Hepatitis Flashcards
Which form of Hepatitis is infectious?
Which are found in serum?
Which is enterically transmitted?
Which is parenterally transmitted?
Which Hepatitis is infectious? - Hepatitis A
Which are found in serum? - Hepatitis B and D
Which is enterically transmitted? - Hepatitis E
Which is parenterally transmitted? - Hepatitis C
Which forms of Hepatitis cause chronic viral hepatitis in the US?
Hepatitis C (3.9 million) and Hepatitis B (1.25 million)
Hepatitis A Virus characteristics (serotypes, transmission, acute vs chronic)
- RNA picornavirus
- Single serotype worldwide
- Acute disease and asymptomatic infection
- Fecal-oral transmission
- Spread - contaminated food, water, raw shellfish
- No chronic infection - protective antibodies develop in response to infection - lifelong immunity
Picornavirus structure
- strand, icosahedral RNA virus
- CAPSID stable to acid, drying detergents
- mRNA translated into 1 polyprotein which is cleaved to form mature products
- Virus is not cytolyic but is shed from cells
HAV is steadily released from infected _______
What is the immune response?
Hepatocytes; NK and cytotoxic T cells eliminate infected cells; Ab response also assists in viral clearance
Hepatitis A - Clinical features
Incubation period:
Jaundice by age group:
Rare complications:
Incubation period: Average 3- days; range 15-50 days
Jaundice by age group:
- <6 yrs (<10%)
- 6-14 years (40-50%)
- >14 years (70-80%)
Rare complications:
- Fulminant hepatitis
- Cholestatic hepatitis
- Relapsing hepatitis
How long is the incubation period for Hepatitis A infection?
3 weeks
Preparation of inactivated Hepatitis A vaccines (3 steps)
- Cell culture adapted virus grown in human fibroblasts
- Purified produce inactivated with formalin
- Adsorbed to aluminum hydroxide adjuvant
Who is reccommended for HAV vaccination?
- Infants
- People working in or traveling to areas with high incidence of HAV
- People with chronic liver disease
- People working with HAV
Hepatitis E virus Characteristics
- Enteric Virus
- Calcivirus family
- sense ss RNA virus
- Icosahedral
Hepatitis E - Epidemiologic Features
- Most outbreaks are associated with fecally contaminated drinking water
- Minimal person-to-person transmission
- US cases usually have history of travel to HEV endemic areas
Hepatitis B Virus ( Structure and Characteristics)
- HepaDNAvirus (genotypes A-H)
- Enveloped virus; receptor is sodium/bile acid co-transporter
- Circular DNA genome, partly double-stranded (ds)
Outcome of Hepatitis B Virus Infection by Age at infection
If infected at birth - higher chance of chronic infection (chance decrease as we age)
If infected at older age - higher chance of symptomatic infection
Pathogenesis of Hep B
- Enveloped virus enters through NTCB receptor
- Genome enters, DNA synthesis occurs to form fully ds DNA
- Genome goes to nucleus, transcribed to mRNA
- mRNA translated in cytoplasm
- mRNA reverse transcribed to ss DNA, DNA made partially ds
- DNA encapsidated into new virion (on ER)
- Virions enveloped and released as well as sub-viral particles of sAG (surface antigen)
- DNA can integrate into chromosome and remain in cell
Risk factors for acute Hepatitis B in US
- Heterosexual sex (32%)
- Unrecognized (25%)
- Intravenous drug use (13%)
- Men having sex with men (MSM) - 12%
HBV spread through the body
- Initial infection → blood → Liver → immune complexes → immune complex diseases OR…
- Initial infection → blood → liver → viremia → bodily fluids → transmission
Clinical outcomes of HBV infection in adults
- 90% Resolution
- 1% fulminant hepatitis
- 9% HBsAG+ for > 6 months
- 50% resolution
- Asymtpmatic
- Chronic persistent hepatitis
- Chronic active hepatitis (rare)
- Hepatic cell carcinoma
Hepatitis D virus (delta)
Hepatitis D is a viroid - can only grow in Hepatitis B infected cells
- small RNA, copied by host RNA polymerase II, catalytically active “ribozyme” that processes itself
- Encodes 1 antigen, becomes packaged in Hepatitis B sAG
Presence of HDV can make it more likely for HBV to lead to what condition?
Fulminant hepatitis
Hepatitis D clinical features
Coinfection:
Superinfection:
Co-infection (with HBV): Severe acute disease; low risk of chronic infection
Superinfection (Subsequent to HBV): usually develop chronic HDV infection; high risk of severe chronic liver disease
Why does chronic HVB infection correlate with a high incidence of hepatocellular carcinoma (HCC)
- Injury to liver → proliferation of cells that are usually quiescent → genetic errors accumulate
- Integration of viral DNA into host causes genomic instability
- Virally-encoded “X” protein linked to signal transduction cascades decreases p53 activity (guardian of the genome)
Prevention and Treatment of HBV
- Blood supply screened
- Vaccination - Subunit vaccine: recombinant HBsAG produced in yeast
- Lifestyle precautions
- Polymerase inhibitors, nuceloside analgos, IFN-α (new approaches to silencing HBV expression)
Hepatitis C (Characterisitics)
- Most prevalent “non A non B” hepatitis virus (NANBH)
- Flavivirus
- strand, RNA virus, enveloped virions
- 9kb VLDL: 10 proteins - involves proteolytic processing
- Encodes multiple immunomodulators enabling virus persistence
Liver damage from HCV is due to…
Immunopathology; viral replication induces robust innate immune response
Hepatitis C Viral lifecycle
- Hepatocyte specific - 1012 virions/day
- Entry
- Uncoating
- IRES-mediated translation/Proteolytic processing
- Membrane associated RNA replication
- Assembly
- Maturation and release
Sources of infections for persons with Hepatitis C
- Injecting drug use (60%)
- Sexual (15%)
- Transfusion (10%)
- Occupational (4%)
What hpapened in 1992 to decrease HCV dramatically in the population
Widespread screening of blood supplies
Clinical outcomes of HCV infection of adults
- Recovery and Clearance (15%)
- Persistent infection (85%)
- Chronic Hepatitis
- Liver failure (6%)
- Cirrhosis (20%)
- Hepatocellular carcinoma (4%)
- Chronic Hepatitis
How/Why does Chronic HCV infection lead to a high incidence of hepatocellular carcinoma
- The HCV core protein interacts with, and regulates, many cellular tumor suppressors
- Induces steatosis (lipid accumulation) leading to oxidative stress and increases cell proliferation
- HCV envelope protein (E2) inhibits natural killer cells
- Viral proteins block action of p53
According to GWAS (genome wide association studies), which gene plays a key role in the outcome of HCV infection
IL28b gene which incodes antiviral cytokine IFN-λ
Which HCV genotype is most prevalent in the US?
HCV genotype 1
Areas of HCV lifecycle targeted by drugs
- Entry
- IRES-dependent translation
- Viral DNA replication
- Particle assembly/release
New 3 drug regimen
- Protease inhibitor
- NS5A inhibitor
- Nonnucleoside polymerase inhibitor
