Viral Hepatitis Flashcards
What is the incubation period of Hep A? Where is it found in the body? How is it transmitted? What are some symptoms? What are the signs? How do these differ depending on age? What are the complications/outcomes of Hep A?
d. Incubation period after exposure:
(1) Average: 4 weeks to initial symptoms
(2) Range: 2-7 weeks
e. Found in
(1) Stool for 1-2 months after infection
(2) Blood transiently just before onset of symptoms (therefore blood-to-blood transmission can happen but is rare)
a. Viral infection transmitted by fecal-oral contamination
• Symptoms:
– Malaise, loss of appetite, fever, abdominal pain, diarrhea
• Signs: jaundice, increased LFTs
Jaundice:
– Age 14 years: 70-80%
– Key point: older people get sicker with acute Hep A
• Complications: liver failure, death
– Death/transplant is very rare: 100-300 annually in U.S.
• No chronic infection develops (boards question!)
• Lifelong immunity after infection
What is the mode of transmission of Hep A? How does liver injury occur? What does Anti-HAV IgM indicate? How Sensitive is it? For how long? What does Anti-HAV total antibody test detect? How long? What is it useful for?
• Mode of transmission
– Fecal-oral: poor hygiene, contaminated food and water, diaper changing, male-male sex
– Blood: only rarely because of short duration of viremia
• Liver injury
– Cytopathic
– Immunologic
• Measure antibodies in the blood
– Anti-HAV IgM indicates recent infection
• Positive in 95% of people at presentation with acute hep. A (jaundice, malaise, loss of appetite)
• Remains positive for 6 months
• Used to diagnose acute HAV infection
– Anti-HAV total antibody test • Detects IgG, IgM, IgA (not just IgG) • Indicates immunity • Persists lifelong after infection • Limited usefulness: – Identify vaccine candidates – Population studies
How is Hep A treated? How can it be prevented?
- Rest for 1-3 months
- Hydration with IV fluids if unable to take oral fluids
- Antiviral agents not needed
- Liver transplantation is rarely needed
- Most patients require 1-2 months disability
• Post-exposure prophylaxis
– Immune globulin within 14 days of exposure
• Prevention of transmission – Good handwashing – Sanitary fresh water supply • Prevention by vaccination – Available since 1986 – Highly effective
What is the incubation period in Hep B? What are the acute clinical manifestations? What are the outcomes? What are the symptoms, signs, and complications of chronic Hep B in adults and in neonates?
• Incubation period after exposure
– Average: 2-3 months to initial symptoms
– Range: 1.5 to 6 months
- Nausea, fatigue, loss of appetite
- Jaundice in 10-30%
- Elevated ALT (up to 10,000 U/L)
• 95-99% of healthy adults have full immune response
• 1-5% go on to develop chronic infection
– HBsAg positive for > 6 months
• 1% acute liver failure
– From over-exuberant immune response
• Symptoms and signs
– Sometimes fatigue, joint aches
– Elevated ALT (normal to 500 U/L)
• Complications
– Cirrhosis
– Hepatocellular carcinoma
– Occasional immune-complex mediated kidney disease
NEONATES
– Immune tolerance to the virus
– Minimal liver disease (used to be called “healthy carriers”)
– 200-fold increased risk of hepatocellular carcinoma
MODES OF TRANSMISSION
- Sex
- IV drugs
- Childbirth
How is liver injury mediated in Hep B? How does it lead to hepatocellular carcinoma?
• Most liver injury is immune mediated
– Immunosuppression reduces injury but promotes infection
– Immune tolerance develops with neonatal infection
• Hepatocellular carcinoma
– Can develop after decades of chronic infection
– Incorporation of viral DNA into host genomic DNA leads to oncogenic mutations
Describe the diagnostic approach with Hep B and how HBsAg, HBcAg, Anti-HBsAg, Anti-HBcAg total antibody, Anti-HBcAg IgM, and quantitative HBV DNA are used. How are they detected? What do they indicate?
– HBsAg
• Presence of HBsAg > 6 months defines chronic infection
• Can also be detected in liver by immunostaining
– HBcAg
• Remains in hepatocytes (c = cellular)
• Detected only by by immunostaining
– Anti-HBsAg
• Presence indicates immunity (after infection or vaccination)-Not present in chronic Hep B
– Anti-HBcAg total antibody (IgG and IgM)
• Presence indicates current or past infection
– Anti-HBcAg IgM
• Presence indicates infection within past 6 months
Might be the only one present during the window phase.
• Quantitative HBV DNA – Decide who should be treated • Treat > 104-105 U/ml – Identify resistance mutations during treatment • Rise in HBV DNA levels change drugs
How is Hep B treated? What are the two categories of drugs? Examples? Preferred examples? What are the treatment goals? CDC prevention strategy?
– Alpha-interferon
– Oral anti-viral agents: lamivudine, adefovir, entecavir, tenofovir
• Nucleoside/nucleotide analogues
• Very effective
• Well-tolerated
• Currently used as single agent therapy
• Resistant mutants a problem, especially with lamivudine
• Entecavir and tenofovir are the preferred drugs
• Treatment suppresses virus, rarely cures infection
– Suppression of viral replication (common)
– Conversion from HBeAg to anti-HBeAg (15%/year)
- Prevent perinatal HBV transmission
- Routine vaccination of all infants
- Vaccination of high risk children
- Vaccination of adults in high-risk groups
- Universal precautions, safe sex practices
Describe Hep D virus. What is its mode of transmission? What effects does it have? How is it diagnosed? Prevented?
• Aka “delta” hepatitis
• Defective circular single-
stranded RNA virus
• Requires HBV coinfection for synthesis of envelope
protein (HBsAg)
• Same modes of infection as HBV
– Sex and IV drugs
– Perinatal transmission is rare
• Simultaneous acute infection with HBV
– Acute liver failure more common (2-20% vs 1% with HBV alone)
– Chronic infection rare
• “Superinfection” = infection of someone with chronic HBV
– Higher risk of progressing to cirrhosis (75% vs 15-30% with HBV alone)
• Diagnosis: Anti-HDV IgG
• Prevention:
– Treat HBV
– Safe behaviors
What are the clinical manifestations of Acute Hep C? Chronic?
• Acute HCV
– Rarely comes to clinical attention
– Fatigue, anorexia (typical of any hepatitis)
– Elevated ALT and AST (up to 1000 U/L)
– Jaundice is uncommon
– 70% of those infected will develop chronic hepatitis C
• Chronic HCV
– Fatigue
– ALT normal (< 40 U/L) to 300 U/L
– No jaundice unless end-stage liver disease has developed
– Cirrhosis can develop in about one third of patients
– Hepatocellular carcinoma can develop after cirrhosis
– Porphyria cutanea tarda can occur
• Blistering on sun exposed skin
• Leaves scars
What are the risks and modes of transmission of Hep C? How does liver injury occur?
• Blood transfusion before 1992
– First EIA May 1990
– Second generation 1992
– Factor VIII, immune globulin preparations were sources
• IVDU
• Sex
– Rare
• Childbirth from HCV positive mother
– 5% chance (higher if mother is HIV positive)
• Not: casual contact, kissing, shared food
• Immune-mediated liver injury may be important
• Direct cytopathic effect too
– Immune suppression –> worse hepatitis in some
How is Hep C diagnosed? Why and when is each test useful?
• Antibody tests
– Detects antibodies of all classes
– Positive when antibodies to any of 3 recombinant hepatitis C proteins are present (c100-3, c22-3, c33c)*
– False positives are a problem when screening low risk populations (e.g. healthy blood donors)
– False negatives are a problem in immunocompromised patients
• Tests for viral RNA in serum
– Highly sensitive detection of serum HCV RNA
– Confirmatory test when antibody is positive
• Question: how often will antibody be positive and RNA negative?
– Quantitative testing
• Useful for assessing response to treatment
• Viral “load” is not a predictor of disease severity
• Genotype test
– Identified as 1a, 1b, 2a, 2b, 3, 4, 5, 6
– Genotype used to decide which treatment is best
• There are no tests to detect viral antigens
• Liver biopsy to assess degree of inflammation and
fibrosis
How is Hep C treated? How is Hep C disabling? How can it be prevented?
• Until 2011
– Alpha-interferon + Ribavirin
• 2011-2014:
– Alpha-interferon + Ribavirin + Protease inhibitor
• 2014 – Protease inhibitors – Nucleoside analogues – Others • Cure rate 85-100% • Very expensive
• Disability because of fatigue
• Prevention efforts – Screening of blood – “Universal Precautions” – Clean needle and dyes for tattooing – Needle programs for drug users – Post-exposure anti-virals is controversial – Barrier protection for sex not needed – C-section for childbirth by infected mother doesn’t help – No vaccine is likely
Describe Hep E. Mode of transmission? Risk factors? Symptoms?
– Like HAV
• Fecal-oral transmission
• No chronic infection
– Outbreaks during monsoons in Asia
– Higher risk in pregnant women
• 20% mortality
– May be a zoonosis (pigs)
• Chronic HEV in immunosuppressed?
Describe the Hepatitis of EBV, CMV, and HSV. Treatment of HSV?
• EBV (Epstein Barr virus, “mono”)
– Jaundice, acute hepatitis picture in some
– No chronic hepatitis
– Biopsy: sinusoidal infiltrates; atypical lymphocytosis
• CMV (cytomegalovirus)
– Usually immunocompromised patients
– Diagnosed by liver biopsy: viral inclusions only seen in
immmunocompromised host
• HSV (herpes simplex virus, either HSV1 or HSV2)
– Immunocompromised host
– Pregnancy
– Hepatitis can be severe
– Diagnose by biopsy: syncytial inclusions surrounding “punched out” necrosis
– Treatment: acyclovir
Describe the pathology and clinical features of acute hep?
C. Acute hepatitis presents as jaundice (mixed CB and UCB) with dark urine (due to CB), fever, malaise, nausea, and elevated liver enzyme s (ALT > AST),
1 . Inflammation involves lobules of the liver and portal tracts and is characterized by apoptosis of hepatocytes (Fig. 11.6).
2. Some cases may be asymptomatic with elevated liver enzymes .
