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

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© 2007 Chettinad Hospital & Research Institute