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Significance of serum HBV RNA in non-cirrhotic HBeAg-negative chronic hepatitis B patients who discontinue effective antiviral therapy
Margarita Papatheodoridi # 1 2 , Eleni Papachristou # 3 , Zissis Moschidis # 3 , Emilia Hadziyannis 4 , Eirini Rigopoulou 5 , Kalliopi Zachou 5 , François Villeret 6 , Gkikas Magiorkinis 3 , Aggeliki Lyberopoulou 5 , Nikolaos Gatselis 5 , Ioannis Vlachogiannakos 1 , Spilios Manolakopoulos 1 , George N Dalekos 5 , Fabien Zoulim 6 , Dimitrios Paraskevis 3 , George V Papatheodoridis 1
Affiliations
Affiliations
1
Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
2
University College of London, Institute of Liver and Digestive Health, Royal Free Campus, London, UK.
3
Department of Hygiene and Epidemiology, Medical School of National and Kapodistrian University of Athens, Greece.
4
2nd Department of Internal Medicine, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Hippokratio", Athens, Greece.
5
Department of Medicine and Research Laboratory of Internal Medicine, Thessaly University Medical School, Larissa, Greece.
6
INSERM U1052 - Cancer Research Center of Lyon (CRCL), 69008, Lyon, France.
#
Contributed equally.
PMID: 35789515 DOI: 10.1111/jvh.13729
Abstract
HBV RNA is considered as a promising predictor in patients who discontinue nucleos(t)ide analogues (NAs). We determined HBV RNA levels in non-cirrhotic HBeAg-negative patients who discontinued NAs and assessed their predictability for 12-month outcomes. Fifty-seven patients of DARING-B study were included. HBV RNA levels were determined in stored monthly serum samples drawn at 0-3 months after end of therapy (EOT). Other markers previously determined in the same cohort including hepatitis B core related antigen (HBcrAg) were also assessed. HBV RNA at EOT was detectable in 7% of patients, who developed virological/clinical relapse and required retreatment at month 2; in patients with undetectable EOT HBV RNA, 12-month cumulative rates of virological relapse, clinical relapse and retreatment were 68%, 28% and 21%, respectively (P≤0.008). HBV RNA at month-1 after EOT was detectable in 19% of patients being associated with higher probability only of virological relapse (P=0.001). HBV RNA levels correlated significantly to HBV DNA, HBcrAg, ALT and interferon-induced protein-10, but not HBsAg levels. Combined EOT HBV RNA and HBcrAg detection and/or HBsAg >1000 IU/mL was associated only with higher probability of retreatment having higher sensitivity and lower specificity than HBV RNA alone. In conclusion, serum HBV RNA is detectable in a minority of non-cirrhotic HBeAg-negative patients under effective long-term NAs therapy offering low sensitivity but 100% specificity for early retreatment due to severe clinical relapses after NA discontinuation. The combinations of EOT HBV RNA with HBcrAg and/or high HBsAg levels increase sensitivity but decrease specificity for prediction of retreatment after NAs withdrawal.
Keywords: HBV RNA; discontinuation; hepatitis B; hepatitis B core related antigen; relapse; retreatment.
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