Researchers are increasingly finding that HBV genotypes or strains—and the mutations that they generate—can determine the severity of a patient’s infection.
Each of the world’s 10 genotypes and their mutations have different characteristics that can increase risk of cirrhosis and liver cancer, determine whether an infection becomes chronic, and basically determine a patient’s destiny, according to a recent study, published in the May issue of the World Journal of Hepatology.
For example, those infected with genotype A are more likely to develop a chronic infection, while those with genotype C have higher rates of viral mutations that promote cirrhosis and cancer. Both chronic infection and cancer-causing mutations frequently occur with genotypes D.
Increasingly, researchers noted, genotype, subgenotypes, and mutations will guide doctors’ decisions in selecting treatment and frequency of monitoring patients for liver disease.(1)
The impact of mutations: In an unrelated article in the May issue of PLOS One, Chinese researchers examined the molecular make-up of HBV from 2,387 HBV untreated male patients to find out what role mutations in the pre-S and S gene region (the hepatitis B surface antigen—HBsAg—the outer protein coat of the virus) played in promoting liver cancer.
Mutations in the surface antigen give HBV a distinct advantage in evading the immune system’s hepatitis B surface antibodies. Researchers examined the S gene in 96 patients who developed liver cancer, and compared it to HBV patients who were cancer-free.
They found patients with S and pre-S mutations had higher rates of liver cancer. Curiously, these mutations were not present when patients were young, they emerged over time as the patients’ immune systems failed to eradicate these mutated antigens.
“In conclusion, our present study showed that HBV pre-S deletions, especially pre-S2 deletions, were associated with the development of liver cancer, irrespective of age, HBeAg status, and HBV genotype. Further prospective studies are needed to confirm the role of these mutations in the development of HCC,” they wrote. (2)
Another mutation, this one in the microRNAs that can either enhance or suppress cancer tumors, also appears to affect the risk of hepatitis B-related liver cancer.
Chinese researchers studied the rate of mutations in microRNAs (called miR-499 rs3746444 and miR-423 rs6505162) in 984 cancer patients and compared them to people without liver cancer. They found liver cancer risk—including development of large liver tumors—was higher in patients with the miR-499 rs3746444 mutation.
Writing in the May issue of the journal Genetic Testing and Molecular Biomarkers, researchers suggest screening of all hepatitis B patients for this mutation. (3)
Source 1: www.ncbi.nlm.nih.gov/pubmed/24833873
Source 3: www.ncbi.nlm.nih.gov/pubmed/24854593