HBV-RNA, Quantitative HBsAg, Levels of HBV in Peripheral Lymphocytes and HBV Mutation Profiles in Chronic Hepatitis B

Abstract

A comprehensive characterization of chronic HBV (CHB) patients is required to guide therapeutic decisions. The cumulative impact of classical and novel biomarkers on the clinical categorization of these patients has not been rigorously assessed. We determined plasma HBV-RNA and HBsAg levels, HBV in peripheral lymphocytes (PBMCs) and HBV mutation profiles in CHB patients. Patient demographics (n = 139) and classical HBV biomarkers were determined during a clinical routine. HBV-RNA in plasma and HBV-DNA in PBMCs were determined by RT-PCR. HBsAg levels were determined using Architect. In samples with HBV-DNA viral load >1000 IU/mL, genotype mutations in precore (PC), basal core promoter (BCP), HBsAg and Pol regions were determined by sequencing. Most patients (n= 126) were HBeAg-negative (HBeAgNeg) with significantly lower levels of HBV-RNA, HBV-DNA and HBsAg compared to HBeAg-positive (HBeAgPos) patients (p < 0.05). HBV genotype D prevailed (61/68), and >95% had BCP/PC mutations. Escape mutations were identified in 22.6% (13/63). HBeAgNeg patients with low levels of HBsAg (log IU ≤ 3) were older and were characterized by undetectable plasma HBV-DNA and undetectable HBV-RNA but not undetectable HBV-DNA in PBMCs compared to those with high HBsAg levels. In >50% of the studied HBeAgNeg patients (66/126), the quantitation of HBsAg and HBV-RNA may impact clinical decisions. In conclusion, the combined assessment of classical and novel serum biomarkers, especially in HBeAgNeg patients, which is the largest group of CHB patients in many regions, may assist in clinical decisions. Prospective studies are required to determine the real-time additive clinical advantage of these biomarkers.

«road Map» of Biomarkers in the Natural History of HBV Infection

“…Все три белка имеют идентичную последовательность из 149 аминокислот, которую с помощью серологического тестирования HBcAg p22cr и HBeAg можно определить как HBcrAg [18,19]. Исследования показывают, что уровни HBcrAg в сыворотке отражают уровень cccDNA в гепатоцитах как у HBeAg-положительных, так и у HBeAg-негативных пациентов.…”

“…Показано, что в отдельных случаях уже после «функционального излечения» в сыворотке все еще обнаруживаются HBcrAg. И хотя прогностическая значимость определения HBcrAg требует дополнительного исследования и аргументации, очевидно, что длительный мониторинг за HBcrAg-положительными и HBcrAg-отрицательными пациентами позволит улучшить прогнозирование и повлиять на исходы ГВ [19,20].…”

Evaluation of reverse transcription-polymerase chain reaction and simultaneous amplification and testing for quantitative detection of serum hepatitis B virus RNA

“…It can also predict the HBV e antigen (HBeAg) seroconversion during antiviral therapy and the virological relapse and HBsAg reversal after drug withdrawal [ 14 , 15 ]. Serum HBV RNA has been included in the Chinese and European guidelines for hepatitis B prevention and treatment as an alternative serological indicator of cccDNA [ 16 , 17 ]. Therefore, HBV RNA is expected to become an important marker for achieving accurate treatment of CHB.…”