Ann Lab Med.  2014 May;34(3):230-234. 10.3343/alm.2014.34.3.230.

Analysis of Reverse Transcriptase Gene Mutations in the Hepatitis B Virus at a University Hospital in Korea

Affiliations
  • 1Department of Laboratory Medicine, College of Medicine, Catholic University of Daegu, Daegu, Korea. chjeon@cu.ac.kr
  • 2Department of Internal Medicine, College of Medicine, Catholic University of Daegu, Daegu, Korea.

Abstract

BACKGROUND
Most mutations in the reverse transcriptase (RT) gene of the hepatitis B virus (HBV) are related to resistance to antiviral agents. Cross-sectional studies on the mutations of this gene are rare. Thus, we analyzed the mutation patterns of RT genes and their biochemical parameters.
METHODS
From 2009 to 2012, 301 blood specimens from patients with chronic hepatitis B at Daegu Catholic University Medical Center were retrospectively analyzed for the RT gene sequence of HBV, ALT, hepatitis B e antigen (HBeAg), and HBV DNA. The mutation patterns of the RT gene were compared with the biochemical parameters.
RESULTS
Of the 301 patients, 100 (33.2%) had no RT gene mutations. The remaining showed the following mutation patterns: rtM204I/V (50.2%), rtL180M (39.2%), and rtA181T/V (19.6%). Combined mutations were found in 146 cases (48.5%). Of these, the combination of amino acid changes at rt180+rt204 (49.3%) was most frequently detected, followed by rt181+rt236 (11.0%) and rt173+rt180+rt204 (9.6%). In the mutated group, HBV DNA and HBeAg positive rates were significantly higher (P<0.05 for both). Phenotypic analysis showed that lamivudine resistance was most frequently detected (34.6%), followed by adefovir resistance (15.6%). Multidrug resistance was detected in 48 cases (15.9%). The adefovir-resistant group had a higher proportion of cases with HBV loads greater than 2,000 IU/mL.
CONCLUSIONS
We found correlations between the mutation status of the RT domain and biochemical parameters such as HBV DNA and HBeAg positive rate. The presence of RT gene mutations could therefore be utilized to predict clinical status.

Keyword

Alanine aminotransferase; Hepatitis B e antigen; Hepatitis B virus; Mutation; Reverse transcriptase

MeSH Terms

Adenine/analogs & derivatives/therapeutic use
Antiviral Agents/therapeutic use
DNA, Viral/analysis
Drug Resistance, Multiple, Viral
Drug Resistance, Viral
Hepatitis B e Antigens/blood
Hepatitis B virus/*enzymology/isolation & purification
Hepatitis B, Chronic/drug therapy
Hospitals, University
Humans
Lamivudine/therapeutic use
Mutation
Organophosphonates/therapeutic use
Phenotype
RNA-Directed DNA Polymerase/*genetics
Republic of Korea
Retrospective Studies
Adenine
Antiviral Agents
DNA, Viral
Hepatitis B e Antigens
Lamivudine
Organophosphonates
RNA-Directed DNA Polymerase

Figure

  • Fig. 1 Comparison of biochemical parameters according to the mutation status of the hepatitis B virus reverse transcriptase gene.Abbreviations: HBV, hepatitis B virus; HBeAg Pos, hepatitis B e antigen positive.

  • Fig. 2 Comparison of clinical parameters according to the drug resistance pattern of the hepatitis B virus reverse transcriptase gene mutation.Abbreviations: HBV, hepatitis B virus; HBeAg Pos, hepatitis B e antigen positive; LAM, lamivudine; ETV, entecavir; ADV, adefovir.


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