antibody, HCV-RNA in plasma and cryoprecipitate, HCV-associated cryoglobulinemia MPGN was first reported in 1994, and then used for specific Monoclonal antibodies to HCV antigen detected HCV-associated protein on renal tissue sections of patients with cryoglobulinous MPGN, and 8 of 12 HCV-positive cryoglobulinemia MPGN patients were in the glomerular capillary wall And mesangial area and HCV antigen deposition, and in HCV-negative cryoglobulinemia MPGN patients did not detect HCV antigen, it is believed that HCV cryoglobulinemia MPGN is HCV immune complex mediated Therefore, HCV antigen-antibody immune complexes are deposited under the endothelium and mesangium, which activates complement and secondary cell proliferation and inflammatory cell infiltration, but whether HCV antigen is independent of cryoglobulin and mediates glomerular damage is still unclear, HCV infection Glomerulonephritis 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 secondary to monoclonal gamma globulin lesions such as multiple myeloma; type II cold globulin is a mixed cryoglobulin, a polyclonal IgG and a single against the IgG Fc segment Cloned IgM composition, in which IgM has rheumatoid factor activity; type III cold globulin is a mixed polyclonal immunoglobulin, more common in inflammation and autoimmune diseases such as systemic lupus erythematosus, etc., about 50% type II cold globulin blood Kidney disease occurs in patients with symptoms, but rarely occurs in patients with type III cryoglobulinemia.
2. Non-cold globulinemia membranous hyperplasia glomerulonephritis non-cold globulinemia MPGN pathology, clinical similar to cryoglobulinemia MPGN, the pathogenesis of HCV in non-cold globulinemia MPGN The role of the above is still controversial.
3. Membrane nephropathy A small number of HCV patients with renal damage is MN, the patient's clinical manifestations of nephrotic syndrome, serum complement normal, cold globulin and rheumatoid factor negative, HCV-related protein was also detected in the patient's kidney tissue sections.
(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 are circulating anti-HCV antibodies, cryoprecipitate containing polyclonal IgG anti-HCV antibody, HCV-RNA in plasma and cryoprecipitate, HCV-associated cryoglobulinemia MPGN was first reported in 1994, and then used for specific Monoclonal antibodies to HCV antigen detected HCV-associated protein on renal tissue sections of patients with cryoglobulinous MPGN, and 8 of 12 HCV-positive cryoglobulinemia MPGN patients were in the glomerular capillary wall And mesangial area and HCV antigen deposition, and in HCV-negative cryoglobulinemia MPGN patients did not detect HCV antigen, it is believed that HCV cryoglobulinemia MPGN is HCV immune complex mediated Therefore, HCV antigen-antibody immune complexes are deposited under the endothelium and mesangium, which activates complement and secondary cell proliferation and inflammatory cell infiltration, but whether HCV antigen is independent of cryoglobulin and mediates glomerular damage is still unclear, HCV infection Glomerulonephritis 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 secondary to monoclonal gamma globulin lesions such as multiple myeloma; type II cold globulin is a mixed cryoglobulin, a polyclonal IgG and a single against the IgG Fc segment Cloned IgM composition, in which IgM has rheumatoid factor activity; type III cold globulin is a mixed polyclonal immunoglobulin, more common in inflammation and autoimmune diseases such as systemic lupus erythematosus, etc., about 50% type II cold globulin blood Kidney disease occurs in patients with symptoms, but rarely occurs in patients with type III cryoglobulinemia.
2. Non-cold globulinemia membranous hyperplasia glomerulonephritis non-cold globulinemia MPGN pathology, clinical similar to cryoglobulinemia MPGN, the pathogenesis of HCV in non-cold globulinemia MPGN The role of the above is still controversial.
3. Membrane nephropathy A small number of HCV patients with renal damage is MN, the patient's clinical manifestations of nephrotic syndrome, serum complement normal, cold globulin and rheumatoid factor negative, HCV-related protein was also detected in the patient's kidney tissue sections.
Prevention
Hepatitis C virus infection and prevention of glomerulonephritis
The main source of HCV infection is blood transfusion and application of blood products. Therefore, anti-HCV screening of blood donors is currently the main measure to prevent HCV infection. HCV contamination in blood products is also an important source of HCV infection, reducing blood pollution. Strict screening of blood donors should be carried out. In the process of blood product production, how to effectively inactivate HCV and maintain the activity of biological products remains to be further studied.
Complication
Hepatitis C virus infection and complications of glomerulonephritis Complications glomerulonephritis chronic hepatitis
Hepatitis C virus infection and complications of glomerulonephritis include renal insufficiency, chronic hepatitis, and liver failure.
1. Renal insufficiency: caused by a variety of causes, the glomerular damage, causing the body to excrete metabolic waste and regulate the water and electrolytes, acid-base balance and other aspects of the clinical syndrome after the disorder. Divided into acute renal insufficiency and chronic renal insufficiency. A serious prognosis is one of the major life-threatening conditions. Renal dysfunction can be divided into four stages: renal function reserve compensation period, renal dysfunction stage, renal failure stage and uremia stage.
2, chronic hepatitis: acute hepatitis B, acute hepatitis C treatment for a long time, the course of disease for more than half a year, and turned into chronic hepatitis. Common symptoms include poor appetite, fatigue, abdominal distension, abdominal pain, and hypochondriac pain.
3, liver failure: liver cells are extensively and seriously damaged, the body's metabolic function is seriously disordered and the clinical syndrome, referred to as liver failure. Liver failure occurs in many serious liver diseases, with sinister symptoms and poor prognosis. Patients usually have symptoms such as jaundice, hepatic encephalopathy, hemorrhage, cerebral edema, lung scuba, and ascites.
Symptom
Hepatitis C virus infection and glomerular nephritis symptoms common symptoms proteinuria hematuria nephrotic syndrome anti-HCVAg positive hypocomplementemia skin purpura cryoglobulinemia hypertension single ALT elevation
1. Clinical manifestations of hepatitis C 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. The clinical performance is generally better than that of hepatitis B. Light, mostly subclinical without jaundice, common single ALT increased, long-term continuous decline or repeated fluctuations, the patient's ALT and serum bilirubin average is lower, jaundice duration is shorter, but also the disease is heavier, clinically difficult It is different from hepatitis B.
Hepatitis C virus infection is more likely to be chronic than hepatitis B virus infection. It is observed that 40% to 50% develop chronic hepatitis, 25% develop cirrhosis, and the rest is self-limiting. Acute hepatitis C develops into chronic ones. For the absence of jaundice, long-term ALT 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 relatively light, but heavy Hepatitis occurs, and HCV-induced severe hepatitis is associated with chronic hepatitis B and 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, peripheral nerve Lesions, hypocomplementemia, etc., renal manifestations include: hematuria, proteinuria (more in the range of nephrotic syndrome), significant hypertension and varying degrees of renal insufficiency, about 25% of patients with nephrotic syndrome as the initial performance, often There is 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, cold globulin and circulating immune complexes can be used in each An acute, chronic liver disease occurs, in addition to common purpura, weakness, joint pain, hepatitis, nephritis, and vasculitis can occur in mixed cryoglobulinemia, hepatitis C antigenemia is also common, in the mix In type of cryoglobulinemia, patients with renal impairment are positive for serum hepatitis C virus RNA (HCV-RNA), positive for anti-HCVAg, positive for cryoprecipitate, and cryoprecipitate includes HCV-RNA viral core antigen and IgG anti-HCV antibody, however, HCV-RNA is not located in the glomerulus, a 39-year-old hepatitis C antibody-positive woman with a history of drug abuse, showing weakness, purpura, joint pain, facial and lower extremity edema, the patient has kidney Proteinuria, loss of renal function, mixed cryoglobulinemia, therefore, the clinical manifestations of this disease are not specific.
Examine
Hepatitis C virus infection and glomerulonephritis
1. Urine examination can appear hematuria and proteinuria, tubular urine, urine protein is mainly albumin, and mostly proteinuria in the range of nephrotic syndrome, acute jaundice hepatitis patients before the appearance of jaundice urinary bilirubin and urinary bladder It can be positive.
2. Blood examination The total number of white blood cells is normal or slightly lower, the neutrophils can be reduced by differential count, and the lymphocytes are relatively increased. When renal insufficiency is accompanied, urea nitrogen, elevated creatinine and hypocomplementemia 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) begins 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, chronic In 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 cell mitochondria (ASTm), and 1/5 in cytosol (ASTs). When mitochondria is damaged, serum AST is significantly increased, reflecting the severity of hepatocyte 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, 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 transaminase, serum. Alkaline phosphatase (ALP) can be significantly increased in intrahepatic and extrahepatic bile duct obstruction, liver occupying lesions, rGT can be increased in cholestasis and hepatocyte damage, can be used to identify whether ALP increase is associated with hepatobiliary disease, alcohol abuse It can cause an increase in rGT. After excluding biliary tract disease from chronic hepatitis, an increase in rGT indicates that the lesion is still active. In liver failure, hepatocyte microsomes are severely damaged, 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 markers for diagnosing cirrhosis. Pre-serum A1b is due to its half-life. Only 1.9 days, the change is more sensitive in the liver parenchymal damage, the extent of the decline is consistent with the degree of hepatocyte damage, and the mechanism of change is similar to Alb.
1 Alpha-fetoprotein (AFP): In acute viral hepatitis, chronic hepatitis and cirrhosis (activity), there may be a short-term, low- and moderate-increased increase in AFP, which marks the regeneration of hepatocytes and has extensive hepatocyte necrosis. Among patients, AFP may have a better prognosis, and 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 sulphate can be increased in patients with cirrhotic portal collateral circulation, ammonia poisoning is one of the main causes of hepatic coma, but blood ammonia level and The occurrence and severity of encephalopathy can also be inconsistent.
(4) Prothrombin time (Pt) and activity (PTA): Reduced synthesis of related coagulation factors in liver disease, can cause prolongation of Pt, 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 below 40%, PTA is reduced to 20 Below %, often predicts poor prognosis, Pt prolongation can also be seen in 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. Some people think that the prognosis is very poor when TC<2.6mmol/L. Serum triacylglycerol (TG) can be increased in hepatocyte injury and obstructive jaundice in and outside the liver.
4. Serological diagnosis of liver fibrosis In the chronic liver disease, the formation of extracellular matrix (ECM) and the degradation of the matrix are unbalanced, resulting in excessive deposition of ECM to form fibrosis, detection of matrix components in serum, degradation products and enzymes involved in metabolism. It can be used as a serum marker for diagnosing 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. Under the electron microscope, dense sediments are fingerprint-like structures. The pathology of the patient may be a primary type III MPGN-like change, and a renal biopsy sees monocyte infiltration and glomerular mass immune complex deposition.
Diagnosis
Diagnosis and diagnosis of hepatitis C virus infection and glomerulonephritis
Diagnostic criteria
At present, there is no unified diagnostic standard for nephritis associated with hepatitis C. The diagnosis of this 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 the renal biopsy can also be negative, renal biopsy confirmed renal small Ball nephritis, and can exclude other secondary glomerular diseases.
In view of the high prevalence of liver disease in China, and HBV and HCV often overlap infection, because HCV and HBV have similar transmission routes, the possibility of infection of both viruses is present, but more is seen in HBV persistence. On the basis of infection, HCV is infected. In order to avoid missed diagnosis, in patients with glomerulonephritis, HBV and HCV antigens should be routinely examined.
Differential diagnosis
HCV-associated nephritis needs to be differentiated from other causes such as hepatitis B-associated nephritis, cold globulin-induced nephritis, and autoimmune diseases such as systemic lupus erythematosus.
