Acute Hepatitis

ACUTE VIRAL HEPATITIS  —  There’s A, B, C, D, E, & G.  What happened to F?  It’s hypothetical; a possible virus got isolated in the 1980s but never confirmed.  Hepatitis G virus may be carried by up to 5% of people, but causes no known illness.

Today’s topic will focus on understanding clinical presentation and lab tests, especially serology.  Click here for capsule summaries of the Natural History of Hep A, B, and C.

A patient presents with anorexia, nausea, vomiting, upper abdominal pain (usually RUQ), with or without jaundice.

FIRST STEP — is it Hepatitis? [ i.e transaminitis: elevated ALT & AST, indicating hepatocellular injury].  [Oldspeak for ALT was “SGPT”, for AST it was “SGOT”].

If these liver function tests (LFTs) are elevated, the main differential diagnosis is obstructive biliary tract disease, e.g. gallstones.  This is usually sorted out by:

  • History: acute gallstones usually present with abrupt onset pain (when stone lodges in duct), which may radiate to right back or shoulder. The onset of viral hepatitis is more insidious.  As noted in previous postings, always define the chronology of illness.
  • If there’s a history of prior similar episodes, think gallstones.
  • Exam: gallstones give a positive Murphy’s sign [not law], deep palpation under the right costal margin causes a sudden ‘gasp!’ of severe tenderness.  Hepatitis tenderness is elicited by liver percussion.
  • Labs: In biliary tract disease, the Alkaline Phosphatase is disproportionately elevated compared to ALT & AST.  In hepatitis, the reverse.

BUT… oftentimes such clinical clues are imperfect, & imaging is required.

Acute Pancreatitis can mimic hepatitis, and cause ↑ LFTs.  Dx by serum Lipase.

A quick word about Jaundice: don’t forget Hemolytic Anemia, especially if there are no other hepatobiliary symptoms.  Also, painless jaundice commonly implies pancreatic cancer.  Get an abdominal CT with contrast.

From now on, let’s say we’re sure we’re dealing with Acute Hepatitis: increased ALT & AST, which overshadow an increased Alk Phos.  The most common etiology is alcohol — not cirrhosis from long-time drinking, but acute alcoholic hepatitis, pure drug toxicity [with high mortality].  Rule this out by history; also R/O a host of other toxins, from medications to environmental exposures to death cap mushrooms.

PEARLS re: Alcoholic Hepatitis:

  • AST is usually higher than ALT, the opposite of viral hepatitis
  • AST rarely exceeds 200-300.

But let’s say there’s no such history, & the ALT & AST are heading toward 1,000 IU/ml or even more.  We’re thinking viral hepatitis.

I had a patient with ALT >10,000!  Lab tech came running.  Was this fulminant, would he die?  What’s the most important parameter?

Prothrombin time.  The liver synthesizes it, so if the INR is elevated, it means the liver isn’t functioning.  Always order a Protime for acute hepatitis of any suspected origin.  Levels of transaminases are completely non-predictive of disease severity.  An INR <1.3 is fine, 1.3 – 1.5 unsure (repeat it); 1.6 & above get admitted.  My patient with ALT>10,000 had a normal protime, and plain-old, benign Hep A.

It’s also important to know average incubation periods from exposure until symptoms:

  • Hep A = 2-6 weeks
  • Hep B = 2-6 months
  • Hep C = usually 6-12 weeks (range 1-26 wks)
  • Hep E = 2 wks – 2 mos.

Now let’s discuss serology [finally!!].  Word of Caution: beware of standard Laboratory Panels.  They don’t always include the relevant tests.

Abbreviations:  “Hep A” is often “HAV” [= “Hep A Virus”], “HBV,”… ASO (“and so on”).

Antibody Fractions:  IgM occurs with acute illness.  IgG persists forever after resolution.

Hepatitis A —  Hep A antibody, IgM fraction, is 100% sensitive & specific for acute Hep A.  Sometimes the lab just looks for “Total Hep A” (IgM plus IgG); if non-reactive, that’s a negative.

  • If “Total” Hep A antibody is reactive, they have to also test for IgM or the result is worthless.
  • Ordering “Total Hep A” without fractionating is only helpful for the completely healthy person who wants to know if they need vaccination or are already immune.

Be sure your lab form’s box for “Hep A” includes “reflex to IgM,” meaning that if the “Total” is positive, the tech automatically tests for the IgM.  Conversely, if you aren’t working up acute illness, & just want to know if a person is a candidate for vaccination (i.e. not immune), be sure the lab doesn’t only look at the IgM.

Hepatitis B  —  This is more complicated.  There are 3 types of serologies (with abbreviations):

  • SURFACE  —  HepB surface antigen and antibody (“HBsAg” and “Anti-HBsAB,” respectively);
  • “E”  —  HepB “e” antigen and antibody (“HBeAg” and “Anti-HBeAB”);
  • CORE  —  HepB core antibody (Anti-HBcAB), either IgM or IgG.  There’s no test for “core” antigen.

When you read the following explanations, say the words “surface,” “E,” and “core” out loud to yourself.  I use bold to emphasize key tests, but get yourself used to distinguishing among the 3 separate components of HepB serologies.

During acute Hep B, both HBsAg and the HepB core IgM antibody are positive.

  • If only HBsAg is positive, they already have chronic HepB, & now a different hepatitis [that’s bad], or maybe a Hep B flare.
  • If only core IgM is positive, it’s the tail end of acute Hep B that’s successfully resolving.

Anyone who ever had Hep B, whether they’re immune or chronically infected, may have core antibody IgG.  It’s not very useful.  Once again, for acute Hep B, you must specifically order the IgM fraction of core antibody.

If  “surface” antibody is positive, the patient is immune to Hep B.  Maybe they were vaccinated.  Maybe they had Hep B, & can never get it again.  There are no IgG’s or IgM’s to this.

The HepB “e” serologies are only sought after having made a diagnosis of chronic Hep B.  We’ll discuss that next posting.

Hepatitis C  —  Real tough, because symptomatic Acute Hep C occurs during the window period of antibody conversion.  Sero-conversion occurs by 12 weeks after symptom onset.  There’s no IgM or IgG to this.

The Viral Load (HCV RNA) is the test to order.  If the HCV RNA is positive and HepC Antibody negative, it’s acute Hep C for sure.

Still, about 50% of Acute Hep C patients seem to be Antibody-Positive when they present (rapid sero-conversion).  So how to tell if they’re acute, or if they have undiagnosed Chronic Hep C with another type of acute hepatitis?

We can’t.  And actually, it doesn’t matter anymore (as of mid-2013).  It used to be important, because if you could identify Acute Hep C in the first 3-6 months, you had a good chance of cure (almost 90%, compared to 50% for Chronic).  But drugs now in the pipeline, due out in 1-2 years, will give high cure rates without the side effects of current regimens.  Since Hep C progresses over years (or decades), there’s no rush to treat.

If you want to distinguish between Acute & chronic Hep C, evaluate when even the most subtle symptoms of hepatitis may have begun, what their risk factors are, and when their last at-risk episode occurred.  Risk factors include:

  • Injection drug use  (IDU)
  • Recent percutaneous exposure [e.g. needlestick, surgery, tattoo, piercing, stabbing]
  • Multiple male sex partners (though the “multiple” aspect makes it impossible to date)

Of course, the greatest risk for Hep C is history of a blood transfusion before 1992 (in US).  So if that history is elicited, & there’d been no prior Hep C antibody ever obtained, there’s a good chance they have chronic illness.  Similarly with long-standing IDU’s; if never tested before, it’ll be impossible to know if today’s result represents acute or chronic infection.

In the absence of acute risk factors, I don’t order a viral load as part of my initial testing, because it’s a little expensive.  But after your first round of tests, if there’s still no diagnosis for a patient’s acute hepatitis, consider the HCV RNA by PCR, since a fair number of persons with Hep C report no discernible risk factors.

Once again, a negative Hep C antibody and positive Viral Load is absolutely diagnostic of acute Hep C, except in the rare HIV patient who may be Hep C Antibody false-negative (the vast majority of co-infected patients do test positive; HIV can even cause a false-positive).

Hepatitis D  —  A defective virus, which can only occur in the presence of chronic Hep B.  Rare in the US.  Acute Hep D is virtually impossible to diagnose, but a flare may mimic new hepatitis, especially if nobody knew that the patient in fact had chronic Hep B to begin with.  Consider the diagnosis in severe hepatitis, especially in injection-drug users.  Order a “Total Hep D antibody” [the only commercially-available test].  I’ve never done so.

Hepatitis E  —  Symptomatic Hep E is a disease of the 3rd World.  Don’t worry about missing it, because there are no commercially-available tests in the US.  It’s self-limiting, except in pregnancy, when mortality may reach 25% in the 3rd trimester.  Worry about the pregnant woman who’s just returned from travel to endemic areas; call the CDC for a diagnostic kit.

Interesting Case —  My colleague’s patient had an ALT of >1,000, persisted 2 weeks, bilirubin reached 15, serologies all negative.  She sought obscure diseases like Wilson’s, imaged for mets [normal].  Hepatology said “we’ll see him next week, if he’s still alive” [!!!!].  He was (protime normal).  The diagnosis?

Mononucleosis, diagnosed by Epstein-Barr antibody, IgM.

SUMMARY REVIEW

A patient presents with 3 days of nausea, anorexia, malaise, maybe upper abdominal discomfort but not such pain as to think obstruction (gallstones).   It’s probably dyspepsia or gastroenteritis.  Order LFTs; maybe a pregnancy test.

Results: transaminases are >1000, bilirubin 4, patient returns 1-2 days later, jaundiced.  It’s an ACUTE  HEPATITIS.

**  Get a history for alcohol, meds, herbs, toxins (esp. death cap mushrooms).

**  If the Alk Phos is real high, wonder about gallstones.

**  Order Serologies for viral hepatitis:

  • Anti-HAV Antibody IgM  [or Total Hep A Antibody with reflex for IgM]
  • HBsAg and  Hep B core IgM Antibody [or Total HBV core AB, with reflex for IgM]
  • HCV Antibody  [if positive may = old, chronic Hep C]

**  Consider HCV viral load by PCR if pt. had Hep C risks within the last 3 months:

  • injection drug use, multiple male sex partners, recent percutaneous exposure [e.g. needlestick, surgery, tattoo, piercing, stabbing].

**  Order a Prothrombin Time.  If INR ≥1.6, hospitalize.

**  Advise abstinence from alcohol [but DON’T stop the oral contraceptives!!]

Protime normal, serology unrevealing, thus no diagnosis?  Order:

**  Abdominal Ultrasound

**  Epstein-Barr antibody IgM

  • the “Heterophile” (= “Monospot”) won’t convert until the 2nd or 3rd week of illness.

**  Consider HCV viral load by PCR

**  Pregnant & recent 3rd World Travel?  Call CDC to R/O Hep E (25% mortality)

**  Follow the transaminases; follow the patient.

Various other microbes can cause hepatitis, such as cytomegalovirus (CMV), toxoplasma, herpesvirus-6 & -7.  They’re all self-limiting; symptoms diminish and transaminases decline.

But if not, and image is normal, keep repeating the Protime, and consult hepatology.

  • If <40 y.o., look for a low serum Ceruloplasmin for rare Wilson’s Disease

Next time: Chronic Hepatitis.

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