Viral Hepatitis Flashcards
Transaminases
-AST occurs in 2 isoenzymes (cytoplasmic and mitochondrial)
-Found in cardiac and skeletal muscle, kidney, pancreas and RBC
=Increase in alcoholic liver injury when ALT normal (ratio>2)
-ALT cytoplasmic
=Low concentration in muscle
=Usually, parallel rise and fall in liver disease
=Increases in HCV and fatty liver when AST normal
Alkaline phosphatase
-Zinc metalloenzymes
-Liver, bone and kidney – same gene but placenta and intestine different gene.
-Increase in last trimester to 2x ULN which may persist for a few weeks following delivery.
-Wheat-germ lectin affinity electrophoresis separates bone and liver isoenzymes
Glutamyl transferase
-Found in liver, kidney, pancreas, intestine and prostate (membrane bound)
-15% of those screened above “normal” levels (4% > 100)
-Activity is not increased in 1/3 of heavy drinkers without liver disease.
-A binge does not increase levels in “healthy” livers
-Levels drop after 2-5 weeks of stopping drinking
-Commonly increased with enzyme-inducing medication
Causes of viral hepatitis
-Common
=Hep A, B(+/- D), C, E
Less common
=Cytomegalovirus
=Epstein-Barr virus
-Rare
=Herpes simplex
=Yellow fever
Describe Hep A
-Enterovirus (picornavirus)
-RNA
-27nm
-2-4-week incubation
-Spread: faeces (faecal-oral), salvia
-Anti-HAV antibodies (IgM) in transient incubation period
-Vaccine/ passive prevention= immune serum globulin (IgG)- marker of previous infection
-No chronic carrier state
Describe Hep B
-Hepadnavirus
-DNA and DNA polymerase enzyme= Dane particle
-42nm
-Incubation 4-20 week
-Spread: Blood, saliva, sexual, vertical
-Chronic infection (6 months HBsAg), often asymptomatic
=HBsAg (Hep B surface antigen indicator of active infection)
=Hep B core IgM (recent infection)
-Vaccine, hyperimmune serum globulin
Describe Hep C
-Flavivirus
-RNA
-30-38nm
-2-26-week incubation
-Spread: blood, saliva
-Chronic infection
-No prevention
Clinical features of acute infection
-Non-specific prodromal illness
=Headache
=Myalgia
=Arthralgia
=Nausea
=Anorexia
=Jaundice
=Dark urine
=Dark stool
=Vomiting
=Diarrhoea
=Abdominal discomfort
-O/E
=Liver tender but only minimally enlarged
=Mild splenomegaly and cervical lymphadenopathy
Complications of acute viral hepatitis
-Acute liver failure
-Cholestatic hepatitis (Hep A)
-Aplastic anaemia
-Chronic liver disease and cirrhosis (Hep B and C)
-Relapsing hepatitis
Investigations of viral hepatitis
-Hepatic LFTs
=Serum transaminases 200-2000 U/L in acute infection
=Plasma bilirubin reflects degree of liver damage
=ALP rarely exceeds twice the upper limit of normal
-Prolongation of PT indicates severity of hepatitis, rarely exceeds 25 seconds except in liver failure
-WCC normal with relative lymphocytosis
Overall management of viral hepatitis
-Drugs such as sedatives and narcotics (metabolised in liver) should be avoided
Overall management of viral hepatitis
-Drugs such as sedatives and narcotics (metabolised in liver) should be avoided
-No alcohol during acute illness
-Elective surgery avoided in acute hepatitis as risk of post-operative liver failure
-Liver transplantation in complications of cirrhosis resulting from chronic hep B/C infection
Source of hep B infection and risk of chronic infection
Horizontal transmission (10%)
* Injection drug use
* Infected unscreened blood products
* Tattoos/acupuncture needles
* Sexual transmission
* Close living quarters/playground play as a toddler (may contribute to high rate of horizontal transmission in Africa)
Vertical transmission (90%)
* Hepatitis B surface antigen (HBsAg)-positive mother (most common cause of infection worldwide, highest risk of chronic infection)
Why may the adaptive immune response to HBV be absent initially in vertical transmission of hep B?
-Introduction of antigen in neonatal period tolerogenic
-Presentation of such antigen within the liver promotes tolerance (absence of significant innate/ inflammatory response
-Very high loads of antigen may lead to exhaustion of cellular immune response
=May be reversed by therapy/ spontaneous changes in innate response (IFN-a, NK), host-mediated immunopathology
Describe the 5 phases of chronic HBV infection
- Immune-tolerant phase
=High viral load so very infectious, normal/ low ALT - Immune-reactive HBeAg +ve chronic hepatitis phase
=Raised ALT, mod/severe necroinflammation - Inactive carrier phase
=Normal ALT, normal/ minimal necroinflammation - HBeAg -ve chronic hepatitis phase
=Fluctuating viral load, raised/ fluctuating ALT, mod/severe necroinflammation - HBsAg -ve phase
=Normal viral load and ALT
