Infectious diseases of liver 16 6-2016

1. INFECTIOUS DISEASES OF
LIVER
© 2008 Chettinad Hospital & Research Institute

2. Lesson Plan
Viral Hepatitis-A,B,C,D:
Epidemiology
Serology
Morphology
Fate

3. VIRAL HEPATITIS
• Hepatotropic viruses (A, B, C, D, E,G)
• Unless otherwise specified, the term “viral hepatitis”
refers to the diseases caused by this group of
hepatotropic viruses
• Yellow fever virus
• Herpes simplex virus and CMV
• Epstein-Barr virus

4. Hepatitis viruses
HAV HBV HCV HDV HEV
Agent ss RNA ds DNA ss RNA ss RNA ss RNA
Route Fecal-
oral
Paren-
teral
Parenteral Paren-
teral
Water
Incuba-
tion
2-6
weeks
4-26
weeks
2-26
weeks
4-7
Weeks
2-8
Weeks
Carrier
state
none 01-1%
donors
0.2-1%
donors
1-10%
chronic None 5-10% >50% <5% None
Cancer No Yes Yes - -

5. HEPATITIS A
• “Infectious hepatitis” – in countries with substandard
hygiene; 25% of clinically evident acute hepatitis
worldwide; Rare after childhood
• Fecal – oral route; virus is shed in feces 2-3 weeks
before & I week after onset of jaundice
• Incubation 2-6 weeks; No carrier state or chronicity
• Mild or asymptomatic in most cases; Rarely fulminant
hepatitis; fatality ~0.1%
• IgM antibody in serum is reliable marker for infection;
IgG antibody provides lifelong immunity

6. Serological diagnosis

7.  Specific antibody against HAV of the immunoglobulin (Ig) M type
appears in blood at the onset of symptoms, constituting a reliable
marker of acute infection
 Fecal shedding of the virus ends as the IgM titer rises.
 IgM response decline in a few months and is followed by the
appearance of IgG anti-HAV.
 IgG anti-HAV- persists for years, perhaps for life, providing
protective immunity against reinfection by all strains of HAV.
 Hence, the HAV vaccine is effective.

8. HEPATITIS B VIRUS
• Causes “Serum hepatitis”
• Clinical spectrum caused by HBV
• Acute hepatitis
• Chronic non-progressive hepatitis
• Progressive chronic hepatitis ending in cirrhosis
• Asymptomatic carrier state
• Backdrop for hepatitis D

9. HEPATITIS B VIRUS
• Hepadnavirus
• Mature virus particle is called Dane particle
• Has
• Core protein (HBcAg & HBeAg)
• Envelope glycoprotein (HBsAg)
• DNA polymerase
• HBX protein is necessary for viral replication &
causation of hepatocellular carcinoma.
• It disrupts normal growth control of infected liver cells
by transcriptional activation of several growth-
promoting genes, such as insulin-like growth factor II
and receptors for insulin-like growth factor I.
• HBx binds to p53 and appears to interfere with its
growth-suppressing activities

10. HEPATITIS B VIRUS INFECTION-Pathogenesis
• Proliferative phase
• Episomal DNA with formation of complete virions &
all antigens
• Cell surface expression of HBsAg & HBcAg lead to
activation of CD8+ T cells
• Integrative phase
• Virus DNA is incorporated into the host cell DNA. With
the cessation of viral replication, infectivity ends &
liver damage subsides.

11. HEPATITIS B
• World wide carrier rate – 300 million
• 300,000 new cases each year in US
• Endemic in Africa & SE Asia
• It is present in all the fluids of the body
• Transmitted by transfusion, IV drug use, dialysis,
homosexual activity, needle stick accidents, trans-
placental

12. Serology

13. HEPATITIS B
• HBsAg – appears before onset of symptoms, peaks during
overt disease & declines in 3-6 months
• HBeAg, HBV DNA, DNA polymerase appear after HBsAg &
indicate replication
• IgM ahti-HBc becomes detectable after onset of
symptoms
• IgG anti-HBs appears after the disappearance of HBsAg
and provides lifelong protection

14. HEPATITIS B
• Disappearance of HBeAg with appearance of anti-HBeAg
is indicative of subsiding disease
• Loss of HBeAg with failure to form Anti-HBeAg is
associated with fulminant course
• Persistence of circulating HBsAg, HBeAg & HBV DNA
usually with anti-Hbc (occasionally with anti-HBs) is
associated with progressive disease

15. Hepatitis B

16. Immunoperoxidase stain for HBsAg from the same case,
showing cytoplasmic inclusions of viral particles.

17. HEPATITIS C
• The most important transfusion associated hepatitis
• 90-95% of all transfusion associated hepatitis
• Also common in homosexuals, hemophiliacs, IV drug
users & hemodialysis patients
• Seroprevalence in US - <0.2%
• In patients with unexplained cirrhosis & liver cancer –
prevalence of anti-HCV =>50%
• Progression to chronic disease - >50%

18. HEPATITIS C
• Incubation – 2 to 26 weeks
• HCV RNA is detectable for 1-3 weeks
• Circulating RNA persists even in the presence of
antibodies
• Clinical course is milder than Hepatitis B
• Persistent infection & chronic hepatitis are hallmarks;
cirrhosis in 5-10 years
• Persistent transaminasemia in chronic cases

20. Chronic viral hepatitis due to hepatitis C virus, showing
portal tract expansion with inflammatory cells and fibrous
tissue and interface hepatitis with spillover of inflammation
into the adjacent parenchyma. A lymphoid aggregate is
present.

21. Potential outcomes of hepatitis C infection in adults

22. HEPATITIS D
• Delta agent
• Absolutely dependent on HBV for multiplication and
causes hepatitis only in the presence of HBV
• Two types of infection
• Co-infection
• Superinfection
• Simultaneous infection leads to more fulminant course
• IgM anti-HDV is a good marker for HDV exposure

23. Differing clinical consequences of two patterns of combined
hepatitis D virus and hepatitis B virus infection.

24. HEPATITIS E
• Epidemics in Asia, (Indian subcontinent) sub-Saharan
Africa & Mexico
• Primarily in young to middle aged
• In most cases self-limited disease
• But in pregnant women, high mortality rate (20%)
• No chronicity

25. CLINICAL SYNDROMES WITH HEPATITIS VIRUSES
• Carrier state – without clinically apparent disease or
chronic hepatitis (healthy or chronic)
• Asymptomatic infection – serologic evidence of infection
only (transaminasemia or antibodies)
• Acute hepatitis – icteric or unicteric
• Chronic hepatitis – without or with progression to
cirrhosis
• Fulminant hepatitis – massive or sub-massive necrosis

26. ACUTE VIRAL HEPATITIS
• Incubation period
• Symptomatic pre-icteric phase – non-specific
constitutional symptoms including fatigue, nausea,
anorexia, weight loss, low fever, serum-sickness like
symptoms
• Symptomatic icteric phase – conjugated
hyperbilirubinemia
• convalescence

27. CHRONIC HEPATITIS
• Symptomatic biochemical or serologic evidence of
continuing or relapsing hepatic disease for more than 6
months with histologically documented inflammation &
necrosis
• Causes
• Hepatitis viruses (particularly HCV)
• Wilson’s disease
• Alpha-1 antitrypsin disease
• Chronic alcoholism
• Drugs (isoniazid, methyl dopa, methotrexate)
• autoimmunity

28. Liver parenchyma showing hepatocytes with diffuse
granular cytoplasm- ground glass hepatocytes

29. Acute viral hepatitis showing disruption of lobular architecture, inflammatory cells in the
sinusoids, and hepatocellular apoptosis

30. Gross:Macronodular cirrhosis

31. BACTERIAL INFECTIONS OF THE LIVER
• Abscess – cholangitic (ascending)
• pylephlebitic (e.g. diverticulitis, appendicitis)
• arterial (sepsis)
• Granulomas
• TB, tularemia, brucellosis
• Diffuse inflammation
• sepsis

32. • Amoebiasis - abscess
• Malaria - hepatomegaly (congestion and uptake of RBC)
• Ascaris - biliary obstruction
• Clonorchis sinensis - periductal fibrosis
• Schistosomiasis - periductal fibrosis
• Echinococcus - cystic hydatid disease
PROTOZOAL AND HELMINTHIC DISEASES

34. Thank you
© 2007 Chettinad Hospital & Research Institute