6/5- Hepatitis Flashcards
How are the different hepatitis viruses transmitted?
- “Infectious”: A
- “Serum”: B, D
- Parenterally: C
- Enterically: E
- Other: F,G
Outcomes of viral hepatitis?
- Acute hepatitis
- Fulminant hepatitis
- Chronic hepatitis
- Hepatocellular carcinoma (HCC)
- Cirrhosis
- Asymptomatic/subclinical hepatitis (common with HepC)
Symptoms of Acute Hepatitis? Signs?
Symptoms (nonspecific):
- Malaise, fatigue, fever, anorexia
- Nausea, vomiting, itching, RUQ pain
Signs:
- Jaundice
- Hepatomegaly
Labs in acute hepatitis?
Elevated:
- Alanine aminotransferase (ALT)
- Elevated aspartate aminotransferase (AST)
- Lactate dehydrogenase (LDH)
- Alkaline phosphatase (alk phos)
- Bilirubin (bili)
Symptoms of chronic hepatitis? Signs?
- Ecephalopathy
- Abdominal swelling
- Edema
- Bleeding, spider telangiectasias
- Palmar erythema
- Splenomegaly
- Varices
- Large or small liver
Labs in chronic hepatitis?
- Hypoalbuminemia
- Prolonged prothrombin time
- Hyperammonemia
- Altered glucose metabolism
Which hepatitis viruses are spread fecal-oral? Which are spread parenterally-or via intimate contact?
Fecal-oral:
- Picornavirus
- Hepevirus
Parenteral-Intimate contact:
- Hepadnavirus
- Unclassified
- Flavivirus
Which is the only hepatitis virus that has DNA rather than RNA?
Hepadnavirus (Hep B)
What percentage of people are ever infected with HepA? B? C?
Hep A: 33%
Hep B: 4-6%
Hep C: < 2%
Epidemiology of viral hepatitis in the US? (table)
Question: Which of the following hepatitis viruses is not associated with persistent/chronic infection in IMMUNOCOMPETENT people?
A. Hepatitis A
B. Hepatitis B
C. Hepatitis C
D. Hepatitis D
Question: Which of the following hepatitis viruses is not associated with persistent/chronic infection in IMMUNOCOMPETENT people?
A. Hepatitis A
B. Hepatitis B
C. Hepatitis C
D. Hepatitis D
General characteristics of Hep A?
- Picornavirus family (genus Hepatovirus)
- ssRNA
- Nonenveloped
- 1 human serotype (vaccines effective)
- Resistant to: heat, ether, acid
What is this?
Hepatitis A virus
Geographic distribution of HAV? (picture)
How is HAV transmitted?
- Contaminated food, water (e.g. infected food handlers, raw shellfish)- most important
- Close personal contact (e.g. household contact, sexual contact, child day care centers)
- Blood exposure (rare) (e.g. injecting drug use, transfusion)
Note: International travel is a risk in ~18%
Concentration of HAV in body fluids: where is it highest? (urine, saliva, feces, serum…)
Most: feces
2nd most: serum
3rd: saliva
None in the urine
Which happens first: HAV found in serum/stool or pt presents with symptoms?
Symptoms/jaundice occur after HAV is found in stool/serum
If you find IgM anti-HAV in blood, what does that indicate?
What about just high total Anti-HAV?
If IgM, then probably “active or recent” HAV infection (in the past 6-12 months); if just total anti-HAV (IgG), then probably more distant infection (“current or past”)
What is the incubation period of Hepatitis A?
~30 days (range 10-50 days)
Jaundice by age group:
- Under 6:
- 6-14:
- > 14:
Jaundice by age group:
- < 6: < 10%
- 6-14: 40-50%
- > 14: 70-80%
Complications of hepatitis A?
- Fulminant hepatitis
- Cholestatic hepatitis
- Relapsing hepatitis
Chronic sequelae of hepatitis A?
There are no chronic sequelae of hepatitis A
Prevention of HAV infections?
Good hygiene and dietary precautions
Pre-exposure prophylaxis:
- inactivated HAV vaccine (active)
- immune serum globulin, or ISG (passive)
Post-exposure prophylaxis:
- Inactivated HAV vaccine! (12 mo - 40 yrs)- worked even after exposure
- ISG for close contacts (<1 or > 40 yrs)
Question:
You screen an unimmunized pt for hepatitis A and receive the following results:
IgM anti HAV (-)
IgG anti HAV (+)
Which of the following characterizes the patient’s clinical status with respect to HAV?
A. Active acute HAV infection
B. Active persistent/chronic HAV infection
C. Resolved/past HAV infection
D. Never infected with HAV
Question:
You screen an unimmunized pt for hepatitis A and receive the following results:
IgM anti HAV (-),
IgG anti HAV (+).
Which of the following characterizes the patient’s clinical status with respect to HAV?
A. Active acute HAV infection
B. Active persistent/chronic HAV infection
C. Resolved/past HAV infection
D. Never infected with HAV
General characteristics of HEV?
- Hepevirus family (genus Hepevirus)
- ssRNA
- Nonenveloped
- 1 serotype; 4 genotypes
Where is Hepatitis E virus cause most disease?
- SE/central Asia
- Middle East
- N and W Africa
- Mexico
Epidemiology of HEV: Highest rates of attack in ____ Animal reservoirs include _____; while risks are involved with ______
Epidemiology of HEV:
Highest rates of attack in adolescents/young adults (15-44 yrs)
Animal reservoirs: rodents and farm animals (pigs, sheep, cattle); game meat and raw pork liver sausage pose risks
How is HEV transmitted (mostly)?
Mostly water-borne
In HEV, increased liver enzyme levels coincide with what process?
Increased viral replication (same as HAV)
Incubation period of HEV?
~40 days (range 15-60 days)
What is the case-fatality rate for HEV?
Which population group is especially at risk?
Overall: 1-3%
Pregnant: 10-30%
Chronic sequelae in HEV?
Rarely persists in immunodeficient hosts
Treatment for HEV?
There is no specific vaccine, immunoglobulin or antiviral therapy available for the public
(although have been clinical trials showing high efficacy in S Asia)
What can be used to make the diagnosis of HEV?
IgM or rising IgG titers (CDC)
Question:
Which of the following statements is NOT characteristic of HEV infxns?
A. Attack rates are highest in adolescents and young adults
B. Mortality rates are highest in pregnant women
C. Persistent infections occasionally occur in immunocompromised individuals
D. Transmission most commonly occurs via the parenteral route
Question:
Which of the following statements is NOT characteristic of HEV infxns?
A. Attack rates are highest in adolescents and young adults
B. Mortality rates are highest in pregnant women
C. Persistent infections occasionally occur in immunocompromised individuals
D. Transmission most commonly occurs via the parenteral route (transmitted fecal-orally, most often via water)
What is/causes chronic hepatitis?
Persistent infection
Outcomes of chronic hepatitis?
- Initially, few symptoms \
- Cirrhosis
- Hepatocellular Carcinoma (HCC)
- Death…
Characteristics of Hepatitis B?
- Hepadnavirus family
- Partially dsDNA
- Enveloped
- Replication involves RNA intermediate
What is this?
Hepatitis B virus
Antigenic characteristics of HBV?
- Coat/surface protein/antigen (HBsAg)
- Core antigen (HBcAg)
Replication strategy of HBV?
Transcription into either:
- Pregenomic RNA (then via RT to (-) DNA and (+) DNA)
- mRNA So HBV is a DNA virus with RNA intermediate
Geographic distribution of HBV?
- Native Americans of Canada/Alaska
- Northern S America
- Africa
- S Asia
Risk factors for acquisition of HBV?
- Heterosexual sexual contact (41%)
- Unknown (31%)
- Injecting drug use (15%)
- Homosexual activity (9%)
- Household contact (2%)
- Health care employment (1%)
When is there increased risk of neonatal infection with HBV?
When mother is HBeAg (+) and when maternal infection occurs in the 3rd TM or early post-partum
For HBV: Risk of persistent infection ____ (increases/decreases) with age. Risk of symptomatic infection ____ (increases/decreases) with age
For HBV: Risk of persistent infection decreases with age. Risk of symptomatic infection increases with age
Thus, if newborn is infected due to mother’s chronic infection, ~90% go on to develop chronic infection as well (?) but they are asymptomatic/have few symptoms, since these are mostly immune system-mediated
Modes of transmission of HBV?
- Sexual
- Parenteral
- Perinatal
Primary site of replication of HBV is where?
Liver
Hepatic injury is probably related to ______?
Hepatic injury is probably related to immune responses (CD8+ cells)
Concentration of HBV in body fluids (where is it high? moderate? low/not detectable?)
High:
- Blood
- Serum
- Wound exudates
Moderate:
- Serum
- Vaginal fluid
- Saliva
Low/not detectable
- Urine
- Feces
- Sweat
- Tears
- Breast milk
Pathogenesis of acute HBV? Virus starts replicating within _____
Virus starts replicating within 1-2 mo
Immune system kicks in as liver is being damaged following intense viral replication
Which is seen first Anti-HBc (core) or Anti-HBs (surface)?
What should be tested to diagnose HBV?
Anti-HBc comes first (starts rising at 3 mo); anti-HBs only starts rising around 5 months after exposure
There’s a 1-2 week window that the only thing positive is IgM (follows fall in PCR)
Pathogenesis of chronic HBV: in those with chronic infection, what marker is different?
Surface antigen (anti-HBs) goes up and stays up
*SURFACE ANTIBODIES ARE THE MARKER OF HAVING CLEARED THE INFECTION*
Incubation of HBV?
~2-3 mo (range 1-6 mo)
What are the stats for those who develop chronic infection:
< 5 yo:
> 5 yo:
What are the stats for those who develop chronic infection:
< 5 yo: 30-90%
> 5 yo: 2-10%
Percentage of premature mortality from chronic liver dz?
What is the acute case-fatality rate?
15-25% (e.g. from cirrhosis or cancer)
Acute case-fatality: 0.5-1%
Extrahepatic manifestations of HBV?
- Rash
- Glomerulonephritis
- Arthritis
- Vasculitis
- Angioneurotic edema
What if just Anti-HBc (core) is positive?
Interpretation unclear;
4 possibilities:
- Resolved infection (most common)
- False-positive anti-HBc, thus susceptible
- “Low level” chronic infection
- Resolving acute infection
Prevention and control of HBV infections?
- Immunization with HBsAg based vaccines (infants, older children, high-risk adults) [recombinant- just the protein is given]
- Hep B immune globulin (HBIG) for post-exposure prophylaxis of susceptible persons
- Screen pregnant women and others at risk
- Vaccine and HBIG should be given to infants of infected mothers
- Antivirals for treatment of persistent infxn
Question:
A pt with a Hx of suspected acute Hep B infxn 10 years ago consults you regarding the status of the infxn. Serology reveals the following:
HBsAg (-)
IgM anti-HBc (-)
total anti-HBc (+)
Anti-HBs (+)
Your answer is what?
A. Acute HBV infection
B. Resolved HBV infection
C. Persistent HBV infection
D. Never infected with HBV
Question:
A pt with a Hx of suspected acute Hep B infxn 10 years ago consults you regarding the status of the infxn. Serology reveals the following:
HBsAg (-)
IgM anti-HBc (-)
total anti-HBc (+)
Anti-HBs (+)
Your answer is what?
A. Acute HBV infection
B. Resolved HBV infection
C. Persistent HBV infection
D. Never infected with HBV ?
Characteristics of Hepatitis Delta virus (HDV)?
- Unclassified; related to plant viruses
- Defective virus; requires concomitant HBV infection
Geographic distribution of HDV (picture)?
Acquisition of HDV infections?
Coinfection: acute infection with HDV and HBV at the same time
Superinfection; infection with HDV of a pt who is persistently infected with HBV
Mode of acquisition = parenteral
Levels/pathogenesis of HDV-HBV Coinfection?
Levels/pathogenesis of HDV-HBV Superinfection?
If never clear B, will always have substrate for D.
Clinical symptoms of coinfection? superinfection?
Coinfection:
- Severe acute disease
- Low risk of chronic infection
Superinfection:
- Usually develop chronic HDV infection
- High risk of severe chronic liver disease
Prevention of HDV coinfection? Superinfection?
Coinfection: pre or post-exposure prophylaxis to prevent HBV infxn
Superinfection: education to reduce risk behaviors among persons with chronic HBV infxn
Question:
Which of the following infections with hepatitis
D virus is most likely to result in persistent HDV infection? A. Co-infection with HBV and HDV
B. Superinfection with HDV in a pt who has chronic HBV infxn
C. Resolved HBV infection followed by acute HDV infection
D. Infection with HDV alone
Question:
Which of the following infections with hepatitis
D virus is most likely to result in persistent HDV infection? A. Co-infection with HBV and HDV
B. Superinfection with HDV in a pt who has chronic HBV infxn
C. Resolved HBV infection followed by acute HDV infection
D. Infection with HDV alone
Characteristics of Hepatitis C?
- Flavivirus family (genus Hepacivirus)
- ssRNA
- Enveloped
- 7 genotypes: 1a and 1b are the most common in the US
What is this?
Hepatitis C virus
Highest prevalence of HCV?
Egypt
Pathogenesis of acute HCV infection?
- Incubation 1-2 mo
- Can detect RNA during infection
- Mostly asymptomatic
- Anti-HCV rises ~2 mo and stays high; NOT PROTECTIVE (if anti-HCV is positive, next test for RNA to see if chronically infected- 85% are. This picture shows acute, because RNA goes down-15%)
Pathogenesis of chronic HCV infection?
- Incubation again 1-2 mo
- Anti-HCV rises and stays high
- If anti-HCV is (+) and RNA is found to be persistently detectable, then the pt is chronically infected (liver abnormalities are sometimes just outside the range of normal)
Incubation period of HCV infection?
~6-7 wks (range 2-26 wks)
Percentage of HCV infections that result in:
- Chronic infection:
- Chronic hepatitis:
- Cirrhosis:
- Mortality from CLD:
Percentage of HCV infections that result in:
- Chronic infection: 55-86%
- Chronic hepatitis: 10-70% (most asx)
- Cirrhosis: 5-20%
- Mortality from CLD: 1-5%
Clinical outcomes of HCV?
Acute infection -> chronic infection (in 80%) -> chronic hepatitis -> cirrhosis (in 20%) -> risk of carcinoma (1-4% per year)
Extrahepatic manifestations of HCV?
- Sjogren’s syndrome
- Porphyria cutanea tarda
- Diabetes mellitus
- Non-Hodgkin’s lymphoma - Urticaria
- Glomerulonephritis
- Neuropathy
- Cryoglubilinemia
- Vasculitis
- Erythema nodosum
Prevention of HCV infections?
- Avoid risky exposures
- Screen blood products
- Avoid alcohol/other hepatotoxins
- Screen for hepatocellular carcinoma
- Liver transplantation
- Vaccinate against HAV and HBV
Treatment of Hep C?
Until recently: Peg-interferon + ribavirin (act on host immunity)- but low success rate and poor tolerability (flu-like illness)
Now: “directly-acting agents” (DAA) with success rates as high as 95%; IFN-based therapy phased out in 2015
Question:
Which of the following is NOT associated with an increased risk of HCV disease progression?
A. Older age at the time of infection
B. Female gender
C. Alcohol consumption
D. HIV co-infection
Question:
Which of the following is NOT associated with an increased risk of HCV disease progression?
A. Older age at the time of infection
B. Female gender
C. Alcohol consumption
D. HIV co-infection
Characteristics of Hep G?
- Flavivirus family (ssRNA)
- Associated with improved AIDS-related outcomes with HIV-infected pts
Which viruses are related to Circovirus family?
- TT and related viruses (including SEN viruses)
Characteristics of Spongiform Encephalopathies?
- Associated with prion protein (altered form of normal HOST-derived protein)
- No virions or nucleic acid identified
- Resistant to inactivation by heat and most chemicals
- Replicate to high titers
- Transmissible to experimental animals
How can you inactivate prions?
- Steam autoclaving 1 hr at 132’C
- Immersion in NaOH for 1 hr at room temp
Pathogenesis of prion dz?
- Prions reproduce by recruiting normal cellular protein (PrPc) and stimulating its conversion to the dz-causing isoform (PrPsc)
- This form is protease-resistant and rich in beta sheets
What is the route of transmission for spongiform encephalopathies?
Often unknown
- Kuru: ritual cannibalism
- CJD: iatrogenic spread: surgical equipment, human growth hormone; corneal and dura mater grafts
T/F: spongiform encephalopathies have no evidence of host inflammatory response
True
Incubation period of spongiform encephalopathies (broadly)?
Incubation period can be prolonged
Where is Kuru found?
New Guinea
Manifestations and pathology of Kuru?
Manifestations:
- Cerebellar ataxia
- Shivering tremor
- Athetosis
- Chorea
Pathology:
- Neuronal loss
- Amyloid plaques
- No inflammation
Where is CJD found?
Worldwide
Manifestations and pathology of CJD?
Manifestations:
- Presenile dementia
- Myoclonus
- EEG changes
Pathology:
- Spongiform changes
- Astrogliosis
- +/- plaques
What is this?
Brain biopsy in TSE
Note: absence of associated inflammatory changes
What is variant CJD?
- Identified in Great Britain (1996)
- Linked to BSE (bovine spongiform encephalopathy), or “mad cow disease”
- Younger age of onset and typical pathologic features (florid plaques in CNS)
Control measures for variant CJD?
- Slaughter of animals and ruminant protein feed ban
- Restriction on blood donation
Question:
A pt presents with a Hx of a rapidly progressive presentile dementia, myoclonus, and visual, speech, and gait disturbances. You suspect CJD. Which of the following findings is uncharacteristic of the typical brain biopsy abnormalities?
A. Astrogliosis
B. Spongiform changes
C. Neuronal loss
D. Inflammatory response
Question:
A pt presents with a Hx of a rapidly progressive presentile dementia, myoclonus, and visual, speech, and gait disturbances. You suspect CJD. Which of the following findings is uncharacteristic of the typical brain biopsy abnormalities?
A. Astrogliosis
B. Spongiform changes
C. Neuronal loss
D. Inflammatory response
Give letter name to the following classes:
Picornavirus = ?
Hepevirus = ?
Hepadnavirus = ?
Unclassified = ?
Flavivirus = ?
Give letter name to the following classes:
Picornavirus = Hep A (HAV)
Hepevirus = Hep E (HEV)
Hepadnavirus = Hep B (HBV)
Unclassified = Hep D (HDV)
Flavivirus = Hep C (HCV)
