Viral Hepatitis Flashcards
Hepatitis:
inflammation of the liver tissue
What are the major causes of hepatitis?
● INFECTIOUS (bacteria, parasites, viruses)
● METABOLIC (alcohol, toxins, drug-induced, herbal or
dietary supplements)
● AUTOIMMUNE (genetic predisposition, association with HLA antigens, auto-antibodies)
● GENETIC (α-1 antitrypsin deficiency, hemochromatosis, Wilson’s disease)
● ISCHEMIC (shock, heart failure, or vascular insufficiency)
What are the three types of hepatitis (based on clinical pattern)?
● ACUTE HEPATITIS: infection then recovery (eg HVA)
● FULMINANT HEPATITIS: massive hepatic cell death, rare, life-threatening (eg HBV)
● CHRONIC HEPATITIS: after acute phase, >6 months
Acute hepatitis:
infection then recovery (eg HVA)
Fulminant hepatitis:
massive hepatic cell death, rare, life-threatening (eg HBV)
Chronic hepatitis:
after acute phase, >6 months
What are the different types of viral hepatitis?
Viral Hepatitis
A B C D E
What is the prevalence of viral hepatitis worldwide?
Hep A & B - widespread
Hep C - broad prevalence everywhere in world
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What is Viral Hepatitis A?
A small NON-ENVELOPED RNA- containing virus
Where family does the Viral Hepatitis A belong to?
belongs to PICORNAVIRUS family
What does Viral Hepatitis A contain?
It contains a positive-sense, single-strand of RNA packaged in a protein shell
What is the stability of a Viral Hepatitis A?
● STABLE in environment for at least ONE MONTH
● Inactivation: heat foods (≥85°C (185°F); 1 min) or disinfect with bleach (1:100 dilution in water)
What is Hepatitis A infection? & what can it cause?
usually a benign, SELF-LIMITING disease
It can cause fulminant hepatitis and hepatic failure leading
to death (not common)
What is the Hepatitis A infection typically by?
● FECAL-ORAL route
● direct: person-to-person
● indirect:
- water/food ingestion, contaminated with fecal
material of infected person (even microscopic amount)
- drinking contaminated milk, water, shellfish from infected waters
What is the population that is at high risk for HAV infection?
● Anyone who has NOT been VACCINATED or previously INFECTED can get infected with HAV.
● In areas where the virus is widespread (HIGH ENDEMICITY), most HAV infections occur during EARLY CHILDHOOD.
What are the risk factors for HAV infection?
● Travelling to areas of high endemicity without being immunized (44-55% cases in Canada linked to travel)
● Poor sanitation; lack of safe water supply
● Living in a household with an infected person
● Use of recreational drugs
● sexual partner of someone with acute hepatitis A;
oral/anal sexual contact
● Inmates in prisons or jails
What is the clinical presentation of acute hepatitis A?
● may be ASYMPTOMATIC (age <5 YEARS)
● non-specific flu-like symptoms (fever, fatigue,
malaise, anorexia)
● nausea, vomiting, diarrhea
● dark urine, pale stool (b/c of elevated bilirubin levels)
● pruritus, abdominal pain
● jaundice: skin, eyes (scleral icterus)
● fulminant hepatitis (rare)
● full recovery <2 MONTHS (up to 9 months)
What are the signs & symptoms of hepatitis A (at each phase)?
● PRE-ICTERIC PHASE
NONSPECIFIC FLU-LIKE symptoms consisting of anorexia,
nausea, fatigue, and malaise
● ACUTE ILLNESS (virus is actively replicating)
ABRUPT ONSET of anorexia, nausea, vomiting, malaise, fever, headache, and right upper quadrant abdominal pain with acute illness
● ICTERIC HEPATITIS
GENERALLY ACCOMPANIED by dark urine, acholic (light-
colored) stools, worsening of systemic symptoms, PRURITIS is often a major complaint of icteric patients
What is the diagnosis of acute hepatitis A?
● Physical examination
● icteric sclera, skin, and secretions
● mild weight loss (2-5 kg)
● hepatomegaly
Laboratory tests (NON-specific)
● positive serum anti-HAV (IgM, IgG)
● ↑ serum bilirubin (mild)
● ↑ liver enzymes
– alanine transaminase (ALT); aspartate transaminase (AST)
– alkaline phosphatase (ALP); γ-glutamyl transferase (GTT)
● total bilirubin in patients with cholestatic illness
What are the precautions in place to prevent hepatitis A?
● Washing hands before eating and drinking
● Avoid contaminated food and water (& swim/bath in water)
● Avoid uncooked foods, shellfish and salads
● Avoid unpasteurized dairy products
● Avoid food from street vendors
● Avoid swimming, wading, bathing or washing cloths in polluted or contaminated water
What are recommendations for HAV vaccination?
● All children at 1 year of age
● Consider older children (2–18 years) in AREAS WITHOUT
existing HAV vaccination programs
● TRAVELING/working in countries that have high/intermediate
endemicity of HAV infection
● Men who have SEX with men
● Illegal-DRUG users
● Persons with OCCUPATIONAL risk for infection (eg work with
HAV-infected primates, HAV research laboratory)
● Patients with CLOTTING factor DISORDERS or CHRONIC LIVER disease
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What is the treatment of hepatitis A?
● Typically, NO SPECIFIC treatment is needed
● Symptoms are usually RESOLVED within 2 MONTHS
● ALMOST ALL patients RECOVER within 6 months (up to 9 months in some patients)
What are the rate complications with hepatitis A?
● relapsing hepatitis
● cholestatic hepatitis
● fulminant hepatitis
What does the Hepatitis B virus (HBV) look like?
● HBV has a CIRCULAR, PARTIALLY DOUBLE- STRANDED DNA
● Along with DNA POLYMERASE contained in an inner NUCLEOCAPSID surrounded by an outer ENVELOPE
What family does the hep B (HBV) virus fall in?
● It is a prototype virus of the Hepadnaviridae family
● A small DNA virus with unusual features SIMILAR to RETROVIRUSES
What does the HBV infect?
● Infects MAINLY HEPATOCYTES but it is also found in kidney, pancreas and mononuclear cells
● IMMUNE response to the virus is CYTOTOXIC to HEPATOCYTES (elevated ALT due to destruction of hepatocytes)
● Antigen NON-specific inflammatory responses are triggered by T CELLS
● Includes MHC class I CD8 cytotoxic T cells and class II CD4 T-helper cells
● CYTOTOXIC T-cell response is IMPORTANT for viral CLEARANCE
● WEAK immune response: MORE likely to develop CHRONIC infection
What is the epidemiology & prevalence of HBV?
● >350 million people worldwide are infected with HBV
● Higher rate in ASIA and WESTERN PACIFIC rim
● About 257 million people have CHRONIC HBV globally
● It is the cause of about 887,000 deaths per year
● Rate has declined since 1980s because of vaccination
● WHO recommends routine hepatitis B SCREENING for
HIGH-RISK populations
● Incubation period: 90 days (60-150 days)
● HBV can cause both ACUTE and CHRONIC infection
*● It is a LEADING cause of CHRONIC hepatitis, liver CIRRHOSIS,
and CANCER worldwide
● Risk of development of CHRONIC HBV is HIGHER in CHILDREN
● About 90% of children infected during or shortly after BIRTH develop CHRONIC HBV
● Risk of CHRONIC HBV if infected at age of ≥5 years is <10%
● MOST patients with CHRONIC HBV have NO symptoms
● About 25% of patients with CHRONIC HBV eventually develop CIRRHOSIS and liver CANCER
What is the incubation period of HBV?
90 days (60-150 days)
What is the HBV transmission?
HBV is transmitted MAINLY by contact with contaminated BLOOD, blood PRODUCTS, and other BODY FLUIDS (eg semen)
What are the HBV different ways of transmission?
● Percutaneous or mucosal contact with infected body fluids
- high concentration in blood and serum
- moderate in semen/vaginal fluid
- saliva (kiss: unlikely; damaged skin)
● Percutaneous insertion
- IV drug use, tattoos, acupuncture, body piercing
- health care workers (accidental needlestick)
● Perinatal infection
- HBV+ mother to newborn during delivery; 10-85%
- infected infants: 90% risk of being chronic careers
● Sexual contacts (most common source reported in MB)
What does the clinical presentation of HBV infection depend on?
- AGE at which the FIRST infection occurs (for child/adult)
- IMMUNE system response to the virus
What does the HBV present as in children?
- Children <5 years and newly infected IMMUNOSUPPRESSED
adults are usually ASYMPTOMATIC - About 30-50% of infected patients >5 years have signs/symptoms
What are the signs & symptoms of HBV infection?
- fever
- fatigue
- loss of appetite
- joint pain
- nausea, vomiting
- abdominal pain
- jaundice
- dark urine
*clay-colored stool
**only difference from HAV is: NO DIARRHEA b/c this is a blood contaminated inf. so not present
What would it be if someone had:
HBsAg Negative
Anti-HBs Negative
Anti-HBc Negative
Susceptible
What would it be if someone had:
HBsAg Negative
Anti-HBs Positive
Anti-HBc Positive
Immune due to natural infection
What would it be if someone had:
HBsAg Negative
Anti-HBs Positive
Anti-HBc Negative
Immune due to Hepatitis B vaccination
What would it be if someone had:
HBsAg Positive
Anti-HBs Negative
Anti-HBc Positive
IgM anti-HBc Positive
Acutely infected
What would it be if someone had:
HBsAg Positive
Anti-HBs Negative
Anti-HBc Positive
IgM anti-HBc Negative
Chronically infected
What would it be if someone had:
HBsAg Negative
Anti-HBs Negative
Anti-HBc Positive
Interpretation unclear; four possibilities:
1. Resolved infection (most common)
2. False positive anti-HBc, repeat test
3. Passive transfer to infant born to HBsAg-positive mother
4. Occult HBV infection: immunosuppressed, antivirus
Describe the prevention of Hep B?
HBV vaccination
* Provides LONG-TERM protection
Who is the CDC HBV recommended for?
- ALL children <19 years
- HIGH RISK individuals (HIV, injection drug users, etc)
- HOUSEHOLD contacts and SEX PARTNERS of persons with chronic HBV infection
- HEALTHCARE/public safety workers (exposure to blood)
- international TRAVELERS who plan to spend >6 months in countries with ↑HBV rate (close contact with local)
- recipients of CLOT-FACTOR concentrates, DIALYSIS patients
What are the HBV vaccines?
- Several HBV vaccines exist:
- Recombivax HB (Merck)
- Engerix-B (GSK)
- Genevac B (Serum Institute)
- Shanvac B (Sanofi)
- Twinrix (against HAV and HBV)
- These vaccines are given by intramuscular route
*** Three doses at different time intervals based on age
What are the treatment goals for HBV infection?
- MINIMIZE further LIVER DAMAGE and prevent progression of liver disease (cirrhosis, cancer)
- Prevent TRANSMISSION to others
- Achieve sustained SUPPRESSION of HBV REPLICATION and increase chances for seroclearance
- NO CURE because virus INTEGRATES into the cell GENOME
- Treatments do NOT CURE HBV but CONTROL the virus to prevent further damage to liver
What are the treatment strategies for HBV infection?
Exposure to HBV <7 days:
Injection of hepatitis B IMMUNE GLOBULIN may prevent development of HBV
Acute hepatitis B:
* NO SPECIFIC treatment (rest, proper nutrition, fluid, monitor)
* In SEVERE cases, ANTIVIRAL DRUGS or hospital stay is needed to prevent complications
Chronic hepatitis B:
* INTERFERON injection
* oral ANTI-VIRAL drugs: lamivudine, adefovir, telbivudine,
tenofovir, entecavir
What is the Viral hepatitis C?
- HBC is a single stranded RNA virus with various genotypes
What is the incubation period for hep C?
50 days (14-160 days)
What are people like when they have hep C?
- INITIAL infection MILD or NO symptoms
** MOST people with CHRONIC HBC are ASYMPTOMATIC (BAD)
- About 80% of those exposed to HCV develop CHRONIC infection
- MOST common cause of CHRONIC hepatitis, CIRRHOSIS, hepatocellular CARCINOMA
- Currently *NO VACCINE against HCV
What is the transmission for HCV?
- blood-to-blood contact
- injection drug use!! (MAJOR)
- blood transfusion
- poorly sterilized medical equipment
- needlestick injuries in healthcare
- tattooing, acupuncture, body piercing
- infected mother to baby during birth
- sexual contact
What is the clinical presentation of HCV?
- NO CLINICAL symptoms
- May have fatigue, lethargy, nausea, reduced appetite,
abdominal pain, jaundice - In about 25% of HCV INFECTED patients, VIRUS DISAPPEARS on its own (no longer infected)
- In about 75% of HCV INFECTED patients, virus remains >6 months (CHRONIC HCV)
What is the clinical presentation of CHRONIC HCV?
- 75% of patients: MILD/MODERATE liver damage over time
- 25% of patients: may lead to serious problems over time (25-30 yrs) such as CIRRHOSIS, LIVER FAILURE, CANCER
What are the lab tests for HCV?
Hepatitis C antibody
Hepatitis C RNA test (if antibody is positive)
HCV genotyping
Hepatitis C antibody lab test
- Negative: not infected with HCV
- Positive: infected with HCV in past but does not tell you:
- if infection is new
- how long patient has had infection
- if infection is still present
Hepatitis C RNA test (if antibody is positive) lab test
- Negative: infected with HCV but virus has been cleared from body (no current infection)
- Positive: has HCV infection
HCV genotyping lab test
- Identify HCV genotype (1-6; 1 most common in Canada)
What is the treatment of HCV infection?
- The primary goal of therapy: ERADICATE (get rid) HCV infection
- PREVENT development of CHRONIC HCV infection
- Since 2010, new therapies called direct acting antivirals (DAAs)
What is the new therapies called direct acting antivirals (DAAs) for HCV?
- act on virus to eradicate it from body
- reported success rate is >90%
- require SHORTER treatment period (8-24 weeks)
- appear to be effective at *ALL STAGES of disease
- LESS side effects than older drugs
- expensive