How is cirrhosis diagnosed?

Cirrhosis Diagnosis

The gold standard for diagnosis of cirrhosis is a liver biopsy, through a percutaneous, transjugular, laparoscopic, or fine-needle approach. Histologically cirrhosis can be classified as micronodular, macronodular, or mixed, but this classification has been abandoned since it is nonspecific to the etiology, it may change as the disease progresses, and serological markers are much more specific. However, a biopsy is not necessary if the clinical, laboratory, and radiologic data suggests cirrhosis. Furthermore, there is a small but significant risk to liver biopsy, and cirrhosis itself predisposes for complications due to liver biopsy.

Lab findings

The following findings are typical in cirrhosis:

• Aminotransferases - AST and ALT are moderately elevated, with AST > ALT. However, normal aminotransferases do not preclude cirrhosis.
• Alkaline phosphatase - usually slightly elevated.
• GGT -- correlates with AP levels. Typically much higher in chronic liver disease from alcohol.
• Bilirubin - may elevate as cirrhosis progresses.
• Albumin - levels fall as the synthetic function of the liver declines with worsening cirrhosis since albumin is exclusively synthesized in the liver
• Prothrombin time - increases since the liver synthesizes clotting factors.
• Globulins - increased due to shunting of bacterial antigens away from the liver to lymphoid tissue.
• Serum sodium - hyponatremia due to inability to excrete free water resulting from high levels of ADH and aldosterone.
• Thrombocytopenia - due to both congestive splenomegaly as well as decreased thrombopoietin from the liver. However this rarely results in platete count < 50,000/mL.
• Leukopenia and neutropenia - due to splenomegaly with splenic margination.
• Coagulation defects - the liver produces most of the coagulation factors and thus coagulopathy correlates with worsening liver disease.

Other laboratory studies performed in newly diagnosed cirrhosis may include:

• Serology for hepatitis viruses, autoantibodies (ANA, anti-smooth muscle, anti-mitochondria, anti-LKM)
• Ferritin and transferrin saturation (markers of iron overload), copper and ceruloplasmin (markers of copper overload)
• Immunoglobulin levels (IgG, IgM, IgA) - these are non-specific but may assist in distinguishing various causes
• Cholesterol and glucose
• Alpha 1-antitrypsin

Imaging

Ultrasound is routinely used in the evaluation of cirrhosis, where it may show a small and nodular liver in advanced cirrhosis along with increased echogenicity with irregular appearing areas. Ultrasound may also screen for hepatocellular carcinoma, portal hypertension and Budd-Chiari syndrome.

Other tests performed in particular circumstances include abdominal CT and liver/bile duct MRI (MRCP).

Endoscopy

Gastroscopy (endoscopic examination of the esophagus, stomach and duodenum) is performed in patients with established cirrhosis to exclude the possibility of esophageal varices. If these are found, prophylactic local therapy may be applied (sclerotherapy or banding) and beta blocker treatment may be commenced.

If biliary pathology is suspected, ERCP may be performed. Generally MRCP (MRI of biliary tract and pancreas) is sufficient for diagnosis, but ERCP allows for particular interventions, such as placement of a biliary stent or extraction of gallstones.

Pathology

Macroscopically, the liver may be initially enlarged, but with progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm and the color is often yellow (if associates steatosis). Depending on the size of the nodules there are three macroscopic types: micronodular, macronodular and mixed cirrhosis. In micronodular form (Laennec's cirrhosis or portal cirrhosis) regenerating nodules are under 3 mm. In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. The mixed cirrhosis consists in a variety of nodules with different sizes.

Microscopically, cirrhosis is characterized by regeneration nodules, surrounded by fibrous septa. In these nodules, regenerating hepatocytes are disorderly disposed. Portal tracts, central veins and the radial pattern of hepatocytes are absent. Fibrous septa are important and may present inflammatory infiltrate (lymphocytes, macrophages) If it is a secondary biliary cirrhosis, biliary ducts are damaged, proliferated or distended - bile stasis. These dilated ducts contain inspissated bile which appear as bile casts or bile thrombi (brown-green, amorphous). Bile retention may be found also in the parenchyma, as the so called "bile lakes"¹.



1. http://en.wikipedia.org/wiki/Cirrhosis