Inova ANA, ANCA, and liver disease serology decision trees HERE. Our gastroenterologists have ordered this non-liver-specific serology test as a screen for autoimmune hepatitis (AIH)...generally
accepted as a marker of autoimmune hepatitis (AIH). If positive, patient is more likely to get a liver biopsy. But, it is said not to be a sensitive AIH screen & can be negative (because it waxes & wanes in low-grade AIH cases [L09-9472?]). And, as shown below, it may not be specific for true & pure AIH. Also, there is a school of thought that if any plasma cells can be seen in the portal areas in a liver biopsy case with hepatocyte injury features (even just mild elevation of SGPT/ALT), there is concern for at least a low-grade AIH-like component of hepatic injury so as to justify a course of steroid "AIH-component-in-mind" therapy. In a potential serological search for confirming evidence of an AIH primary or component injury, there are other named and as-yet-un-named autoantibodies (which may or may not be reflected in elevated serum IgA or IgM elevations or SPE beta-gamma bridging).
Being directed biologically at smooth muscle actin microfilaments, this auto-antibody is directed against actin, troponin, and tropomyosin. We have used animal-tissue substrate at a beginning dilution
of patient's serum of 1:20. The use of animal tissue avoids interference
from human HLA and/or blood group Abs that may occur if human substrate
were used. Incidental Abs may show up in this system such as APCA, ANA, ARA, ABBA, anti-canalicular
Ab, anti-liver cell membrane Ab, anti-ribosomal
Ab, and anti-granular-leukocyte (polys). And, ASMA may unexpectedly & incidentally show up in the smooth muscle component of other IFA substrates, such as with anti-endomysial (CN09-87...she was ASMA 1:80). At a starting dilution of patient's serum of
1:20, there are many "false positives" for ASMA at this
low-titre level. So, "reactive" but, by convention, not "positive" is <1:40;
and "a nonspecific positive titer" is 1:40-1:160, quite possibly reflective of a minor but treatable auto-immune component complicating some other primary hepatidite. We
have documented instances of levels >1:160 that were not AIH...so,
liver biopsy findings are crucial to proper total case interpretation prior to heavy medical therapy.
ASMA can be seen in infectious mononucleosis & other viral infections, SLE, in breast & ovarian carcinoma, in melanoma. It can also be seen in about 50% of cases of PBC cirrhosis (overlap?), alcoholic related cirrhosis, and cases of biliary duct obstruction.
A 1972 paper providing results of community screening for ASMA found positivity in 1.2% of "normal" people under age 40 and in 3.5% of those over 70 years of age3.
As of 2011: additional IFA antibodies & a large variety of additional EIA-type antibodies has become more easily commercially available so that we may be able to use a decision-tree type workup through LML. (CHART HERE)
F-actin: Actin filaments are made by polymerization of globular actin (G-actin) subunit monomer into microfilaments forming F-actin & thence into actin. F-actin antibodies (IgG) have been shown to have greater sensitivity and specificity for autoimmune liver disease than anti-smooth muscle antibodies4. BUT, F-actin can still be false positive [L12-7423]. Here is an example (slow loading) decision tree HERE.
The non-organ-specific antibodies: AMA (a number of antimitochondrial antibodies = M1 or MIT-1 for SLE, Sjogrens, progressive systemic sclerosis; M2 or MIT-2 for PBC; M3 or MIT-3 for pseudolupus syndrome; M4 or MIT-4 for PBC; M5 or MIT-5 for non-specific collagenoses; M6 or MIT-6 seen in variety of disorders & Iproniazide-induced hepatitis; M7 or MIT-7 in acute myocarditis and cardiomyopathies; M8 or MIT-8 in PBC; and M9 or MIT-9 in PBC & other forms of hepatitis); ANA (a "basket" of many specific antinuclear antibodies); LKM (a number of liver-kidney-microsomal antibodies: LKM-1 in AIH [directed against the antigen cytochrome P450 2D6, also known as CYP2D6] & LKM-2 in drug induced hepatitis & LKM-3 [directed against the family of 1 UDP glucuronosyl transferases, also known as UGT1A] in chronic hepatitis D); antiactin antibody; ASMA (anti-smooth-muscle antibody); LP (anti-liver-pancreas antibody); and pANCA antibody.
Liver-specific antibodies: ASGPR (anti-asialoglycoprotein receptor antibody directed against asialoglycoprotein receptor); LSP (liver-specific lipoprotein); LC1 (anti-liver cytosol type 1 antibody directed against formiminotransferase cyclo deaminase [FTCD]); LMA (liver membrane antigen); and SLA (anti-soluble liver antigen antibody directed against tRNP(SER)Sec).
implying hepatocyte-component-directed auto-antibodies: ANA, ASMA, LKM-1, F-actin, SLA, LP, LC1, LKM-3, atypical p-ANCA.
implying biliary-component-directed auto-antibodies: AMA, PDH-E2 (antibody against human pyruvate dehydrogenase complex enzyme 2), MS Ep(MIT3), gp210, sp100, atypical p-ANCA.
other: LM (liver-only microsomal antibody against CYP1A2) in APECED hepatitis (autoimmune polyendocrinopathy candidias ectodermal dystrophy6).
Associations with undetectable ASMA ab:
Associations with elevated levels of ASMA ab:
extra-hepatic biliary obstruction1.
- cases of liver biopsy "concern for AIH component " when biopsy shows some portal plasma cells...but could this non-reactivity be a false negative?
- autoimmune (chronic active) hepatitis: always think of AIH and of Wilson's in a young adult; 50-80%
of cases1, 70% at >1:1002;
our lab considers >1:160 to be "significant serologic
evidence, suspicious for autoimmune hepatitis, especially if
liver biopsy contains lots of plasma cells".
- primary biliary
cirrhosis (PBC) 0-50% of cases1
- cryptogenic cirrhosis 0-1% of cases1
viral hepatitis 1-2% of cases1
- suggests a minor autoimmune component when present & plasma cells present along with some other primary hepatidite.
- AIH-complication on top of another liver disease (I believe that many/most in the chart below had OTHER obvious liver disease but a more minor & complicating AIH component, an angle that I...EBS...did not become familiar with until later in 2009).
- A B C's of Interpretive Laboratory Data, 2nd Ed., Seymour Bakerman,
MD, PhD, 1984
- Lex. Med. Lab. procedure manual and its references as of 7/01
- Rochman H, et. al., textbook: Clinical Pathology in the Elderly...,, 1988, 222 pages.
- ARUP F-actin file HERE.
- from MedScape web site, "Diagnostic and Therapeutic Implications of Bile Duct Injury in Autoimmune Hepatitis", HERE.
- Am. Assoc. for Study of Liver Diseases (AASLD) 2010 "AASLD Practice Guidelines: Diagnosis and Management of AIH"...all about serology tests HERE.
- Beland Kathie, et. al., "Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection", Journal of Autoimmunity 22(2):159-166, March 2004 HERE
- Kanel GC & Korula J, Atlas of Liver Pathology, 2nd Ed., 2005, 355 pages.
- EUROIMMUN's Liver Mosaic 16 page handout 4/28/2010, English version with references.