D-type viral hepatitis

Introduction to hepatitis D virus Viral hepatitis (viralhepatitis type D) is an acute and chronic hepatic inflammatory lesion caused by hepadnaviruses such as hepatitis D virus (HDV) and hepatitis B virus. HDV is a defective virus with few HDV infections and can only be found in HBV-infected individuals and certain hepadnavirus-positive antigen-positive animals. The clinical manifestations of hepatitis D depend to some extent on the concomitant status of HBV infection. HDV and +HBV overlap infection, can promote liver damage, and easy to develop chronic active hepatitis, cirrhosis and severe hepatitis. Hepatitis D is mainly transmitted through blood transfusions and blood products, similar to the mode of transmission of hepatitis B. basic knowledge The proportion of illness: this disease is rare, must be attached to the basis of hepatitis B patients, the combined infection rate of hepatitis B patients is about 0.04%-0.05% Susceptible people: no specific population Mode of infection: blood transmission Complications: cirrhosis

Cause of hepatitis D virus

(1) Causes of the disease

The intact HDV particles are spherical, 35-37 nm in diameter, containing HDV RNA and HDAg, and the outer shell is HBsAg. HDV RNA is the genome of HDV, consisting of 1679-1683 nucleotides, which is single-stranded, circular, and Folded into a non-branched rod-like structure, HDV-RNA has 9 coding regions (ORF), ORF5 encodes HDAg, HDAg is a nuclear protein that enables the body to induce anti-HDIgM and anti-HDIgG, anti-HDIgM Earlier, it is usually positive in the early stage of acute HDV infection, and the recovery period gradually disappears. The high titer of anti-HDIgM indicates chronic disease, and anti-HD IgG appears later, and it can be maintained for many years after 3 to 8 weeks after onset. Low titer positive, anti-HDIgG increased when the disease activity, the current infection often showed anti-HDIgM positive, the previous infection was anti-HDIgM negative, and anti-HDIgG positive, anti-HD is not neutralizing antibody, still positive It can be contagious.

HDV infection can significantly inhibit the synthesis of HBV DNA. Serological tests show that HDAg is consistent with the decrease of HBV DNA in serum. When HDAg expression is increased, HBV DNA is decreased. When HDAg expression is at a peak, HBV DNA often disappears, but with With the appearance of HDAg-negative and anti-HD, HBV DNA returned to its original level. It was previously thought that the assembly of HDV relied on the synthesis of HBsAg, and its replication and expression also required the assistance of HBV or other hepadnaviruses. The replication of HDV-RNA and the expression of HDAg do not require the help of hepadnavirus. HDV itself can be done independently, but in the formation of intact HDV, it must be provided by a hepadna virus.

(two) pathogenesis

Clinical and animal experiments showed that after HDV infection, liver function damage was directly proportional to serum and intrahepatic HDAg titer. In situ hybridization was used to detect the distribution of HDV RNA in liver cells in areas with obvious damage to liver cells. Therefore, HDV is considered to be directly Caused by hepatocyte injury, some scholars also found that chronic hepatitis B or HBsAg carriers overlap in HDV infection after clinical manifestations of severity, liver tissue from normal, mild inflammation to severe hepatic necrosis, accompanied by heavier inflammatory cells in the portal area Infiltration, suggesting that the incidence of hepatitis D is related to the host's immune response in addition to the direct cytotoxicity of HDV.

D-type viral hepatitis prevention

1. Strict screening of blood donors to ensure the quality of blood and blood products is an effective way to reduce the incidence of hepatitis D after transfusion.

2. For people with HBV susceptibility, extensive vaccination with hepatitis B vaccine is a powerful measure to finally eliminate the carrier status of HBsAg, and it is also a feasible method to control HDV infection.

D-type viral hepatitis complications Complications cirrhosis

Easy to develop chronic active hepatitis, cirrhosis and severe hepatitis.

D-type viral hepatitis symptoms Common symptoms Liver HDAg only... Liver lesions diffuse jaundice and lack of appetite

1. HDV and HBV infection at the same time, seen in the absence of HDV infection, infection of HDV and HBV, showing acute hepatitis D. The incubation period is 4 to 20 weeks. The clinical manifestations and biochemical characteristics are similar to those of acute hepatitis B alone, which may include fatigue, loss of appetite, jaundice and liver swelling and pain. Some patients have two peaks of transaminase. Two increases in bilirubin and ALT were seen during the course of the disease. HBsAg in the serum first appeared, then HDAg positive in the liver. In patients with acute phase, HDAg positive in serum persists for several days, then it is negative for anti-HD IgM, with short duration and low titer. Anti-HD IgG was negative. The majority of HDV/HBV infections have a good prognosis. The risk of developing chronic hepatitis is no higher than that of HBV infection alone. A few patients can develop severe hepatitis.

2. HDV and HBV overlap infection, chronic hepatitis D: refers to overlapping HDV infection on the basis of the original chronic HBV infection, and its clinical course mainly depends on the status of HBV infection and the degree of liver damage during HDV infection. More common in chronic HBV infection, the symptoms are mainly determined by chronic HBsAg carriers before HDV infection, or HB chronic liver disease. In the case of HBsAg carriers, acute HBsAg-positive hepatitis appears after infection with HDV, but anti-HBV IgM is negative, which is heavier than HBV infection alone. In the case of HBV chronic liver disease, due to persistent infection of HBV, HDV is continuously replicated, which makes the existing liver tissue lesions worse, which may manifest as acute exacerbation of hepatitis, or accelerate the development of slow-lived liver and cirrhosis. Therefore, in the case of chronic hepatitis B, the original condition is stable, sudden symptoms worsen, and even liver failure, similar to severe hepatitis, should be considered as the possibility of overlapping infection of HDV. Can have the following performance.

(1) Self-limiting hepatitis D: The course of disease is short, the general clinical symptoms are not serious, and there is a tendency to self-limiting recovery. It can also be expressed as typical acute HBsAg-positive hepatitis. After HBV carriers were infected with HDV, HDAg first appeared in the liver, followed by HDAgemia, and serum anti-HDIgM and IgG were positively converted. Once HDV is cleared, anti-HDIgM decreases, while anti-HD IgG maintains high levels for several years. Most patients with overlapping infections are prone to develop chronic hepatitis, and only patients with this self-limiting have been cured.

(2) Chronic progressive hepatitis D: When chronic hepatitis B or HBsAg carriers are infected with HDV, the clinical manifestations are worse, or similar to acute hepatitis attacks in the chronic process. HDAg in the nucleus of the liver cells continued to be positive, but serum HDAg only transiently appeared, and anti-HDIgM and anti-HD IgG showed high titers and did not decrease. The most common histological change is chronic hepatitis or cirrhosis. The age of the HDV-positive cirrhosis group was much younger than that of the HDV-negative group, indicating that HDV-positive hepatitis is more likely to evolve into cirrhosis.

(3) HDV and severe hepatitis: Li Qifen reported that 34 cases of HDV/HBV double infection in 105 cases of severe hepatitis corresponded to 34.3% of patients. Govindarajan reported that of 71 cases of acute severe hepatitis, 24 cases corresponded to 33.8% of patients with serum HDV markers, while in the control group of 118 cases of common acute jaundice type hepatitis B, only 5 cases corresponded to 4.2% of patients with HDV markers. Other authors have found similar situations, and these reports suggest that considerable emphasis should be placed on overlapping HDV infections in severe hepatitis.

In the case of HBsAg carriers, hepatitis B patients, and severe hepatitis patients with obvious fluctuations or progressive deterioration, the possibility of simultaneous or overlapping HDV infection should be considered and confirmed by laboratory tests.

Acute HDV/HBV infection: Patients with acute hepatitis, except for acute HBV infection markers, were positive for serum anti-HDIgM, positive for anti-HDIgG low titers, or positive for serum and/or intrahepatic HDAg and HDV-RNA.

HDV/HBV overlap infection: chronic hepatitis B patients or chronic HBsAg carriers, serum HDV-RNA and/or HDAg positive; or anti-HDIgM and anti-HD IgG high titer positive; or intrahepatic HDV-RNA and (or ) HDAg positive.

Examination of hepatitis D virus

Blood picture

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.

2. Urine

Patients with acute jaundice hepatitis can be positive for urinary bilirubin and urobilinogen before the onset of jaundice.

3. Liver function test

(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 appearance of jaundice, peaked 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.

Aspartate aminotransferase (AST): AST is about 4/5 in cell mitochondria (ASTm), 1/5 in cytosol (ASTs), serum AST is significantly elevated when mitochondria is damaged, reflecting the severity of hepatic lesions. .

In viral hepatitis, the ALT value is higher than the AST value, especially in acute cases, the AST increase is less than ALT, the ALT/AST ratio is close to 1 when the chronic viral hepatitis lesions continue to activity, and the AST in cirrhosis is often significantly higher 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 (r-GT) 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 increased in intrahepatic and extrahepatic bile duct obstruction, liver occupying lesions, r-GT can be increased in cholestasis and hepatocyte damage, can be used to identify whether ALP increased with hepatobiliary disease Related, alcohol abuse can also cause r-GT increase, chronic hepatitis in the exclusion of biliary tract disease, increased r-GT indicates that the lesion is still active, liver cell microsomes are severely damaged during liver failure, r-GT synthesis is reduced, blood r-GT is also reduced .

(3) Protein metabolism test: Low albumin (Alb) is an important indicator of liver disease, and its degree of reduction depends on the severity and stage of liver disease. Low A1bemia and hyperglobulinemia are diagnosed with cirrhosis. The characteristic serological index, the pre-serum Alb 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.

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, in the presence of 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.

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 inhibits cerebral blood flow, glucose metabolism and energy supply, and directly acts on neurons Membrane, 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.

Plasma amino acid profile analysis is of great significance for the diagnosis and prognosis of hepatic encephalopathy. The branched chain amino acids in patients with severe hepatitis and cirrhosis are close to normal or reduced, and the aromatic amino acids are significantly increased, resulting in a decrease in the ratio of branch/aromatic (normal 3.0 to 3.5). Hepatic encephalopathy can even be inverted.

(4) Prothrombin time (PT) and activity (PTA): The reduction of clotting factor synthesis in liver disease can cause PT prolongation. The degree of PT prolongation indicates the degree of hepatocyte necrosis and liver failure, and its related clotting factor 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 patients with congenital coagulation factor deficiency, diffuse intravascular coagulation and Vitk deficiency, etc., should be noted.

(5) Lipid metabolism related tests: serum total cholesterol (TC) is significantly reduced in severe hepatitis. Some people think that the prognosis is very poor when TC<2.6mmol/L, and TC can be significantly increased in cholestatic hepatitis and extrahepatic obstruction. Serum triglyceride (TG) can be increased in hepatocyte injury and intrahepatic or extracranial obstructive jaundice.

4. Serological diagnosis of liver fibrosis

In chronic liver disease, the formation of extracellular matrix (ECM) and the degradation of 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 can be used as serum for diagnosis of liver fibrosis. landmark.

5. Detection of HBV virus markers

The significance of HBV antigen antibody system

(1) HBsAg and anti-HBs: HBV-infected patients 2 to 8 weeks before the elevation of serum transaminase, HBsAg can be detected in serum, HBsAg is an antigen that occurs early in acute HBV infection, generally lasts for 2 to 6 months Chronic hepatitis, hepatitis cirrhosis and serum of HBsAg carriers can be positive and last for more than half a year. HBsAg positive is one of the signs of HBV infection and does not reflect viral replication, infectivity and prognosis.

Anti-HBs appear in the HBV infection recovery period or after vaccination with hepatitis B vaccine, which is a neutralizing antibody, reflecting the body's protective immunity against HBV. The anti-HBs titer and protective ability are parallel, and the titer is less than 10000U/ L, can not prevent HBV reinfection, a small number of patients with anti-HBs and HBsAg formed early immune complexes, causing rash, arthritis, nephritis, etc., transient HBsAg-positive patients, serum may not be detected Anti-HBs, carriers of chronic HBV due to immune tolerance, B cell-deficient ability to form antibodies, it is difficult to produce anti-HBs, in the case of acute severe hepatitis, the body's immune response is hyperactive, can produce high titers of anti-HBs.

In addition, analysis of synthetic peptides has confirmed that pre-S1 of HBV is a ligand adsorbed to target cells, pre-S2 plays a supporting role in adsorption, and adsorption of peripheral blood mononuclear cells by HBV mainly involves pre-S2, pre-S1 and pre-S2. The clinical significance lies in: 1 as an indicator of viral replication; 2 as one of the reference indicators for evaluating the efficacy of drugs; pre-S1 and pre-S2 antibodies are found in the acute phase of hepatitis B and early recovery, indicating that the virus is or has been cleared, and the prognosis is good. In the serum of HBsAg carriers and patients with chronic hepatitis B, the pre-S antibody was not detected, and the pre-S antibody did not appear, indicating a poor prognosis.

(2) HBeAg and anti-HBe: serum HBeAg positive can be seen in acute, chronic hepatitis and asymptomatic carriers, from the early stage of HBV infection incubation period to clinical symptoms for 10 weeks, can be measured in serum, and then gradually weakened to disappear, HBeAg negative after 3 to 4 months after the onset of acute hepatitis B indicates a good prognosis. Continuous positive HBeAg indicates chronic inflammation of the liver. HBeAg is closely related to HBV DNA, DNA polymerase activity and Dane particles, and is a marker of viremia. , indicating that the patient is contagious.

Anti-HBe appeared in the disappearance of HBeAg, anti-HBe positive indicates that the infectivity is weakened or disappeared, but in some patients with chronic hepatitis B or carriers, although anti-HBe positive, HBV DNA can still be detected in the blood circulation, indicating anti-HBe Positive is not necessarily non-infectious. The detection rate of anti-HBe in patients with chronic hepatitis, cirrhosis and liver cancer increases sequentially, indicating that anti-HBe positive does not necessarily have a good prognosis.

(3) HBcAg and anti-HBc: HBcAg is the core component of HBV and contains viral nucleic acid. HBcAg positive indicates viral replication and is contagious. HBsAg is encapsulated in HBcAg outside the circulation, and a small amount of free HBcAg can be converted into HBeAg or Anti-HBc binds to immune complexes, so HBcAg cannot be detected from patient serum by general methods, but can only be detected in liver cells. With the improvement of detection technology, when Dane particles are treated with detergent, HBcAg Can be released, HBsAg high titer, HBeAg and DNA polymerase positive, HBcAg is mostly positive.

Anti-HBc is the total antibody of hepatitis B virus core antigen. The first to appear after HBV infection is IgM type core antibody (anti-HBc IgM). High titer anti-HBc IgM is an important marker of HBV acute or recent infection in chronic hepatitis. The active phase of inflammation is also often positive. The core antibody is not a neutralizing antibody. Anti-HBc IgG can last for many years and is an indicator of HBV infection. Detection of anti-HBc can increase the detection rate of HBV infection and contribute to diagnosis. And epidemiological investigations.

(4) HBV DNA and DNA polymerase: HBV DNA can be directly detected by nucleic acid hybridization technology. Some patients are HBsAg, HBeAg-negative and HBV DNA-positive, indicating that HBV is replicating and infectious.

DNA polymerase acts as a reverse transcriptase during viral replication. The higher the activity, the more vigorous the virus replication activity. The determination of DNA polymerase can reflect the efficacy of antiviral drugs more sensitively.

The current infection of HBv can be established by any of the following indicators: 1 serum HBsAg positive; 2 serum HBV DNA or DNA polymerase positive; 3 serum IgM anti-HBc positive; 4 intrahepatic HBcAG and/or HBsAg positive, Or HBV DNA is positive.

Regular abdominal B ultrasound, understand the liver and other conditions.

Diagnosis and identification of hepatitis D virus

Diagnosis depends on laboratory tests

1. Acute HDV/HBV infection: Patients with acute hepatitis, except for acute HBV infection markers, serum anti-HDIgM positive, anti-HDIgG low titer positive; or serum and/or intrahepatic HDAg, HDV-RNA positive.

2. HDV/HBV overlap infection: chronic hepatitis B patients or chronic HBsAg carriers, serum HDV-RNA and/or HDAg-positive; or anti-HDIgM and anti-HD IgG high titer positive; or intrahepatic HDV-RNA and (or) HDAg positive.

The disease is easy to distinguish from hepatitis A, hepatitis C, drug-induced liver disease and other liver diseases.

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