Viral hepatitis is an infectious disease that seriously endangers human health and is caused by a variety of hepatitis viruses, with degenerative necrosis of liver parenchymal cells as the main lesion.
The pathogen mainly includes seven types of viruses: A, B, C, D, E, G and blood transfusion. Hepatitis B is common and can occur at any time of pregnancy. The incidence of hepatitis in pregnant women is about 6 times higher than that in non-pregnant women, and the incidence of fulminant hepatitis is 66 times higher than that in non-pregnant women. It is one of the leading causes of maternal mortality. Combined viral hepatitis in pregnancy is a serious threat to maternal life, and the disease accounts for the second leading indirect cause of maternal death, after combined heart disease in pregnancy.
The main manifestations of patients with viral hepatitis in pregnancy are.
1, serum protein The total serum protein value is lower than 60g/L for about half of them due to blood dilution, mainly albumin is reduced.
2, serum enzyme activity Glutamic-alanine aminotransferase and glutamic-oxalacetic aminotransferase are mostly within the normal range, and a few are slightly elevated in late pregnancy. Alkaline phosphatase, which is mildly elevated in the first half of pregnancy, can be twice as high after 7 months of pregnancy as in non-pregnancy, and its elevation mainly comes from the placenta.
3, coagulation function examination In late pregnancy, plasma fibrinogen increases by 50% compared with non-pregnancy, coagulation factors II, V, VII, VIII, IX and X increase by 0.2 to 0.8 times, and prothrombin time is normal.
I. Effect of pregnancy on viral hepatitis
The incidence of severe hepatitis increases significantly compared to non-pregnancy, which is related to the following factors:
(1) A significant increase in metabolism during pregnancy, an increase in nutritional consumption and a decrease in glycogen reserves in the liver, which is not conducive to disease recovery;
(2) The production of large amounts of estrogen during pregnancy requires inactivation in the liver and hinders the liver’s transport of fat and bile excretion;
(3) Fetal metabolites need to be detoxified in the maternal liver;
(4) The liver is often damaged by complications of gestational hypertension and is susceptible to acute hepatic necrosis;
(5) Physical exertion, hypoxia, and increased production of acidic metabolites during delivery can aggravate liver damage.
Second, the impact of viral hepatitis on pregnancy
1, the impact on the mother
① Early pregnancy can aggravate the early pregnancy reaction;
② Late pregnancy is prone to gestational hypertension, which may be related to the reduced inactivation of aldosterone in hepatitis;
(3) During delivery, the rate of postpartum hemorrhage is increased due to impaired liver function and reduced synthesis of coagulation factors;
④In case of severe hepatitis, DIC is often complicated by the tendency of systemic bleeding, which directly threatens the life of mother and child. Some data reported that the death rate of pregnant women with viral hepatitis was 18.3%, which was significantly higher than the 5.6% in the non-pregnant hepatitis control group, including 14 cases of severe hepatitis, and 7 cases of death among the 8 cases that occurred in the late pregnancy. Another domestic data reported a death rate of 1.7% to 8.1%.
2, the impact on the fetus
①The incidence of fetal malformation is about 2 times higher when the disease is toxic hepatitis in early pregnancy;
②Miscarriage, preterm birth, stillbirth, stillbirth and neonatal mortality are significantly higher. Some data reported that the perinatal mortality rate of pregnant women with abnormal liver function is as high as 4.6%.
3, mother-to-child transmission The transmission of hepatitis virus from one generation to the next is called vertical transmission, mainly seen in hepatitis B virus. Mother-to-child transmission varies depending on the type of virus.
(1) hepatitis A virus (varial hepatitis A): hepatophilic RNA virus, mainly through the fecal-oral route of transmission. hav does not infect the fetus through the placenta, so the disease during pregnancy without abortion or induction of labor; only around the time of delivery maternal hepatitis A viraemia, there is a threat to the fetus.
(2) Hepatitis B virus (varial hepatitis B): a hepatophilic DNA virus. HBV is transmitted from mother to child through the placenta in utero, through the soft birth canal during delivery, through maternal blood and amniotic fluid, and through postnatal contact with mother’s saliva or breast milk.
The reported data of mother-to-child transmission of HBV: ①About 70% of fetuses infected with acute hepatitis B in late pregnancy; 25% of fetuses infected with acute hepatitis in mid pregnancy; none of fetuses infected with acute hepatitis in early pregnancy. ②Infants infected during the perinatal period, 85-90% become chronic virus carriers. ③Pregnant women with positive HBsAg, about half of their newborns are positive. ④Pregnant women who are positive for HBeAg indicate a period of infection, and most of their fetuses are infected.
(3) Hepatitis C virus (varial hepatitis C): there is mother-to-child transmission. HCV infection is likely to lead to chronic hepatitis and eventually develop into cirrhosis and liver cancer. information on mother-to-child transmission of HCV: ① the vertical transmission rate of mother-to-child transmission is 4%-7%; ② many newborns with intrauterine infection are spontaneously reverted within one year after birth.
(4) Hepatitis D virus (varial hepatitis D): is a defective RNA virus. Concurrent hepatitis B virus infection is required, and this is a necessary condition. Mother-to-child transmission is rare and can be co-infected with HBV or overlapping infections on top of hepatitis B.
(5) Hepatitis E virus (varial hepatitis E): its transmission route and clinical manifestations are similar to hepatitis A, but pregnant women are susceptible and prone to severe disease, with a high mortality rate. During the epidemic period of hepatitis E in a domestic province, the number of seriously ill pregnant women was 6 times that of non-pregnant women. The total mortality rate of hepatitis E patients was 5.2%, of which pregnant women accounted for 70% to 80%. There is less research on mother-to-child transmission of hepatitis E, and no cases of mother-to-child transmission have been found.
(6) Hepatitis caused by blood transfusion-transmitted virus: mainly transmitted by blood transfusion.
(7) Hepatitis G virus (varial hepatitis G): mother-to-child transmission can occur, especially in patients with chronic hepatitis B and C.
III. Diagnosis
The diagnosis of viral hepatitis in pregnancy is more difficult than in non-pregnancy, especially in late pregnancy, because it can be accompanied by abnormal liver function caused by other factors, and the diagnosis of hepatitis cannot be made solely on the basis of elevated transaminases.
(I) Medical history History of close contact with patients with viral hepatitis, history of receiving blood transfusion or injection of blood products within six months.
(B) Incubation period of viral hepatitis Hepatitis A is 2-7 weeks; hepatitis B is 1.5-5 months; hepatitis C is 2-26 weeks; hepatitis D is 4-20 weeks; hepatitis E is 2-8 weeks.
(C) clinical manifestations
1. Symptoms.
1)Loss of appetite, aversion to oily food, nausea and vomiting, abdominal distension, and pain in the liver area, followed by weakness, chills, and fever.
2)Yellow staining of skin, mucous membrane and sclera, dark urine and light-colored stools.
3)Generalized swelling and ascites formation.
4)Mental symptoms.
2. Physical signs.
1)Large liver with percussion pain in the liver area (common type)
2)Progressive shrinkage of the liver, liver odor.
3.Auxiliary examination
1)Liver function tests: SGPT and SGOT are elevated, SGPT is the most sensitive, jaundice index, qualitative and quantitative bilirubin; albumin amount and ratio.
2)Hepatitis typing (to determine the type).
3)Coagulation function measurement: prolonged prothrombin time, decreased plasma fibrinogen, prolonged euglobulin cleavage time, positive 3P test, decreased platelet count.
4)Ultrasound: changes in liver size and its waveform.
The diagnosis can be confirmed whenever there are different degrees of hepatitis symptoms, signs and abnormal results of laboratory tests as mentioned above.
(D) Diagnostic points of severe hepatitis combined with pregnancy
(1) Severe gastrointestinal symptoms, showing extreme loss of appetite, frequent vomiting, abdominal distention and the appearance of ascites.
(2) Rapid deepening of jaundice with serum total bilirubin value >171μmol/L (l0mg/dl).
(3) Appearance of hepatic odor, progressive liver shrinkage, markedly abnormal liver function, enzyme-biliary separation, and albumin/globulin inversion.
(4) Coagulation dysfunction and generalized bleeding tendency.
(5) Rapid onset of hepatic encephalopathy manifestations, irritability, lethargy, coma.
(6) Hepatorenal syndrome with acute renal failure.
(E) Hepatitis B virus serological markers and their clinical significance
With the increasing development of molecular biology technology, polymerase chain reaction (PCR) and other techniques are gradually and widely used in clinical practice. The detection of viral DNA or RNA fragments is an accurate and effective means of diagnosing viral hepatitis. A positive test is considered to have virus replication in the body.
Differential diagnosis
1. Liver damage caused by severe pregnancy vomiting
(1) Mild jaundice and mildly elevated ALT;
②positive urinary ketone bodies;
③After correction of acid-base imbalance and water and electrolyte disorders, the condition improves rapidly;
④Serological markers of hepatitis virus antigen system help to identify.
2. Liver damage caused by hypertensive disorders in pregnancy
(1) Mild or moderate elevation of ALT and AKP;
②Gastrointestinal symptoms are not obvious;
(3) Hypertension, proteinuria and edema, HELLP syndrome patients may be combined with hemolysis and thrombocytopenia;
④The disease resolves rapidly after the end of pregnancy;
⑤ However, it should be noted that hepatitis in pregnancy is often combined with hypertensive disease in pregnancy.
3. Intrahepatic cholestasis during pregnancy (ICP)
(1) There is often a family history or a history of these symptoms after taking oral contraceptives;
(ii) It is a syndrome that appears around 28 weeks of gestation, showing pruritus and mild jaundice;
(3) The incidence of ICP is second only to viral hepatitis, accounting for more than 1/5 of jaundice during pregnancy. It develops due to bile accumulation in the capillary bile ducts of the central region of the liver lobules;
The clinical manifestation is generalized pruritus, followed by jaundice, which rapidly subsides after delivery and often recurs in second pregnancies;
(5) Cholestasis in placental tissue also causes swelling of trophoblastic cells and interstitial edema of villi, and insufficient perfusion of placental blood flow, which can easily lead to fetal distress, preterm delivery, miscarriage, stillbirth, and increased perinatal mortality.
(6) The patient is in good general condition and has no gastrointestinal symptoms;
(7) Obstructive jaundice with elevated serum direct bilirubin, mostly not exceeding 102.6 μmol/L;
⑧ALT is normal or mildly elevated. Early diagnosis depends on the determination of serum bile acid, which is ≤5μmol/L when normal, but significantly increased when suffering from this disease.
4.Acute fatty liver in pregnancy
(1) It is a unique disease in late pregnancy;
(ii) Most of the patients are primiparous and have hypertensive disease in pregnancy;
(3) There are gastrointestinal symptoms, jaundice, bleeding tendency and liver and kidney failure similar to those of severe hepatitis, which can be easily misdiagnosed as acute severe hepatitis;
④The etiology is unknown. Although the disease has obvious jaundice, urine bilirubin is mostly negative, which may be related to the thickening of glomerular basement membrane and the inability of bilirubin filtration;
⑤ B-mode ultrasound showed a strongly echogenic “bright liver”;
(6) CT shows a large hypodense area in the liver, which is very helpful for diagnosis;
(7) Acute steatosis of hepatocytes in the center of the lobules of liver biopsy is very different from the extensive necrosis of hepatocytes in acute severe hepatitis.
5, drug-related liver damage during pregnancy
①History of application of hepatocyte-damaging drugs (chlorpromazine, phenobarbital, erythromycin, isoniazid, rifampin, etc.);
②No history of hepatitis exposure, no typical symptoms of hepatitis;
③The main manifestations are jaundice and ALT elevation;
④Sometimes there is rash, skin itching, and eosinophil increase;
⑤ Most of the patients can recover after stopping the drug.
V. Prevention
Pregnant women should strengthen nutrition, take high protein, high carbohydrate and high vitamin food. Pay attention to personal hygiene and dietary hygiene.
1.Strengthen perinatal health care Pay attention to pregnancy monitoring, include liver function and hepatitis virus serological antigen and antibody testing as prenatal testing routine, and review regularly.
2.Immunoprophylaxis of hepatitis A Pregnant women with a history of close contact with hepatitis A can receive 2-3 ml of intramuscular gammaglobulin within 7 days after contact, and their newborns can receive 1 injection of gammaglobulin at birth and 1 week after birth to prevent infection. Breastfeeding is prohibited during the acute period of hepatitis A.
3, hepatitis B immunoprophylaxis effective way is the injection of HBIG or hepatitis B blood source vaccine. Our newborns are routinely immunized after birth.
1)Pre-birth prevention
(1) Prevention of mother-to-child transmission should begin before pregnancy, pregnant women with acute hepatitis should be at least six months after the hepatitis is cured, preferably two years before pregnancy.
(2) If one of the spouses has hepatitis, condoms should be used to avoid cross-infection.
(3) All pregnant women should be screened for HbsAg in both spouses and further checked for serum markers in asymptomatic carriers.
(4) During delivery of HBsAg and HBeAg positive pregnant women, a strict sterilization and isolation system should be implemented to prevent birth injuries and neonatal injuries, amniotic fluid aspiration, etc. to reduce vertical transmission.
2) Prevention after birth
(1) Active immunization: newborns are given 30μg of hepatitis B vaccine intramuscularly within 24 hours after birth, and 10μg at 1 month and 6 months after birth, respectively. newborns have a good immune response to the vaccine and produce HBsAb in their bodies, which can effectively protect the liver from HBV infection, with an immunization rate of 75%.
(2) Passive immunization: Immunoglobulin HBIG 0.5m1 is injected intramuscularly into newborns immediately after birth, and then 0.16ml/kg is injected intramuscularly at 1 month and 3 months after birth, which can reduce or prevent HBV from entering the liver, with an immunization rate of 71%.
(3) Combined immunization:Hepatitis B vaccine was administered as described above, and HBIG was changed to intramuscular injection of 0.5m1 once 48 hours after birth. Passive immunity was obtained before active immunity was established. Make the effective protection rate of 94%.
4, prevention of hepatitis C There is no specific immunization method for hepatitis C virus. Hepatitis C is mainly transmitted from medical sources. In Japan, 95% of acute hepatitis infected by blood transfusion is hepatitis C. Reducing medical-derived infections is an important part of hepatitis C prevention.
(1) Protect susceptible people with passive immunization of the population with gammaglobulin.
(2) Against infants of HCV-positive mothers, immunoglobulin injection before 1 year of age can be protective for infants.
VI. Treatment
(1) Principles of management of viral hepatitis during pregnancy
1, pay attention to rest, strengthen nutrition, high vitamin, high protein, adequate carbohydrate, low fat diet.
2.Apply drugs and actively carry out liver-protective treatment.
3.People with jaundice should be hospitalized immediately and treated as severe hepatitis.
4.Avoid the application of drugs that may damage the liver (sedatives, anesthetics, estrogen).
5.Pay attention to the prevention of infection, strict disinfection during delivery.
6, and use broad-spectrum antibiotics to prevent endogenous infection induced hepatic coma.
(B) the main points of treatment of severe hepatitis during pregnancy
1, liver preservation treatment: the combined application of glucagon – insulin – glucose can improve the abnormal metabolism of amino acids and ammonia, and has the effect of preventing hepatocyte necrosis and promoting hepatocyte regeneration.
1) Combined application of glucagon and insulin: glucagon 1~2mg + insulin 6~12U + 10% glucose 500ml intravenously once a day, a course of treatment for 2~3 weeks.
2) Promotion of hepatocyte regeneration therapy.
(1) Human albumin 5g + 10% glucose 250ml intravenously, 2-3 times a week;
(2) fresh plasma 200-400ml intravenous drip, 2-4 times a week;
(3) application of potassium magnesium mentholate: potassium magnesium mentholate 40ml + 10% glucose 500ml slow intravenous infusion, once a day, because it contains potassium ions, hyperkalemia hepatitis patients use with caution.