Pediatric sclerosing cholangitis

　　First, the cause of the disease

　　1. The cause The cause of the disease is not yet clear. It is generally believed that there are:

　　(1) Bacterial or viral infection factors: Chronic cholangitis causes fibrosis of the bile duct wall, and the lumen gradually narrows.

　　(2) Allergic reaction factors: It is sometimes accompanied by other autoimmune diseases, such as ulcerative colitis and Crohn's disease.

　　(3) Congenital genetic factors: It is reported in literature that sclerosing cholangitis may be an autoimmune disease with a genetic predisposition. Children born to parents who are closely related have a higher chance of developing this disease. Some scholars believe it is an autosomal recessive genetic disease. Children with primary sclerosing cholangitis often show a significant increase in tissue compatibility antigen HLA-B8 (a specific human leukocyte antigen) compared to the control group, and some believe it is a disease of immune function regulation disorder.

　　2. Classification The disease has two types:

　　(1) Primary: no cause of the disease can be found in clinical practice, treatment is difficult, and the prognosis is poor.

　　(2) Secondary: direct or indirect causes of the disease can be found, such as chronic cholangitis, stones, postoperative and traumatic conditions, and pediatric primary cases are more common.

　　Second, pathogenesis

　　Early liver biopsy may show portal and tract inflammation, fibrous tissue proliferation, infiltration of lymphocytes and plasma cells, and interlobular bile duct hyperplasia. The fibrosis of the bile duct wall is gradually replaced by fibrous tissue, the wall thickens and hardens, and the lumen narrows until it is sealed. It is divided into diffuse type, localized type, and segmental type (also called skip type) according to the extent of bile duct involvement.

　　Commonly associated with chronic diarrhea and malnutrition, in the late stage it can lead to cirrhosis and portal hypertension. A few cases may involve the gallbladder and pancreatic duct, gallbladder and/or bile duct stones, mainly bile duct stenosis and recurrent bacterial cholangitis, which may be accompanied by chronic ulcerative colitis or retroperitoneal fibrosis. Bile duct cancer may occur. Venous varices around the ileoanal anastomosis after rectal and colonic resection (peristomal varices) and other associated diseases with PSC are reported frequently in literature, mainly belonging to autoimmune diseases. The most common is IBD, with early reports of a prevalence rate of 25% to 30% in PSC patients, and recent reports of 54% to 100%; in the IBD associated with PSC, CUC is the most common, exceeding 70%, Crohn's colitis about 13%, and there is no report that Crohn's enteropathy only involves the small intestine and does not involve the colon.

　　The main manifestations are chronic progressive obstructive jaundice, accompanied by significant itching, chronic pain or discomfort in the upper right abdomen, loss of appetite, nausea and vomiting, chronic diarrhea, malnutrition. Some children may have a long-term low fever or high fever, physical examination may palpate an enlarged liver, the liver is hard, in the late stage it can develop into biliary cirrhosis and portal hypertension. Some children often have chronic ulcerative colitis, splenic colitis, Crohn's disease, and so on, and there are growth delays and delayed puberty.

　　Early to bed and early to rise, exercise the body. Insufficient sleep can weaken the body's immune function and is also prone to excitement and fire, causing external and internal injuries. Maintain a peaceful mind. In spring, it is taboo to be angry, and one should not be too impulsive in dealing with matters, and one should always maintain a peaceful mind. The diet should be light, nutritious, and easy to digest, with less greasy, fried, and spicy foods. The diet should avoid fatty, sweet, and spicy foods to prevent the worsening of symptoms and affect treatment.

　　First, liver function tests

　　Serum bilirubin levels are elevated, mainly direct bilirubin, with alkaline phosphatase levels often 2 to 3 times the normal value, and transaminase levels slightly elevated.

　　Two, peripheral blood smear

　　Leukocytosis.

　　Three, other tests

　　Serum IgM is also higher than normal, IgA, IgG, serum copper increased, urine copper increased, and serum ceruloplasmin increased.

　　Four, percutaneous cholecystography and intraoperative bile duct造影

　　Chen divides the imaging of the intrahepatic and extrahepatic bile ducts in primary biliary cholangitis into the following types:

　　1. Intrahepatic type:It is divided into: Type I: The bile duct contour is slightly irregular, there is local lumen stenosis, and there is no obvious obstruction in the terminal bile duct, Type II: The lumen is linearly narrow, the distal bile duct is slightly dilated, the terminal bile duct bifurcation is sparse, showing a 'withered branch' shape, Type III: The terminal bile duct is completely occluded, and the central bile duct locally shows a spindle-shaped, cystic, or bag-like dilation, the stenosis between the dilated segments is 'bead-like', Type IV: The terminal bile duct is irregular, stenotic or occluded, only the central bile duct is filled, and there is no bile duct in the peripheral liver.

　　2. Extrahepatic type:It is divided into: Type I: The extrahepatic bile duct shows general or segmental irregular changes without obvious stenosis, Type II: The bile duct shows segmental stenosis, the lumen is smooth or irregular, Type III: Irregular stenosis, all extrahepatic bile ducts show bead-like changes, Type IV: The lumen is extremely irregular, with alternating dilation and stenosis, severe lesions, and diverticulum-like.

　　Five, liver and gallbladder MRI examination

　　It can detect thickening of intrahepatic bile ducts, abnormal changes at the lesion site, and can exclude other diseases such as metastatic liver cancer, pancreatic cancer, and other bile duct obstruction diseases.

　　Six, B-ultrasound

　　In the extrahepatic type, the common bile duct is not visible, the extrahepatic bile duct is narrow and thickened, and the wall echo is strong with intrahepatic bile duct dilation.

　　Avoid foods that produce gas, such as milk, soy milk, and foods rich in rough fiber, such as celery, soy sprouts, onions, etc. Fatty foods should also be avoided, and if the body can tolerate soft rice, fatty foods should not be eaten early, such as mother chicken soup, meat soup, lamb, fatty meat, beef bone soup, turtle soup, etc. Dog meat, lamb, sparrow meat, sparrow eggs, bamboo shoots, scallions, pumpkin, beef, coriander, smoked fish, smoked meat, chili, chives, garlic sprouts, and sea cucumber should be avoided.

　　First, treatment

　　The main treatment is symptomatic, including anti-inflammatory, choleretic, immunosuppressive drugs, antifibrotic therapy, and treatment of complications. Liver transplantation is advisable in the terminal stage. Broad-spectrum antibiotics can control the occurrence of acute cholangitis, and traditional Chinese medicine can also be used for anti-inflammatory and choleretic effects, and to enhance nutrition. The indications for surgical treatment are: when the lesion is localized with dilated bile ducts, biliary-enteric or jejunal anastomosis can be performed to drain bile into the digestive tract. In cases of sclerosing cholangitis with an etiology, the cause can be removed by surgical means.

　　1. The treatment of cholestasis and liver dysfunction can adopt the following targeted measures:

　　(1) Supportive therapy: Maintain water and electrolyte balance, maintain positive nitrogen balance, promote regeneration of liver cells, maintain liver function, correct coagulation mechanism disorders, etc.

　　(2) Dietary adjustment: Reduce the content of cholesterol and saturated fatty acids in the diet, provide medium-chain triglycerides and linoleic acid esters, increase sugar and protein content (except in cases of hepatic encephalopathy), appropriately limit sodium intake, and provide essential diet for advanced cases.

　　(3) Itching: Colestipol (cholestyramine), barbiturates, antihistamines, rifampin, ursodeoxycholic acid, and opiate receptor antagonists can be selected.

　　(4) Deficiency of fat-soluble vitamins: Vitamin A deficiency accounts for 40%, vitamin D deficiency for about 14%, and vitamin E deficiency for about 2%. Prevention and treatment should be carried out separately; for vitamin K deficiency, vitamin K should be administered parenterally. If it still cannot be corrected, it indicates liver dysfunction, and supportive therapy should be strengthened.

　　(5) Steatorrhea: It is related to reduced concentration of intestinal bile acids, insufficient fat emulsification/absorption, and may also be caused by concurrent chronic pancreatitis/pancreatic exocrine insufficiency, or abdominal diseases (chronic malabsorption syndrome)/dysbiosis of the intestinal flora. In addition to adjusting the diet, pancreatic enzyme preparations, adjusting intestinal flora preparations, and appropriate oral antibiotics can be given.

　　(6) Osteoporosis: Sodium fluoride and bisphosphonate compounds, etc.

　　2. Use immunosuppressive drugs to block the progression of the disease:

　　(1) Immunosuppressive drugs used alone: The following immunosuppressive drugs have been used in experimental treatments:

　　① Corticosteroids: Early oral administration of corticosteroids showed that it could improve biochemical indicators, but there is a lack of long-term controlled studies; later, local treatment with corticosteroid biliary灌洗 was compared with the control group, proving that there was no significant effect.

　　② Azathioprine: It was previously believed to have some therapeutic effect, but now it has been proven to be ineffective.

　　③ Cyclosporine: The treatment results were not satisfactory.

　　④ Methotrexate: Randomized double-blind controlled trials have been conducted to treat, proving that there is no significant improvement in the treatment group.

　　⑤ Tacrolimus: A new type of immunosuppressive drug, some open-label treatment studies have shown that it can improve serum enzyme levels in PSC patients, but its efficacy needs further confirmation.

　　⑥ Penicillamine: In addition to having immunosuppressive effects, it also has a chelating effect on copper. It has been proven that the liver tissue of PSC patients contains increased copper content, so this drug was once used for the treatment of PSC. A prospective, randomized, double-blind, placebo-controlled study, followed up for 36 months, conducted a comprehensive analysis based on clinical manifestations, biochemical tests, radiological imaging, liver biopsy, and survival time, showing that penicillamine has no effect on the progression of PSC and the survival rate of patients, and has significant adverse reactions, especially proteinuria caused by nephrotoxicity, with up to 20% of patients discontinuing the drug due to toxicity. It is now no longer used.

　　(2) Immunosuppressive drugs/ursodeoxycholic acid (UDCA) combination therapy:

　　Lindor showed through a 2-year open-label treatment trial that there was no improvement in serum biochemical indicators and liver histology, and there was a progressive change, indicating that the combined treatment is ineffective.

　　Lindor reported that the combination therapy of methotrexate and ursodeoxycholic acid (UDCA) is not helpful for improving liver function and is prone to complications such as toxic reactions when compared with the treatment group receiving only ursodeoxycholic acid (UDCA).

　　3. Application of antifibrotic therapy:Colchicine inhibits liver fibrosis to delay the progression of the disease. Recently, Olsson conducted a multicenter, prospective, double-blind, randomized controlled study on 48 PSC patients, with colchicine/placebo: 1mg/d, oral, for 3 years. Conclusion: Colchicine has no effect on the clinical symptoms, serum biochemical indicators, liver histology, and survival time of PSC patients.

　　4. Treatment of complications includes:Gallbladder and/or bile duct calculi, main bile duct stenosis and recurrent bacterial cholangitis, bile duct cancer, and peristomal varices around the ileal anastomosis after rectal and colonic resection, etc.

　　(1) Gallbladder and/or bile duct calculi: Cholesterol stones are caused by chronic cholestasis, pigment stones are caused by bacterial cholangitis, which are prone to cause bacterial cholangitis:

　　① Symptomatic gallbladder calculi should be treated with cholecystectomy.

　　② Biliary calculi: Stone retrieval baskets can be placed under bileoscope to retrieve stones, or irrigation fluid can be used for flushing.

　　(2) Main bile duct stenosis and recurrent bacterial cholangitis:

　　① Balloon dilation: Under ERCP/PTC guidance, balloon dilation can be performed to expel sludge-like bile from the bile duct. The efficacy of balloon dilation depends on the degree of intraportal bile duct stenosis; it is effective for mild stenosis but not for severe stenosis. About 50% of PSC patients experience symptom improvement for 2 years after balloon dilation, and one-third of patients can undergo repeated balloon dilation when restenosis occurs. This method is a relatively effective treatment for relieving itching, reducing jaundice, and reducing the recurrence of bacterial cholangitis.

　　② Stent placement: After 6 months of stent placement in the stenotic area, it can improve serum liver function, with a median follow-up time of 29 months, 57% of patients can still remain asymptomatic. However, in the early stage of placement, about 14% of patients develop bacterial cholangitis, and about 1/3 of people develop recurrent bacterial cholangitis in the middle and late stages of placement.

　　③ Broad-spectrum antibiotics: Ciprofloxacin has a high concentration in the bile duct, effective against Gram-positive cocci and Gram-negative bacilli, and can be used as a prophylactic drug for bacterial cholangitis, with long-term use reducing the frequency and severity of bacterial cholangitis episodes.

　　④ Biliary-enteric Stenting Anastomosis: Reconstruction of the hepatic duct bifurcation with long-term transhepatic stents through liver placement of stents: Anastomosis/stent reconstruction, suitable only for extrahepatic strictures, for early patients in whom balloon dilation/endoscopic stent placement is ineffective, ineffective for patients with existing liver cirrhosis and severe intraportal strictures, for whom liver transplantation should be considered.

　　(3) Cholangiocarcinoma: surgical treatment, chemotherapy, and radiotherapy for cholangiocarcinoma have been proven ineffective, and all patients who undergo liver transplantation will relapse; combined chemotherapy and radiotherapy followed by liver transplantation, this experimental treatment is still ongoing and is expected to improve the prognosis of patients with concurrent cholangiocarcinoma.

　　(4) Perirectal varices: in patients with IBD/CUC, the veins around the ileal anastomosis site after rectal and colonic resection occur varices due to portal hypertension caused by liver cirrhosis, often accompanied by severe bleeding. Measures to control bleeding include:

　　① Local surgical treatment/injection of sclerosing agents, but the effect is not ideal.

　　② The use of drugs to reduce portal hypertension, such as octreotide.

　　③ Transjugular intrahepatic portosystemic shunt.

　　④ Severe liver failure, liver transplantation is the best choice.

　　(5) Complications of liver cirrhosis: seen in advanced patients, similar to decompensated liver cirrhosis caused by other reasons, common symptoms include gastrointestinal bleeding, ascites, spontaneous peritonitis, and hepatic encephalopathy.

　　5, Treatment of End-Stage Liver Transplantation Patients: Liver transplantation (OLT) is the most appropriate choice, with 1-year and 5-year survival rates of 90% to 97% and 85% to 88%, respectively. The ideal time for liver transplantation is very important for the success rate of the operation, and the Mayo risk score is generally used as a reference index for surgery. Patients with a high risk score have a high mortality rate after surgery, while those with a low risk score have the opposite. Generally speaking, the presence of refractory/obstinate symptoms, signs, biochemical changes, and end-stage liver cirrhosis complications are the basic criteria for choosing OLT.

　　Second, Prognosis

　　Secondary sclerosing cholangitis, removal of the cause can alleviate and improve the condition. Primary sclerosing cholangitis can cause biliary cirrhosis, portal hypertension, upper gastrointestinal bleeding, and hepatic encephalopathy, leading to death after 5 to 7 years of repeated cholangitis and biliary stenosis. 7% to 10% of primary sclerosing cholangitis patients may develop cholangiocarcinoma, and the best time for liver transplantation to prevent this complication is not clear.