The impact of liver disease on maternal safety is emphasized Shanghai Science and Technology Commission Scientific Research Grant Project: Application Research on Comprehensive Treatment Plan for Severe Pregnancy Liver Disease in Yangtze River Delta Region (Project No. 1495810900) Pregnancy causes a series of physiological changes in various organs of pregnant women, and it also increases the burden of liver, kidney, heart and other organs. The impact of liver disease on the safety of pregnant women is discussed here. As the largest substantive organ in the body, the liver is not only the largest gland in the body, but also the most important metabolic and defensive organ and has many functions. The most important ones are synthesis and storage: synthesis of glycogen, plasma proteins, lipoproteins, cholesterol, bile salts and other important substances, storage of glycogen, vitamins, iron, etc.; detoxification: secretion of bile to help digestion and absorption of fats; defense: the liver is the main component of the body’s defense system. All the above-mentioned functions of laboratory tests constitute the entire examination of liver function. It is worth noting that many obstetricians are often accustomed to judge the degree of liver damage by observing changes in bilirubin and transaminases, but this is not comprehensive. Severe liver injury during pregnancy has become one of the main causes of maternal mortality in China, and dealing with severe liver disease in pregnancy is one of the important research topics to improve the quality of obstetrics and reduce maternal mortality. A common cause of liver disease in pregnancy 1, the impact of physiological changes in pregnancy to increase the burden on the liver: pregnancy metabolism, fetal respiration and excretion and other functions need to be completed by the mother; liver is the main site of sex hormone metabolism and inactivation, endocrine changes in pregnancy produced by a large number of sex hormones need to be metabolized and inactivated in the liver, the body’s caloric needs during pregnancy than non-pregnancy 20% higher, iron, calcium, various If the pregnant woman is malnourished, the liver function will be reduced, which will aggravate the disease and increase the burden on the liver. 2, the impact of comorbidities and complications on the liver: hypertensive disease during pregnancy can cause small blood vessel spasm, reducing blood flow to the liver and kidneys, and kidney function damage, metabolite excretion is blocked, which can further aggravate liver damage, if combined with hepatitis, easy to cause massive necrosis of liver cells, and even liver failure. In combination with hepatitis, hepatocyte necrosis and even liver failure may occur. Childbirth, surgical trauma, anesthesia, upstream infection and other factors may cause re-injury to the liver, therefore, pregnant women with hepatitis are more prone to serious changes than ordinary people. 3, relative ischemia of the liver during pregnancy: Although the whole body blood volume increases by 35% to 40% during pregnancy, the blood flow to the liver does not increase significantly due to the shunt of the fetus, so the liver blood flow is relatively reduced, and the liver is in a relative ischemic state, which makes the original unhealthy liver even worse or even overwhelmed. 4, changes in the immune system and the influence of viruses and other infectious factors: After pregnancy, in order to reduce the maternal immune rejection of the fetus, to protect the embryo from the maternal immune system and to maintain a normal pregnancy, the cytokine interleukin-10 (IL-10), which is secreted by Th2 cells and has immunosuppressive functions, is increased. However, IL-10 also inhibits CD4 cell proliferation activity and monocyte-dependent antigen expression, which gives the pathogenic microorganisms, especially hepatitis B virus, an opportunity to reactivate and increase viral replication and aggressiveness, breaking through the body’s immune tolerance period, leading to a real threat of infectious factors in a stable state, accelerated liver damage, post-hepatitis cirrhosis, early onset of cirrhosis loss phase, and the incidence of severe hepatitis. The arrival of the liver, the increased incidence of severe hepatitis, and even maternal death. This shows that the liver is at high risk during pregnancy. As an obstetrician, you must know the importance of closely observing changes in liver function, be familiar with the clinical types and diagnosis of liver diseases in pregnancy, deal with liver damage and protect liver health in a timely and skillful manner, and be able to make timely and appropriate referrals in conjunction with internal medicine doctors and provide effective treatment in order to ensure the safety of pregnant women’s lives. Common clinical types of obstetric liver diseases (a) Pregnancy combined with liver disease 1, viral hepatitis: the current clear viral hepatitis are A, B, C, D and E viral hepatitis hepatitis, in recent years also found hexa (HFV), hepatitis G (HGV) viral hepatitis, as well as blood transfusion virus infection (TTV), herpes simplex virus hepatitis. These viruses can cause severe liver damage and even liver failure under certain conditions. Hepatitis B virus is the most common pathogen of viral hepatitis in China, and hepatitis B virus infection or mixed infection with other hepatitis viruses is the main cause of viral hepatitis. According to the data of Shanghai Public Health Clinical Center, among 2137 cases of liver disease during pregnancy admitted in 10 years, 1561 cases (73.0%) were combined with viral hepatitis during pregnancy, including 52 cases (3.3%) of hepatitis A, 1409 cases (90.3%) of hepatitis B, 42 cases (2.7%) of hepatitis C, and 58 cases (3.7%) of hepatitis E. Clinical types: 61 cases of severe hepatitis (3.9%), 368 cases of acute hepatitis (23.6%), 829 cases of chronic hepatitis (53.1%) [1]. The prognosis of pregnant women and perinatal infants with combined viral hepatitis in pregnancy is closely related to the stage of pregnancy at which the disease develops, the early and late consultation, and the number of antenatal visits. Clinical types related to the type of infecting virus and multiple viral overlapping infections: all types of hepatitis B are seen, overlapping infections of hepatitis B and hepatitis E are common with slow plus acute hepatitis, overlapping infections of hepatitis B and hepatitis C are common with slow plus acute, cirrhotic loss of appreciation, chronic heavy hepatitis, hepatitis E is mostly common with acute, herpes simplex virus infectious hepatitis is rare but dangerous,. 2, drug induced liver injury (DILI): In recent years, the incidence of DILI is increasing year by year, more than 50% of acute liver failure in the United States is caused by drugs, and for which a national drug liver injury monitoring network was established. In China, a study found that 10%-50% of adults with elevated transaminases were drug-induced. DILI pathogenesis: (1) direct drug damage: direct toxicity is often predictable, toxicity is proportional to the dose, and the latency period between drug exposure and liver damage is usually very short (usually only a few hours). Immune-specific liver damage, unpredictable, occurs only in certain individuals or populations (idiosyncratic), or there is family clustering. (2) Metabolism-specific liver injury: most of them appear long after drug administration, without allergic symptoms. Acute and subacute drug-related liver injury is common. The drug enzyme activity in female liver particles is slightly lower than that in males, which may lead to a higher incidence of drug-related liver injury in females than in males. At the same time, the increased liver load during pregnancy affects the metabolism of drugs in women, leading to an increased risk of drug-related liver damage. This should be of particular concern to obstetricians. Once drug-related liver damage is detected, the drug should be discontinued immediately and detoxification and supportive treatment should be provided. In cases of acute liver failure, artificial liver plasma replacement or liver transplantation may be used. In obstetrics, we need to strengthen the observation of intrauterine growth and fetal heart monitoring, and terminate the pregnancy when appropriate. (2), pregnancy complications of liver disease 1, acute fatty liver of pregnancy (AFLP): AFLP is an idiopathic serious complication that occurs in late pregnancy, the onset of the disease is rapid, dangerous, the main lesion is liver steatosis, often accompanied by multi-organ damage, maternal and infant mortality rate is very high, the incidence of 1/67 00 ~The incidence of AFLP has been increasing in recent years, which may be related to the enhanced level of modern screening rather than a real increase in incidence. Current studies mainly suggest that AFLP is associated with long-chain 3-hydroxy coenzyme A dehydrogenase (LCHAD) deficiency. AFLP is diagnosed by the following diagnostic criteria: (1) A high prevalence in primigravida, no history of liver disease or hepatitis exposure, and negative for various viral hepatitis markers. (2) Sudden onset of unexplained nausea, vomiting, epigastric pain and progressive jaundice in late pregnancy. (3) Laboratory tests: abnormal liver and renal function, elevated serum bilirubin, negative urine bilirubin, elevated uric acid, creatinine, urea nitrogen, persistent hypoglycemia, significantly elevated white blood cell count, decreased platelet count, and coagulation dysfunction. (4) Ultrasound suggests diffuse dense light spots in the liver area, snowflake-like, with uneven intensity. (5) Hepatic lobules were intact on liver puncture biopsy. The pathological changes are diffuse microdrop steatosis in the cytoplasm of the hepatocytes, with no obvious inflammation or necrosis, of which liver biopsy is the gold standard for diagnosis. the principle of treatment for AFLP is rapid termination of pregnancy upon diagnosis and maximum supportive therapy. The fetus in utero is already in a state of hypoxia and its ability to withstand the compression of the birth canal in vaginal delivery is significantly reduced, which can easily lead to fetal distress and intrauterine death. Our research data show that the morbidity and mortality rate of cesarean delivery in AFLP patients is significantly lower than that of vaginal delivery, so cesarean delivery is recommended. In addition to obstetric management, multidisciplinary treatment is the key to successful resuscitation. Supportive treatment includes blood volume replenishment, correction of hypoglycemia, electrolyte disorders and acidosis, replenishment of coagulation factors, anti-infection and correction of DIC, hepatoprotective therapy and a series of other symptomatic treatments. Strengthening pregnancy monitoring, accurate diagnosis, timely termination of pregnancy, and rational use of drugs are important links to reduce maternal mortality. Intrahepatic cholestasis of pregnancy (ICP) The etiological mechanism of ICP is still unclear, and most studies suggest that hormonal, genetic and environmental factors play an important role. The onset of ICP is mostly in the middle and late stages of pregnancy, but in recent years, it has been reported to be earlier than 16 weeks or even earlier. 70% of the cases have itchy skin without rash, mainly on the palms of the hands, feet and limbs, and in severe cases, the itchiness is worse at night and lighter at day. In severe ICP, peripheral blood bile acid is 10 times higher than normal, and bile acid deposition in the placental villous space leads to narrowing of the villous space, reduced placental perfusion, fetal distress due to hypoxia, and even perinatal death. Cholestasis in pregnant women with incomplete removal of bile acids by the liver and accumulation in the plasma, resulting in a 10- to 100-fold increase in total serum bile acids and abnormal liver function.ICP in pregnant women with reduced absorption of fat-soluble vitamin K and reduced production of synthetic coagulation factors due to impaired liver function may lead to abnormal coagulation and postpartum hemorrhage. Strengthening prenatal testing and early diagnosis and treatment can significantly improve the prognosis of mother and child. 3, liver damage caused by severe vomiting in pregnancy: Occurs in early pregnancy, individual can be up to 20 weeks of pregnancy. Due to prolonged starvation and repeated vomiting, it leads to water loss, electrolyte disorders, urinary ketone body positive metabolic acidosis, abnormal liver and kidney function, and even Wernicke’s encephalopathy. In particular, a high percentage of pregnant women requiring hospitalization have abnormal liver enzymes and mildly elevated bilirubin, while liver biopsies show normal liver tissue. The mechanism of hyperbilirubinemia is unknown and may be related to malnutrition and impaired bile secretion. If the water-electrolyte and acid-base balance are corrected and the condition improves, liver function can be completely restored to normal, and if the treatment is timely and reasonable, the newborn rarely has malformations, low birth weight and/or abortion, preterm birth and stillbirth. HDCP and HELLP syndrome: 50% of pregnant women with preeclampsia-eclampsia have varying degrees of liver function abnormalities, with 15% to 20% of deaths due to liver damage, and there are reports of functional liver damage developing into organic liver damage. The pathogenesis of HELLP syndrome is not fully understood. The pathogenesis of HELLP syndrome is not fully understood. It may be due to activation of the endogenous coagulation system, increased vascular tension, platelet agglutination, altered thromboxane and prostacyclin ratios, resulting in systemic microvascular damage causing microvascular hemolytic anemia, thrombocytopenia, and periportal hepatocyte necrosis. The portal vein becomes engorged with blood, localized hepatocytes are squeezed, and hepatocytes become necrotic after ischemia, resulting in liver damage. The main clinical symptoms are epigastric pain with nausea and vomiting, significant weight gain and swelling can be seen. If the gestational age is > 34 weeks, labor can be induced or cesarean section can be performed in a timely manner. Corticosteroids administered before 32 weeks can also promote fetal lung maturation, and magnesium sulfate should be used appropriately for antispasmodic and antihypertensive drugs to control blood pressure. According to the American Society of Liver Diseases (ASSLD), acute fatty liver disease in pregnancy has in common with HELLP syndrome: liver failure due to hepatic steatosis occurring at the end of pregnancy, with rapid progression, aggressive disease and high mortality. It mostly presents with a triad of jaundice, coagulation disorders and platelet drop during the second trimester of pregnancy, sometimes accompanied by hypoglycemia, and manifestations of pre-eclampsia such as hypertension and proteinuria are common. Patients may experience intrahepatic hemorrhage or liver rupture requiring emergency resuscitation and invasive supportive therapy. 5. Severe infection and hemophagocytic syndrome (HPS): It is an abnormal proliferation disease of the systemic histiocyte system. Clinical features include high fever, hepatosplenomegaly, hepatocytopenia, abnormal liver function, coagulation dysfunction, and large phagocytic cells in bone marrow smear. HPS is divided into primary and secondary, with severe infections often being the precipitating factors for secondary HPS, such as Salmonella, hepatitis B virus, herpes zoster virus, and other infections. Few cases of HPS in combination with pregnancy have been reported in China and abroad, and those that have been cured have been cases of timely termination of pregnancy, so it is important to consider whether there is some correlation with pregnancy. For treatment, due to the specificity of the maternal population, after aggressive symptomatic treatment, choose an appropriate time to terminate the pregnancy by cesarean section. Secondary HPS should be clarified as soon as possible, and the primary disease should be treated aggressively while targeting HPS with the etoposide + cyclosporine + dexamethasone regimen. Due to the small number of cases and insufficient clinical experience as well as experimental studies, further observational studies are needed in the future to improve maternal and child survival in pregnancy combined with hemophagocytic syndrome. Several rare diseases with impaired liver function: autoimmune liver disease, hepatomegaly, acute intermittent porphyria, Bu-plus syndrome, and liver tumors are extremely rare diseases that impair liver function and are not suitable for pregnancy. In case of pregnancy combined with these diseases, appropriate management should be made according to the gestational age and the comprehensive situation of the pregnant woman at that time. The diagnosis and management of obstetric liver failure should be familiar to reduce the maternal mortality rate. The combination of pregnancy with severe obstetric liver disease is a serious complication of obstetrics, and requires multidisciplinary clinical collaboration and joint efforts during treatment. Acute hepatic failure in pregnancy (AHF) is a syndrome of acute, massive hepatocellular necrosis or severe dysfunction of intrahepatocellular organelles caused by different causes during pregnancy, resulting in short-term progression to hepatic encephalopathy. Treatment of hepatic failure in pregnancy is extremely difficult because it is not only a serious disease of the liver itself, but also a serious complication of the body, such as hepatic encephalopathy, microcirculatory disorders, endotoxemia, coagulation disorders, and renal failure. Childbirth is an important part of the rapid change in the condition of patients with severe hepatitis in pregnancy due to the effects of surgical trauma, anesthesia, bleeding and upstream infection. The condition often worsens rapidly in the short term after delivery. Therefore, it is necessary to develop a comprehensive medical and surgical treatment centered on rescuing the mother, focusing on protecting the safety of the perinatal baby, based on supportive treatment to ensure the stability of the internal environment and promote liver cell regeneration, supported by antiviral therapy and artificial liver, and liver transplantation as the final treatment method, with the coordinated intervention of administrative leaders and informed cooperation of family members, in order to minimize maternal and neonatal mortality and ensure the safety of mother and baby. We aim to minimize maternal and neonatal mortality and ensure the safety of mother and child. High-quality pregnancy screening plays an important role in the prevention of liver failure during pregnancy. Pregnant women with liver disease during pregnancy should have appropriately shortened obstetric examinations to achieve early identification and treatment, and centralized treatment should be achieved if available. Terminate pregnancy immediately after short-term treatment and partial correction of coagulation. Cesarean section can reduce the morbidity and mortality rate, and there should be adequate preoperative preparation before surgery, continuous strict intraoperative monitoring, postoperative admission to the ICU ward, immediate monitoring of relevant indicators and dynamic observation to grasp the changes in the condition and adjust the treatment plan comprehensive monitoring and treatment, especially to carefully prevent and effectively treat complications, but also pay attention to the continuous medical treatment after liver failure.