Viral Hepatitis Flashcards
A 52y/o male presented to the hospital August 12th with increasing nausea, vomiting, jaundice over 2-3 weeks duration. The patient has no significant comorbid illnesses. He does drink alcohol occasionally but denies illicit drug use. He takes no medications. On June 14, he had unprotected sex with a female prostitute and was treated for gonorrhea.
What is the syndrome?
Hepatitis (most likely Hep B but coud also be C but not as common)
What are the signs and symptoms of hepatitis?
Fatigue, nausea, vomiting, malaise, abdominal pain (localizing to the RUQ), nausea, loss of appetite, change in stool (chalky/clay-colored), chills, headache, myalgias.
Signs include jaundice and icterus
Which hepatitis virus can be sexually transmitted? What are the characteristics of this virus?
Hepatitis B (virion is also known as Dane particle)
Hep B is Hepadnah virus. Actually partially ds DNA virus, has reverse transcriptase and gets its envelope from the ER.
Describe the replication cycle of Hep B
Viral entry >> uncoating >> viral genome transported to nucleus and kept as CCC dna >> dna can then be transcribed using reverse transcriptase and kept as progeny DNA genome or following transcription, translated in the cytoplasm
**know that cccDNA persists in the host indefinitely and the folks in whom cccDNA persists have chronic disease**
Hep B has a few antigens important for Dx and its function. Which antigens exist inside the virus’ core? Which ones are on the virus’ surface?
Core antigen is in the center of the virus. There’s also the e antigen (indicator of transmissibility – that’s the one that correlates well to viral dna load according to B/B)
Outer coat of the virus has Hep B surface antigen (made of small, medium, large proteins)
T/F: Hepatitis B infection is directly responsible for damage to the host liver
Falsehood. Damage to liver is immune mediated damage to infected hepatocytes
How is Hep B transmitted?
Hep B is transmitted thru blood, sexual contact and from mother to child (in the absence of prophylaxis)
There are 2 categories of tests you can conduct for Hep B. What are they?
What are the proteins you’ll be testing for each group?
Markers of Hep B virus: HBV dna (viral load), HB e Ag, HB s Ag
Antibodies to the antigens: anti Hb core (IgM/IgG to tell acute vs chronic), anti Hb e; anti Hb s
Explain the graph below, depicting Hep B testing
Total anti-HBc represents IgM and IgG
Window period (around 28 weeks): point at which HB surface antibody isn’t high enough yet and surface antigen in no longer detectable so the only detectable entity is total core antigen
Almost everyone with acute hepatitis will have +ve surface antigen
**so at infection or right after infection: the first thing to pop up is Hep B surface antigen, then antibodies to Hep B core antigen, then anti-Hb surface antibodies pop up later on**
What test results would you expect to determine if pt has resolved acute Hep B infection?
Which serological marker will be +ve during the window period?
If pt is seen after resolution of infection, the only things that’ll be +ve are IgG to HB core ag, and surface antigen (surface antigen itself will be negative)
The IgM to hepatitis core antibody will be positive during the window period
23 year old Asian female presents to establish her primary care. She was born in China and is a college student. She does not drink, does not use illicit drugs and is not sexually active. She has no complaints and a normal physical exam. She was referred based on +ve Hep surface antigen test but all other lab values including liver enzymes and function tests are normal. She has a very high HBV dna load.
Since she has no other risk factors for infection, where could she have acquired it?
She most likely acquired HBV at birth and has chronic infection.
**remember that infants born to mothers with untreated HBV can get chronic infection and also she was born in an endemic area - #China**
What does the Hep B graph of a pt with chronic infection look like (i.e. which antigens/antibodies will be high, which ones are low/absent etc)?
Notice how she never makes the antibodies to the Hep B surface antigen because she’s chronically infected, and that HB e antigen is prolonged (note also that she has a very high viral load)
How do the Hep B markers differ in a vaccinated person vs a resolved infection?
The difference between a vaccinated person and someone who’s resolved an acute infection is the core antibody. Every marker will be the same except the core antibody will be negative in the vaccinated person
Describe the natural history of Hep infection (as in, what happens after people get to chronic infection)
**see image below**
(note that chronic infection by itself can increase risk of liver hepatocellular carcinoma without having to have cirrhosis first)
Between younger and older pts, who is more likely to develop chronic disease vs clear the infection?
Older patients will be more symptomatic but have a higher likelihood of clearing the infection because of the host immune response (remember it’s the immune response that gets us to being symptomatic so in younger folks who have a less robust immune response, they can be asymptomatic but will have a higher likelihood of developing chronic infection)
What are extra hepatic manifestations of HBV?
Polyarteritis nodosa (PAN) and other vasculitidies
Glomerulonephritis
Serum sickness (acute)
Arthralgias
Who gets treated for HBV?
There are generally 2 categories of treatment for HBV. What are they and which drugs fall into each group?
We treat people who have evidence of liver damage or those with high viral loads (mainly to suppress replication)
Reverse transcriptase inhibitors, and immune therapy
** RTIs: Entecavir (another nucleoside analogue) and Tenofovir (nucleotide analogue) ** don’t use lamivudine or any of those other ones as first line (lam esp has low barrier to resistance)
**Immune therapy: interferon - Peginteferon alpha 2a (used in Europe a lot b/c it would be a shorter course)**
What are two ways to prevent Hep B?
Hep B Immune Globulin (gives temporary passive immunity to folks post exposure, or to kids born to infected moms - or also folks who have received a transplant)
Hep B vaccine
___ is a defective Hepatitis virus that can only co-infect someone who has Hep B infection
Hepatitis D (literally the D is defective)
Describe the difference between Hep B co-infection with Hep D and super infection? Which group will have better clearance of acute infection? Which group will have more progressive disease?
Hep D co-infection with Hep B can have a higher clearance of acute infection but the risk of developing liver disease is higher
Superinfection is basically co-infection with Hep D when you’re already chronically infected with Hep B.
Generally, folks with Hep D and Hep co-infection have more progressive liver disease than Hep B alone
How do you Dx Hep D?
What is the Rx for hep D?
Serology looking for anti-HDV antibodies
Hep D viral RNA PCR
**
Treatment for Hep D:
Pegilated interferon (peg-inteferon) for 48+ weeks (low efficacy and tolerability)
other therapies like the RTIs used for Hep B don’t work
A 54 y/o AAM referred to hepatitis clinic for evaluation of hepatitis C. PMH: hypertension. Pt denies symptoms and repeatedly states “I feel fine, I don’t know why I have to be here.” Social History: ½ PPD tobacco, drinks ETOH rarely and used IV heroin in the early 1980’s
Baseline labs done by PCP:
Hepatitis C Ab positive
Hepatitis B surface Ab positive
Hepatitis B core Ab positive
Hepatitis B surface antigen negative
Hepatitis A antibody negative
HCV RNA 1.2 million IU/mL
HCV Genotype 1a
Does the pt have Hep B? Does the pt have Hep C?
Pt has resolved Hep B infection (remember that is Hep B surface antibodies are +ve, that means you’re either currently experiencing infection or you had it before but in this case its resolved because then Hep B surface antigen is negative, meaning he doesn’t currently have infection, so that must mean its resolved)
Since he has +ve Hep C viral load and Hep C genotype, pt has Hep C
Describe the characteristics of Hep C virus
Hep C is a Flavivirus (like WNV and St LEV) so its a +ve sense, ss RNA, enveloped virus with multiple genotypes that vary in response to therapy
Describe the replication cycle of Hep C virus
Note that the virus replicates in the cytoplasm (specifically on the endoplasmic reticulum), gets its envelope from the ER and is secreted out of hepatocytes using lipid secretory mechanisms
