Anti-HCVAg positive

Introduction
Cause
Examine
Diagnosis

Introduction

Introduction Anti-HCVAg positivity is one of the symptoms of the diagnosis of noncryoglobulinic 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: cryoglobulinemia glomerulonephritis (cryoglobulinemic MPGN), non-cold globulin Noncryoglobullinemic MPGN 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. The presence of cryoglobulin and immune complexes, 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.

Cause

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 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 Clonal IgM composition, 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

Examine

an examination

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, 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, 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 can occur hematuria and proteinuria, tubular urine, 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 examination The total number of white blood cells is normal or slightly lower, the neutrophils can be reduced in the differential 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) is significantly reduced in severe hepatitis. It is considered that TC glycerol (TG) can be increased in hepatocyte injury and obstructive jaundice in and outside the liver.

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.

Diagnosis

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.

Hepatitis B nephritis: Clinically, patients must have a history of hepatitis B virus infection or hepatitis B before or at the time of onset. Hepatitis B surface antigen, hepatitis B e antigen or hepatitis B core antibody continued to be positive or hepatitis B deoxyribonucleic acid was repeatedly positive, with or without elevated transaminase, with hematuria, edema, hypertension and other nephritis manifestations or manifested as nephrotic syndrome. Symptoms are not typical, often accompanied by liver enlargement, and the condition is changeable. The onset of nephritis is the main cause of onset. After a period of time, it is converted to kidney disease, and there is no rule to follow. Serum complement is normal or decreased, circulating immune complexes are positive, and some are found in renal tubular endothelial cells. Renal biopsy or immunoelectron microscopy can help confirm the diagnosis.

Most patients with hepatitis B nephritis have a prolonged course of disease, poor drug efficacy, and are mostly resistant to glucocorticoids and cytotoxic immunosuppressive agents, resulting in the development of chronic renal insufficiency. However, the disease has certain self-limiting nature. Some patients have been treated with liver protection. After self-medication and symptomatic active treatment under the guidance of a doctor, the clinical symptoms can be alleviated, gradually disappeared, and there is a tendency to self-heal. Hepatitis B nephritis is clinically characterized by nephrotic syndrome or non-proteinuria, often with microscopic hematuria, and also with onset of nephrotic syndrome. Membranous nephritis rarely has hypertension or renal insufficiency; about 40% of patients with membrane proliferative nephritis have high blood pressure and 20% have renal insufficiency. There are no obvious history of hepatitis contact or clinical symptoms of hepatitis. The diagnosis is based on three aspects:

1. The serum hepatitis B virus antigen is positive;

2. Hepatitis B virus is found in the kidney tissue section;

Third, suffering from glomeruli and can exclude secondary glomerular diseases such as lupus nephritis.

Cryoglobulinemia nephritis: cryoglobulinemia MC often associated with kidney damage, kidney involvement, more common in women. Type II MC kidney damage is more common. In patients with type III MC with renal damage, glomerular injury is different, which is a non-specific lesion; while type II MC has IgM monoclonal component, causing glomerular damage with characteristic changes, called For "cold globulinemia glomerulonephritis." The majority of patients with type II MC have been diagnosed at 50 to 60 years of age because many patients are diagnosed 10 to 20 years after the onset of symptoms. Many patients have found kidney disease several years to decades after HCV infection. However, a small number of patients can have kidney and extrarenal symptoms and signs at the beginning of the onset. The clinical manifestations of renal lesions vary widely, with some patients presenting with proteinuria, microscopic hematuria and/or hypertension, often accompanied by mild renal dysfunction. Twenty percent of patients present with nephrotic syndrome, and another 20% to 30% of patients present with acute nephritic syndrome at the onset of onset, with microscopic hematuria or gross hematuria, proteinuria, and progressive renal dysfunction. The most common pathological changes in kidney tissue are diffuse hyperplasia and exudative nephritis, similar to membrane proliferative nephritis (MPGN). Often accompanied by intravascular thrombosis, intraglomerular mononuclear cell infiltration, glomerular basement membrane dual-track formation, and small to moderate vascular inflammatory lesions. A small number of critically ill patients may be associated with mesangial damage.

Systemic lupus erythematosus SLE: is a systemic disease in which skin, muscle, bone, heart, lung, liver, spleen, kidney, brain, eyes, nose, ears, teeth, and hair can develop lesions. Such as: fever, fatigue, loss of appetite, general malaise, joint swelling and pain, muscle aches, weight loss, hair loss, facial erythema, fingertip rash, white or purple after hand and foot cold, repeated oral ulcers, superficial lymphadenopathy Large, menstrual bleeding, skin purpura, anemia, white blood cells, decreased platelet count, headache, hallucinations, auditory hallucinations, stupor state, intractable diarrhea, vomiting, jaundice, palpitations, shortness of breath, squatting, pleural effusion, pericardial effusion, etc. . The classification criteria revised by the American College of Rheumatology in 1982 are currently used:

1, facial butterfly erythema;

2, disc-shaped erythema;

3, sun allergy;

4. Oral or nasopharynx ulcers;

5. Non-erosive arthritis;

6, serositis;

7, kidney damage;

8, neuropathy: seizures or mental illness;

9, abnormal blood: hemolytic anemia, leukopenia, lymphopenia or thrombocytopenia;

10. Immunological abnormalities: positive for lupus cells, positive for anti-ds-DNA antibodies, positive for anti-SM antibodies, or false positive for anti-syphilis serum test for 6 months;

11. Positive for antinuclear antibodies. Clinically, if other symptoms are excluded, if there are 4 or more of the above 11 criteria, it can be diagnosed as SLE.

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.

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.

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.

(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.

(5) Lipid metabolism related tests: Serum total cholesterol (TC) is significantly reduced in severe hepatitis. It is considered that TC glycerol (TG) can be increased in hepatocyte injury and obstructive jaundice in and outside the liver.

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