Primary Sclerosing Cholangitis - Diagnosis

Laboratory research

Blood serum examination reveals signs of cholestasis with an increase in alkaline phosphatase activity 3 times higher than normal. Bilirubin levels fluctuate significantly and rarely exceed 10 mg% (170 μmol/l). As in all patients with cholestasis, the content of copper in the blood serum and ceruloplasmin, as well as copper in the liver, increases. The levels of γ-globulins and IgM increase in 40-50% of cases.

Low titers of anti-smooth muscle antibodies and antinuclear antibodies may be detected in the serum, but antimitochondrial antibodies are absent.

Eosinophilia is occasionally observed.

Histological changes in the liver

Perfusion examination of the bile ducts of the liver removed during transplantation reveals tubular and saccular expansion of the intrahepatic ducts, their transformation into fibrous strands up to complete disappearance.

Histologically, the portal zones are infiltrated with small and large lymphocytes, neutrophils, sometimes macrophages and eosinophils. Periductal inflammation is found around the interlobular bile ducts, in some cases accompanied by epithelial desquamation. Inflammatory infiltration may be observed within the lobules, Kupffer cells are swollen and protrude into the lumen of the sinusoids. Cholestasis is noticeable only with severe jaundice.

Over time, fibrosis develops in the portal tracts, causing bundles of connective tissue to form around the small ducts in the form of onion skins. The remains of the bile ducts can only be identified as fibrous rings. The portal zones acquire a star-shaped appearance.

Histologic changes are nonspecific, but decreased bile duct count, tubular proliferation, and significant copper deposits along with stepwise necrosis suggest primary sclerosing cholangitis and warrant cholangiography.

Histological examination of the common bile duct reveals fibrosis and inflammation, which have no diagnostic value.

Cholangiography

Endoscopic retrograde cholangiopancreatography is the method of choice, although transhepatic cholangiography can be used successfully. The diagnostic criterion is the detection of areas of uneven narrowing and widening (beading) of the intra- and extrahepatic bile ducts.

Strictures are short (0.5-2 cm), cause kinking of the ducts and alternate with unchanged or slightly dilated sections of the bile ducts. Protrusions resembling diverticula may be found along the common bile duct.

During cholangiography, the lesion may be limited to only intrahepatic ducts, only extrahepatic ducts, or even only one hepatic duct.

When small ducts are affected, there are no changes on cholangiograms.

Visual diagnostic methods

Ultrasound examination reveals thickening of the walls of the bile ducts, and computed tomography reveals minimally dilated areas along the bile ducts; a similar picture is observed in the rare diffuse cholangiocarcinoma.

Cholangiocarcinoma

Cholangiocarcinoma occurs in approximately 10% of patients with primary sclerosing cholangitis. It may complicate both small and large duct involvement and is usually seen in patients with ulcerative colitis. Survival averages 12 months.

Cholangiocarcinoma is very difficult to diagnose. It can be suspected if the patient has progressive jaundice. Cholangiography suggests cholangiocarcinoma by local dilation of the bile ducts, progressive stricture, and intraductal polyps. The possibility of cholangiocarcinoma can be considered in the presence of thrombophlebitis of the superficial veins and dysplasia of the bile duct epithelium in areas where the tumor is absent. Cholangiography with cytological examination of bile and scrapings, as well as bile duct biopsy, are mandatory. Determination of serum tumor markers, such as CA 19/9, is also useful. The diagnostic accuracy with a combination of CA 19/9 and carcinoembryonic antigen reaches 86%.

Diagnostics

Diagnostic criteria

• the presence of obstructive jaundice of a progressive type;
• absence of stones in the bile ducts (no previous operations have been performed in the hepatobiliary area);
• detection of widespread thickenings and narrowing of the extrahepatic bile ducts during laparotomy; the patency of their intrahepatic sections is confirmed by surgical cholangiography;
• absence of malignant neoplasms;
• exclusion of primary biliary cirrhosis of the liver based on morphological examination of liver biopsy.

Primary sclerosing cholangitis can be differentiated from primary biliary cirrhosis by cholangiography and the absence of antimitochondrial antibodies. The onset of primary sclerosing cholangitis may resemble chronic hepatitis, especially in children, or cryptogenic cirrhosis. The key to the diagnosis is an increase in alkaline phosphatase activity; the diagnosis is verified by cholangiography.

If there is a history of surgery on the bile ducts or gallstones are detected, secondary sclerosing cholangitis, which develops as a result of postoperative strictures of the bile ducts or choledocholithiasis, should be excluded.

In addition, primary sclerosing cholangitis should be differentiated from ischemic injury to the bile ducts as a result of the introduction of floxuridine into the hepatic artery, congenital anomalies of the bile ducts, infectious cholangiopathy in patients with AIDS or who have undergone liver transplantation, as well as bile duct tumors and histiocytosis X.

Laboratory data

1. Complete blood count: increased ESR, signs of anemia, leukocytosis.
2. Urine analysis - positive reaction for bilirubin.
3. Biochemical blood test: increased levels of alkaline phosphatase, bilirubin (mainly conjugated), alanine aminotransferase in the blood, possibly increased copper levels.

Instrumental data

1. Laparoscopy: the liver may appear unchanged in the initial stages, later developing into cirrhosis. Its color ranges from dark cherry to green, but of lesser intensity than in subhepatic cholestasis. On the surface of the liver, star-shaped retractions are detected, combined with pronounced fibrosis, small nodes of purple-red or black color, resembling metastases. In advanced stages, a "large green liver" is macroscopically observed, caused by chronic cholestasis, but on its surface there are no dilated bile capillaries, characteristic of obstructive jaundice.
2. Retrograde endoscopic cholangiopancreatography: the simplest and most convenient type of examination for confirming the diagnosis. Cholangiograms reveal bead-like changes in large intrahepatic bile ducts, combined with depletion of small intrahepatic ducts (a picture resembling a "dead" tree). Characteristic, chaotically scattered, short finger-like constrictions are described, replaced by normal-sized bile ducts and combined with widespread strictures, diverticulo-like protrusions and microgases, which causes unevenness of the duct walls. In addition to intrahepatic, extrahepatic bile ducts are also affected. The absence of suprastenotic dilation is an important sign of primary stenosing cholangitis, distinguishing it from secondary cholangitis.
3. Liver biopsy: fibrotic inflammation of the bile ducts, possibly elevated copper levels.

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