Hepatitis — Blood Tests

We diagnose Hepatitis in general through common blood tests.  Sometimes a person feels sick (see Acute Hepatitis (symptoms).  Sometimes we just happen to notice abnormal liver enzymes on a routine lab test (Chronic Hepatitis).  In either case, to determine the cause, we have to do additional tests (see Types of Hepatitis and also Liver Diseases for discussions of these different illnesses).

We order certain tests if a person has acute hepatitis, other tests if it’s chronic.  Many clinicians get very confused by these, and order wrong ones.  Sometimes they check or click a box “Hepatitis Panel,” and the lab does inappropriate testing (too many, and omitting the right ones).  Here are the tests that we need to order, when looking for the specific viruses (names are abbreviated as in medical jargon, but you can figure it out).

Warning — this topic is quite complex.  Most clinicians don’t understand it offhand.  We are including it here just in case it might happen to be of special, or personal, interest to you.  We’ll begin with summaries of the necessary tests, then go on to explain them.

To Diagnose Acute Hepatitis (for a patient who’s actively & recently ill)

We order the following tests to begin:

• Hep A Antibody, IgM fraction    (anti-HepA IgM Ab)
• Hep B core Antibody, IgM fraction    (anti-HepBc IgM Ab)
• Hep B surface Antigen     (HBsAg)
• Hep C Antibody     (anti-HepC Ab)
• Maybe Monospot, or Epstein-Barr Virus IgM Antibody (for Mononucleosis)

Interpretation:

• If anti-HepA IgM Ab is positive  →   it’s Hepatitis A
• If anti-HepBc IgM Ab is positive  →   it’s Acute Hepatitis B
• If HBsAg is positive  →   they have Hepatitis B virus, likely Acute (if currently ill), maybe Chronic
• If anti-HepC Ab is positive  →   either resolving Acute Hep C, OR Chronic Hep C (but see below)
• If anti-HepC Ab is negative & turns positive a few weeks later  →    Acute Hep C
• If Monospot or Epstein-Barr IgM is positive  →   it’s Mononucleosis
• If Monospot negative & Epstein Barr not done, could still be Mono →   repeat weekly

If all are Negative, consider other causes, & order the following:

• Hep C Viral Load (RNA), OR Repeat Hep C Antibody in 2-3 months
• Mononucleosis tests as above if not done

Explanations of the Above Tests:

Hep A —  There are 2 forms of antibody (Ab): IgM and IgG.  IgM occurs when you’re sick, then goes away.  IgG develops later, remains forever, & makes you immune for life.  The standard Hep A test actually measures Total Ab which includes both IgG and IgM. 

If the IgM is positive, they have Hepatitis A.  If it’s negative, they don’t.  IgG doesn’t count.

• Order “Total Hep A Ab with reflex to IgM,” meaning if the initial test is positive, the lab looks for IgM; if Total is negative, there’s none anyway.
• Or order “anti-HepA IgM Ab” to get right to the point.  The difference would only be cost, which depends on a lab’s price list (sometimes more tests cost less than fewer tests!)

The only reason to order Total Ab without reflex is to see if you need the Hep A vaccine (see below).

Hep B  —  There are lots of tests for Acute Hep B:

• Hep B surface Antigen (HBsAg)  —  “antigen” means it’s a part of the virus itself
• Hep B surface Antibody (anti-HBs Ab)  —  a protective antibody that makes us immune
• Hep B core Antibody IgM (anti-HBc IgM Ab)  —  elevated when we’re acutely ill
• Hep B core Antibody IgG (anti-HBc IgG Ab)  —  elevated forever after having had Hep B
• Total Hep B core Ab  —  Both the IgM and IgG combined

If a patient is ill with acute hepatitis, and we want to see if it’s due to Hepatitis B, we order:

• 1)  HBsAg  and also  2) anti-HBc IgM Ab
• Instead of the 2nd test, we could order Total Hep B core Ab with reflex to IgM, meaning if the initial test is positive, the lab looks for IgM; if Total is negative, there’s no IgM anyway.

See below for how we test to see if Hep B vaccine is needed.

Hep C  —  The main test is Hep C Antibody.  But it doesn’t turn  positive until about 12 weeks after you get infected.  Symptoms occur sooner, and may get better before antibody shows up.  so if someone is ill with acute hepatitis:

• Hep C Ab  —  If negative, could have acute Hep C.  Positive means they had it already (may or may not still be infected)
• Hep C Viral Load (Hep C RNA)  —  detects the virus itself

If Antibody negative, and Viral Load positive, they have Acute Hepatitis C.  But the viral load test is expensive.  Since no treatment is absolutely necessary for Acute Hepatitis C, it’s also OK to skip the viral load test and repeat Hep C Antibody in 3 months.  If it goes from negative to positive, they had Acute Hepatitis C.  See below for how to tell if its chronic infection persists.

Hep D  —  Only occurs in patient with chronic Hepatitis B infection.  Rare.

Hep E  —  Rare in the U.S.  No easy reliable tests available.

Mononucleosis (Epstein-Barr Virus)  —  The Monospot is a test for Heterophile Antibodies; they mean the same thing.  A positive test diagnoses mononucleosis (“Mono”).  There are false-negatives, 25% in the first week of illness, fewer later.  One strategy is to repeat the test every week (there’s no treatment for Mono).  Another is to test for Epstein-Barr IgM antibodies (depending on cost).

To Diagnose Chronic Hepatitis

(for example, if we happen to find abnormal liver enzymes on a blood test from a healthy patient).

First Step  —  We begin by looking for Hepatitis B & C viruses with the following tests:

• Hep B surface Antigen     (HBsAg)
• Hep C Antibody     (anti-HepC Ab)
• Other viruses do not cause chronic liver disease

     Interpretation:

• If HBsAg is positive →  they have Hep B virus.  Next, need to see if it’s harming their liver
• If anti-HepC Ab is positive →  They’d gotten Hep C.  Next, need to see if it’s still there

Next Step  —  We order the following tests depending on what we’d already found

>>   If HBsAg was positive:

• Repeat in 6 months.  If negative, they’re cured.  If positive →  they have Chronic Hep B
• For Chronic Hep B: we mainly order the viral load to count virus particles (HepB DNA)
• If HepB DNA (viral load) is negative or very low, patient is just a Hep B Carrier (not ill with Hep B, but still contagious because HBsAg is positive)
• If HepB DNA is somewhat high, they have Chronic Hepatitis B (risks for liver failure & liver cancer).  Treatment depends on DNA level, and tests for HepB “e” Antigen.  See topic Types of Hepatitis & Other Liver Diseases

>>   If Hep C Antibody was positive:

• Order Hep C Viral Load (HCV RNA) to see if they still have it.  If negative, repeat in 6 months to be sure.  If still negative, they got infected with Hep C & are cured (20% of infected people) (but they can get it again).
• If Hep C Viral Load is positive, they have Chronic Hep C.  See topics Types of Viral Hepatitis.

Finally  —  If both HBsAg and Hep C antibody are negative, the liver enzymes are not elevated from either Hep B or C.  So we look for other rare Chronic Liver Disease with blood tests:

• For Hemochromatosis — Transferrin Saturation % (by ordering Iron & “TIBC“)
• For Wilson’s Disease  —  Ceruloplasmin (is very low with the disease)
• For Auto-immune Hepatitis  —  Anti-Nuclear Antibody (ANA), also total Immunoglobulin G (IgG); if very high, then anti-Sm (also called “Actin smooth muscle”)
• For alpha-1 antitrypsin deficiency  —  alpha-1 antitrypsin levels
• Maybe Celiac Disease  —  anti-Tissue Transglutaminase IgA Antibody (must be IgA)

We do the tests so as not to miss a possibly fatal & also treatable condition  —  but the results are almost always negative!  And the liver enzymes are still elevated.  We send the patient to a Hepatologist (liver specialist).  They may do a liver biopsy.  Then they almost always diagnose “Fatty Liver,” a new, common, upcoming disease that poses significant dilemmas, in terms of both diagnosis and treatment.

To Determine if a Person Needs Vaccination for Hepatitis A or B. We order the following tests:

• Total Hep A Antibody (without reflex).  If positive, they’re immune forever, no vaccine.  If negative, they could benefit from vaccination
• anti-Hep B surface Antibody (anti-HBs Ab).  If positive, they’re immune forever, no vaccine needed.  If negative, and HBsAg is negative (see below), they may benefit from vaccine
• Hep B surface Antigen (HBsAg).  If positive, they have Chronic Hep B infection (see above).  So vaccine is useless.