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PLoS One. 2014 Jul 17;9(7):e102573. doi: 10.1371/journal.pone.0102573. eCollection 2014.

Distinct distribution pattern of hepatitis B virus genotype C and D in liver tissue and serum of dual genotype infected liver cirrhosis and hepatocellular carcinoma patients.

Author information

1
Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
2
Department of Gastro-Intestinal surgery, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
3
Centre for Liver and Biliary Surgery, Indraprastha Apollo Hospital, New Delhi, India.
4
Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
5
Department Gastroenterology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.

Erratum in

  • PLoS One. 2014;9(10):e110932. Chakraborty, Bidhan [corrected to Chakraborty, Bidhan Chandra]; Roy, Sukanta [corrected to Ray, Sukanta].

Abstract

AIMS:

The impact of co-infection of several hepatitis B virus (HBV) genotypes on the clinical outcome remains controversial. This study has for the first time investigated the distribution of HBV genotypes in the serum and in the intrahepatic tissue of liver cirrhotic (LC) and hepatocellular carcinoma (HCC) patients from India. In addition, the genotype-genotype interplay and plausible mechanism of development of HCC has also been explored.

METHODS:

The assessment of HBV genotypes was performed by nested PCR using either surface or HBx specific primers from both the circulating virus in the serum and replicative virus that includes covalently closed circular DNA (cccDNA) and relaxed circular DNA (rcDNA) of HBV from the intrahepatic tissue. The integrated virus within the host chromosome was genotyped by Alu-PCR method. Each PCR products were cloned and sequences of five randomly selected clones were subsequently analysed.

RESULTS:

HBV/genotype D was detected in the serum of all LC and HCC patients whereas the sequences of the replicative HBV DNA (cccDNA and rcDNA) from the intrahepatic tissue of the same patients revealed the presence of both HBV/genotype C and D. The sequences of the integrated viruses exhibited the solo presence of HBV/genotype C in the majority of LC and HCC tissues while both HBV/genotype C and D clones were found in few patients in which HBV/genotype C was predominated. Moreover, compared to HBV/genotype D, genotype C had higher propensity to generate double strand breaks, ER stress and reactive oxygen species and it had also showed higher cellular homologous-recombination efficiency that engendered more chromosomal rearrangements, which ultimately led to development of HCC.

CONCLUSIONS:

Our study highlights the necessity of routine analysis of HBV genotype from the liver tissue of each chronic HBV infected patient in clinical practice to understand the disease prognosis and also to select therapeutic strategy.

PMID:
25032957
PMCID:
PMC4102524
DOI:
10.1371/journal.pone.0102573
[Indexed for MEDLINE]
Free PMC Article

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