ORGB 423 Lecture Notes - Lecture 13: Viral Hepatitis, Hdv, Alkaline Phosphatase
12 Jun 2018
School
Department
Course
Professor
MIMM466 Viral Pathogenesis
2018-01-29 LEC 13, 14 Hepatitis Viruses
What is hepatitis?
• The word means inflammation of the liver
• 5 main hepatitis viruses: HAV, HBV, HCV, HDV, HEV
o Vaccine available for all except HCV
• 400M cases of HBV and HCV worldwide
• 1.4M people die of hepatitis every year
• 90% of HCV, which used to be a fatal and required liver transplantation, can now be cured
• Spreading of virus:
o HAV, HEV are enteroviruses that replicate in the GI tract. We catch them by ingesting water or food
that has fecal contamination
o HBV, HCD, HDV are transmitted by blood, sperm, or other bodily fluids
Signs of Liver Damage
• Hepatocellular enzymes in bile reflect spillage of intracellular contents of hepatocytes
• Hepatocellular injury (e.g. hepatitis)
o damaged liver cells develop leaky membranes
o intracellular enzymes such as aspartate
aminotransferase (AST) escape into the
circulation
• Cholestasis (e.g. biliary obstruction or hepatic
infiltration)
o obstructed/damaged hepatic bile ducts induce
elevated synthesis of alkaline phosphatase (ALP)
o ALP reflects damage of biliary cells
• Bilirubin is not useful for distinguishing between
cholestasis and hepatocellular injury
o may be elevated in both
Stained hepatocytes at various stages of infection
Healthy Liver
Progression toward cirrhosis
Nodular cirrhosis of the liver
Smooth, homogenous surface,
with few islands of fibrous tissue
Slightly nodular, abnormal
hepatocytes, more fibrous tissue
Large nodules, fibrosis surrounds
areas of normal liver tissue
Scar tissue prevents hepatocytes
from regenerating normally
Eventually get loss function and
liver failure
Hepatocytes are stained red, fibrous tissue stained blue
Types of viral hepatitis
Name
Group
Transmission
Carrier/Chronic State?
HAV
Picornavirus
Fecal/oral
N
HBV
Hepadnavirus
Blood/sex
Y
HCV
Flavivirus
Blood
Y
HDV
Viroid-like
Blood
Y
HEV
Calcyvirus
Fecal/oral
N
HFV
--
Fecal /oral
--
• HDV is a plant pathogen
• HFV causes rare scattered epidemics in Asia, similar disease to Hep A through E, but tests negative
HAV
• Tiny RNA viruses with protein capsids can be immunoprecipitated from fecal material
• Reported cases are much lower than estimated cases
o Since 1990s, both reported and estimated cases have declined
• Geography: distribution is mostly in 3rd world countries
• Many cases occur in community-wide outbreaks
o no risk factor identified for most cases
o highest attack rates in 5-14 year olds
o children serve as reservoir of infection
• Persons at increased risk of infection: travelers, homosexual men, injecting drug users
o Vaccination strategy: vaccinate children and groups at risk
HBV
• No envelope, encased in a surface protein with a helical nucleocapsid inside
• Some viral particles have protrusions, which are actually agglomerations of surface Ag
• In the blood: some particles had the viral core + surface Ag, but some were only made up of virus surface Ag
o Overproduction of surface Ag in the liver leads to secretion into the circulation
• E Antigen (HBeAg): part of the polymerase complex
o Circulating E Ag indicates high levels of virus replication and infectivity
• Genome: 3kb, 4 ORFs which partially overlap and anre transcribed in different directions
o The 4 ORFs encode:
§ S: large protein from which pre-S1 and S2 are cleaved
§ P: Polymerase
§ C: core structural protein
§ X: a non-structural protein that also has polymerase function in infected
cells
o Every single nucleotide is a coding nucleotide
o 2 strands, 1 is a complete circle (L strand) and the other is an incomplete strand
(S strand)
• Transcription: after infection, genomic circular RNA is repaired into a closed circle
which is either:
o (1) Transcribed into (+) mRNA to make proteins
o (2) Transcribed into genomic ssRNA, and used as template for making new genomic DNA
• HBV has RT activity and is essentially a retrovirus that encapsulates a different part of their life cycle into the
virus particle
• Since vaccine became available (1980s), incidence has sharply dropped
• Viral concentration in body fluid:
o Highest in blood, serum, and wound exudates
o Moderate in semen and vaginal fluid
o Lowest in urine, feces, sweat, tears, breastmilk, and saliva
Document Summary
We catch them by ingesting water or food that has fecal contamination: hbv, hcd, hdv are transmitted by blood, sperm, or other bodily fluids. Smooth, homogenous surface, with few islands of fibrous tissue. Large nodules, fibrosis surrounds areas of normal liver tissue. Hepatocytes are stained red, fibrous tissue stained blue. Calcyvirus: hdv is a plant pathogen, hfv causes rare scattered epidemics in asia, similar disease to hep a through e, but tests negative. Hbv: no envelope, encased in a surface protein with a helical nucleocapsid inside, some viral particles have protrusions, which are actually agglomerations of surface ag. S: large protein from which pre-s1 and s2 are cleaved. Hbeag+ mothers are more likely to transmit to their offspring. This is the main mode of transmission in high risk populations. E. g. in china, where 40% of pop are chronic carriers. Initial rise in surface ag (hbsag), and then decreases. Rise in igm anti-hbc, which then decreases.
