Pediatric liver disease (referred to as pediatric liver disease) has attracted more and more attention. Since the late 70’s, France, Britain, the United States, Canada and other countries have published monographs on pediatric liver disease and biliary system diseases, and some have established research centers for pediatric liver disease. With the development of medical science and the clinical application of high technology, new progress has been made in the study of etiology and pathogenesis of pediatric liver diseases, means of diagnosis and treatment, and preventive measures. The physiological and anatomical characteristics of the liver at all ages in the pediatric period are somewhat different from those of adults, and the younger the age, the more significant the difference. Regardless of systemic or localized diseases that cause primary or secondary enlargement of the liver or hepatosplenomegaly, liver function abnormalities such as elevated aminotransferases or even gangrene, they are all causes of liver diseases. In China, pediatric liver and gallbladder diseases are extremely common as respiratory diseases. Its etiology is many, clinical manifestations except jaundice, often symptoms are not obvious, difficult to detect, but its harmfulness is still more serious, the light only have liver function (sALT) mild increase, the heavy can occur cirrhosis or liver failure. Classification of etiology of pediatric liver disease: it can be divided into infectious and non-infectious 1, infectious liver disease (1) viral hepatitis: viral hepatitis is an inflammation caused by a group of hepatophilic viruses with hepatocellular lesions as the main cause. The main viruses are hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus and hepatitis G virus. Other viruses, although not exclusively hepatophilic, can also invade the liver such as cytomegalovirus, EBV, rubella virus, herpes simplex virus, and enteroviruses (coxsackievirus, echovirus, etc.). In addition, measles virus and other hantaviruses, etc. can cause inflammatory reactions in the liver. Viral hepatitis A: it is an acute infectious disease caused by hepatitis A virus (HAV), common in children and adolescents, the incidence rate of hepatitis A in children is second only to hepatitis B, accounting for 17,3% of the total number of hepatitis cases, and its main epidemiological features are: ① the source of infection is patients with hepatitis A and subclinical infections, with the late latent phase and jaundice before and after the emergence of the strongest contagious 1 week. ② mainly through fecal-oral route of transmission, food and water sources of infection can cause outbreaks. Recently reported, there are cases of blood and blood products transmission. ③The body has lasting immunity after infection. ④ Clinical manifestations are acute jaundiced hepatitis, acute non-jaundiced hepatitis, sludge hepatitis and severe hepatitis. ⑤ Hepatitis A antigen-antibody test is the basis for diagnosing the disease. ⑥ The wide application of hepatitis A vaccine will effectively control the epidemic of hepatitis A. The incidence of hepatitis A is mostly related to dietary hygiene. The prevalence of hepatitis A is closely related to the living conditions, hygiene habits and education, to prevent the onset of hepatitis A, in addition to hygiene, can be vaccinated against hepatitis A. Hepatitis B: Hepatitis B is the main childhood hepatitis in our country, and it is mostly a vertical infection with strong immune tolerance. Statistics show that the incidence of hepatitis B accounts for 60,3% of the total hepatitis. Pediatric acute hepatitis B is rare, the vast majority of chronic hepatitis B, accounting for 93.5% of the total number of hepatitis B. The majority of children with acute hepatitis B is chronic, accounting for 93.5% of the total number of hepatitis B. Analysis of the severity of the disease suggests that the disease is mostly mild, a small number of moderate, slow and severe liver and complications of cirrhosis and liver cancer are rare, which may be related to immune tolerance, the condition of light evolution into cirrhosis and liver cancer is also reduced. Due to the insidious onset of chronic hepatitis B in pediatric patients, 60.8% of the cases were found on physical examination, so the duration of the disease cannot accurately reflect the real condition. It is observed that with the gradual increase of age, the degree of fibrosis gradually increased, so in determining the condition, age is also an important reference index, and mother-to-child vertical transmission of children, the incidence and severity of liver fibrosis did not increase, but rather than other children to reduce. In the pathogenesis of chronic hepatitis B, immune factors play a dominant role, the clearance of the virus and the decrease of the amount of virus is through the process of immune damage. In the course of treatment, not only antiviral drugs should be used, but also attention should be paid to adjusting the immune function in order to obtain ideal results. Family history, history of hepatitis B vaccination, screening for hepatitis B virus markers, including hepatitis B penta, HBV-DNA, anti-HBc-IgM and ultrasound should be performed.HBV infection can cause acute hepatitis B, chronic hepatitis B, hepatitis B carrier status, severe hepatitis, cirrhosis, and can also overlap with HAV and HEV infections. HBV infection in childhood is mostly due to immune tolerance manifested as chronic carrier state, with the gradual growth of age, from immune tolerance into the immune clearance state before liver function abnormalities, usually no symptoms and positive signs, mainly through physical examination detection. Some children with liver function abnormalities can be seen at a young age, mainly manifested as elevated ALT, rarely jaundice, high HBV-DNA levels, which requires antiviral treatment. (iii) Hepatitis C: It is an infectious disease caused by Hepatitis C Virus (HCV) that mainly damages the liver. If you have a history of blood transfusion surgery, you should be alert to hepatitis C virus infection, according to the latest information released by WHO, there are currently 170 million hepatitis C virus-infected people around the world. The vast majority of them have insidious onset of disease and have no obvious symptoms. After tracing the history of the disease, there is a history of blood product contact or blood transfusion surgery at a young age, manifested by a mild elevation of ALT, bilirubin is very rare, and the laboratory tests are positive for anti-HCV and HCV-RNA. The treatment of choice is interferon plus ribavirin, with an expected course of 1 year. The earlier the age of treatment, the better the prognosis and the lower the chance of future cirrhosis. HCV is transmitted by transfusion of blood or blood products, and mother-to-child transmission is an important route of transmission of pediatric HCV infection.The clinical manifestations of HCV infection are usually mild and subclinical, but severe hepatitis may occur in a small number of children. In acute HCV infection, 80% can become chronic, of which 20% develop cirrhosis after 10-30 years, and 1%-5% can develop hepatocellular carcinoma. The diagnosis is based on serum anti-HCV positivity and HCVRNA positivity. Pediatric chronic hepatitis C (CHC) has a more insidious onset, fewer symptoms, and a worse prognosis than pediatric chronic hepatitis B (CHB). Some studies have shown that the early appearance and severity of perisinusoidal and interstitial fibrosis in pediatric hepatitis C characterized by pathological changes compared with adult hepatitis C is one of the reasons that it is more likely to lead to chronicity and cirrhosis in a short period of time, and the ultramicro-pathological changes in pediatric CHC are different from the localized destruction of hepatocyte membranes and severe alterations of blood sinusoids that are commonly seen in pediatric CHB, and the main changes in hepatocytes are in the endoplasmic reticulum, with the slippery-surface endoplasmic reticulum being more The mechanism needs to be studied in depth. Cytomegalovirus hepatitis: Cytomegalovirus hepatitis is common in infancy. Cytomegalovirus (CMV) infection is very common in China. Maternal anti-CMVIgG positivity rate is about 95%. The transmission pathways are: ① mother-to-child transmission: mainly through intrauterine, birth canal and breast milk transmission; ② horizontal transmission: intra-family transmission, collective institutional transmission and medical transmission. The main clinical manifestations are diverse, and common damages include meningoencephalitis, microcephaly, intracranial calcification, hydrocephalus, cerebral palsy, optic atrophy, deafness, pneumonia, hepatitis, and so on. Diagnosis is mainly based on blood CMV-IgG and CMV-IgM and CMV viral culture.The prevalence of CMV infection in children, especially hepatitis in infants, is high and can even exceed that of hepatitis B virus infection. CMV infection can cause damage to the hepatobiliary system in infants, and the lesions can involve hepatocytes and intrahepatic bile duct epithelial cells, causing inflammatory reactions in the bile ducts leading to cholestasis or biliary atresia. Pathologic studies have demonstrated that children with infantile hepatopathy syndrome caused by CMV are prone to intrahepatic cholestasis, and the presence of CMV antigens in the liver and bile ducts has been confirmed by antigenic staining, and ultrasound has demonstrated that hepatic involvement is the main clinical manifestation of CMV infection in infancy. It has been confirmed that the percentage of CD3+ and CD4+ cells decreased significantly after CMV infection in adults, but there was no significant change in CD3+ and CD8+ cells. As for infants and young children, T lymphocyte subsets are also dysregulated after CMV infection, but different from the adult situation, manifesting as an elevated absolute number of CD4+ lymphocytes and a decreased percentage, an elevated absolute number and percentage of CD8+ lymphocytes, an elevated absolute number of CD3+ lymphocytes, and a significant decrease in the CD4+/CD8+ ratio.The decrease in CD4+ lymphocytes is mainly due to the fact that CMV infection The decrease in CD4+ lymphocytes was mainly due to CMV infection, which inhibited their activation and also reduced IL-2 and IFN, thus affecting the production of anti-CMV effector cells. In addition CMV infection tends to involve peripheral blood mononuclear cells, reducing the CD4+ proliferative response to PHA that it induces, resulting in fewer CD4+ cells. Many previous studies have focused on changes in the relative content of T-lymphocyte subpopulations, but it is difficult to be objective in judging the immune system’s response solely from changes in percentage content. Recent studies have reported an increase in the absolute number of CD3+, CD4+, and CD8+ T lymphocytes, suggesting that the immunosuppression caused by CMV infection in pediatric patients may only be a “relative suppression”, but it also produces a certain amount of stimulation of the immune system, which leads to an increase in the absolute number of T lymphocytes, including CD4+ lymphocytes. This effect leads to an increase in the absolute number of T-lymphocytes, including CD4+ lymphocytes, followed by a gradual decrease in CD4+ cells in response to the various mechanisms described above, and a series of corresponding immune dysregulation manifestations. Currently, there is no specific treatment for CMV infection, and the need for treatment of symptomatic CMV infection is a matter of debate. Whether immunomodulators can be preferred to immune activators for the clinical management of infantile liver disease syndrome will be further explored in future studies. ⑤ Other viral hepatitis: other viruses, although not exclusively hepatophilic, can also invade the liver, e.g., EBV-induced infectious mononucleosis is more common in those who involve the liver, often with hepatosplenomegaly and other systemic symptoms. Rubella virus infection in the congenital rubella painted signs, 20% may present with hepatitis symptoms, and may be accompanied by other congenital defects. Enteroviruses such as coxsackieviruses and echoviruses can cause severe hepatic lesions or systemic infections in children, especially infants, sometimes resulting in epidemics. Measles with hepatic involvement is also not uncommon, and can be as high as 75%, mostly occurring in the later stages of the rash. Hepatic abnormalities have been reported in 32 or 56% of infantile rotavirus enteritis in China. Some authors have also reported that herpes virus infection can involve the liver. (2) Infectious toxic hepatitis and bacterial liver abscess: common pathogens include Staphylococcus aureus, Escherichiaceae, Salmonella, Shigella, Mycobacterium tuberculosis and Borrelia burgdorferi. Bacterial infections are mostly caused by systemic or localized infections, such as sepsis, pyothorax, liver abscess, intestinal and biliary tract infections. Staphylococcus, S. typhi and E. coli are the most common pathogens. China’s pediatric typhoid fever complication liver disease has been repeatedly reported, the prevalence rate can be as high as 72, 22%. (3) Parasitic liver disease: common pathogens include amoeba, toxoplasmosis, Giardia lamblia, schistosoma, Schistosoma oryzae, and Plasmodium. Toxoplasma gondii hepatitis in infant hepatitis syndrome accounted for 9,3%, pediatric malaria liver damage accounted for 26,3%; black fever up to 54,5%. In China’s pediatric Kawasaki disease, accompanied by liver and gallbladder damage can be up to 20, 20% of larger children with liver damage easily accompanied by gallbladder effusion. (4) fungal liver abscess and hepatitis 2, inborn genetic metabolic liver disease: genetic metabolic liver disease is due to genetic mutations leading to metabolic substances synthesis and decomposition of a class of diseases. At present, there are more than 4,000 types of these diseases, which can be diagnosed, and they mainly show lesions on the morphology and structure and/or function of the liver, and are often accompanied by damages of other organs. Although inherited metabolic liver diseases are not common in clinical practice, they still account for a certain percentage of pediatric liver diseases. The liver is the main organ for metabolizing various substances in the body. Various metabolic diseases caused by inborn enzyme defects often involve the liver, and their clinical manifestations, such as vomiting, diarrhea, jaundice, convulsions, and abnormal urine odor, are similar to those of common liver diseases. In recent years, with advances in chemistry, enzymology or molecular biology, many of these diseases can be correctly diagnosed by abnormal metabolite enzyme activity or genetic defects. In children with unexplained hepatomegaly, jaundice or developmental delay, the possibility of inherited metabolic liver disease should be considered. Although all kinds of metabolic liver diseases have their common features, they also have their characteristic manifestations, which can be examined by liver function, blood glucose, blood lactic acid, cupric acid protein and liver puncture, and combined with clinical manifestations to make a definite diagnosis. (1) Carbohydrate metabolism disorder: galactosemia, hereditary fructose intolerance, hepatic glycogen accumulation disease, etc.. Hepatic glycogenosis is a disorder of glucose metabolism caused by inborn enzyme defects. According to the European data, the incidence rate is 1/(20,000-2,500,000), and typical phytocellular mosaic arrangement can be seen as its characteristic change under light microscopy of liver puncture biopsy, with positive PAS staining, and a large number of high-electron-density glycogen particles can be seen in the cytoplasm of the cytoplasm under electron microscopy. Glycogen accumulation disease, as a genetic disease with a clear pathogenic gene, DNA testing can be a necessary supplement to clinical diagnosis and can provide a basis for early diagnosis of the disease. (2) Abnormalities of amino acid metabolism: tyrosinemia, etc. (3) Defective fatty acid oxidation: dihydroxyaciduria. (4) Abnormalities of trace element metabolism: hemochromatosis, Wilson’s disease. Wilson’s disease, also known as hepatomegaly, is an autosomal recessive inherited copper metabolism defective disease, clinically characterized by hepatic damage, neurological abnormalities, corneal limbal K-F ring, and decreased serum copper blue protein. Inborn inherited metabolic disorders are most frequently characterized by hepatomegaly, which is often misdiagnosed as chronic hepatitis, cirrhosis, severe hepatitis, or even acute xanthogranulomatous viral hepatitis. Regardless of the presence or absence of neurologic symptoms, attention should be paid to the exclusion of hepatomegaly, the age of onset and clinical symptoms of which vary greatly. Hepatomegaly is caused by mutations in the gene encoding copper-conjugating P-type ATPase, resulting in large amounts of copper storage in the bean-shaped nuclei of the liver and brain tissues as well as the corneal margins, and its incidence is 1/(500,000-1,000,000). Typical K-F can be seen in the eye examination, and the copper-orchid proteins are lower than normal, and the cytoplasm can be seen as the lipofuscin granules and granules containing rounded translucent vacuoles of varying sizes under electron microscopy. Overseas clinical data show that most patients with hepatomegaly are admitted with severe hepatic insufficiency and no encephalopathic symptoms, and that early D-penicillamine administration is associated with survival in non-transplant situations. Symptoms are often atypical, and there may be no corneal K-F ring or no low blood copper blue protein, so that a definitive diagnosis is not made for a long time and treatment is delayed. In pediatric chronic liver disease, the possibility of this disease needs to be considered, and appropriate specific tests need to be performed if necessary, in time to try to give copper repellent therapy before the appearance of neurological symptoms. In addition to the routine administration of penicillamine and zinc sulfate, liver transplantation has been reported as a successful treatment for pediatric hepatomegaly. (5) Lysosomal accumulation disease: Gaucher disease, Niemann-Pick disease, mucopolysaccharidosis, lipid deposition disease. Niemann’s disease belongs to lipid metabolism disease, is due to acidic sphingomyelinase deficiency caused by sphingomyelin deposition, this disease is more common in Jews, the incidence rate is as high as 1/25000. due to sphingomyelin deposition in the liver, spleen, bone marrow, brain and other tissues, so children can appear hepatosplenomegaly, liver function abnormalities, elevated lipids and other manifestations. Hepatopancreatic tissue light microscopy shows stacks of foam-like vacuolated cells, i.e. Niemann-Pick cells, and electron microscopy shows a large number of membrane-encapsulated electron-lucent vacuoles in hepatocytes and macrophages. Bone marrow changes are more common in this disease, and repeated bone marrow aspiration at different sites may increase the detection rate of Niemann-Pick cells. It has been reported that hepatic lipid deposition is also formed when certain enzymes such as carnitine palmitoyltransferase-1 (GPT-1) are absent in the carnitine circulatory pathway, suggesting that this kind of lipid deposition is related to fat metabolism disorders. (6) Abnormal bile acid metabolism: Byler’s disease, Aagenaes syndrome, Zellweger syndrome. Dubin-Johnoson syndrome is caused by congenital defects of hepatocytes, resulting in impaired excretion of bilirubin and other organic anions into the capillary bile ducts, leading to elevated serum bilirubin. As a result, children with the disease may have yellow staining of the skin and sclera, elevated direct and indirect bilirubin, etc. Liver tissue appears black to the naked eye, and microscopic deposition of coarse brown pigment particles in the hepatocytes is obvious, which accounts for about 0.3% of the liver biopsy cases. (7) Other metabolic abnormalities: α-antitrypsin deficiency, cystic fibrosis, urea metabolism disorder. (8) Drug liver disease: drug liver disease can be seen in the long-term application of anti-rheumatic antipyretic and analgesic drugs, anti-tuberculosis drugs, adrenocorticotropic hormone, and cyclic amine phosphate, erythromycin and other drugs, can cause liver damage. Accidental ingestion of toxic mushrooms or pesticides such as zinc phosphide poisoning can also lead to liver disease. In recent years, the clinical use of drugs more and more, due to pediatric anatomical and physiological characteristics, drug elimination sites such as the kidneys, hepatobiliary system, lung excretion and biotransformation effect is poor, many drugs can cause liver damage, should be alert to drug liver disease. The incidence of drug-induced liver disease in children is high, but it is difficult to find, mainly because clinicians do not pay enough attention to the symptoms of poisoning is not significant or the symptoms are slow to occur, or transient liver damage or confusion with the original liver disease. 3, drug toxic liver disease common clinical manifestations are: ① acute hepatitis, often reactive metabolites caused by toxic hepatitis or immune allergic hepatitis; ② lipid accumulation liver disease; ③ subacute and chronic liver damage, manifested as subacute hepatitis, chronic hepatitis and cirrhosis, cholestasis and bile ducts; ④ hepatic vasculopathy, such as hepatic arterial and portal vein lesions, or hepatic venous occlusion; ⑤ tumor (hepatocellular carcinoma, hepatoblastoma, hepatocellular carcinoma, hepatocellular carcinoma, hepatocellular carcinoma, hepatocellular carcinoma, hepatoblastoma). ⑤ Tumors (hepatocellular carcinoma, hepatoblastoma, etc.). Autoimmune liver disease: The diagnosis of autoimmune liver disease needs to be improved. It is reported abroad that autoimmune liver disease accounts for about 3.2% of pediatric liver diseases, and the average age is 8.5 years old, and the possibility of autoimmune hepatitis is high in female children. It is characterized by: ① insidious onset, often difficult to detect; ② chronic development process; ③ often develop into cirrhosis and liver insufficiency. According to the appearance of serum specific autoantibodies, pediatric autoimmune liver disease is mainly divided into three types: Type I-type is related to antinuclear antibody (ANA) and anti-smooth muscle antibody (SMA), and Type II-type is related to anti-liver and kidney microparticle antibody (anti-LKM-1); pediatric autoimmune liver disease is diagnosed according to the positive of ANA and SMA, or the positive of anti-LKM-1/anti-LKM-1 and SMA; the diagnosis is based on the positive of ANA and SMA, or positive of LKM-1 and SMA, or positive of LKM-1 and SMA. LKM-1 and SMA are positive and other known liver diseases are excluded. Suggestion: autoimmune hepatitis in children has a progression to the stage of cirrhosis at the time of diagnosis. Unlike the diagnostic criteria for adults, autoantibody titers are much lower in pediatric AIH, and the presence of autoantibodies at any titer in combination with other necessary elements confirms the diagnosis. Because AIH in children progresses more rapidly than in adults, corticosteroid therapy should be initiated as soon as the diagnosis is made and over a longer period of time. Almost all children show improvement in liver function during the first 2-4 weeks of treatment with prednisone alone or prednisone in combination with azathioprine. 80%-90% of children show laboratory remission at 6-l2 months. Most regimens recommend high-dose prednisone therapy: 2 mg/(kg?d) for 2 weeks, then tapered to a maintenance dose over a 6-8 week period, usually 0,1-0,2 mg/(kg?d) or 5 mg/d. 5. Nutritional disorders of the liver. 6.Sludge and ischemic liver disease: such as chronic heart failure due to various reasons, hepatic venous occlusion. 7.Tumor and blood disease-related liver disease: hepatoblastoma, leukemia, lymphoma, histiocytosis and so on. 8, Hepatobiliary developmental abnormalities: hepatic fibrosis, intrahepatic bile duct developmental abnormalities, choledochal cysts, extrahepatic biliary atresia and so on. In conclusion, children’s liver and gallbladder diseases have different characteristics at different ages. As long as certain ideas are followed and comprehensive examinations are conducted, pediatric liver diseases can be diagnosed early and treated in time. In recent years, as the study of hepatology has been deepening, the use of liver histology has become more and more urgent. Although morphological examination is still a reliable basis for determining liver lesions and their extent, morphological examination must be combined with complete clinical data to make a correct diagnosis of complex cases, and correct diagnosis is a prerequisite for correct treatment. It is necessary to avoid the tendency of emphasizing on pathology but not on clinic, and to overcome the tendency of relying only on clinical experience. Therefore, it is one of the important issues that need to be solved urgently in the field of pediatric liver diseases in China to actively carry out and apply liver histology research, improve the clinical application level of histopathology, explore the correlation and law between clinic and pathology, and achieve accurate diagnosis and timely treatment. At present, the use of liver function as an indicator for evaluating the presence or absence of active liver lesions, the need for antiviral treatment and prognosis judgment has certain defects. In recent years, antiviral treatment for chronic hepatitis B and C in pediatric liver disease has achieved certain efficacy, and the scope of indications for antiviral treatment is also expanding. At present, despite the efficacy of antiviral therapy, especially with the clinical application of pegylated interferon, the efficacy of antiviral therapy can be further improved, but there are still some children with chronic hepatitis B and chronic hepatitis C who are non-responsive or relapsed. Therefore, the optimal regimen of antiviral therapy in different situations, such as sequential therapy, timing of combination therapy, and drugs to be used in combination, need to be further studied. The vast majority of children with liver disease in China rely on symptomatic treatment to obtain symptomatic improvement, but antiviral therapy for chronic viral hepatitis is the key to treatment. Therefore, it is necessary to improve the level of evidence-based medical prevention and treatment of pediatric liver disease as soon as possible, standardize antiviral therapy, and develop a national diagnostic and treatment plan for pediatric viral hepatitis, thereby reducing the incidence of adult liver disease and advanced severe liver disease. Hepatobiliary system diseases in children have different clinical features from those of adults and exist in different age groups. The soundness of liver function is crucial to the growth and development of children. We will further strengthen cross-regional and interdisciplinary collaborative research on pediatric liver diseases to improve the diagnosis and management of pediatric liver diseases in China for the benefit of children.