Viral Hepatitis I and II Flashcards
Which hep virus(es) are spread principally by fecal-oral route?
Hep A and E
Which hep virus(es) are spread by blood (parenterally or sexually)?
B, C, D
What other viruses (not hep a,b,c,d,e) can cause acute hepatitis?
EBV, CMV, yellow fever and Rubella
What is viral hepatitis characterized by (labs and symptoms)?
Elevation of liver enzymes such as aminotransferases (ALT/AST), and bile (bilirubin) in the blood causing yellowing of the skin and eyes (jaundice)
Hepatitis A (name, virus type, symptoms)
“Infectious Hepatitis”
ssRNA containing picornavirus
Asymptomatic or symptomatic. Usually self-limiting.
Abrupt onset of symptoms that can include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice.
Frequent cause of acute hepatitis in US
In children, 70% of patients.
Is Hep A acid labile or stable?
Stable
Because it’s an enterovirus
How is Hep A contracted
Fecal-oral route
Local epidemics occur from eating raw seafood, usually shellfish, or fecal contaminated produce like green onions and other salad bar items.
Is there a Hep A vaccine?
Yes
prepared from killed virus, capsid protein antigens
There is only one serotype of HAV, therefore this vaccine is efficacious around the world.
Recommended for travelers visiting developing countries of the world. HAV vaccine is now universally recommended for all children in the US, however, HAV infections are common in the US because many children and many adults have not received the vaccine.
Passive immunization to Hep A
Rarely used now. Instead we just vaccinate with killed vaccine even post-exposure and that works well enough.
Because the incubation period of HAV infections is long enough (usually more than 2 weeks), people exposed to HAV can be treated with immune serum globulin to prevent or to decrease the severity of disease. If people are given immune serum globulin within one week of their infection their disease can be prevented.
can receive passive and active vaccination simultaneously
Hep E (type of virus)
Hepeviridae family
Naked, postive-sense ssRNA virus
Where are Hep E infections most common?
Developing world
HEV infections are not common in US
What population is most concerning when infected with Hep E?
Pregnant women (3rd trimester) Fulminant hepatitis in pregnant women (mortality up to 40%)
Hep B Virus
dsDNA (some is ds some is ss; kind of a mess of DNA)
Enveloped
Hepadnavirus
HBV antigens
HBsAg: HBV surface antigen, is the envelope of the virus and sub-viral 22nm particles. Not infectious. Found in the blood of infected individuals in large numbers and serve as diagnostic marker of acute, and chronic hepatitis. The recombinant vaccine consists of HBsAg particles.
Anti-HBsAg: marker of convalescence and subsequent immunity.
HBcAg: HBV core antigen, capsid. AntiHBcAg (IgM) is one of the markers of acute infection.
HBeAg: Found in the blood of chronic hepatitis patients. Marker associated with infectivity, AntiHBeAg is not protective but is an early indicator of resolution of hepatitis and favorable prognosis.
HBxAg: Viral regulatory protein, likely player in the development of hepatocellular carcinoma.
HBV replication
Uses reverse transcriptase on the way out of the cell (unlike retroviruses that use it on the way into the cell)
DNA virus BUT replicates via an RNA intermediate. The viral genome transcribes a genome-length RNA molecule termed pregenome that is converted into DNA by a reverse transcriptase (P) encoded by the virus. The product of this activity is a partially double stranded DNA molecule found in the virions. Core particles exit from hepatocytes after being packaged with HBsAg/envelope or recycle through nucleus.
HBV transmission
Liberated from the liver into the blood, and as little as 0.0001 ml of infectious blood can cause infection.
Occupational hazard for dentists, surgeons, dialysis unit personnel, and drug users.
Infection can also occur by sexual transmission and by close contact through abrasions.
Neonatal transmission occurs between infected mother and infant.
HBV disease
Infection begins with acute hepatitis, which is often self-limited.
Less commonly, a persisting injury causes chronic inflammation giving rise to diffuse scarring (cirrhosis), portal hypertension and liver failure.
Approximately 85-90% of all infections are asymptomatic.
High risk of hepatocellular carcinoma
What causes liver damage in Hep B?
Liver damage is not due to virus killing cells but rather a vigorous cytotoxic immune response directed against the virus-infected cells.
Is there a Hep B vaccine?
YES! Surface antigen vaccine
Recombinant hepatitis B vaccine is the best protection. It is given in three doses.
Health care workers should be vaccinated. Drug-injection users who share needles are at a high risk of acquiring infection. Administration of HBIG after exposure significantly reduces symptoms of hepatitis B.
Hep D virus
“Delta ‘d’ Agent”
circular ssRNA deltavirus
Defective satellite virus that can replicate ONLY in HBV-infected cells.
HBV provides the HBsAg for packaging the delta viral RNA genome. HDV contains a small circular RNA genome similar to plant viroids.
Superinfection can increase the severity of liver disease and accelerate the pace of chronic HBV infections.
HBV vaccine also protects against HDV!
Hep C epidemiology
Leading cause of chronic liver disease worldwide
HCV causes about 15,000 deaths annually in the United States (more deaths in the US than those caused by HIV)
What type of virus is Hep C? Structure?
hepacivirus genus in the family Flaviviridae
ssRNA
Relatively long 5’ untranslated region (UTR) that functions as an IRES (internal ribosome entry site) element and regulates translation of a long open reading frame that encodes a polyprotein of 3010 amino acid residues, followed by a unique 3’UTR.
Very error prone and high mutation rate
Treatment of Hep C
Combination of pegylated Interferon and Ribavirin was the standard treatment until 2011, with about 40% efficacy against HCV genotype 1 infections. In 2011, a combination of pegylated Interferon & ribavirin along with an HCV protease inhibitor (telaprevir or boceprivir) became the standard of care. The addition of a protease inhibitor decreased the treatment period (from ~48 to 24 weeks of treatment) and increases the efficacy (from ~40% SVR previously to ~80% SVR for the new regimen).
HCV nonstructural proteins are targeted by several new and emerging direct-acting antivirals (DAAs).
The HCV protease (NS3) is targeted by protease inhibitors (telaprevir and boceprevir and paritaprevir).
NS5A is targeted by ledipasvir and ombitasvir.
NS5B encodes a viral RNA-dependent RNA polymerase (the target of sofosbuvir and dasabuvir).
Clinical course of HCV
15%- Recovery and clearance
85%- Persistent Infection (chronic hepatitis)
Out of those 85% who get chronic hep c:
6%- liver failure
20%- cirrhosis
4%- Hepatocellular carcinoma
