(Medicare National Coverage Determinations Manual)

As well as being a very specific marker of hepatobiliary function, GGT is also a very sensitive marker for h epatocellular damage.  Abnormal concentrations typically appear before elevations of other liver enzymes or bilirubin are evident.  Obstruction of the biliary tract, viral infection (e.g., hepatitis, mononucleosis), metastatic cancer, exposure to hepatotoxins (e.g., organic cimetidine, barbiturates, phenytoin, and carbamazepine) all can cause a moderate to marked increase in GGT serum concentration.  In addition, some drugs can cause or exacerbate liver dysfunction (e.g., atorvastatin, troglitazone, and others as noted in FDA Contraindications and Warning.)   The GGT is useful for diagnosis of liver disease or injury, exclusion of hepatobiliary involvement related to other disease, and patient management during the resolution of existing disease or following injury.  Indications   1. To provide information about known or suspected hepatobiliary disease, for example:   a. Following chronic alcohol or drug ingestion  b. Following exposure to hepatotoxins   c. When using medication known to have a potential for causing liver toxicity (e.g., following the drug manufacturers recommendations)   d. Following infection (e.g., viral hepatitis and other specific infections such as amebiasis, tuberculosis, psittacosis, and similar infections)   2. To assess liver injury/function following diagnosis of primary or secondary malignant neoplasms   3. To assess liver injury/function in a wide variety of disorders and diseases known to cause liver involvement (e.g., diabetes mellitus, malnutrition, disorders of iron and mine ral metabolism, sarcoidosis, amyloidosis, lupus and hypertension)   4. To assess liver function related to gastrointestinal disease   5. To assess liver function related to pancreatic disease  6. To assess liver function in patients subsequent to liver transplantation   7. To differentiate between the different sources of elevated alkaline phosphatase activity   Limitations   When used to assess liver dysfunction secondary to existing non- hepatobiliary disease with no change in signs, symptoms, or treatment, it is generally not necessary to repeat a GGT determination after a normal result has been obtained unless new indications are present.   If the GGT is the only liver enzyme abnormally high, it is generally not necessary to pursue further evaluation for liver disease for this specific indication.   When used to determine if other abnormal enzyme tests reflect liver abnormality rather than other tissue, it generally is not necessary to repeat a GGT more than one time per week.   Because of the extreme sensitivity of GGT as a marker for cytochrome oxidase induction or cell membrane permeability, it is generally not useful in monitoring patients with known liver disease.   190.33 - Hepatitis Panel/Acute Hepatitis Panel  (Rev. 17, Issued: 07- 02-04) (Effective/Implementation: Not Applicable) PM AB -02-110  This panel consists of the following tests:    Hepatitis A antibody (HAAb), IgM antibody;    Hepatitis B core antibody (HBcAb), IgM antibody;    Hepatitis B surface antigen (HBsAg) and;    Hepatitis C antibo dy;  Hepatitis is an inflammation of the liver resulting from viruses, drugs, toxins, and other etiologies.  Viral hepatitis can be due to one of at least five different viruses, designated hepatitis A, B, C, and E.  Most cases are caused by hepatitis A vi rus (HAV), hepatitis B virus (HBV), or hepatitis C virus, (HCV).   The HAV is the most common cause of hepatitis in children and adolescents in the United States.  Prior exposure is indicated by a positive IgG anti -HAV.  Acute HAV is diagnosed by IgM anti -HAV, which typically appears within four weeks of exposure, and which disappears within three months of its appearance.  IgG anti -HAV is similar in the timing of its appearance, but it persists indefinitely.  Its detection indicates prior effective immuniza tion or recovery form infection.  Although HAV is spread most commonly by fecal -oral exposure, standard immune globulin may be effective as a prophylaxis.  The HBV produces three separate antigen (surface, cores and e (envelope) antigens) when it infects the liver, although only hepatitis B surface antigen (HBsAg) is included as part of this panel.  Following exposure, the body normally responds by producing antibodies to each of these antigens; one of which is included in this panel: hepatitis B surface an tibody (HBsAb) -IgM antibody, HBsAg is the earlier marker, appearing in serum four to eight weeks after exposure, and typically disappearing within 6 months after its appearance.  If HBsAg remains detectable for greater than 6 months, this indicates chronic  HBV infection.  HBcAb, in the form of both IgG and IgM antibodies, are next to appear in serum, typically becoming detectable 2- 3 months following exposure.  The IgM antibody gradually declines or disappears entirely 1 -2 years following exposure, but the IgG usually remains detectable for life.  Because HBsAg is present for a relatively short period and usually displays a low titer, a negative result does not exclude and HBV diagnosis.  HBcAb, on the other hand, rises to a much higher titer and remain elev ated for a longer period of time, but a positive result is not diagnostic of acute disease, since it may be the result of a prior infection.  The last marker to appear in the course of a typical infection is HBsAb, which appears in serum 4 -6 months followi ng exposure to infected blood or body fluids; in the U.S., sexual transmission accounts for 30- 60 percent of new cases of HBV infection.   The diagnosis of acute HBV infection is best established by documentation of positive IgM antibody against the core antigen (HBcAb -IgM) and by identification of a positive hepatitis B surface antigen (HBsAg).  The diagnosis of chronic HBV infection is established primarily by identifying a positive hepatitis B surface antigen (HBsAg) and demonstrating positive IgG antibody directed against the core antigen (HBcAb -IgG).  Additional tests such as hepatitis B e antigen (HBeAg) and hepatitis B e antibody (HBeAb), the envelope antigen and antibody, are not included in the hepatitis panel, but may be of importance in asse ssing the infectivity of patients with HBV.  Following completion of a HBV vaccination series, HBsAB alone may be used monthly for up to 6 months, or until a positive result is obtained, to verify an adequate antibody response.  HCV is the most common caus e of post -transfusion hepatitis; overall HCV is responsible for 15- 20 percent of all cases of acute hepatitis, and is the most common cause of chronic liver disease.  The test most commonly used to identify HCV measures HCV antibodies, which appear in blood 2- 4 months after infection.  False positive HCV results can occur.  For example, a patient with a recent yeast infection may produce a false positive anti -HCV result.  For this reason, at present positive results usually are confirmed by a more specific technique.  Like HBV, HCV is spread exclusively through exposure to infected blood or body fluids.  This panel of tests is used for differential diagnosis in a patient with symptoms of liver disease or injury.  When the time of exposure or the stage of the  disease is not known, a patient with continued symptoms of liver disease despite a completely negative hepatitis panel may need a repeat panel approximately 2 weeks to 2 months later to exclude the possibility of hepatitis.  Once a diagnosis is establishe d, specific tests can be used to monitor the course of the disease.   Indications   1. To detect viral hepatitis infection when there are abnormal liver function test results, with or without signs or symptoms of hepatitis.   2. Prior to and subsequent to liver tra nsplantation.   Limitations   After a hepatitis diagnosis has been established, only individual tests, rather than the entire panel, are needed.   190.34 - Fecal Occult Blood Test  (Rev. 17, Issued: 07- 02-04) (Effective/Implementation: Not Applicable) PM AB 02 -110  The fecal occult blood test (FOBT) detects the presence of trace amounts of blood in stool.  The procedure is performed by testing one or several small samples of one, two or three different stool specimens.  This test may be performed with or without evidence of iron deficiency anemia, which may be related to gastrointestinal blood loss.  The range of causes for blood loss include inflammatory causes, including acid- peptic disease, non- steroi dal anti -inflammatory drug use, hiatal hernia, Crohns disease, ulcerative colitis, gastroenteritis, strongyloides, ascariasis, tuberculosis, and enteroamebiasis.  Vascular causes included angiodysplasia, hemangiomas, varices, blue rubber bleb nevus syndrome, and watermelon stomach.  Tumors and neoplastic causes include lymphoma, leiomyosarcoma, lipomas, adenocarcinoma and primary and secondary metastases to the GI tract.  Drugs such as nonsteroidal anti -inflammatory drugs also cause bleeding.  There are ex tra gastrointestinal causes such as hemoptysis, epistaxis, and oropharyngeal bleeding.  Artifactual causes include hematuria, and menstrual bleeding.  In addition, there may be other causes such as coagulopathies, gastrostomy tubes or other appliances, factitial causes, and long distance running.   Three basic types of fecal hemoglobin assays exist, each directed at a different component of the hemoglobin molecule.  1. Immunoassays recognize antigenic sites on the globin portion and are least affected by diet o r proximal gut bleeding, but the antigen may be destroyed by fecal flora.   2. The heme- porphyrin assay measures heme -derived porphyrin and is least influenced by enterocolic metabolism or fecal storage.  This assay does not discriminate dietary from endogenous heme.  The capacity to detect proximal gut bleeding reduces its specificity for colorectal cancer screening but makes it more useful for evaluating overall GI bleeding in case finding for iron deficiency anemia.   3. The guaiac -based test is the most widely used.  It requires the peroxidase activity of an intact heme moiety to be reactive.  Positivity rates fall with storage.  Fecal hydration such as adding a drop of water increases the test reactivity but also increases false positivity.   Of these three test s, the guaiac- based test is the most sensitive for detecting lower bowel bleeding.  Because of this sensitivity, it is advisable, when it is used for screening, to defer the guaiac- based test if other studies of the colon are performed prior to the test.  Similarly, this tests sensitivity may result in a false positive if the patient has recently ingested meat.  Both of these cautions are appropriate when the test is used for screening, but when appropriate indications are present, the test should be done despite its limitations.   Indications   1. To evaluate known or suspected alimentary tract conditions that might cause bleeding into the intestinal tract.   2. To evaluate unexpected anemia.   3. To evaluate abnormal signs, symptoms, or complaints that might be associated with loss of blood.  4. To evaluate patients complaints of black or red -tinged stools.  Limitations   1. The FOBT is reported once for the testing of up to three separate specimens (comprising either one or two tests per specimen).   2. In patients who are  taking non- steroidal anti- inflammatory drugs and have a history of gastrointestinal bleeding but no other sign, symptoms, or complaints associated with gastrointestinal blood loss, testing for occult blood may generally be appropriate no more than once ev ery 3 months.  When testing is done for the purpose of screening for colorectal cancer in the absence of signs, symptoms, conditions, or complaints associated with gastrointestinal blood loss, report he HCPCS code for colorectal cancer screening; fecal -occult blood test, 1- 3 simultaneous determinations) should be used.   Transmittals Issued for this Chapter