Hepatitis B question - oncogenesis

[Phloston]

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A couple months ago, some people on this forum had spoken of a Hepatitis B viral protein, called HBx, that UWorld supposedly mentions as knocking out p53 (TP53 gene). This in turn was discussed to be the oncogenesis of HCC in Hep B infection.

Anyway, now that I'm on Kaplan QBank, I got a question about the oncogenesis of HCC in Hep B infection, and I immediately clicked on "inactivation of tumor suppressor gene," but "integration of viral genome" was the answer.

I then did a bit more reading up on HBx, and I could find nothing that said it interferes with p53, so either UWorld is possibly wrong if it says that (I haven't done UWorld yet), or some people on this forum had no idea what they were talking about.

Does anyone have any input?

 

[pizdun]

from my notes


Hepatitis B infection progresses through two phases – proliferative and integrative

Proliferative phase:
viral HBsAg and HBcAg are expressed in conjunction with the MHC class I molecule. This serves to activate cytotoxic CD8+ T lymphocytes, which respond by destroying the infected hepatocyte.The virion itself does not have a cytopathic effect
Integrative phase:
HBV DNA is incorporated into the host genome of those hepatocytes that survived the immune response.
If HBV DNA becomes incorporated into the cell – and the cell is not destroyed - there is now an increased risk for HCC

Mechanism of HBV carcinogenesis
HBV is incorporated into the genome
HBV DNA results in chronic liver cell injury and regenerative hyperplasia – increasing the number of hepatocytes susceptible to genetic mutations

HBV DNA encodes for a HBx protein
• Stimulates cell proliferation by activating synthesis of insulin like growth factors
• Inactivates p53

 

[RedSoxSuck]

A couple months ago, some people on this forum had spoken of a Hepatitis B viral protein, called HBx, that UWorld supposedly mentions as knocking out p53 (TP53 gene). This in turn was discussed to be the oncogenesis of HCC in Hep B infection.

Anyway, now that I'm on Kaplan QBank, I got a question about the oncogenesis of HCC in Hep B infection, and I immediately clicked on "inactivation of tumor suppressor gene," but "integration of viral genome" was the answer.

I then did a bit more reading up on HBx, and I could find nothing that said it interferes with p53, so either UWorld is possibly wrong if it says that (I haven't done UWorld yet), or some people on this forum had no idea what they were talking about.

Does anyone have any input?

That's what I have annotated into fa from uworld. Hep B in terms of hepatocellular carcinoma, hep b DNA is integrated into host genome.
Hep b also produces a protein called HBx which does two things: 1) disrupts growth control of infected cells by activating growth promoting genes. 2) It also binds to p53 and slows down its action of growth suppression.

 

[Boardz]

That's what I have annotated into fa from uworld. Hep B in terms of hepatocellular carcinoma, hep b DNA is integrated into host genome.
Hep b also produces a protein called HBx which does two things: 1) disrupts growth control of infected cells by activating growth promoting genes. 2) It also binds to p53 and slows down its action of growth suppression.

ditto on the above.

despite all this I would say: "HBV has NO DIRECT cytotoxicity." even though there's this magic HBx protein that is at least partly cytotoxic. And of course, the mechanism of oncogenesis is integration into host genome > HBx

http://en.wikipedia.org/wiki/HBx
http://etd.ohiolink.edu/view.cgi?acc_num=ucin1014751166

(interesting... from the 2nd link, apparently P53 keeps alpha-fetoprotein silent and HBx can disrupt P53 resulting in alpha-fetoprotein expression. cool.

 

[Aclamity]

A couple months ago, some people on this forum had spoken of a Hepatitis B viral protein, called HBx, that UWorld supposedly mentions as knocking out p53 (TP53 gene). This in turn was discussed to be the oncogenesis of HCC in Hep B infection.

Anyway, now that I'm on Kaplan QBank, I got a question about the oncogenesis of HCC in Hep B infection, and I immediately clicked on "inactivation of tumor suppressor gene," but "integration of viral genome" was the answer.

I then did a bit more reading up on HBx, and I could find nothing that said it interferes with p53, so either UWorld is possibly wrong if it says that (I haven't done UWorld yet), or some people on this forum had no idea what they were talking about.

Does anyone have any input?

It doesn't inactivate the gene; it inhibits the p53 protein (gene is still functional)

 

[Phloston]

Thanks for the input, guys.

 

[Belleza156]

Do you happen to know the treatment for hepatitis B ? I got that question on my exam and all the options were the gamet of the HIV drugs. Is never heard of treatment for hepatitis B besides supportive. At the end I answered an NRTI, figured the whole reverse transcriptase activity of hepatitis B maybe was involved.

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[alternatego]

Do you happen to know the treatment for hepatitis B ? I got that question on my exam and all the options were the gamet of the HIV drugs. Is never heard of treatment for hepatitis B besides supportive. At the end I answered an NRTI, figured the whole reverse transcriptase activity of hepatitis B maybe was involved.

Sent from my PC36100 using SDN Mobile

I think it is IFN + ribavirin

 

[Belleza156]

That's the treatment for Hepatitis C. But those weren't options anyways. Only the HIV drug classes were options.

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[Phloston]

Ribavirin is hepatitis C, not B.

From doing practice questions, I recall that for Hep B:

Interferon-alpha
Adefovir
Lamivudine

For Hep C:

Pegylated interferon-alpha
Ribavirin

 

[ijn]

The new standard of care for Hep C genotype 1 includes boceprevir or telaprevir in addition to interferon and ribavirin.

 

[Phloston]

The new standard of care for Hep C genotype 1 includes boceprevir or telaprevir in addition to interferon and ribavirin.

Where did you encounter that?

 

[ijn]

That's the treatment for Hepatitis C. But those weren't options anyways. Only the HIV drug classes were options.

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The answer probably was lamivuidine or another NRTI.

 

[ijn]

Where did you encounter that?

I guess I first heard about it in lecture. It's a grade 1A recommendation from UpToDate, which is as strong as it gets.

• For patients with chronic HCV genotype 1 who are candidates for therapy, we recommend triple therapy with peginterferon, weight-based ribavirin, and a protease inhibitor (telaprevir or boceprevir) rather than dual therapy with peginterferon and weight-based ribavirin (Grade 1A). Treatment with peginterferon and weight-based ribavirin alone results in sustained virologic response rates of 40 to 50 percent in patients with chronic HCV genotype 1. With the addition of a protease inhibitors (telaprevir or boceprevir), the rate increases to 70 to 80 percent. (See 'Treatment regimens' above and 'Efficacy of protease inhibitor containing regimens' above.)

 

[Phloston]

Great info. Thanks. Just annotated that over into FA.

 

[Belleza156]

Great info. Thanks. Just annotated that over into FA.

Where did you guys come across the hepatitis B treatment in your studying? I dont remember it bring kaplan or uworld and i didnt learn it in class either.

Besides uptodate is this info readily available. Does everyone know the treatment to hepatitis B except for me?

 

[Dallas]

I had a question on the real step about the carcinogenic mechanism of hep b.
I narrowed it down to 2 choices, either integration into the genome close to oncogenes, or inactivation of p53. I picked the p53 but I was not sure, I hope this was correct.

Hope I havent breached any copyright or TOS, if I have please tell me and I will remove this post.

 

[Boardz]

Where did you guys come across the hepatitis B treatment in your studying? I dont remember it bring kaplan or uworld and i didnt learn it in class either.

Besides uptodate is this info readily available. Does everyone know the treatment to hepatitis B except for me?

it's in first aid i have the 2011 so i ccan't tell you the 2012 page. but for 2011 pg. 198: my mnemonic is:

interferon A for hep B and hep C and Kaposi's (idk ABCK helped me remember).

also, ribavirin plus pegylated interferon or whatevertf is for hep C i think that's pretty common knowledge.

 

[ijn]

Where did you guys come across the hepatitis B treatment in your studying? I dont remember it bring kaplan or uworld and i didnt learn it in class either.

Besides uptodate is this info readily available. Does everyone know the treatment to hepatitis B except for me?

I don't remember learning it from USMLE review materials really. We were taught the current treatments for HepB/C by clinicians during second year in our GI block.

 

[Belleza156]

I had the same question on my step exam, twice! One question mentioned E6 and another mentioned E7, so I chose p53 and RB respectively. Goljan said it twice in his recordings. "Nasty little bugs" he kept saying.

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[Dallas]

I had the same question on my step exam, twice! One question mentioned E6 and another mentioned E7, so I chose p53 and RB respectively. Goljan said it twice in his recordings. "Nasty little bugs" he kept saying.

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I thought E6 was associated with HPV not HBV?

 

[Phloston]

I had a question on the real step about the carcinogenic mechanism of hep b.
I narrowed it down to 2 choices, either integration into the genome close to oncogenes, or inactivation of p53. I picked the p53 but I was not sure, I hope this was correct.

Hope I havent breached any copyright or TOS, if I have please tell me and I will remove this post.

That seems like a really slick way of wording the question. Doesn't it both integrate into the genome and inactivate p53? However, I don't recall it activating/integrating adjacent oncogenes, but rather next to "growth factor pathways," so perhaps integration next to oncogenes is incorrect and inactivation of p53 is correct. I'd like to hear someone's thoughts on this.

Btw, USMLE Rx had like 10-15 questions on HepB/C treatments. They were very big on them.

And, Dallas, E6/7 are HPV. I think she's just reiterating from previous discussion the fact that repeats do occur.

 

[Myxedema]

Robbins Basic Pathology, 9th Edition, p. 616:

HBV-X protein, which acts as a transcriptional transactivator for many viral and host genes through interaction with various transcription factors. HBV-X is required for viral infectivity and may have a role in the development of hepatocellular carcinoma by regulating p53 degradation and expression