Primary sclerosing Cholangitis
Primary sclerosing cholangitis is a chronic cholestatic syndrome characterized by patchy inflamation.fibrosis, and strictures of the intrahepatic and extrahepatic bile ducts. Eighty percent of patients have inflammatory bowel diseases often ulcerative colitis.
Symptoms of fatigue and pruritus develop late.
Diagnosis is based on contrast cholangiography ( with ERCP) or magnetic resonance cholangiopancreatography.
Disease leads eventual obliteration of the bile ducts with cirrhosis, hepatic failure and sometimes cholangiocarcinoma. Liver transplantation is indicated for advanced disease.
Etiology
The cause is unknown. However primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease, occurring in about 5% of patients with ulcerative colitis and in about 1 % with crohn’s disease.
This association and the presence of several autoantibodies (e.g anti-smooth muscle and perinuclear antineutrophilic antibodies [p-ANCA] ) suggest immune-mediated mechanisms.
T lymphocytes appear to be involved with the destruction of the bile ducts, suggesting disordered cellular immunity. A genetic predisposition is suggested by tendency for the disease to develop in multiple family members and higher incidence in those with HLA-B8 and HLA-DR3, which are often correlated with autoimmune diseases. An unknown trigger (e.g bacterial infectio or ischemic duct injury) probably causes PSC to develop in genetically predisposed patients.
Sclerosing cholangitis in HIV-infected patients may be due to cryptosporidiosis or cytomegalovirus.
Symptoms and Signs
Mean age at diagnosis is 40yrs. 70% of patients are men.
The onset I usually insidious, with progressive fatigue and pruritus. Jaundice tends to develop later.
Repeated episodes of right upper quadrant pain and fever, possibly due to ascending bacterial cholangitis,occur in 10 to 15 % of patients at presentation .
Steatorrhea and deficiencies of fat-soluble vitamins can develop.
Persistent jaundice harbingers advanced disease. Sypmtomatic gallstones and choledocholithiasis tend to develop in about one-third of patients.
Some patients are asymptomatic until late in the course of the disease, first presenting with hepatosplenomegaly or cirrhosis,portal hypertension, ascites, and liver failure.
Despite the association between PSC and inflammatory bowel disease the two diseases tend to run separate courses. UI-cerative colitis may appear years before PSC , yet tends to have a milder course when associated with PSC. The presence of both diseases increases the risk of colorectal carcinoma, regardless of whether a liver transplantation has been performed for PSC.
Similary total colectomy does not change the course of PSC. Cholangiocarcinoma develops in 10 to 15% of patients with PSC.
Diagnosis
PSC is suspected in patients with unexplained abnormal liver biochemistry tests, if the patients has inflammatory bowel disease, suspicion is even higher. A cholestatic pattern in liver biochemistries is typicall, with alkaline phosphatase and gamma-glutaryl-transferase usually elevated more than aminotransferases. Gamma globulin and IgM levels tend to be elevated and antismooth muscle and p-ANCA are usually positive.
Antimitochondrial antibody, positive in primary biliary cirrhosis,is characteristically negative.
Imaging of the hepatobiliary system usually begins with ultrasound to exclude extrahepatic biliary obstruction. The diagnosis of PSC necessitates demonstration of multiple strictures and dilation involving the intrahepatic bile ducts, which requirescholangiography (Ultrasound can only suggest such damage)
Direct cholangiography eg by ERCP has been the Gold standard , however , magnetic resonance cholangiopancreatography (MRPCP) provides excellent images and is becoming a first choice noninvasive altenative. Liver biopsy is generally not required for diagnosis.
When performed for another reason ,it reveals bile duct proliferation,periductal fibrosis,inflammation and loss of bile ducts .
As the disease progress,fibrosis extends from the portal regions and eventually leads to bilary cirrhosis.
Surveilance using ERCP with brush cytology may help predict development of cholangiocarcinoma.
Prognosis and treatment
Some patients may be asymptomatic for many years,but the disorder tends to progress. The time from diagnosis to hepatic failure is about 12 years.
Asymptomatic patients generally require only monitoring (e.g physical examination and liver function test twice a year)
Ursodeoxycholic acid may reduce itching and improve biochemical markers.
Chronic cholestasis and cirrhosis may require treatment. Recurrent bacterial cholangitisi streated with antibiotics and ERCP as needed.
If one dominant stricture exits ( in about 20%),endoscopic dilation is necessary to relieve symptoms and exclude tumor development by brushings. Any underlying infection (e.g cryptosporidiosis,cytomegalovirus) is treated.
Liver transplantation is the only treatment that improves life expectancy in idiopathic PSC, it may be curative.
Recurrent bacterial cholangitis or complications of end-stage liver disease, such as intractable ascites, portal systemic encephalopathy , or bleeding esophageal varices are reasonableindications for liver transplantation.
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