Clin Infect Dis. 2020 Jan 8. pii: ciaa013. doi: 10.1093/cid/ciaa013. [Epub ahead of print]
Hepatitis B virus RNA as Early Predictor for Response to PEGylated Interferon Alfa in HBeAg Negative Chronic Hepatitis B.
Farag MS1,2, van Campenhout MJH3, Pfefferkorn M4, Fischer J4, Deichsel D4, Boonstra A3, van Vuuren AJ3, Ferenci P5, Feld JJ1, Berg T4, Hansen BE1,6, van Bömmel F4, Janssen HLA1.
Author information
1
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada.
2
Institute of Medical Science, University of Toronto, Toronto, Canada.
3
Department of Gastroenterology & Hepatology, Erasmus Medical Centre Rotterdam, Rotterdam, Netherlands.
4
University Hospital Leipzig, Department of Gastroenterology and Rheumatology, Section of Hepatology, Leipzig, Germany.
5
Department of Internal Medicine 3, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
6
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
Abstract
BACKGROUND:
Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA) which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients.
METHODS:
HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study). Patients received PEG-IFN α-2a for 48 weeks. HBV-RNA was measured from baseline through week 144. Response was defined as HBV-DNA below 2,000 IU/ml and ALT normalization at week 72. Kinetics of HBV-RNA were compared with HBV-DNA, HBsAg, and HBcrAg.
RESULTS:
Mean HBV-RNA at baseline was 4.4 (SD 1.2) log10 c/mL. At week 12, HBV-RNA declined by -1.6 (1.1) log10 c/mL. HBV-RNA showed a greater decline in responders compared to non-responders early at week 12 (-2.0 [1.2] vs -1.5 [1.1] log10 c/mL, P=0.04). HBV-RNA level above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value of 91% at week 12 and 93% at week 24 (P=0.01) for response. Overall, HBV-RNA showed a stronger correlation with HBV-DNA and HBcrAg (0.82 and 0.80, P<0.001) and a weak correlation with HBsAg (0.25). At week 12, HBV-RNA was significantly lower among patients with lower HBsAg (< 100 IU/ml) or HBsAg-loss at week 144.
CONCLUSIONS:
During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a fast and significant decline that correlates with treatment response and HBsAg-loss at long-term follow-up.https://clinicaltrials.gov/ct2/show/NCT00114361, NCT00114361.
在一项国际随机对照试验（PARC研究）中，对133名HBeAg阴性CHB患者的HBV-RNA水平进行了测量。患者接受PEG-IFNα-2a治疗48周。从基线到第144周测量HBV-RNA。反应定义为在2,000 IU / ml以下HBV-DNA和在72周时ALT正常化。将HBV-RNA的动力学与HBV-DNA，HBsAg和HBcrAg进行比较。
结果：
基线时的平均HBV-RNA为4.4（SD 1.2）log10 c / mL。在第12周时，HBV-RNA下降了-1.6（1.1）log10 c / mL。在第12周初，与无反应者相比，HBV-RNA的反应者下降幅度更大（-2.0 [1.2] vs -1.5 [1.1] log10 c / mL，P = 0.04）。高于1700 c / mL（3.2 log10 c / mL）的HBV-RNA水平在第12周的阴性预测值为91％，在第24周的阴性预测值为93％（P = 0.01）。总体而言，HBV-RNA与HBV-DNA和HBcrAg的相关性更强（0.82和0.80，P <0.001），与HBsAg的相关性较弱（0.25）。在第144周时，HBsAg（<100 IU / ml）或HBsAg减少的患者中HBV-RNA显着降低。
结论：