Virology

Epidemology
diagnostics
At the endo of this session participant should be
able to
 Understand the basic concepts of HBV
 Recognize the different clinical m/n and
complications related to HBV
 Identify when and whom should receive HBV
treatment
 HEPATITIS B

Member of Hepadnaviridae that primarily infects liver

cells
small, circular, 3200-basepair size, DNA Virus
DNA codes for four sets of viral products ( 4
genes)
– Consists of surface and core, polymerase, & X-protein
Known carcinogen
The virus
HBV genome
Various forms of HBsAg particles

Whole infectious
HBV virions

HBsAg
filaments
HBsAg
spherical
bodies

Moucari R et al, Liver Intern 2011

Genotypes
 Hepatitis B Virus Life Cycle

Eradication of
Chronic HBV difficult
1)Stable, latent
cccDNA
2)Error prone HBV
replication
3)Mutants in pre-
core region

*Courtesy Ray Chung, MGH

 Serology for HBV
• Hepatitis B surface Antigen (HBsAg)

• Hepatitis B core Antigen (HBcAg)

 antigen expressed on the surface of the
nucleocapsid core
 sequestered within HBsAg coat HBcAg
is not detectable routinely in the serum
• Anti-HBc Abs
 Marker of infection during “window”
period

• Hepatitis B e Antigen(HBeAg)
 is immunologically distinct from intact
HBcAg but is a product of the same C gene.
 marker of HBV replication and relative
infectivity.
 Persistence beyond the first 3 months may
be predict chronic infection
Serological Patterns of Acute & Chronic Hepatitis B

HBsAg
Serologic Patterns of Hep B Inf.
Anti-HBs Anti-HBc HBeAg Anti-HBe Interpretation
Acute HBV Infection
+ - IgM + - HIGH INFECTIVITY
Chronic HBV Infection
+ - IgG + - HIGH INFECTIVITY
Chronic / Late acute HBV Inf
+ - IgG - + LOW INFECTIVITY
1. Acute HBV Infection
- - IgM +/- +/- 2. “Window Period”
1. False Positive
- - IgG - - 2. Less likely – inf romote past
Recovery from HBV infection
- + IgG - +/-
1. Immunization
- + - - - 2. Remote Infection
Precore mutation (Meditteranean)
+ - IgG - - HIGH INFECTIVITY
 Mode of transmission

100 times more infectious than HIV

10 times more infectious than HCB
 Whom do you Screen?
• Screening all individuals
– Prior to
• Priority should be given immunosuppressive or
to– : Health care workers (including cancer therapy
health professionals and – Organ transplant recipients
supporting staffs) – Blood or organ Donors
– Hemodialysis patients
– Persistently elevated liver
– I.V drug users(rare)
–
enzymes (AST, ALT)
People with high risk sexual
behavior
– Partner of HBV Infected Persons
– HIV positive patients
– HCV Positive patients
– Pregnant mothers
• Progression from acute HBV to chronic HBV
 depends largely on age of acquisition
 Nearly 95% resolves and about 5% develop chronic hepatitis B in
healthy adults.
 Natural course of chronic HBV

risk of HCC is 2%-5%/yr

• Cumulative 5-year incidence of cirrhosis is 8%-20%

• 5-year cumulative risk of hepatic decompensation is 20%
• Untreated patients with decompensated cirrhosis have a poor prognosis,
with 15–40% survival at 5 years
 Chronic HBV
• Chronic HBV and HCV infection
– are the leading cause of liver disease world-wide
• ≈ 400 million people world wide are infected with HBV & HCV
• WHO estimates that 296 million people were living with chronic hepatitis B
infection in 2019, with 1.5 million new infections each year.
– the majority of infections are asymptomatic
– are silent killers
– Majority of those infected do not know their sero-status
– Without treatment they are associated with significant
morbidity and mortality
• HBV +HCV accounts for > 60% of CLD and > 80% of HCC in Ethiopia
Majority of mortality is from HBV & HCV
 ………cont’d
• The majority of these individuals will not experience
complications
– but 15% - 40% will have serious sequelae.
• In highly endemic regions:
– 8% or more of the population are chronic HBV carriers,
– the lifetime risk of infection ranges from 60% to 80%.
• In intermediate risk areas:
– the lifetime risk of infection is b/n 20% and 60% &
• in low risk areas
– the lifetime risk of infection is bellow 20%.

• Ethiopia
– is in highly endemic region(sero-prevalence = 9.4%)
– M:F = 63% Vs 37% &most common among 21-40 year olds
– Substantial perinatal and childhood transmissions occur
– Healthcare providers at greatest risk of infection
Factor associated with risk of progression
to cirrhosis and HCC
Current classification of chronic HBV
Natural Progression of Chronic HBV

www.AASLD.org (2010)
Clinical manifestation & complications
• Variable ranges from asymptomatic to serious
complications.
• HBV can cause HCC even in the absences of cirrhosis
• Once symptomatic the presentation in relation to liver insult
may not be different from other causes of liver disease
• Extra-hepatic complications
– Arthritis-Dermatitis
– Polyarteritis Nodosa
– Glomerulonephritis/NS
– Cryoglobulinemia
Assessment of Liver Disease

• Liver function tests

• HBV DNA
• HBsAg quantification
• Imaging (USS, CT Scan and/or MRI)
• Non-Invasive methods of evaluation of fibrosis- APRI score , FIB-4,
Fibroscan
• Liver biopsy
• Other relevant tests, e.g. HAV, HIV,HCV,HDV
LIVER FUNCTION TESTS

• ALT - is a more specific marker of liver inflammation

• AST
• ALP
• Bilirubin
• Albumin
 HBV DNA

• Gives an idea as to the load of the virus in the patient

• It is important for the identification of occult HBV infection
• It is an important marker for deciding whether a patient goes on
treatment or not.
 HBsAg Quantification

• This is the surface antigen secreted by the S gene and it is very

abundant in the blood of patients with CHB
• It can also be used to determining true inactive carriers (<1,000
IU/ml)
• HBsAg quantification now used as a means of determining likelihood
of development of immune control if treatment is instituted
 LIVER IMAGING

• Abdominal USS - can give information on the structure, architecture,

echogenicity, size and the presence of focal lesions in the liver
• It can also provide information on the vessels, biliary tree, gall bladder,
pancreas, presence or absence of ascites etc.
• CT scan and/or MRI - may be more informative where ultrasound scan
report is non-specific.
 Non-invasive Markers of Fibrosis

• Fibroscan (Normal ≤11KPa)

• FIB-4 (Normal range =/< 2)
– Age (yrs) x AST (IU/L) / platelet count (109/L) x ALT1/2
• APRI score (Normal range =/< 2)
– AST / ULN x 100 / platelet count (109/L)
 Liver Histology

• Liver biopsy (Moderate to severe necro-inflammation and/or

moderate fibrosis constitute significant liver disease)
• Immunohistochemistry (for detection of viral antigens e.g.
HBsAg)
 Treatment of chronic HBV
• Goals of antiviral
– suppression of HBV DNA,
– loss of HBeAg in HBeAg-positive
– Current GOAL of HBV Rx
• loss of HBsAg( difficult and rare )
• Currently eradication of the virus is difficult due to:
• persistent cccDNA
• Integrate to host genome
• Definition of cure
 Partial cure: suppression of HBV-DNA
 Functional cure: Loss HBsAg + above
 Complete cure: loss of cccDNA
 Steralizing cure: loss of integrated DNA
©AASLD, Lok (2014)
Who should be treated …. Ethiopian guideline

National guideline, 2021 draft

Conti…..

National guideline, 2021 draft

Other guidelines
 2018 AASLD Guidance:
What to Start as Initial HBV Therapy