Limjoco - Hepatitis Flashcards
Hepatotropic viruses (A, B, C, D, E, G) have an affinity for the liver.
Name 5 other viruses (systemic) that can cause Viral Hepatitis?
- EBV (infectious mononucleosis)
- CMV
- HSV
- Adenovirus (neonates, immunosuppressed)
- Yellow Fever
Mnemonics for Viral Hepatitis
AcutE Hepatitis: A and E (never chronic)
*Note: HEV is bad in immunocompromised hosts, pregnant women
Consonants B, C, D: can cause Chronic Disease
Hepatitis B can be transmitted by Blood, Birthing and Bonking.
Which Hepatitis?
80% or more develop chronic hepatitis and 20% of these people develop cirrhosis
Hep C (Chronic and Cirrhosis)
Typical Course for What Condition?
Incubation period: asymptomatic
Symptomatic Pre-icteric period: malaise, fatigue, anorexia, nausea, fever
*2 weeks post-exposure
Acute Viral Hepatitis
Typical Course for What Condition?
Icteric Phase (1-2 weeks after prodrome, last up to 6 weeks)
jaundice, dark urine, clay-colored stools, hepatomegaly
Convalescence (6-8 weeks post-exposure): dinminishing jaundice
Acute Hepatitis
When is an individual with Viral Hepatitis most infectious?
Last asymptomatic days of Incubation Period
What do lab results look like for Viral Hepatitis?
- Liver Enzymes?
- ________bilirubinemia (hyper/hypo)
- Viral Serology; also RNA or DNA detection by PCR
High Levels of ALT, AST (>1000 U/L)
Hyperbilirubinemia
After how many months of infection, do you have chronic hepatitis?
6 months
Definition (Viral Hepatitis).
- harbors orgs without signs & symptoms
- either no liver damage or with liver damage –> reservoirs for future infection
Carrier State
During a Viral Hepatitis Infection, hepatocellular damage is due to the host’s ________ immune response to viral protein expressed by infected cells.
It is not due to direct viral cytopathic effect.
What immune cells are activated and what damage ensues?
adaptive
T Cells
- ->Necroinflammatory activity
- ->Apoptosis (“cell suicide” - elimination of infected/damaged cell)
Which Hepatitis?
- Family: Picornavirus
- Genus: Hepatovirus
- Small, naked +SS RNA
- Benign, self-limited course, rare relapse
- NO chronic or carrier state
- history of travel to endemic areas*
Hep A
Which Hepatitis?
- fecal-oral route
- ingested through contaminated water and food
- contaminated undercooked shellfish concentrates virus
- endemic in countries with poor sanitation
- in developed countries, better hygience but NO herd immunity
- older age group will be more symptomatic an severe
Hepatitis A
Serology for Hepatitis A.
_____ (what Ab): rises with onset of symptoms; marker of ACUTE infection
_____ (what Ab): rises on decline of IgM after months, persists
confers LIFELONG IMMUNITY AGAINST REINFECTIONS WITH
ALL STRAINS
NOTE: there is no direct detection for IgG. It is derived from [Total Ig - IgM]
IgM
IgG
Total Anti-HAV Antibody = Ig____ + Ig_____
IgM + IgG
How is HAV spread rapidly?
Fecal shedding of HAV Virus occurs _____ weeks before and ____ week after the start of jaundice.
2-3 weeks before
1 week after
Which Hepatitis?
- more sporadic than HAV
- **India, Asia, Africa, ME, China, mexico
- Developed world: pig farms
- High mortality rate in Pregnant Women
Hep E
Which Hepatitis?
Genus: Hepevirus
- naked +SS RNA
- virions shed during acute illness
- RNA and Virions detectable in stool/serum prior to symptoms appearing
CLINICAL: Inc. AST/ALT
Inc. IgM
-self-limited, resolves in 4-6 weeks
Hep E
Which Hepatitis?
Family: Flavivirus
- small +SS RNA virus
- RNA codes only for 1 polyprotein, processed into functional proteins
- RNA polymerase, poor fidelity in copying (Antigenic variation)
Hep C
Hepatitis C
_____ envelope glycoprotein (target of anti-HCV antibodies) is the MOST VARIABLE region of the genome.
New virus strains can escape neutralizing antibodies.
E2
Why no vaccine for Hep C?
Anti-HCV Ig____ produced after infection does NOT confer immunity –> HIGH RATE OF CHRONICITY
genomic instability, antigenic variation (Exonuclease lacks proofreading capacity in the 3’-5’ so the RNA is prone to frequent mutations)
IgG
What are the top 3 Risk factors for contracting Hep C?
- IV Drug use
- Multiple sex partners
- Undergoing surgery in the last 6 months
Others: Needle Sticks, Multiple contacts w/HCV-infected person, Work in medical/dental field, perinatal infections
True or False.
There is a higher risk for HCV than HIV by needle stick.
True!
Which Hepatitis?
Incubation period: 4-26 weeks (1-6 months)
Majority Asymptomatic
Best Diagnostic method: PCR to detect RNA in blood together with elevated AST, ALT levels
-milder clinical course than HBV
Hep C
Fact. Hepatitis C - Acute and Chronic Infection Serum HCV RNA Levels
Hepatitis C
- majority develop chronic hepatitis –> up to 20% develop __________.
- despite Ab production, HCV _____ remains in the blood
- _____________ remain elevated (inc or dec but never normalize)
- *Need close follow-up*
cirrhosis
RNA
Transaminases
FACT: Drugs for Hep C
Pegylated INF-alpha, Ribavirin
Newer Drugs with Better Response: ABT-450
Ombitavir
Dasabuvir (+/- Ribavirin)
Response Depends on:
HCV Genotype: 2,3 best response
Host Genotype: IL28B gene (encodes IF-lambda)
____________ is the primary reason for liver transplantation.
HCV-related Cirrhosis
True or False.
HCV infection recurs in transplants.
Cirrhosis recurs in 20-30% of transplants.
TRUE!!
Which Hepatitis?
-Family: Hepadnavirus
-Circular, Double-Shelled (enveloped)
-partially DS DNA virus
-resistant to extreme temps/humidity
-it’s own Polymerase Complex (Reverse transcriptase, DNA polymerase)
so replication DNA –> RNA –> DNA
Hep B
Name the Antigen for Hepatitis B Virus (HBV)
Nucleocapsid CORE: ______
Envelope Glycoprotein: _______
Lipid envelope glycoproteins (surface): __________
HBcAg
HBeAg
HBsAg
What is the name of the particle that is the complete virion for Hepatitis B and is infectious?
Dane Particle
What antigen of the Hepatitis B Virus aggregates to form subviral particles that are non-infectious small spheres and filaments?
HBsAg
What Serological markers are present during the Acute Stage of Hep B Infection?
HBsAg
HBeAG
HBV DNA
HBcAB: IgM
IgM is replaced by ______ anti-HGcAb after several months of Hep B Infection.
IgG
What Serological markers are present during the Chronic Stage of Hepatitis B Infection?
HBsAg
HBeAg
HBV DNA
HBcAb: IgG
Summary of Hepatitis B Antigens and Antibodies.
Modes of Tranmission for Hepatitis B?
- ____________: high prevalence regions
- ____________: intermediate prevalence regions
- ____________: low prevalence regions
- Childbirth/vertical
- Horizontal
- Sexual/IV Drug
Fact: Potentital Outcomes of Hep B Infection
Fact: Hepatitis B
- Most Self-Limited
- Small % may progress to cirrhosis and/or develop HCC
- AGE at time of infection predicts chronicity
- -> Younger: more likely becomes chronic
- -> Vertical Transmission (mom-to-baby)
Why is it hard to achieve complete cure in chronic cases of Hepatitis B?
Virus inserts itself in to the host DNA. Thus, host cannot mount effective response via production of HBsAb and virus persists.
What is the treatment for Hepatitis B?
Slow down progress of disease and Limit damage to liver (prevent cirrhosis or HCC).
The outcome of Hepatitis B Infection depends on Host Immune Response.
Early Stage: ______________ (natural killer T cells, interferon) protects the individual
If CD4+ and CD8+ produce INF-y, etc. and clear infected cells –> _____________ (result?)
If weak immune response, some infected cells not killed/cleared –> ____________ (result?)
Innate Immune Response
resolution
chronicity
What antigen of the Hep B virus is incorporated in to the HDV envelope, needed for assembly of HDV virion.
HBsAg
Which Hepatitis?
- very small molecule
- Circular, -RNA, enveloped
- uses host’s RNA polymerase to replicate through RNA-directed RNA synthesis
- delta antigen (HDAg) protein produced by virus
Hep D
Hepatitis D
Absolute requirement for ________ (which hepatitis?) for replication –> needs HBsAg in envelope.
Delta agent, defective virus, is directly cytopathic to cells.
HBV
Self-limited infection for Hep B & D EXCEPT FOR ___________ –> leads to acute liver failure.
IV Drug abusers
Two possible scenarios of Infection by Hepatitis D Virus
- ____________: simulataneous infection with HBV, HDV –> Acute, self-limited; rarely chronic
- ____________: when HBV carrier gets HDV 30-50 days later –> Severe acute hepatitis. Worsens the Hep B Infection (likely bc of direct viral toxicity of HDV)
- Coinfection
- Superinfection
Fact: Histopathologic changes in hepatitis are essentially similar in all viral, autoimmune and drug-induced hepatitides.
Fact: Liver Biopsy - Why Do It?
- Confirm the clinical diagnosis
- Exclude simultaneous conditions
- Grade extent of inflammation and injury
- Stage the degree of fibrosis
- Monitor treatment effectiveness
Interpret the Lab Results:
HBsAg: negative
anti-HBc: negative
anti-HBs: negative
Susceptible (no protective immunity exists - HBsAB: IgG)
Interpret the Lab Results:
HBsAg: negative
anti-HBc: positive
anti-HBs: positive
Immune due to natural infection (protective IgG - HBsAB)
Interpret the Lab Results:
HBsAg: negative
anti-HBc: negative
anti-HBs: positive
Immune due to Hep B Vaccination (no antibodies against the core antigen, only antibodies against surface antigen - protective IgG)
Interpret the Lab Results:
HBsAg: positive
anti-HBc: positive
IgM anti-HBc: positive
anti-HBs: negative
Acutely Infected (no IgG antibody - HBsAg)
Interpret the Lab Results:
HBsAg: positive
anti-HBc: positive
IgM anti-HBc: negative
anti-HBs: negative
Chronically Infected (HBcAB = IgG)
Interpret the Lab Results:
HBsAg: negative
anti-HBc: positive
anti-HBs: negative
Interpretation unclear; 4 possibilities:
- Resolved infection (MOST COMMON)
- False-positive anti-HBc; thus susceptible
- “Low level” chronic infection
- Resolving acute infection
What do you see?
Spotty/Lytic Necrosis
What do you see?
Interface hepatitis (AKA “piecemeal necrosis” in older literature)
What do you see?
Hallmark of Hepatitis B-infected cells: “ground-glass” cells
Large cells with pale, finely granular cytoplasm with peripheral halo = surface antigens in endoplasmic reticulum
What do you see?
Inflamed portal tract (bile ductule at arrow) with lymphoid follicle = typical of Hepatitis C infection
What do you see?
See picture.
What do you see?
Systemic infection with herpes simplex virus (HSV)
(non-hepatotropic virus): infected hepatocytes with Cowdry bodies
Apoptotic or acidophil bodies seen in various hepatitides
