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J Viral Hepat. 2018 Oct;25(10):1121-1131. doi: 10.1111/jvh.12914. Epub 2018 May 9.

Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co-infected patients from Western Africa.

Author information

1
INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Paris, France.
2
Programme PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.
3
Department of Infectious and Tropical Diseases, Treichville University Teaching Hospital, Abidjan, Côte d'Ivoire.
4
Medical School, University Felix Houphouet Boigny, Abidjan, Côte d'Ivoire.
5
Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.
6
Université Paris-Diderot, Paris, France.
7
INSERM U1052- Cancer Research Center of Lyon (CRCL), Lyon, France.
8
INSERM, U1219, Bordeaux, France.
9
University of Bordeaux, ISPED, Bordeaux, France.
10
INSERM U941, Paris, France.
11
University of Lyon, UMR_S1052, CRCL, Lyon, France.
12
Department of Hepatology, Hospices Civils de Lyon, Lyon, France.
13
Department of Infectious and Tropical Diseases, Saint-Antoine Hospital, AP-HP, Paris, France.
14
INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France.

Abstract

The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)-infected patients. Whether this mutation affects the therapeutic course of HIV-HBV co-infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)-naïve HIV-HBV co-infected patients from Côte d'Ivoire, initiating ARV-treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV-DNA, hepatitis B "e" antigen (HBeAg) seroclearance (in HBeAg-positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV-initiation, median HBV-DNA was 6.04 log10 copies/mL (IQR = 3.70-7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg-negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24-36). Cumulative proportion of undetectable HBV-DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV-DNA levels and anti-HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti-HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.

KEYWORDS:

precore ; antiviral treatment; basal core promoter; genetic variability; immunosuppression

PMID:
29660214
DOI:
10.1111/jvh.12914

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