Acute Hepatitis

Today we discussed a case of acute hepatitis NYD with moderate-severe liver enzyme elevation. This is not an uncommon referral to Internal Medicine.

Here's a very useful review from CMAJ in 2005 on elevated liver enzymes.

Some points about marked liver enzyme elevation (>5x the upper limit of normal):

1. Remember that the "liver function tests" are bilirubin, INR, albumin +/- glucose and can reflect the synthetic function of the liver. Conversely, the "liver enzymes" - AST, ALT, ALP and GGT are NOT liver function tests as they offer no information on the liver's synthetic function but merely are a marker of hepatocyte integrity and/or cholestasis.

2. The differential diagnosis of moderate to severe transaminitis includes: viral hepatitis, toxic hepatitis, ischemic hepatitis, severe obstruction, autoimmune and alcoholic hepatitis.

3. Decide what the predominant pattern is to help you guide investigations:
a) Hepatic (increased AST, ALT > ALP)
b) Cholestatic (increased ALP > AST, ALT)

4. How elevated are the enzymes? 5x vs. 5-10x vs. >10x of normal? What is the trend? Is there synthetic dysfunction (increased INR, bilirubin, decreased albumin)? Typically liver enzyme values at this level represent acute liver injury.

5. In acute viral hepatitis, the liver enzymes often peak before the bilirubin and the patient may have non-specific symptoms such as fatigue, arthralgias and a low grade fever (as in our patient) .

6. Consider ischemic hepatitis in the right clinical context and an ALT/LDH ratio of less than 1.

7. Hepatitis screen: Hep A IgM Ab, Hep B core Ab (IgM), Hep B surface Ag and Ab, Hep C Ab.

8. Always ask about Tylenol use, herbal and over the counter medications, periods of illness (hypotension), autoimmune symptoms and alcohol.

9. Some form of abdominal imaging (usually ultrasound) is often appropriate to assess for evidence of hepatitis and/or obstruction.

10. Once the common causes of moderate to severe transaminitis have been ruled out, consider testing for auto-immune hepatitis and other viral causes such as EBV and CMV.

Fulminant hepatic failure

Defined as rapid onset of encephalopathy and marked decrease in liver synthetic function within 28d of symptom onset in patient without chronic liver disease

Major etiologies are 1)acetaminophen OD, 2) idiosyncratic drug reaction, 3) Hep B, 4) Hep A, 5) others

Coagulopathy usually precedes encephalopathy, which may quickly progress to coma

It is important to determine the etiology, since specific causes may have specific treatments:
NAC for acetaminophen, penicillin for amanita mushroom poisoning, delivery for acute fatty liver of pregnancy, zinc/trientine for Wilson's.

Pts should be admitted to ICU and transferred to a transplant centre.

Supportive care includes:
glucose (may need d10 drip)
electrolyte replacement
fluids
reversal of coagulopathy
neurochecks >q6h

FFP (4u) may normalize coags for 6h (for procedure or bleeding)

Empiric abx for any sign of infection

Poor prognostic indicators predicting need for transplant:
pH below 7.3 after resuscitation
PTT over 100
Cr over 290
Gr 3 or 4 encephalopathy
Lactate over 3.3 4h post admission


Major causes of transaminases in the thousands:

1) Ischemia
-inflow (hypotension- shock liver, PV thrombosis)
-outflow (CHF, Budd-Chiari)

2) Viral
HAV, HBV (rarely HCV)
Others- EBV, HSV, CMV

3) Drugs/toxins

4) Autoimmune

5) Obstruction/stone

6) Acetaminophen and EtOH both (but rarely EtOH alone)

Link:
Click here for a NEJM case of fulminant hepatic failure from HSV infection that discusses management considerations
Click here for a paper on approach to increased liver enzymes

Fever in the Returning Traveler

Fever in the Returning Traveler....a very common situation.

There are some very pertinent questions that must be asked: above and beyond your medical history and physical exam, it is important to ask the following questions...

1. Where did you go? (exactly)


2. How long were you there?


3. What did you do?


4. What is the date you left, date you returned home, and date of every stop along the way?


5. Exposures: Water, animals (eg mosquito's, tics, farms), sexual?


6. Did you get pre-travel advice? What was the advice? Did you take the advice?
   

An approach: Think about what causes fever...

• Infection related to where patient was traveling.


• Infection not-related to travel.


• Non-infectious causes of fever.
  

What are the 4 "biggies" for infection in the returning traveler?

• Malaria


• Dengue fever


• Viral hepatitis (A)


• Typhoid fever

Some good review papers:

1. Here is the sentinel article from NEJM (written by local talent) looking at the spectrum of diseases in ill returning travelers.
   
2. Here is a great review on malaria prophylaxis from NEJM.