hepatocellular carcinoma - Hep B, Hep C

[soon2Bmd2005]

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hi all, i'm trying to figure out the mechanism for hepatocellular carcinoma in Hep B and Hep C. All sources say that the mechanism for oncogenesis in Hep C is a result of the constant killing/regeneration of hepatocytes induced by CD8 T cells. However, for Hep B....some sources say hepatocellular carcinoma is a result of integration of viral genome leading to a direct oncogenesis..but then others say it's the same mechanism as Hep C because Hep B doesn't contain any oncogenes. any thoughts? thanks!

 

[medhacker]

The pathogenesis of HBV induced hepatocellular carcinoma is DNA integration. Followed by production of protein HBX which inactivates P53 and activates growth promoting genes in the hepatocytes thus increasing the risk of HCC.

Source: Usmle World

 

[HIJay]

The pathogenesis of HBV induced hepatocellular carcinoma is DNA integration. Followed by production of protein HBX which inactivates P53 and activates growth promoting genes in the hepatocytes thus increasing the risk of HCC.

Source: Usmle World

i concur.

and also HBV is a DNA virus, thus the ability the integrate its DNA.

 

[soon2Bmd2005]

that's what i thought too..however..robbins review of path (question book) chapter 18 (liver/biliary tract) question 9 answer explanation...says that HBV doesn't contain an oncogene. the questions asks if it inserts near c-myc...which is wrong...but the explanation goes on to say that no oncogene exists at all and the mechanism for transformation is the same as hep C. i don't have the robbins big book on hand to see what it says. i can't decide whom to trust. what do you guys think?

 

[InternationlDoc]

I saw the exact same question on Kaplan Qbank and they agree with UWorld. Just like the OP I was WTF (since Robbin's doesn't agree), but I think I'd buy whatever UWorld has to say and I read about the Hep B integrating its DNA blah blah on pubmed somewhere

 

[HIJay]

perhaps its one of those newly discovered mechanisms, and robbins has not yet update the info yet?

 

[Blesbok]

I personally believe robbins. I had the same thing come up the other day when I got that question in world.

 

[Blesbok]

I saw the exact same question on Kaplan Qbank and they agree with UWorld. Just like the OP I was WTF (since Robbin's doesn't agree), but I think I'd buy whatever UWorld has to say and I read about the Hep B integrating its DNA blah blah on pubmed somewhere

It does integrate, I just don't think that has anything to do with the pathogenesis of HCC

 

[ASDIC]

Hep B: viral integration of its genome ==> unknown mechanism ==> carcinogenesis
I reviewed several articles on Pubmed and many authors seem to disagree about p53 being involved in all forms of liver carcinogenesis but they do agree about the viral integration of the genome.
Hep C: repeated inflamm, injury and regeneration of hepatocytes ==> increased frequency of mutations ==> carcinogenesis

 

[alpha06]

I believe UW is correct. And Robbins confirms it.

This is from my Robbins 7ed. Unit II Chapter 18 p.892

Excerpt:"....A protein from the X region, HBx, which is necessary for virus replication and acts as a transcriptional transactivator of the viral genes and a wide variety of host genes. HBx modulation of gene transcription affects viral replication and the function of hepatocyte cell cycle checkpoints. HBx may play a role in deregulation of hepatocyte replication and development of hepatocellular carcinoma in HBV-infected patients."

 

[Blesbok]

I believe UW is correct. And Robbins confirms it.

This is from my Robbins 7ed. Unit II Chapter 18 p.892

Excerpt:"....A protein from the X region, HBx, which is necessary for virus replication and acts as a transcriptional transactivator of the viral genes and a wide variety of host genes. HBx modulation of gene transcription affects viral replication and the function of hepatocyte cell cycle checkpoints. HBx may play a role in deregulation of hepatocyte replication and development of hepatocellular carcinoma in HBV-infected patients."

Ya, but what robbins is saying is that the gene product of HBx is involved in cell cycle checkpoint alteration and genesis of HCC. It isn't saying that the actual integration of the gene into the genome is what causes HCC, which is what world is saying.

 

[medhacker]

Chronic hepatocyte injury and regenerative hyperplasia is also part of the pathogenesis of HBV induced HCC according to UW. It also states HBV is what codes for the Hbx protein.


And this is what Robbins says about HBV DNA integration:
"Indeed, molecular analysis of tumor cells in HBV-infected individuals reveals that each case is clonal with respect to HBV DNA integration pattern, suggesting that viral integration precedes or accompanies a transforming event.

• For reasons that are not clear, genomic instability is more likely in the presence of integrated HBV DNA, giving rise to chromosomal aberrations such as deletions, translocations, and duplications. "