Biliary obstruction, autoimmune diseases of the liver
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Biliary obstruction, autoimmune diseases of the liver John J OLeary
Learning objectivesUnderstand bile duct obstruction [causes and effects]Understand what is meant by the term auto-immune liver disease:Primary biliary cirrhosis [PBC]Primary sclerosing cholangitis [PSC]Autoimmune hepatitis [AIH]
Pathological effects of biliary obstructionBiliary obstruction
High local concentration of bile salts
Fibrosis & scarring Biliary fistula
Fibrosis and scarring
Biliary stasis Liver atrophy
Repeated cholangitis Biliary cirrhosis & portal HTN (very late)
Causes of Benign strictures
Causes of Malignant strictures
Symptoms and history:Biliary colicObstructive jaundiceCholangitis Charcots triadjaundice; fever, usually with rigors; and right upper quadrant abdominal pain. Reynolds pentad+ hypotension and an altered mental state Past history of cholecystectomy/ other GI surgery (eventful)History s/o pancreatitis, trauma, radiation, alcohol abuse
Signs:Icteruss/o hepatocellular failureCourvoisier's signe/o biliary fistula, peritonitis, bilomaNutritional deficienciespale stoolsdark urineitchiness (pruritus)
Under a microscope, the individual hepatocytes will have a brownish-green stippled appearance within the cytoplasm, representing bile that cannot get out of the cell.
Canalicular bile plugs between individual hepatocytes or within bile ducts may also be seen, representing bile that has been excreted from the hepatocytes but cannot go any further due to the obstruction.
When these plugs occur within the bile duct, sufficient pressure (caused by bile accumulation) can cause them to rupture, spilling bile into the surrounding tissue, causing hepatic necrosis. These areas are known as bile lakes, and are typically seen only with extra-hepatic obstruction. HISTOPATHOLOGY
Strasberg classification of biliary injury & stricture
Laboratory investigations Bilirubin Alkaline phosphatase & GGT PT Anemia, amylase & lipase, ESR, LDH Tumor markers: CA 19-9, CEA, AFP
Imaging studies:UltrasoundCT scanMRCPHIDA scanERCPEndoscopic ultrasoundPTCFistulography
Ultrasonography:Detects intra/extra hepatic ductal dilatationLess accuracy in defining etiologySensitivity 94% if bilirubin > 10mg% 47% otherwise
Endoscopic ultrasound:Extra hepatic bile duct readily visualizedDetects choledocholithiasis (>95%)Sensitive in diagnosis & staging of malignancy
CT Scan:Highly sensitive (esp. with contrast)Detects site & cause of obstructionBetter anatomical delineationCT cholangiography
MRI & MRCP:Bile high signal intensity on T2 weighted imagesVisualises biliary dilatation (97-100%), site of obstruction (87%), hepatic parenchyma & vasculatureOnly diagnostic
HIDA Scan[Hepatobiliary Imino-Diacetic Acid scan]Helps in diagnosing biliary leaksProvides functional assessment of incomplete strictures and surgical anastomosissuggest complete biliary obstruction if the small intestine is not visualized in 60 minutesinsensitive for helping detect biliary dilatation or the site and cause of bile duct obstruction
Cholangiography:Gold standardEndoscopic/ percutaneousFeatures:define the anatomy of the proximal biliary treedecompression of the biliary systemNon-operative dilation of bile duct stricturesallow for the simultaneous placement of drainage cathetersof assistance with regard to surgical reconstruction
Treatment:Options:Endoscopic or percutaneous balloon dilatation and insertion of an endoprosthesisSurgery
Pre-procedure antibiotic prophylaxis
RX of malignant strictures:Depends on:resectability & stagegeneral condition
Resectable (15-20%) Radical resection with biliary enteric anastomosis
Palliative endoscopic stenting percutaneous transhepatic stentingPalliative resection with surgical bypass (mortality 33%)
RX of benign strictures:Operative managementto surgically re-establish bile flow within the biliary tree and into the proximal gastrointestinal tract in a manner that prevents cholestasis, cholangitis, sludge and stone formation, restricture, or biliary cirrhosis
Nonoperative managementto correct the increased resistance to biliary flow caused by a reduction in the diameter of the lumen
Autoimmune diseases of the liver
Autoimmune liver diseasePrimary biliary cirrhosisPrimary sclerosing cholangitisAutoimmune hepatitis
Primary biliary cirrhosis
Primary biliary cirrhosis is an autoimmune disease of the liver marked by: the slow progressive destruction of the small bile ducts (bile canaliculi) within the liver. when these ducts are damaged, bile builds up in the liver (cholestasis) and over time damages the tissue. this can lead to scarring, fibrosis and cirrhosis. it was previously thought to be a rare disease, but more recent studies have shown that it may affect up to 1 in 3-4,000 people; the sex ratio is at least 9:1 (women to men) PRIMARY BILIARY CIRRHOSIS
In some areas of the US and UK the prevalence is estimated to be as high as 1 in 4000. This is much more common than in South America or Africa, which may be due to better recognition in the US and UK.
First-degree relatives may have as much as a 500 times increase in prevalence, but there is debate if this risk is greater in the same generation relatives or the one that follows.
After liver transplant, the recurrence rate may be as high as 18% at 5 years, and up to 30% at 10 years. There is no consensus on risk factors for recurrence of the disease
The following signs may be present in PBC: Fatigue Pruritus (itchy skin) Jaundice (yellowing of the eyes and skin) Xanthelasmata (focal collections of cholesterol in the skin, especially around the eyes) Complications of cirrhosis and portal hypertension: Fluid retention in the abdomen (ascites) Hypersplenism Esophageal varices Hepatic encephalopathy, up to coma, in extreme cases. Association with extra-hepatic autoimmune disorder[s] such as Rheumatoid arthritis or Sjgren's syndrome (up to 80% incidence).
To diagnose PBC, distinctions should be established from other conditions with similar symptoms, such as autoimmune hepatitis or primary sclerosing cholangitis (PSC).
Diagnostic blood tests include: Abnormal liver function tests (high alkaline phosphatase, elevated AST, ALT) Presence of certain antibodies: antimitochondrial antibody, antinuclear antibody (the M2-IgG antimitochondrial antibody is the most specific test) Abdominal ultrasound or a CT scan is usually performed to rule out blockage to the bile ducts. Previously most suspected sufferers underwent a liver biopsy, and - if uncertainty remained - endoscopic retrograde cholangiopancreatography (ERCP, an endoscopic investigation of the bile duct). Now most patients are diagnosed without invasive investigation since the combination of anti-mitochondrial antibodies (see below) and typical (cholestatic) liver function tests are considered diagnostic. However, a liver biopsy is necessary to determine the stage of disease.
Anti-nuclear antibodies appear to be prognostic agents in PBC. Anti-glycoprotein-210 antibodies, and to a lessor degree anti-p62 antibodies correlate with progression toward end stage liver failure. Anti-centromere antibodies correlate with developing portal hypertension. Anti-np62 and anti-sp100 are also found in association with PBC.
STAGES OF DISEASE
Stage 1 - Portal Stage: Normal sized triads; portal inflammation, subtle bile duct damage. Granulomas are often detected in this stage.
Stage 2 - Periportal Stage: Enlarged triads; periportal fibrosis and/or inflammation. Typically characterized by the finding of a proliferation of small bile ducts.
Stage 3 - Septal Stage: Active and/or passive fibrous septa.
Stage 4 - Biliary Cirrhosis: Nodules present; garland or jigsaw pattern.
The cause of the disease is unknown at this time
an immunological basis for the disease, making it an autoimmune disorder. most patients (>90%) have anti-mitochondrial antibodies (AMAs) against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in mitochondria. an increase in GGT could indicate presence of Primary Biliary Cirrhosis. 57% of patients with acute liver failure have anti-transglutaminase antibodies suggesting a role of gluten sensitivity in primary biliary cirrhosis, and primary biliary cirrhosis is considerably more common in gluten sensitive enteropathy than the normal population. in some cases of disease protein expression may cause an immune tolerance failure, as might be the case with gp210 and p62, nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients. Both proteins appear to be prognostic of liver failure relative to anti-mitochondrial antibodies.
Course and cure of the disease:
no known cure, but medication may slow the progression ursodeoxycholic acid (Ursodiol) is the most frequently used treatment. This helps reduce the cholestasis and improves blood test results (liver function tests). to relieve itching caused by bile acids in circulation, which would normally be removed by the liver, cholestyramine (a bile acid sequestrant) may be prescribed to absorb bile acids in the gut and be eliminated, rather than re-enter the blood stream. alcoh