Viral Hepatitis

Question 1

Definition and aetiology of viral hepatitis

Answer 1

Definition:
Viral infection of hepatocytes- necrosis+ inflammation of liver

Aetiology :
~ hepato-tropic viruses: A, B, C, D , E - all are RNA except B
~ A& E: cause infectious hepatitis - faecal oral route
~ B,C,D : serum hepatitis: parental , sexual —> in progress to cirrhosis + HCC
~ Hepatitis virus cannot be identified- non- A-E

Question 2

Hepatitis A virus

Answer 2

~ non-enveloped, 27nm, RNA virus
~ Outer capsid protein - HAVAg
~ source of infection: acutely infected person ( virus is excreted in stool/ feces )
~ diseases is maximum infectious before onset of jaundice

~ transmission: Feco-oral route
~ IP : 3-6 weeks

~ benign, self Ltd, acute hepatitis
~ does not produce chronic hepatitis or carrier State

Lab diagnosis
1.Prodromal stage:
~ serum BiliRubin normal
~ Bilirubinuria
~ AST, ALT raised

2.Icteric stage
~ serum BiliRubin raised
~ AST raised
~ ALP <300 IU/L

DIAGNOSIS
~ virus in feces - electron microscope in preicteric phase
~ antibody detection: IgM anti-HAV - reliable marker of acute infection
IgG anti- HAV - provides lifelong immunity

Prophylaxis
~ Improve sanitary practises + prevention of faecal contamination

Question 3

Hepatitis B virus

Answer 3

~ dsDNA virus, virion is double layered, Dane particle/ complete, viral particle
~ HbsAg - surface antigen, immunogenic, secreted in blood, ground glass appearance in cytoplasm, stain orange with Ocrein stain
~ HBcAg- core antigen, intra cellular, does not circulate, not detectable in serum, sanded nuclei appearance
~HBeAg- precore antigen, secreted in serum, marker for high levels of replication
~HBV polymerase- needed for viral replication
~ HBxAg- necessary for virus infectivity

Source of infection : human suffering from hepatitis or carrier
Mode of transmission : vertical or congenital, horizontal ( parenteral - percutaneous, mucous membranes, intravenous Route, sexual Route)

IP : 4-26 weeks

Outcome of infection
~ acute hepatitis
~ chronic hepatitis
~ fulminant hepatitis
~ cirrhosis
~ asymptomatic carrier
~ HCC

Question 4

Hepatitis C virus

Answer 4

~ small enveloped, ssRNA
~ mode of transmission: vertical transmission ,parenteral route , sexual contact
~IP: 2-26 weeks
~ Viral RNA polymerases: gives rise to new genetic variants
~ emergence of endogenous, newly mutated strain, its genomics, instability and anti-genic variability, makes it difficult to produce effective vaccine
~ 6HCV genotypes
~ quasi-species: each patient gets infected with a population of divergent but closely related variants

Life cycle :
~ viral envelope proteins, attaches to receptor on hepatocytes
~ virus enters the liver cell to receptor mediated endocytosis
~ fusion and uncoating
~ release RNA genome into cytoplasm
~ viral proteins: viral protease, NS5A, viral RNA polymerases
~ translation and protein processing
~ R.NAreplication
~ Viral assembly
~ release of HCV

Outcome of infection
~ acute hepatitis
~ chronic hepatitis
~ cirrhosis
~ fulminant hepatic failure

Question 5

Hepatitis D virus

Answer 5

~ defective RNA virus. Requires HBV for replication and expression
~ found only in HBV carriers
~ causes Delta hepatitis
~ acute coinfection: exposed simultaneously to both B &D
~ super infection: already infected with HBV , exposed to new dose HDV
~ parental route and sexual Route

Outcome of infection
~ coinfection of B & D (acute and chronic hepatitis)
~ super infection with HDV in chronic HbsAg carrier(acute, chronic, cirrhosis, HCC)

Serological markers
~ HDV RNA - Early days of acute disease
~ Anti- HDV : IgM - most reliable indicator of recent exposure

Question 6

Hepatitis E virus

Answer 6

~ un enveloped, RNA, 32-34 nm
~ primarily in young to middle-aged adults
~ source of infection :zoonotic animal reservoirs
~ Mode of transmission : enterically, water phoren
~ IP: 6 weeks

Outcome
~ self-limiting acute hepatitis
~ high mortality in pregnant woman

Diagnosis
~HEV RNA detection - before clinical illness
~anti- HEV IgM - onset of clinical illness
~anti- HEV IgG- after recovery

Question 7

Clinical features of viral hepatitis

Answer 7

1. Asymptomatic infection with recovery.
   ~ mild elevation of serum transaminase, presence of anti-viral antibodies
2. Acute hepatitis: four phases
   ~ incubation period
   ~ symptomatic preicteric period- nausea, loss of appetite, abdominal pain
   ~ symptomatic icteric period- jaundice, yellow sclera, dark coloured urine (hyperbilirubinaemia), pruritus (bile salt accumulation)
   ~ convalescence
   ~ investigations: biochemical, serological, microscopic
3. Fulminant hepatitis
   ~ Massive hepatic necrosis
4. Chronic hepatitis
5. Chronic carrier state

Question 8

Morphology of acute hepatitis

Answer 8

Gross:
~ swollen, diffuse or patchy involvement
~ muddy red, green discolouration due to jaundice

Micro:
~ hepatocyte injury: ballooning degradation- swelling, pale clumped cytoplasm
~ hepatocyte necrosis: dropout necrosis ( rupture of cell membrane - cell death - necrotic dropout - collapse of collagen reticulin framework - aggregation of macrophages
~ acidophilic or apopptotic or council main body: due to cytotoxic T cells- eosinophilic, pyknotic, fragmented nuclei- remnants of extruded into sinusoids
~ bridging necrosis- Portal to portal tract, central to Central vein,portal to Central
~ inflammation: mononuclear cells, lobular hepatitis or spotty, necrosis, interface hepatitis
~ kupffer cells: hypertrophy and hyperplasia
~ lobular disarray: disruption of normal architecture