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Hepatology. 2018 Sep;68(3):839-847. doi: 10.1002/hep.29872. Epub 2018 Apr 27.

Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment.

Author information

1
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
2
University Hospital Leipzig, Department of Gastroenterology and Rheumatology, Section of Hepatology, Leipzig, Germany.
3
Institute of Health Policy, Management and Evaluation, University of Toronto.
4
Toronto Center for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, Canada.

Abstract

Hepatitis B virus (HBV) RNA in serum is a novel biomarker for intrahepatic HBV replication and treatment response. For its proper use, it is essential to identify factors influencing serum HBV RNA level. Using a rapid amplification of complimentary DNA (cDNA) ends (RACE) PCR technique (lower limit of detection [LLD], 800 copies/mL [c/mL]), serum HBV RNA levels were measured in samples of 488 untreated individuals with chronic HBV infection who were eligible to treatment according to currently used recommendations. We explored the association of serum levels of HBV RNA with patient- and virus-associated factors. HBV genotype distribution was 21/10/20/46/3% for A/B/C/D/other. Mean HBV RNA serum level was 5.9 (1.6) log10 c/mL (hepatitis B e antigen [HBeAg]-positive chronic hepatitis B [CHB], 6.5 [1.2] log c/mL; HBeAg-negative CHB, 4.1 [1.2] log c/mL; P < 0.001). By multivariable linear regression, factors associated with lower HBV RNA level were HBeAg negativity (β = -0.69; P < 0.001), HBV genotypes A (β = -0.13; P = 0.002), B (β = -0.07; P = 0.049), and C (β = -0.61; P < 0.001) in comparison to D, and presence of HBV basal core promoter mutation either alone (β = -0.14; P = 0.001) or in combination with precore mutation (β = -0.22; P < 0.001). Higher serum alanine aminotransferase (ALT) was associated with higher HBV RNA (β = 0.23; P < 0.001). HBV RNA correlated strongly with HBV DNA (HBeAg-pos, r = 0.72; P < 0.001; HBeAg-neg, r = 0.78; P < 0.001) and moderately with quantitative hepatitis B surface antigen (qHBsAg; HBeAg-pos, r = 0.54; P < 0.001; HBeAg-neg, r = 0.19; P = 0.04) and quantitative hepatitis B surface antigen (qHBeAg; r = 0.41; P < 0.001).

CONCLUSION:

In this multiethnic cohort of 488 untreated individuals with CHB, factors associated with serum HBV RNA level were HBeAg status, serum ALT, HBV genotype, and presence of basal core promotor mutations. For the future use of serum HBV RNA as a clinical marker, it seems mandatory to take these factors into consideration. (Hepatology 2018).

PMID:
29514389
PMCID:
PMC6175227
DOI:
10.1002/hep.29872
[Indexed for MEDLINE]
Free PMC Article

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