Viral Hepatitis Flashcards

1
Q

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?

A

Hepatitis (most likely Hep B but coud also be C but not as common)

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2
Q

What are the signs and symptoms of hepatitis?

A

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

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3
Q

Which hepatitis virus can be sexually transmitted? What are the characteristics of this virus?

A

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.

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4
Q

Describe the replication cycle of Hep B

A

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**

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5
Q

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?

A

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)

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6
Q

T/F: Hepatitis B infection is directly responsible for damage to the host liver

A

Falsehood. Damage to liver is immune mediated damage to infected hepatocytes

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7
Q

How is Hep B transmitted?

A

Hep B is transmitted thru blood, sexual contact and from mother to child (in the absence of prophylaxis)

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8
Q

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?

A

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

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9
Q

Explain the graph below, depicting Hep B testing

A

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**

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10
Q

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?

A

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

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11
Q

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?

A

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**

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12
Q

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)?

A

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)

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13
Q

How do the Hep B markers differ in a vaccinated person vs a resolved infection?

A

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

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14
Q

Describe the natural history of Hep infection (as in, what happens after people get to chronic infection)

A

**see image below**

(note that chronic infection by itself can increase risk of liver hepatocellular carcinoma without having to have cirrhosis first)

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15
Q

Between younger and older pts, who is more likely to develop chronic disease vs clear the infection?

A

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)

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16
Q

What are extra hepatic manifestations of HBV?

A

Polyarteritis nodosa (PAN) and other vasculitidies

Glomerulonephritis

Serum sickness (acute)

Arthralgias

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17
Q

Who gets treated for HBV?

There are generally 2 categories of treatment for HBV. What are they and which drugs fall into each group?

A

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)**

18
Q

What are two ways to prevent Hep B?

A

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

19
Q

___ is a defective Hepatitis virus that can only co-infect someone who has Hep B infection

A

Hepatitis D (literally the D is defective)

20
Q

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?

A

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

21
Q

How do you Dx Hep D?

What is the Rx for hep D?

A

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

22
Q

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?

A

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

23
Q

Describe the characteristics of Hep C virus

A

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

24
Q

Describe the replication cycle of Hep C virus

A

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

25
Q

The non structural proteins of Hep C virus are the main targets of treatment. Which 3 proteins are the main therapeutic targets?

A

NS3-4A: Protease

NS5B: Polymerase

NS5A: No enzymatic activity but critical for viral replication

26
Q

How is Hep C transmitted?

A

Mostly blood borne thru IV drug use or contaminated blood products.

Others: sexual and perinatal although both rare

**note that unlike HBV, most peope who have acute HCV infection will progress to chronic infection**

27
Q

How is Hep C infection diagnosed?

What are the differences in presentation between Hep B virus and Hep C virus?

A

HCV diagnosis: screen with antibody test then confirm with HCV RNA

No real differences in presentation between the 2 other than the fact that acute HCV tends to be less symptomatic

28
Q

Name 2 extrahepatic manifestations of Hep C infection

A

Rashes (porphyria cutanea tarda, lichen planus)

Lymphoma

29
Q

Why might someone have a positive HCV antibody but negative RNA?

A

Either the patient spontaneously cleared the virus after acute infection (about 15% will clear) or successful treatment of HCV

30
Q

Describe the natural history of Hep C virus

A

see image below

**the thing to remember is that most people WILL infact progress to chronic disease, however most of those folks will be stable and getting treated significantly reduces chance of progression**

31
Q

What makes HCV is a completely curable disease unlike HBV or HIV?

A

HCV doesn’t have any of its genome being integrated into the host genome nor does it have a dna form that stays there in the host nucleus so when you bust the virus, you destroy it for good

32
Q

How is HCV infection treated?

A

NS5B (polymerase inhibitors)

NS5A inhibitors (that’s the protein that people don’t really know what it does)

NS3 (protease inhibitors)

33
Q

Describe the characteristics of Hep A. How is Hep A transmitted?

A

Hep A is the H in the PERCH of Picornaviruses

Hep A (along with Hep E) is transmitted via fecal oral contamination (or consumption of raw seafood)

34
Q

Describe the pathogenesis of Hep A (remember that this is fecal oral transmission)

A

Oral cavity >> GI tract >> liver via blood

35
Q

Describe the presentation of Hep A

A

Essentially the same as described with HBV infection (non-specific illness: fatigue, abdominal pain, loss of appetite, intermittent nausea, vomiting; + jaundice and elevated liver enzymes, dark urine and clay colored stool)

Most cases resolve spontaneously in 2-4 weeks; most people have jaundice (adults more symptomatic)

36
Q

How do you Dx Hep A infection?

A

Just the IgM. Most infections are acute so you’ll be looking for Hep A IgM (note that there’s no chronic HAV infection)

37
Q

How is Hep A treated?

A

Mainly supportive care but there is immunoglobulin given pre and post exposure, and a vaccine

38
Q

Describe the characteristics of Hep E

A

Actually a member of the Hepeviruses, NOT Herpesvirus (Hepeviruses are basically animal viruses but somehow this one made its way to being a human virus)

Its a non-enveloped RNA virus with 4 genotypes that cause disease in humans

(Genotypes 1,2: human epidemic hepatitis (fecal-oral transmission; Genotype 3,4 swine viruses- human accidental host (transplant and other immunosuppressed hosts) - may be acquired after ingestion of raw/undercooked pork or venison

39
Q

Describe the presentation of Hep E virus infection

A

Hep E is for all intents and purposes, the same as Hep A BUT there’s a very HIGH mortality in pregnant women

40
Q

You need to see this one

A