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HBV genotyping

HBV genotyping. 12/21/07 Carrie Marshall. Received a send-out request for HBV genotyping on a 52y man. Hepatitis B Genotyping. Is this a mistake? What difference does it make? Isn’t everyone getting vaccinated anyway?.

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HBV genotyping

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  1. HBV genotyping 12/21/07 Carrie Marshall

  2. Received a send-out request for HBV genotyping on a 52y man

  3. Hepatitis B Genotyping • Is this a mistake? • What difference does it make? • Isn’t everyone getting vaccinated anyway?

  4. While chronic Hep B is not common in the US, there are 350-400 million patients world wide • New studies suggest that the genotype can play a part in the prediction of acute liver disease, development of HCC and/or cirrhosis, and response to antivirals • Test requests will likely increase in the future

  5. Hepatitis B Virus is divided into eight genotypes (A through H) based upon genetic variation • If there is greater than 8% divergence at the DNA sequence level, then it is a separate genotype • The geographical distribution of genotypes is unequal (your genotype depends on your ethnicity and place of birth)

  6. East Asia Types B and C • Europe Types A and D • India Types A and D • Africa Types A, D, and E • United States predominately A • West 75% B and C • Southeast 63% A • Midwest 69% A and C

  7. In areas of the world where chronic HBV infection is the most common, there is also less variability of genotypes (hard to see if there is a difference between groups) • In the US, where all 8 genotypes are found, there are fewer patients to enroll into studies

  8. Clinical Concerns • Patients with chronic HBV have a 15%-25% lifetime risk of developing HCC and/or cirrhosis (NEJM 2004) • Who should be monitored? How frequently? How aggressively? (CT, MRI, Bx?) • Some evidence that Genotype C has a higher risk for progressing to cirrhosis, and is less responsive to interferon therapy

  9. Natural History of HBV

  10. So what do we want to know about the patient in question? • Audience participation

  11. Natural History of HBV

  12. Is that True? • Sometimes. That is probably the way it goes for genotypes A and D. • Testing for HBVeAg and HBVeAb (~$7.00) is a good way to follow those patients, in combination with ALT • But genotypes B and C there is an association with 2 mutations which interfere with the production of HBVeAg

  13. Pre-core mutation will prevent the expression of HBVeAg, without changing the ability of the virus to replicate and is associated with genotypes D (55%), B (44%) and C (22%) • Rare in genotype A (3%) • Numbers based on a US study • Overall in the US, 27% of patients with Chronic HBV have a precore mutation (will not express HBVeAg)

  14. Core promoter mutation can lead to a reduced production of HBVeAg, and is associated with genotypes C (60%), A (41%) and D (40%) • Least common in genotype B (26%) • Again these are US numbers • Overall in the US, 44% of patients with Chronic HBV have a core promoter mutation • Mixed results on whether these mutations lead to more injury, or higher viral loads

  15. What does this mean? • Should there be a change in the way chronic HBV patients are followed? • Should we just follow viral load ($252)? • Should everyone get genotyped ($134)? • Should patients (or only HBVeAg -) patients be tested for PC/CP mutations?

  16. I don’t know! • Serial viral loads would be ideal, but costs a lot more. • Maybe just LFTs are good enough? Certainly patients with high viral loads and increased LFTs are at risk for cirrhosis/HCC, but not so clear what the risk is for patients with high viral loads but normal LFTs

  17. Genotyping would be a one-time (?) expense, and could guide the decision to treat, and choice of therapy • Could also predict the likelihood of a PC/CP mutation (and the non-usefulness of following HBVeAg) I couldn’t find convincing evidence that PC/CP mutations have an effect on therapy, and/or risk of cirrhosis and HCC

  18. Related Reading • Chu CJ et al. Hepatitis B virus genotypes in the United States: results of a nationwide study. Gastroenterology, 2003;125:444-451. • Chu CJ et al. Prevalance of HBV precore/core promoter variants in the United States. Hepatology, 2003;38(3):619-628.

  19. Related Reading • Grandjacques C et al. Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity. Journal of hepatology, 2000;33:430-439. • Genotype C hepatitis B virus infection is associated with a higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: A longitudinal study of hepatitis B e antigen-positive patients with normal aminotransferase levels at baseline. Journal of hepatology, 2005;43:411-417.

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