OVERVIEW
Hepatitis C virus associated nephritis (HCV) refers to hepatitis C virus (HCV) infection through the cryoglobulin-mediated and non-cryoglobulin-mediated immune complex glomerulonephritis, the clinical in addition to hepatitis manifestations, there are often hematuria, proteinuria, hypertension and different degrees of renal insufficiency. Treatment of severe HCV nephritis should start with plasma exchange combined with immunosuppressive therapy.
Etiology
HCV is mainly transmitted through blood products and the use of intravenous drug use. HCV antigen-antibody immune complexes are deposited in the subendothelium and the tunica, activating complement secondary cell proliferation and inflammatory cell infiltration, leading to hepatitis C-associated nephritis. Currently, there are 3 main types of HCV-associated nephritis: (1) cryoglobulinemic membranoproliferative glomerulonephritis; (2) non-cryoglobulinemic membranoproliferative glomerulonephritis; (3) membranous nephropathy.
Symptoms
Clinical manifestations vary widely, and may manifest as abnormal urinalysis, proteinuria in the range of nephropathy, microscopic and/or gross hematuria, hypertension, renal insufficiency, or even acute nephritic syndrome. The renal pathologic changes are diverse, and commonly include membranoproliferative glomerulonephritis, membranous nephropathy, and crescent formation.
Examination
1. Urine examination
Hematuria, proteinuria and tubular urine can be seen, and urine protein is mainly albumin. And mostly proteinuria within the scope of nephrotic syndrome. Urinary bilirubin and urinary bilinogen can be positive in patients with acute jaundice hepatitis before the appearance of jaundice.
2. Blood test
Blood routine: the total number of leukocytes is normal or slightly low, the neutrophil count can be reduced, and the lymphocyte count is relatively increased. Hypocomplementemia is often present. When accompanied by renal insufficiency, urea nitrogen and creatinine can be elevated.
3. Liver function tests
The following tests can be performed in patients with symptoms of acute hepatitis:
(1) Serum bilirubin: serum bilirubin increases day by day during the jaundice period, and mostly reaches the peak in 1~2 weeks.
(2) Serum enzyme measurements: ① serum alanine aminotransferase (ALT) begins to rise before the appearance of jaundice, and reaches the peak in the extreme stage of the disease. Acute hepatitis can have extremely high enzyme activity, and slowly decreases with serum bilirubin in the recovery period. Chronic hepatitis ALT can fluctuate repeatedly, severe hepatitis in bilirubin rises sharply when the ALT on the contrary, for the “enzyme jaundice separation”, is a sign of seriousness of the disease. Glutamine transaminase (AST): when mitochondrial damage, serum AST is obviously elevated, reflecting the severity of hepatocellular lesions. (iii) ALT/AST ratio: ALT value is higher than AST value in acute viral hepatitis cases, ALT/AST ratio is close to 1 in chronic viral hepatitis when the lesion is persistently active, and the increase of AST in cirrhosis is often more significant than ALT.
(3) Protein metabolism function test: ①Low albumin (Alb) anemia is an important indicator of liver disease, and low Alb anemia and hyperglobulinemia are characteristic serological indicators for the diagnosis of liver cirrhosis. Serum pre-Alb is more sensitive to change when liver parenchyma is damaged, and the decline is consistent with the degree of hepatocyte damage. ② Alpha-fetoprotein (AFP): in acute viral hepatitis, chronic hepatitis and cirrhosis (active) there can be a short-term low, moderate elevation of AFP increases mark the regeneration of hepatocytes active, there is extensive hepatocellular necrosis of patients with increased AFP may have a better prognosis. (3) Blood ammonia measurement: in heavy hepatitis liver failure, ammonia cannot be synthesized into urea for excretion; blood ammonia can be increased in patients with cirrhosis who have good portal-branch circulation.
(4) Prothrombin time (Pt) and activity (PTA): the degree of Pt prolongation marks the degree of hepatocellular necrosis and liver failure, and it can reflect liver failure more rapidly. In severe hepatitis, PTA is mostly below 40%, and a decrease in PTA to below 20% often indicates a poor prognosis.
(5) Tests related to lipid metabolism: serum total cholesterol (TC) is significantly reduced in severe hepatitis, and it is believed that the prognosis is very poor if TC＜2.6mmol/L. Serum triglycerides (TG) can be increased in hepatocellular injury and intra- and extra-hepatic obstructive jaundice.
Diagnosis
There are no standardized diagnostic criteria for hepatitis C-associated nephritis. In addition to meeting the diagnosis of hepatitis C, a definitive clinical diagnosis should be made with:
1. Proteinuria or hematuria.
2. positive serum hepatitis C virus RNA (HCV-RNA) and positive anti-HCVAg.
3. the definite presence of cryoglobulins and immune complexes, i.e., positive cold precipitates, in which there are HCV-RNA viral core antigen and IgG anti-HCV antibodies.
4. Renal biopsy shows severe mononuclear cell infiltration and a large number of glomerular immune complex deposits, because HCV-RNA immune deposits are not necessarily localized in the glomeruli, so the renal biopsy can also be negative. Renal biopsy confirms glomerulonephritis and may exclude other secondary glomerular diseases.
Differential diagnosis
HCV-associated nephritis should be differentiated from other causes such as hepatitis B-associated nephritis, cryoglobulin-induced nephritis, and autoimmune diseases such as systemic lupus erythematosus.
Treatment
1. General treatment
The treatment of HCV-associated glomerulonephritis is similar to that of other proteinuric glomerular diseases.
(1) Diet: low-salt diet, moderate amount of high-quality protein diet.
(2) Antihypertensive and lipid-lowering: when there is hypertension, hypertension and hypercholesterolemia should be actively controlled, and nifedipine and cardioplegia should be given 3-4 times/day.
(3) Control proteinuria: Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists should be given to reduce proteinuria if necessary, and ACEI-type or ARB-type drugs can be given orally.
2.Antiviral treatment
Specific treatment for HCV nephritis includes interferon alpha and ribavirin antiviral therapy. The main side effects of interferon alpha (IFN-α) are flu-like symptoms, insomnia and malaise. Certain HCV-infected patients with interferon alpha (IFN-α) may induce or aggravate renal lesions, which should be noted.
3.Treatment of acute severe HCV nephritis
In case of acute renal failure and neuropathy, plasma exchange combined with immunosuppressive therapy should be used first to remove circulating cryoglobulins and prevent new antibody production. Methylprednisolone is given intravenously for 3 days followed by regular oral prednisone; cyclophosphamide may be added. Interferon alpha (IFN-alpha) antiviral therapy can be started only when the prednisone dose is reduced to 20 mg/d.