HBV Genotype A Carries Higher Viral Titers Than Other Genotypes

Bob Roehr

December 07, 2010

December 7, 2010 (San Jose, California) — A new study examining the prevalence of different hepatitis B virus (HBV) genotypes in a database of approximately 2400 specimens showed approximately equal representation of genotypes A, B, and C, at 34%, 30%, and 23%, respectively; genotype A was associated with the highest viral titers. The research was presented here at the Association for Molecular Pathology 2010 Annual Meeting.

Researchers from the Laboratory Corporation of America in Research Triangle Park, North Carolina, led by Joseph Sebastian, PhD, used the Roche High Pure extraction kit and COBAS TaqMan assay to analyze the specimens, measuring the highly conserved pre-Core/Core region of the HBV genome and sequencing a 561 base pair region of the HBV polymerase gene. The assay generally requires more than 200 U/mL HBV DNA.

The specimens were fairly evenly divided among genotype A (34%, 828 samples), genotype B (29.5%, 713 samples), genotype C (23%, 558 samples), genotype D (6.5%, 158 samples), genotype E (3%, 74 samples), and genotypes F and G (1%, 24 samples). The assay detected 2 or more genotypes in the balance of the specimens (2.6%, 63 samples).

A subset of about 800 specimens also had viral load data available, for which the researchers determined prevalence by genotype: genotype A (28%, 227 specimens), genotype B (30%, 244 specimens), genotype C (25.7%, 207 specimens), genotype D (7.6%, 61 specimens), genotype E (4.9%, 39 specimens), genotypes F and G (1.2%, 10 specimens), and mixed genotype (2%, 16 specimens).

As has been observed before, Dr. Sebastian and colleagues reported that on average, genotype A had significantly higher viral titers (23 million IU/mL) than the others: genotype B had 13 million IU/mL, genotype C had 13 million IU/mL, genotype D had 14 million IU/mL, and genotypes E to H had 15 million IU/mL.

Historically, there is an association between high viral titers and a positive response to treatment, the researchers note in their abstract, so they looked at viral loads that were greater than 110 million IU/mL. They found that a much higher portion of specimens containing genotype A (43%) were above that mark than those containing genotype B (26%), genotype C (21%), genotype D (7%), genotype E (4%), and genotype G (1%).

They concluded that there was a very good correlation between the data from the subset of 800 and the overall dataset of 2400 specimens.

Donna Wolk, PhD, a microbiologist at the University of Arizona, Tucson, said the study was "compelling to me because it is a very large assessment of the genotypes. It gives people the ability to identify the different genotypes accurately and perhaps link them directly to different disease progressions or response to treatment."

However, she cautioned that results with amplification of different genotypes can vary, depending on the primers used. "While some associations can be made, I think further work will need to be done to confirm the accuracy of the viral loads with multiple laboratory assays."

That is why Dr. Wolk sees assays such as this new molecular assay as a tool that can possibly better qualify nuances of diseases in the context of different genotypes and perhaps gauge a patient's response to treatment.

The study was funded and conducted by employees of the Laboratory Corporation of America. Dr. Wolk has disclosed no relevant financial relationships.

Association for Molecular Pathology (AMP) 2010 Annual Meeting: Abstract ID66. Presented November 19, 2010.

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