Chronic Hepatitis B infection

Incidence

Age

Sex - M > F

Geography - common in developing countries - vertical transmission
- mainly in high risk groups in the UK

Aetiology
- ? deficiency in recognition of HBV antigens by cytotoxic T cells
- healthy carrier state occurs in patients with a very poor cell-mediated immune response
- patients with a better cell-mediated immune response have continuing hepatocellular damage and develop chronic liver disease

- replicative and integrated phases
- in replicative phase there is active viral replication, patient is highly infectious
- in integrated phase, viral genome is incorporated into host DNA; HBV DNA serum level is low, HBeAg is -ve, HBe antibody-positive. HCC develops during this phase
- incorporation of viral genome is thought ot be an important factor in carcinogenesis

- ? inactivation of p53-induced apoptosis

Presentation History
- there is often no history of an acute attack
- may be asymptomatic
- may present as mild progressive hepatitis
- 50% present with establiched chronic liver disease

Investigations
LFTs
- mild rise in AST/ALT
- slightly raised ALP
- bilirubin is often normal

Liver biopsy, histology and immunohistochemistry
- HBsAg and HBcAg may be detected in liver biopsy

Macro

Micro - variable - normal with some interface hepatitis - cirrhosis
- chronic inflammatory cell infiltrates comprising lymphocytes, plasma cells ± lymphoid follicles are present in the portal tracts
- there may be interface hepatitis, lobular change, focal lytic necrosis, apoptosis and local inflammation

Staging

Serum markers - HBeAg
- HBsAg
- HBV DNA

Management
Conditions for treatment
- HBsAg, HBsAg and HBV DNA present in serum
- abnormal AST/ALT
- chronic hepatitis seen on liver biopsy

Do not treat if:
- normal aminotransferases
- decompensated liver disease

Medical
- aim is seroconversion, with disappearance of HBeAg and HBV DNA from serum
- spontaneous seroconversion rate is 10-15% per year

a-Interferon
- 5M units daily or 10M units three times weekly for 4-6 months
- drug treatment can be accompanied by systemic symptoms - acute, flu-like illness shortly after first injection; malaise, headaches, myalgia, depression, diarrhoea, reversible hair loss and bone marrow depression are common (30%) - monitor platelet count
- patients with decompensated liver disease often have severe side-effects
- patients with HBeAg -ve liver disease or concomitant HIV infection generally respond poorly

Famciclovir and lamivudine are better tolerated and under evaluation

Prognosis
- response rate to a-interferon therapy is 25-40%

Good prognostic indicators
- short duration of disease
- high serum AST/ALT
- acute liver disease with fibrosis on histology
- low levels of HBV; HBeAg +ve virus
- absence of immunosuppression

- most patients in whom HBeAg disappears remain in remission; they remain carriers with HBsAg present, but many will become HBsAg negative

Complications - HCC

Hepatobiliary medicine

Main Page

Incidence
Age
Sex	- M > F
Geography	- common in developing countries - vertical transmission - mainly in high risk groups in the UK
Aetiology	- ? deficiency in recognition of HBV antigens by cytotoxic T cells - healthy carrier state occurs in patients with a very poor cell-mediated immune response - patients with a better cell-mediated immune response have continuing hepatocellular damage and develop chronic liver disease - replicative and integrated phases - in replicative phase there is active viral replication, patient is highly infectious - in integrated phase, viral genome is incorporated into host DNA; HBV DNA serum level is low, HBeAg is -ve, HBe antibody-positive. HCC develops during this phase - incorporation of viral genome is thought ot be an important factor in carcinogenesis - ? inactivation of p53-induced apoptosis
Presentation	History - there is often no history of an acute attack - may be asymptomatic - may present as mild progressive hepatitis - 50% present with establiched chronic liver disease
Investigations	LFTs - mild rise in AST/ALT - slightly raised ALP - bilirubin is often normal Liver biopsy, histology and immunohistochemistry - HBsAg and HBcAg may be detected in liver biopsy
Macro
Micro	- variable - normal with some interface hepatitis - cirrhosis - chronic inflammatory cell infiltrates comprising lymphocytes, plasma cells ± lymphoid follicles are present in the portal tracts - there may be interface hepatitis, lobular change, focal lytic necrosis, apoptosis and local inflammation
Staging
Serum markers	- HBeAg - HBsAg - HBV DNA
Management	Conditions for treatment - HBsAg, HBsAg and HBV DNA present in serum - abnormal AST/ALT - chronic hepatitis seen on liver biopsy Do not treat if: - normal aminotransferases - decompensated liver disease Medical - aim is seroconversion, with disappearance of HBeAg and HBV DNA from serum - spontaneous seroconversion rate is 10-15% per year a-Interferon - 5M units daily or 10M units three times weekly for 4-6 months - drug treatment can be accompanied by systemic symptoms - acute, flu-like illness shortly after first injection; malaise, headaches, myalgia, depression, diarrhoea, reversible hair loss and bone marrow depression are common (30%) - monitor platelet count - patients with decompensated liver disease often have severe side-effects - patients with HBeAg -ve liver disease or concomitant HIV infection generally respond poorly Famciclovir and lamivudine are better tolerated and under evaluation
Prognosis	- response rate to a-interferon therapy is 25-40% Good prognostic indicators - short duration of disease - high serum AST/ALT - acute liver disease with fibrosis on histology - low levels of HBV; HBeAg +ve virus - absence of immunosuppression - most patients in whom HBeAg disappears remain in remission; they remain carriers with HBsAg present, but many will become HBsAg negative
Complications	- HCC