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INFECTIOUS DISEASES OF LIVER
© 2008 Chettinad Hospital & Research Institute
Lesson Plan
Viral Hepatitis-A,B,C,D:EpidemiologySerologyMorphologyFate
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
Hepatitis virusesHAV 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
4-7Weeks
2-8Weeks
Carrier state
none 01-1% donors
0.2-1% donors
1-10%
chronic None 5-10% >50% <5% NoneCancer No Yes Yes - -
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
Serological diagnosis
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.
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
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
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.
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
Serology
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
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
Hepatitis B
Immunoperoxidase stain for HBsAg from the same case,
showing cytoplasmic inclusions of viral particles.
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%
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
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.
Potential outcomes of hepatitis C infection in adults
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
Differing clinical consequences of two patterns of combined
hepatitis D virus and hepatitis B virus infection.
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
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
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
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
Liver parenchyma showing hepatocytes with diffuse granular cytoplasm- ground glass hepatocytes
Acute viral hepatitis showing disruption of lobular architecture, inflammatory cells in the sinusoids, and hepatocellular apoptosis
Gross:Macronodular cirrhosis
BACTERIAL INFECTIONS OF THE LIVER• Abscess – cholangitic (ascending)
• pylephlebitic (e.g. diverticulitis, appendicitis)• arterial (sepsis)
• Granulomas• TB, tularemia, brucellosis
• Diffuse inflammation• sepsis
• 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
Thank you
© 2007 Chettinad Hospital & Research Institute