Scott Lu - A Gap in Hepatitis B Understanding

Scott Lu - A Gap in Hepatitis B Understanding

by Scott Lu -

Hepatitis B virus (HBV) is an asymmetrically replicating member of the Hepadnaviridae family.  Owing to the lack of proofreading activity during replication, the estimated mutation rate of HBV 2 x 10(4) base substitutions/site/year.  Current classification through phylogenetic analysis includes 10 genotypes (A to J) based on an 8-percent or greater divergence in the nucleotide sequence.  There is growing evidence suggesting that genotypes have an influence on clinical outcome, including response to interferon therapy.   Of these, genotypes G through J have sparse data based on very few numbers of patients in a few countries only.  Additionally the clinical consequences of coinfection with multiple genotypes is unknown, though it has been noted that genotype G appears to have an association with genotype A.


Interferon is a mainstay of treatment of HBV.  Currently a number of reports suggest: response rates in terms of HBeAg loss is higher in patients with genotype B compared to genotype C, and overall response rates are higher in patients with genotype a compared to D.  


References:

Summers J, Mason WS. Replication of the genome of a hepatitis B--like virus by reverse transcription of an RNA intermediate. Cell 1982; 29:403.

Girones R, Miller RH. Mutation rate of the hepadnavirus genome. Virology 1989; 170:595.

Norder H, Couroucé AM, Magnius LO. Complete genomes, phylogenetic relatedness, and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes. Virology 1994; 198:489.

Kao JH, Wu NH, Chen PJ, et al. Hepatitis B genotypes and the response to interferon therapy. J Hepatol 2000; 33:998.

Wai CT, Chu CJ, Hussain M, Lok AS. HBV genotype B is associated with better response to interferon therapy in HBeAg(+) chronic hepatitis than genotype C. Hepatology 2002; 36:1425.



Re: Scott Lu - A Gap in Hepatitis B Understanding

by Timothy -

Hi Scott, I am not sure I understand what the intervention you want to focus on within the topic of hepatitis B subtypes. Beyond a lack of scientific knowledge around specific genotypes treatment Is there a specific clinical practice that is not being implemented? Are clinicians not obtaining genotypes? Or using genotype directed therapy? Or screening for hepatitis B in the first place?


What practice intervention might address the gap you identify?


Re: Scott Lu - A Gap in Hepatitis B Understanding

by Scott Lu -

Hi Timothy,


Sorry for the confusion, I cut out a bit too much of my original post.


To clarify my point: there is evidence that suggests that the specific genotype of HBV may play a role in the clinical outcome and optimal treatment of Hepatitis B.  It is, however, not always the case that genotyping is done and when it is done it does not always affect the initial treatment regimen the patient is put on, such as using interferon over entacavir.


On another note, I could only find the above references when looking into this.  Would it be better to find a gap with a stronger foundation in research than this?


Thanks,

Scott