This document summarizes chronic viral hepatitis caused by hepatitis B, C, and D viruses. It describes the modes of transmission, clinical manifestations, laboratory diagnosis, and morphology of each virus. Chronic hepatitis B and C can lead to cirrhosis and liver cancer over many years. Hepatitis B and D viruses can only replicate in hepatocytes infected with hepatitis B virus. Laboratory tests for hepatitis B, C, and D include detecting viral antigens, antibodies, RNA, and liver enzymes to determine infection and disease status.

1. CHRONIC VIRAL HEPATITIS

2. Chronic hepatitis
• Symptomatic, biochemical/serologic evidence of continuing or
relapsing hepatic disease for 6 months with histologically
documented inflammation & necrosis.
• Causes:
1. Hepatotrophic agents (Chronic viral hepatitis) : HBV, HCV, HDV
2. Other causes:
• Chronic alcoholism
• Wilson’s disease
• Alpha1 antitrypsin deficiency
• Drugs – INH, methyldopa, methotrexate
• Autoimmunity

3. Hepatitis B
• Hepatitis B also k/a serum hepatitis caused by HBV infection.
• Incubation period 4 to 26 weeks
• may occur at any age
• affects 400 million people worldwide, with the highest prevalence
(>8%) in Africa, Asia, and the Western Pacific rim.

4. Mode of Transmission
1. High Prevalence: vertical transmission during child birth (90%)
2. Intermediate prevalence: Horizontal transmission esp in early
childhood by minor cuts and breaks in skin/mucous membranes
3. Low Prevalence: Unprotected sex and IV drug abuse

5. Spectrum of Disease
1. acute hepatitis followed by recovery
2. acute hepatic failure with massive liver necrosis
3. chronic hepatitis with or without progression to cirrhosis
4. Asymptomatic carrier state
• HBV-induced chronic liver disease is an important precursor for
development of HCC

6. • Carrier state defined as:
• individuals who harbor one of the virus but has no liver disease
• individuals who harbor one of the virus and have non-progressive liver
damage but essentially free of symptoms or disability.

7. The Hepatitis B virus morphology
• Partially dsDNA, Hepadna virus family
• Eight genotypes
• 42nm, spherical double layered “Dane Particle”
• Outer surface envelope of protein, lipid and carbohydrate
• Inner: electron dense 28 nm slightly hexagonal core
• Genome partially double-stranded circular DNA molecule having 3200
nucleotide with four open reading frames.

8. VIRAL GENOME
• Four Open Reading Frames Coding For:
1. Nucleocapsid “Core” protein (HBcAg),
HBeAg; produced from pre-core
protein
2. Envelope Glycoproteins (HBsAG)
• Large (pre S1, Pre-S2, and S)
• Middle (Pre-S2 and S)
• Small (Only S)
3. Polymerase (Pol)
• Exhibits both DNA polymerase and reverse
transcriptase activity
4. HBx protein
• Necessary for viral replication
• Implicated in the pathogenesis of HCC

9. PATHOGENESIS
• The virus replicates in the liver and virus particles, as well as excess
viral surface protein, are shed in large amounts into the blood.
• Viraemia is prolonged and the blood of infected individuals is highly
infectious

10. PATHOGENESIS HBV (2 PHASES)
1. PROLIFERATIVE PHASE:
• Formation of complete virion
• HBsAg & HBcAg in association with MHC-Class1 CD8+cytotoxic T
lymphocytes
• Hepatocyte destruction occurs.

11. 2. INTEGRATED PHASE:
• viral DNA is incorporated into the host genome.
• With cessation of viral replication within hepatocytes and the appearance of
anti viral antibodies, infectivity ends and liver damage subsides
• HBV genome integrated into the host genome, the risk of hepatocellular
carcinoma persists

12. Laboratory diagnosis
• HBsAg:
• appears before the onset of symptoms and peaks in acute, symptomatic
disease.
• In those who clear the infection, it often declines to undetectable levels in 12
weeks, but can be present for as long as 24 weeks.
• By contrast, HBsAg persists in cases that progress to chronicity.

13. • Anti-HBs antibody:
• begins to rise following the resolution of acute disease, generally after the
disappearance of HBsAg.
• In some cases, the appearance of anti-HBs antibody is delayed until weeks to
months after disappearance of HBsAg; in such instances, the serologic
diagnosis can be made by detection of IgM anti-HBc antibody.
• Anti-HBs antibodies tend to persist for life, conferring protection

14. • HBeAg, HBV DNA, and HBV DNA polymerase
• are detectable in the serum soon after HBsAg and signify active viral
replication.
• Persistence of HBeAg is an important indicator of continued virus replication,
infectivity, and probable progression to chronic hepatitis.
• Window phase – HBcAg is positive

15. • Anti-HBe antibody:
• signifies that acute infection has peaked and is on the wane,
• HBeAb indicates low transmissibility
• whereas in cases that progress to chronic infection, anti-HBe antibody is not
produced or appears only late in the disease course.

16. Laboratory diagnosis
• Supporting investigations:
• CBC
• Bilirubin- Increased after the detection of HBsAg
• AST/ALT: Extent of liver damage, Shortly after HBsAg
• PT: Increased, Albumin: decreased
• Histopathology

17. Clinical manifestations
• Acute HBV infection is mild or subclinical in nearly two-thirds of adults
• others have nonspecific constitutional symptoms such as anorexia, fever, jaundice, and
upper right quadrant pain.
• Acute liver failure is rare(0.1% to 0.5%)
• most cases, the infection is self-limited and resolves without treatment.
• The infection persists and becomes chronic in 5% to 10% of infected individuals.
• The risk of chronic infection is inversely related to age and is greatest (90%) in infants
who are exposed to the virus through transmission from their mothers at the time of
birth.
• Individuals who acquire HBV at birth and who subsequently develop chronic hepatitis are
also at greatest risk of developing hepatocellular carcinoma

18. Hepatitis C
• Most common chronic blood borne infection
• In contrast to HBV, progression to chronic disease in majority cases
• Mode of transmission:
• Intravenous drug abuse
• Multiple sex partners
• Needle stick injury
• Multiple contacts with HCV infected person
• Unknown (32%)

19. • Incubation Period: 4-26 wks (Mean = 9 wks)
• Clinical Course: Milder than that of HBV
• 20% : Cirrhosis over 5-20 yrs

20. • Spectrum of Disease: Same as that of HBV; More (20-30%) go to
chronic hepatitis, Fulminant hepatitis is rare
• Strong immune response involving CD4+ and CD8+ T cells are
associated with self-limited infections

21. HCV morphology
• member of the Flaviviridae family
• single-stranded, enveloped RNA virus,
• diameter of 30-60 nm.
• HCV genome has about 3000 amino acids.
• Consists of two envelope proteins E1 and E2 and five core proteins

22. PATHOGENESIS
HCV induces hepatocellular injury by cell-mediated immune mechanism is
supported by the following:
1. host lymphoid cells are infected by HCV.
2. HCV-activated CD4+ helper T lymphocytes that stimulate CD8+ T lymphocytes
via cytokines elaborated by CD4+ helper T cells.
3. CD8+T lymphocytes produce antiviral cytokines against various HCV antigens.
4. Natural killer (NK) cells also seem to contribute to containment of HCV
infection.

23. Laboratory Diagnosis
• HCV RNA detectable: 1-3wks
• Anti-HCV Ab: detectable in only 50-70% of symptomatic patients
• In remaining, Anti-HCV Ab: after 3-6 wks
• In chronic HCV infection: HCV RNA persist
• Hence testing for the virus essential to confirm diagnosis

24. Laboratory Diagnosis
• Diagnostic:
• HCV RNA (Confirmation + Assess viral replication)
• Anti-HCV Ab (only in minority)
• Supporting:
• AST/ALT: Episodic elevations, intervening normal or near-normal periods
• CBC
• Bilirubin
• PT
• Albumin
• HISTOPATHOLOGY

25. Hepatitis D Virus
• Also called ‘ the Delta Agent’
• Unique RNA virus dependent on HBV for its life cycle
• Replication of virus is thru RNA-directed RNA synthesis by host RNA
polymerase
• 5% of HBV-infected individuals are co-infected with HDV

26. Mode of transmission
• Parenteral route
• intravenous drug use
• multiple blood transfusions.

27. •35nm double shelled particle
•Externl coat: HBsAg
•Internal coat: Delta antigen
•Genome RNA is a single-stranded
•Delta agent is a defective virus because its
genome does not code for its own envelope
protein
•Thus it can only replicate HBV infected
cells
HDV morphology

29. Lab Diagnosis
1. HDV identification in the blood and in the liver cell nuclei.
2. HDAg detectable in the blood and on fixed liver tissue specimens.
3. Anti-HD antibody in acute hepatitis which is initially IgM type and later
replaced by IgG type anti-HD antibody which persists for life to confer
immunity against reinfection.
4. In HDV superinfection, HBsAg is present in serum, and anti-HDV
antibodies persist for months or longer.

30. Thank you