Primary sclerosing cholangitis

Introduction to primary sclerosing cholangitis Primary sclerosing cholangitis (PSC), also known as stenotic or occlusive cholangitis, is a rare biliary tract lesion with unknown causes and slow course. It is characterized by extensive fibrosis of the intrahepatic and extrahepatic biliary tracts, the wall of which is obviously thickened and the lumen is significantly narrow. The clinical manifestations are other than obstructive jaundice. If the patient fails to get timely diagnosis and treatment, it can eventually lead to biliary cirrhosis. And portal hypertension, and death due to liver failure and upper gastrointestinal bleeding, the majority of onset age is 30 to 50 years old, more men than women. It is currently believed that bacterial and viral infections, immune dysfunction and certain congenital genetic factors are possible pathogenic factors in this disease. basic knowledge Sickness ratio: 0.0001% Susceptible population: Most of the age of onset is 30 to 50 years old, more men than women Mode of infection: non-infectious Complications: ascites, hepatic encephalopathy, diarrhea, liver abscess, bacteremia, cholangiocarcinoma, gallstones, cirrhosis, ulcerative colitis

Cause of primary sclerosing cholangitis

(1) Causes of the disease

It has not been fully elucidated so far, and may not be a single factor. The causes of the disease are as follows:

1. Chronic non-specific infection is considered to be associated with ulcerative colitis. In the case of infectious bowel disease, intestinal bacteria invade the biliary system from the portal vein, forming chronic inflammation, hyperplasia of the bile duct wall, and narrowing the bile duct wall. In the case of colonic resection due to ulcerative colitis, the portal vein blood is cultured to grow bacteria; bacteria are injected into the portal vein of the animal, and inflammation is found around the bile duct, but some people think that the disease is not fundamentally related to ulcerative colitis, whether or not With ulcerative colitis, does not change the natural course and outcome of primary sclerosing cholangitis.

2. Autoimmune diseases In addition to ulcerative colitis, some diseases are also associated with segmental enteritis, chronic fibrotic thyroiditis (Riedls thyroiditis) and retroperitoneal fibroinflammatory sclerosis, patients The immune complexes in serum are often higher than normal. When these substances precipitate in tissues, they can cause local inflammation. Badenheimer measures the immune complexes in the serum of patients with primary sclerosing cholangitis, with or without ulcerative colitis. Their immune complexes in serum were significantly higher than those in healthy controls, patients with ulcerative colitis, anti-nuclear antibodies in serum, and anti-smooth muscle antibodies were positive in a certain proportion, supporting the pathogenesis and immune factors of these patients. Related views, but the application of hormone or immunosuppressive drugs, although it can improve symptoms, but does not improve the pathological changes of the bile duct, can not change the patient's course of disease, so whether primary sclerosing cholangitis and immune factors are still to be further Research confirmed.

3. Precancerous lesions Some patients with primary sclerosing cholangitis clinically, after a period of follow-up, and finally diagnosed as primary sclerosing cholangiocarcinoma, so some people think that the disease is a slow-developing cholangiocarcinoma, Or think that the disease will be converted into cholangiocarcinoma, many authors report that primary sclerosing cholangitis and primary sclerosing cholangiocarcinoma are not easily distinguishable histologically.

4. Other factors Some people reported that the disease is related to congenital factors, such as roundworm infection, alcoholism, and lithocholic acid.

(two) pathogenesis

The main pathological changes of the disease, infiltration of inflammatory cells around the bile duct wall and bile duct in the intrahepatic portal area, mainly lymphocytes, few polynuclear white blood cells, occasionally visible macrophages and eosinophils, and with the development of lesions Focal small point necrosis and fibrous tissue hyperplasia, bile duct epithelial cells gradually shrink and disappear, and the wall hardening is not smooth and thickened, eventually causing extreme fibrosis of the bile duct wall, resulting in thickening of the wall and abnormal lumen The stenosis is a string of balls. The smallest lumen is only a pencil lead, but the diameter is only 2mm. The lesions sometimes only involve a segment of the common bile duct, but most of the common bile ducts are even left and right hepatic ducts are involved. Most cases With chronic cholecystitis and hepatoduodenal ligament adhesions into a strip-like shape, almost no bile duct-like structure, obstructive jaundice and biliary cirrhosis, portal vein hypertension and liver function Depletion.

Primary sclerosing cholangitis prevention

The etiology of primary sclerosing cholangitis is currently unknown, but related to factors such as autoimmune inheritance, so there is no effective way to prevent it.

Primary sclerosing cholangitis complications Complications ascites hepatic encephalopathy diarrhea liver abscess bacteremia cholangiocarcinoma gallstone cirrhosis ulcerative colitis

Patients with PSC were followed up for 5 to 10 years, and found that 50% of patients may have chronic liver disease, portal hypertension, ascites, portal hepatic encephalopathy, bone metabolic diseases, diarrhea, lipid rafts, fat-soluble vitamin deficiency and liver failure. A series of consequences of liver damage can occur as the disease progresses.

The specific complications of PSC are bacteremia, cholelithiasis and cholangiocarcinoma.

1. Bacteremia can occur repeatedly, may be secondary to chronic biliary tract infection or bacterial spread, the frequency and severity of bacteremia in patients with PSC is difficult to estimate, may lead to liver abscess or infection of other organs (such as heart valves) .

2. About one-third of patients with cholelithiasis have a history of cholecystectomy at some stage of the disease process, of which about 20% are asymptomatic gallstones, and ultrasound examination of PSC patients shows that 25% have gallstones due to large Most PSC patients are young men, so this indicates an increased incidence of cholelithiasis in PSC, and bile duct stones may also be associated with PSC, but because cholangitis may occur in patients with PSC without bile duct stones, the diagnosis is more difficult, for suspects should be Direct cholangiography was performed to confirm that some recurrent cholangitis was caused by bile duct stones, and the removal of bile duct stones by treatment can eliminate seizures and slow the progression of PSC.

3. The autopsy report of cholangiocarcinoma PSC shows that 50% of cholangiocarcinoma occurs on the basis of PSC pathology. PSC with cholangiocarcinoma is usually accompanied by cirrhosis, portal hypertension and long-term ulcerative colitis (UC), usually older than Large and cholangiography progressive changes, such as cystic dilatation of the biliary tract, suggesting that cholangiocarcinoma occurs in PSC, if the bilirubin in PSC patients rises from 85.5mol/L (5mg/dl) to 171mol/L (10mg/dl) in a short time. The malignant transformation should be considered, but it needs to be confirmed by biopsy or surgery. However, in the recent Mayo Center, 60 cases of PSC were transplanted, and only one case of the liver was found in the liver and the epithelial papillary dysplasia of the left and right hepatic ducts. May be non-invasive nipple dysplasia), no bile duct dysplasia and cholangiocarcinoma, so the incidence of PSC cholangiocarcinoma may not be high, the incidence is generally considered to be 10% to 15%.

Primary sclerosing cholangitis symptoms common symptoms liver lesions diffuse gallbladder contractile dysfunction fatigue abdominal pain skin itching cold gallbladder dyskinesia jaundice biliary cirrhosis ascites

The incidence of primary sclerosing cholangitis is more concealed. There are no obvious auras and specific symptoms at the beginning. Occasionally, jaundice is often found and progressively worsened. Patients are often not completely obstructed due to bile ducts. There are few gray-white stools, which are often misdiagnosed clinically. "Acute infectious hepatitis", jaundice after skin aggravation, such as combined biliary tract infection, may have right upper abdominal pain, fever and chills, with the development of the disease, the jaundice time prolonged, the patient developed liver, splenomegaly, late liver failure Ascites, oliguria, hepatic encephalopathy, etc. may occur.

Primary sclerosing cholangitis is classified into asymptomatic and symptomatic according to clinical symptoms:

1. Asymptomatic: The patient has no obvious symptoms, often pre- or early stage of the disease, although the imaging examination is consistent with the manifestation of sclerosing cholangitis, and the patient has no jaundice.

2. Symptoms: Divided into mild and severe cases: mild patients have discomfort, fatigue, anorexia, weight loss, abdominal pain, fever, jaundice, itchy skin, without symptoms and signs of portal hypertension, severe jaundice in critically ill patients , liver splenomegaly, ascites, encephalopathy or esophageal varices bleeding and other symptoms of cirrhosis.

Examination of primary sclerosing cholangitis

Blood biochemical examination can show multiple abnormalities of obstructive jaundice, increased serum total bilirubin (very large fluctuations in different periods of the same patient), alkaline phosphatase increased significantly, and it is not easy to fall to normal level after treatment. , serum transaminase mild or moderate increase, blood routine examination in addition to the obvious increase in white blood cells in the presence of cholangitis, lymphocytes may also be found, or occasionally abnormal lymphocytes or eosinophils, immunological examination of some patients Immunoglobulins, antinuclear antibodies, anti-smooth muscle antibodies, 4% of patients with elevated IgM, 75% of patients with increased ceruloplasmin and increased urinary copper excretion, but anti-cell mitochondria negative, HLA-DRW52a antigen positive up to 100 %, some cases have some damage to kidney function.

Cholangiography

It is the most convincing method for PSC to determine the diagnosis and extent of lesions, including ERCP, PTC, intraoperative cholangiography and T-tube retrograde cholangiography. Among them, ERCP has the most advantages, which not only can ideally display intrahepatic and biliary morphological changes. It can also display pancreatic duct lesions, etc. The catheter for ERCP can be inserted into the cystic duct to obtain detailed information of the intrahepatic bile duct. It is often necessary to use balloon blocking technology to assist, and PTC only has half the success rate. Most of them are used for ERCP failure, or have undergone biliary jejunostomy, intraoperative cholangiography, T-tube retrograde cholangiography is suitable for surgical treatment or postoperative assisted diagnosis. PSC biliary development features are: 1 lesion The bile duct is irregular multiple stenosis, and the bile duct mucosa surface is smooth; 2 stenotic lesions are localized or diffuse, and can also be segmental changes; 3 stenotic bile duct proximal dilatation; 4 lesions involving intrahepatic bile duct, It can be seen that the branch of the intrahepatic bile duct is reduced, and the stiffness is thin like a dendritic or beaded shape. The hemisphere is dilated, and the inner diameter is 2 to 3 mm. In about 80% of the cases, the outer bile duct is involved at the same time, and 20% only affects the extrahepatic. The bile duct, the common bile duct (CBD) has an inner diameter of less than 4 mm, the wall is significantly thickened, and the biliary system has no stones and tumor signs. When the gallbladder is involved, the gallbladder wall is thick, and the function is reduced or disappeared. When cholangiography proves the presence of intrahepatic or extrahepatic bile duct stricture, And without evidence that non-PSC, the diagnosis of PSC can be established, so typical radiological changes are confirmed to be the gold standard for PSC diagnosis.

2.B type ultrasound examination

Because endoscopic retrograde cholangiography and transhepatic cholangiography are invasive procedures, B-mode ultrasound has become a non-invasive alternative to PSC diagnosis. Although ultrasound itself cannot confirm PSC, PSC cannot be ruled out, but Screening of PSC suspicious patients to determine further injury examinations, as well as differential diagnosis may be of great help, the typical B ultrasound imaging is:

1 The bile duct lumen is obviously narrow, mostly uniform, generally 4mm, and the bile duct can be seen in the segmental or localized PSC;

2 the bile duct wall is obviously thickened, generally 4 to 5 mm;

3 intrahepatic bile duct echo enhancement;

4 involving the gallbladder visible wall thickening, weakened;

5 sound image without stones and tumors, it is very important to learn to recognize the performance of PSC in ultrasound. The accurate judgment of the above sonogram depends on the experience of the ultrasound practitioner's clinical practice.

3. Magnetic resonance cholangiography (MRC)

Biliary tree imaging technology is helpful in diagnosing PSC. The slight expansion of peripheral bile ducts that are not connected to the central bile duct in several hepatic lobes is an MRI sign of PSC, but it is difficult to resemble ERCP or PTC due to limited spatial resolution of MRC. A small degree of bile duct stenosis and dilatation was found, reducing its role in revealing bile duct stricture.

4.99mTc-DISIDA scan

A biliary scintigraphy with 99mTc-labeled diisopropylcarbamoimide acetoacetate is a non-invasive test for suspected patients with PSC. After intravenous injection, continuous gamma imaging is determined by the delay of liver parenchyma clearance. The obstruction of different branches of the main bile duct shows that the intrahepatic dilatation of the bile duct and the liver, the location and extent of the stenosis of the outer bile duct, and the low resolution are its disadvantages.

5. CT can show the expansion and deformation of intrahepatic bile duct in patients with PSC. If CT shows irregular branch or focal expansion of biliary tree, it suggests the possibility of PSC.

6. Liver histology

Histological abnormalities can be seen in most biopsies of PSC patients. Common histological abnormalities include: peripheral biliary fibrosis and inflammation, edema and fibrosis, focal proliferation of bile ducts and ductules, focal Obstruction and loss of bile ducts, copper deposition and cholestasis, typically manifested as concentric fibrosis of the peripheral bile duct with or without hepatic bile duct hyperplasia, but these changes are only visible in wedge biopsies, while fine needles It is rarely seen when puncture.

Diagnosis and differential diagnosis of primary sclerosing cholangitis

diagnosis

1. Diagnostic basis The diagnosis of PSC must be based on its clinical features, biochemical indicators of biliary obstruction, typical biliary tract abnormalities and liver histology, etc., for comprehensive analysis, to be accurate, currently Most scholars believe that PSC diagnosis must have the following points:

(1) History of no bile duct surgery.

(2) History of no common bile duct stones.

(3) thickening and hardening of the bile duct wall, and progressive obstructive jaundice.

(4) Long-term follow-up excludes cholangiocarcinoma.

(5) No congenital bile duct abnormalities.

(6) No primary biliary cirrhosis.

2. Characteristics of PSC According to the aforementioned etiology, pathology, clinical manifestations, laboratory and auxiliary examinations, PSC can summarize the following characteristics for reference during diagnosis.

(1) Young men.

(2) biliary stricture liver disease.

(3) The onset is slow.

(4) Cholangiography showed multiple stenosis, irregular and "spherical" signs of intrahepatic and extrahepatic bile ducts.

(5) Liver histology revealed fibrosis around the bile duct, inflammation and visible cholestasis.

(6) It is associated with inflammatory bowel disease, especially ulcerative colitis.

(7) Associated with HLA, AI-B8-DR3.

(8) There is a high risk of developing cholangiocarcinoma.

3. Diagnostic Criteria The PSC diagnostic criteria were established by LaRusso et al in 1984 and revised by the same group in 1993 and 1999. This standard is a very accurate indication of the diagnostic and differential diagnosis principles of PSC.

(1) Abnormal biliary tract signs with PSC characteristics (segmental or extensive biliary changes).

(2) Abnormal clinical, biochemical and liver histological findings (although often non-specific).

(3) Exclude the following:

1 biliary calcification (except in the quiescent period);

2 biliary surgery (excluding simple cholecystectomy);

3 congenital biliary tract abnormalities;

4 acquired biliary tract disease associated with immunodeficiency syndrome;

5 ischemic stenosis;

6 biliary tumors;

7 exposed to irritating chemicals (eg formalin);

8 other liver diseases (such as primary biliary cirrhosis or chronic active hepatitis).

4. Clinical classification PSC can have a variety of clinical manifestations. According to the location and extent of the lesion, Thompson divides it into 4 types according to the site: type I: distal choledochal sclerosing cholangitis; type II: secondary to Sclerosing cholangitis of acute necrotizing cholangitis; type III: chronic diffuse sclerosing cholangitis; type IV: chronic diffuse sclerosing cholangitis with intestinal inflammatory disease.

According to the scope of sclerosing cholangitis, it is divided into:

1 diffuse type, throughout the liver, outer bile duct;

2 extrahepatic bile duct segment type;

3 intrahepatic, external bile duct sclerosis with cirrhosis.

Differential diagnosis

PSC needs to be differentiated from chronic active hepatitis, secondary sclerosing cholangitis, primary cholangiocarcinoma, primary biliary cirrhosis and autoimmune overlap syndrome.

1. Chronic active hepatitis Previously, there was a report that PSC was diagnosed as chronic active hepatitis. The main reason was the discovery of debris-like necrosis in the histological examination of these patients. This phenomenon is now considered to be a feature of PSC, relying on biliary tract. Contrast can solve the difficulty of differential diagnosis. In addition, patients with chronic active hepatitis often have acute hepatitis, often have history of hepatitis contact, or blood transfusion, injection pollution, etc., the age of onset is light, usually after 2 to 3 weeks of onset of jaundice Gradually subsided, serum ALT increased significantly and GGT and ALP did not increase or only slightly increased, which can be identified.

2. Secondary sclerosing cholangitis This disease has a history of recurrent biliary tract disease or history of biliary tract surgery. The inflammatory stenosis of the bile duct is mostly ring-shaped, the stenosis is short, the biliary mucosal epithelial damage is obvious, and there may be erosion, ulcer and granulation. The swelling is formed, often accompanied by stones, and the bile duct stenosis of PSC is longer, and the lesion is mainly in the submucosa, which is fibrotic and the bile duct mucosa is intact, which is the main difference between the two.

3. A small number of PSC cases of primary cholangitis are only intrahepatic or extrahepatic bile ducts before the onset. When there is only intrahepatic bile duct disease, attention should be paid to the identification of primary cholangitis. Primary cholangitis is A disease that occurs mostly in young women, histologically manifested as non-suppurative cholangitis, serum containing high titers of antibodies, no lesions in the extrahepatic bile duct, and PSC mostly occurs in men, many patients with ulcerative Colitis, serum-free labeling or low antibody titers can be identified.

4. Primary cholangiocarcinoma The age of onset of the disease is usually 40 to 50 years old, often with weight loss or weight loss. Surgical exploration and histological examination can confirm the diagnosis. For PSC cases of segmental or diffuse bile duct stricture, due to biliary tract Wide stenosis and extensive fibrosis of biliary tree, it is more difficult to distinguish it from cholangiocarcinoma, especially when the intrahepatic bile duct is not invaded, the extensive expansion of intrahepatic bile duct is more common in cholangiocarcinoma and not common in PSC, but Patients with extrahepatic bile duct stricture must consider the possibility of cholangiocarcinoma. If necessary, cytology or biopsy may be used to exclude cholangiocarcinoma. It is worth noting that PSC has a malignant tendency, and malignant transformation should be considered at the time of initial diagnosis or follow-up. The possibility of jaundice suddenly aggravated, cholangiography showed biliary or biliary tract segmental expansion, polypoid mass, and diameter 1.0cm, progressive stenosis or dilation, etc., should consider the occurrence of cholangiocarcinoma, in this case Serum tumor markers (CEA, C19-9) and biliary cytology, magnetic resonance cholangiography and ECT can be exciting results for the diagnosis.

5. Primary biliary cirrhosis The age of onset of the disease is more common in 20 to 40 years old, the course of disease is slow, the jaundice is fluctuating, accompanied by liver and spleen, serum anti-mitochondrial antibody is positive, immunoglobulin is significantly increased, diagnosis, differential diagnosis Less difficult.

6. Autoimmune Overlap Syndrome (AIH/PSC) This syndrome has autoimmune hepatitis (AIH) and PSC symptoms, and meets the diagnostic criteria of both, hyperglobulinemia, antinuclear or anti-smooth muscle antibody positive, Liver biopsy demonstrates that patients with autoimmune hepatitis with biliary tract changes and hepatic hilar necrosis-inflammatory activity should consider the possibility of concurrent PSC (AIH/PSC overlap syndrome), where cholangiography is required to confirm or exclude autoimmunity Overlap syndrome.

It should be noted that in patients with ulcerative colitis and persistent liver dysfunction, there is indeed autoimmune active hepatitis, but not as common as PSC.

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