HBV

HEPATITIS B: One of 3 stages of Infection 
  • Acute (sAg present) - cIgM positive
  • Chronic (sAg present) - cIgM negative - has 4 stages (please review BMJ article Figure 2)
    • Immune tolerance:
    • Immune Clearance:
    • Immune Control or low replicative 
    • Immune escape or reactivation 
    • 5th: Remission 
  • Resolved: Ab of previous infection present without any marker of active infection






















Case Based Learning

BM 
58 yo M is seen for HIV. Also, has Hep B. How should the patient be treated?

Answer the following questions. 

Is it an active infection or not?
Check for sAg. If present is and active infection. Here, sAg is present, so it is an active infection. 

Is it acute or chronic active infection?
Check for cIgM. If present, acute, otherwise, chronic. 

Here, cAb is positive. But, we do not know whether it is cIgG or cIgM. Likely, cIgM is negative. So, it is chronic hepatitis infection. 

What stage is this chronic hepatitis?
  • Immune tolerance: 
  • Immune Clearance: LFT are increased. Hence, it is NOT
  • Immune Control: 
  • Immune escape: LFT are increased. Hence it is NOT

What stage of the following chronic hepatitis it is then? (see the above diagram) 2 ways to differentiate 
  • Immune tolerance: 
  • Immune Clearance: LFT are increased. Hence, it is NOT
  • Immune Control: 
  • Immune escape: LFT are increased. Hence it is NOT
1. Check for eAg, and eAb : If eAg is present, and eAB absent, then it is Immune tolerance. If eAb is present, and eAg is absent then it is Immune Control. 

Our patient has eAb present, but eAg is negative. Hence, it is immune control stage. 

2. What is the DNA level? (see above diagram)
Typically, DNA is high in immune tolerant stage and low in immune control stage. 

Answer: 
Our patient has Immune Control stage. 

Next step to do. 
Hep B DNA by PCR. 

Case Based Learning
RT: Patient is seen for abdominal pain with following lab work 
  


Is it an active infection or not?
Check for sAg. If present is and active infection. Here, sAg is present, so it is an active infection. 

Is it acute or chronic active infection?
Check for cIgM. If present, acute, otherwise, chronic. Hence, this is an Acute Hepatitis. 

Flare up of chronic hepatitis can give Hep B C IgM positive. Hence, additional test to differentiate would be 
  • Hep B C IgG : If present chronic. Not available
  • HBV DNA PCR is done, and shows very high number. Consistent with Hep B Acute Infection. But can occur in chronic infection as well. 
  • eAB is absent. Hence, less likely to be Immune control or Immune escape phase. Even less likely to be immune control phase as HBV DNA level will be low, and LFT will be normal. Can still be Immune clearance phase of chronic hepatitis where eAB is not formed yet, and LFT are high and DNA is in the initial stage of decreasing. Less likely to be Immune tolerance, as LFT are increased. 


Is the acute hepatic failure? 
PT 6.1
INR 1.3 
No evidence of encephalopathy. 

IN the absence of coagulopathy and encephalopathy, it is not acute hepatic failure


However, flare of chronic hepatitis can give the lab of this patient. Hence, we should check for IgG anti-HBc. If present it is flare up of chronic hepatitis. 

How should this patient be treated?
  • Most patients are managed symptomatically
  • Treatment considered if INR > 1.5 or Bi > 10 for > 4 weeks
  • If treated, consider mono therapy of  tenofovir disoproxil fumarate (DF) or entecavir 
  • Ref: Uptodate
BM 
58 yo M is seen for HIV. Also, has Hep B. How should the patient be treated?
 

How should the next step?
Genetic testing ?
HBV DNA level

Also check for Hep C. 

Hep C is positive. However, viral count is not detectable. 
Patient has stage 4 CKD with nephrotic range proteinuria. LFT are normal. 

sAg is present hence, active infection. 
cIgM is not checked, hence difficult to say if it is acute or chronic. 


But, eAg is negative, and has eAb with normal LFT. Hence, likely it is a immune control stage. 

  • Next tests to order are HBV DNA level. 
  • Monitor, every 6-12 months. 
SCE
68 yo is seen for positive acute hepatitis profile. 

How should this patient be managed? 
  • Acute vs chronic. Likely Chronic as Ab C IgM is negative. 
Next step to do will be, 
  • LFT 
  • HBV DNA 
  • eAb
  • eAg
These tests will help define the stage of the chonic hepatitis B. 

cAb IG Total can be ordered as well, expect it to come positive. 

Case based studies
FK 
39 yo is seen for positive acute hepatitis profile in 2013 for cAb IgM. 


Repeat Tests in 4/2 is positive as well for cAB, IgM. 

sAg is negative. 

What is it likely. 
  • Less likely acute hepatitis that has resolved as it was present over a year. 
  • More likely chronic infection. 
Next step. 
  • HBV DNA 
  • eAg
  • eAb
  • LFT
LFT is normal. eAg is negative. 
Confirms it is not a active infection at this time. 

Other tests that would be useful will be 
  • sAb. If sAb is present, then likely it represents resolved infection .
Only stage of chronic infection that it can represent is chronic infection - immune control. 
  • But as HBV DNA is not detectable, it may not be Immune Control stage. That depends on test technique as well. cIG M should have been not detected by now, but sometime it remains positive. 

NC
63 yo is seen for positive test in acute hepatitis panel in 2/2016. 


What other tests should be ordered to differentiate acute vs chronic infection?
  • cIgM vs cIg G
    • c ig M is negative, hence it is not an acute infection. 

It is likely a chronic infection. What stages identifies the stages of chronic infection
  • LFT 
  • eAb
  • eAg
  • DNA level
LFT is essentially normal. Hence, likely either Immune Tolerance or Immune Control

eAg is negative, e Ab is positive. Hence, likely it is Immune Control stage. 

DNA level is detected at 350 copies .

That confirms the Immune Control stage. 


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