Dr. Rose's Peripheral Brain-"LIVER FUNCTION TEST" ABNORMALITIES

"LIVER FUNCTION TEST" ABNORMALITIES

Note--Elevations of transaminases (ALT, aka "SGPT" and AST, aka "SGOP") are generally indicative of hepatocellular injury. Active liver disease may be present histologically with normal transaminases. The following table describes some causes of elevations of ALT and AST and diagnostic tests for those conditions:

ETIOLOGY	DIAGNOSTIC TEST(s)
Alcohol abuse	Hx, GGT, MCV
Other hepatotoxins	Hx, acetaminophen level (if acute)
Hemochromatosis	Fe/TIBC, ferritin, genetic screening for the C282Y gene
Wilson's Disease	Ceruloplasmin, urine copper excretion (elevations < 3x normal are nonspecific for Wilson's); liver Bx for copper quantitation; genetic screening
Viral Hepatitis	HBSAg, Hep C Ab, CMV serology; if acute, IgM for hepatitis A
Autoimmune Hepatitis	ANA for screening; anti-smooth muscle antibody, C3, C4, SPEP to help support the dx; if suspect that because of advanced disease the autoantibodies are waning, consider HLA typing for haplotypes B8 Dr3 or 4
Ischemic liver damage	n/a
Biliary tract obstruction	Alkaline phosphatase, imaging (u/s, ERCP, percutaneous transhepatic cholangiography)
Non-alcoholic steatohepatitis	Imaging (u/s); liver bx
Primary Biliary Cirrhosis	Anti-mitochondrial antibody
Primary sclerosing cholangitis	Antineutrophil cytoplasmic antibodies
Autoimmune cholangitis	ANA
Tuberculosis	Chest x-ray
Sarcoidosis	Chest x-ray
Other	Liver biopsy (see below)

Other notes:

Per Canadian guidelines (see ref. below), all pts with at least one abnormal liver screening test should have: GGT, albumin, bilirubin (including direct if the total bilirubin is elevated) and prothrombin time
AST is less sensitive and specific for liver disease than ALT
ALT:AST ratio can help differentiate different types of liver disease:
- > 1 suggests:
  - Viral hepatitis
  - Drug-induced liver disease
  - Autoimmune disorders
- < 1 are suggests:
  - Alcohol-induced liver disease
  - Ischemic damage (passive congestion or under perfusion)
  - Biliary tract obstruction
  - Predominantly mitochondrial hepatocyte injury (fatty liver of pregnancy, tetracycline toxicity, Reye’s syndrome)
- With progression of liver disease to cirrhosis, common for a previously elevated ALT to AST ratio to fall to < 1
- In acute, severe hepatocellular injury (aminotransferase values in excess of 1000 IU/L) the ALT to AST ratio is not of diagnostic value.

Elevated alkaline phosphatase found in conditions below; fractionation can help clarify
- Cholestatic liver disease
- Early hepatitis C infection
- Cytomegalovirus (in immunocompromised hosts)
- Pregnancy
- Bone disease
- Inflammatory bowel disease
GGT
- Useful in confirming that elevated ALP levels reflect hepatobiliary disease (can get false normals in preg. women; otherwise quite sensitive)
- Nonspecific--can be elevated from:
  - Use of certain anticonvulsants
  - Recent ingestion of alcohol
  - Renal disease
  - Pancreatitits
  - Diabetes mellitus
  - Coronary artery disease
  - Prostate Ca
  - 10% of general population have GGT elevations yet no underlying hepatobiliary disease, per Canadian guidelines (see ref. below)
Liver biopsy for unexplained transaminase elevations
- Canadian guidelines (see ref. below) recommend liver bx if: unexplained transaminase elevations > 2.5x normal x > 6mos
- In a case series of 81 pts with > 50% elevations in either AST or ALT over a 6mo span (all w/o alcohol abuse, use of hepatotoxic drugs, HBV, HCV, hemochromatosis, or autoimmune hepatitis), 8 had normal bx's and 73 had fatty change; only 2 had cirrhosis; none of the bx's yielded specific dx's (Am. J. Gastroent. 94:3010, 1999--JW)
- In a retrospective study of 67 pts with negative hepatitis serologies and elevated ALT x 6mos or more, elevation of ALT to > 2x upper limit of normal, and elevation of AST were sig. ass'd with risk of NASH with severe fibrosis on liver bx(OR 7.4 and 12.1, respectively). BMI > 25 was sig. ass'd with risk of NASH (OR 7.5). (Eur. J. Gastroent. Hepatol. 16:879, 2004--JW)

(Sources include Minuk GY. Canadian Association of Gastroenterology Practice Guidelines: evaluation of abnormal liver enzyme tests. Canadian Journal of Gastroenterology. 12(6):417-21, 1998 Sep.)