Hepatitis B Virus - Diagnosis

Question 1

HBsAg

Answer 1

marker of infection

Question 2

HBeAg

Answer 2

marker of replication and infectivity

previously used as monitor for treatment response
no longer reliable; use HBV DNA instead

Question 3

HBV DNA

Answer 3

marker of replication and infectivity

more reliable monitor for treatment response
also a marker of HBV reactivation if HBV DNA >log 4

Question 4

anti-HBeAg

Answer 4

only measured if HBeAg found to be negative
indicates e-seroconversion
patients less infective

Question 5

anti-HBcIgM

Answer 5

marker of acute infection

may be the only marker detectable during window period between disappearance of HBsAg and appearance of anti-HBs

unreliable alone as it can persist up to 2y after initial infection

Question 6

HBcAg

Answer 6

never checked as HBcAg is an INTRACELLULAR antigen expressed within infected hepatocytes

thus it is normally not detectable in serum

Question 7

anti-HBc IgG

Answer 7

marker of past infection

Question 8

anti-HBs IgG

Answer 8

HBV immunity

Question 9

List groups that require HBV screening

Answer 9

High risk groups

1) Patients born in countries w/HBVprevalence ≥2%
2) Hx multiple sex partners
3) Hx STI
4) Hx IVDU
5) Hx MSM
6) HCV patients
7) HIV patients
8) Hx hemodialysis

Groups w/potential for complications

1) Pregnancy
2) Patients requiring hemodialysis

Question 10

Outline the pathophysiology of HBsAg and anti-HBs in HBV infection

Answer 10

1) HBsAg in serum 1-10w after HBV exposure
- BEFORE hepatitic symptoms + ALT elevation
- i.e. 1-10w incubation period

2) HBsAg negative in 4-6m for patients who recover from acute HBV hepatitis

3) HBsAg positive at >6m after HBV exposure implies chronic HBV infection
- 0.5% annual clearance rate

4) HBsAg negative is followed by anti-HBs positive

Question 11

What is the clinical significance of HBcAg and anti-HBc IgM in HBV infection?

Answer 11

1) In the window period between HBsAg disappearance and anti-HBs appearance neither one of these serological markers may be detectable
2) In this window period, serological diagnosis of HBV infection can be made by anti-HBcIgM –> common in fulminant HBV hepatitis
3) Its presence suggests acute HBV infection but may persist in serum for up to 2y so it is not always reliable
4) HBcAg is cytoplasmic and never goes into serum so its never measured –> useless serological marker

Question 12

What is the clinical significance of anti-HBc IgG?

Answer 12

1) Present in patient recovered from acute HBV hepatitis
2) Present in patient w/HBsAg progressing to chronic HBV hepatitis

i.e. useless ==

Question 13

What is the clinical significance of HBeAg and anti-HBe in HBV infection?

Answer 13

1) HBeAg produced from precore protein
2) Marker of replication and infectivity
3) e-seroconversion occurs before s-serocoversion
4) e-seroconversion delayed in chronic HBV hepatitis
5) e-seroconversion associated w/drop in HBV DNA and remission of liver disease (drop in ALT)

Question 14

Outline the diagnosis of acute HBV hepatitis

Answer 14

1) HBsAg +ve
2) anti-HBc IgM +ve
3) HBeAg +ve
4) HBV DNA +ve

Question 15

List differentials for patients w/HBsAg +ve hepatitis

Answer 15

1) acute HBV hepatitis
2) exacerbation of chronic HBV hepatitis
3) reactivation of chronic HBV hepatitis
4) superinfection of chronic HBV carrier w/HAV, HCV, HDV, or HEV
5) acute toxin/drug hepatitis in chronic HBV carrier

Question 16

Outline the diagnosis of past HBV infection w/acquired immunity

Answer 16

1) anti-HBc IgG +ve

2) anti-HBs +ve

Question 17

Outline the diagnosis of chronic HBV infection

Answer 17

1) HBsAg +ve for >6m
2) HBeAg +ve to assess level of replication and infectivity
3) HBV DNA +ve to assess level of replication and infectivity

Question 18

What investigations are needed in a HBeAg -ve patients with persistently elevated ALT levels?

Answer 18

1) HBV DNA

Question 19

Explain why HBeAg -ve patients may still have elevated ALT levels

Answer 19

These patients are infected by a special type of HBV

1) Wild type
2) HBeAg -ve HBV variants
- these variants have mutations in precore or basal core promotor region
- this reduces or may abolish HBeAg production

Thus despite the lack of HBeAg production the HBV virus will still be actively replicating thus eliciting an immune response to actively damage HBV infected hepatocytes causing elevated ALT

Question 20

Outline the diagnosis of chronic HBV infection

Answer 20

1) HBsAg +ve >6m
2) HBV DNA > 5log (20000IU/mL)
3) ALT >2x normal