Artificial Neural Network Accurately Predicts Hepatitis B Surface Antigen Seroclearance
et al. (2014) Artificial Neural Network Accurately Predicts Hepatitis B Surface Antigen
Seroclearance. PLoS ONE 9(6): e99422. doi:10.1371/journal.pone.0099422
Artificial Neural Network Accurately Predicts Hepatitis B Surface Antigen Seroclearance
Ming-Hua Zheng 0
Wai-Kay Seto 0
Ke-Qing Shi 0
Danny Ka-Ho Wong 0
James Fung 0
Ivan Fan-Ngai Hung 0
Daniel Yee-Tak Fong 0
John Chi-Hang Yuen 0
Teresa Tong 0
Ching-Lung Lai 0
Man-Fung Yuen 0
Isabelle A. Chemin, CRCL-INSERM, France
0 1 Department of Infection and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang , China , 2 Department of Medicine, the University of Hong Kong, Queen Mary Hospital , Hong Kong , China , 3 Department of Nursing Studies, the University of Hong Kong, Queen Mary Hospital , Hong Kong , China , 4 State Key Laboratory for Liver Research, the University of Hong Kong, Queen Mary Hospital , Hong Kong , China
Background & Aims: Hepatitis B surface antigen (HBsAg) seroclearance and seroconversion are regarded as favorable outcomes of chronic hepatitis B (CHB). This study aimed to develop artificial neural networks (ANNs) that could accurately predict HBsAg seroclearance or seroconversion on the basis of available serum variables. Methods: Data from 203 untreated, HBeAg-negative CHB patients with spontaneous HBsAg seroclearance (63 with HBsAg seroconversion), and 203 age- and sex-matched HBeAg-negative controls were analyzed. ANNs and logistic regression models (LRMs) were built and tested according to HBsAg seroclearance and seroconversion. Predictive accuracy was assessed with area under the receiver operating characteristic curve (AUROC). Results: Serum quantitative HBsAg (qHBsAg) and HBV DNA levels, qHBsAg and HBV DNA reduction were related to HBsAg seroclearance (P,0.001) and were used for ANN/LRM-HBsAg seroclearance building, whereas, qHBsAg reduction was not associated with ANN-HBsAg seroconversion (P = 0.197) and LRM-HBsAg seroconversion was solely based on qHBsAg (P = 0.01). For HBsAg seroclearance, AUROCs of ANN were 0.96, 0.93 and 0.95 for the training, testing and genotype B subgroups respectively. They were significantly higher than those of LRM, qHBsAg and HBV DNA (all P,0.05). Although the performance of ANN-HBsAg seroconversion (AUROC 0.757) was inferior to that for HBsAg seroclearance, it tended to be better than those of LRM, qHBsAg and HBV DNA. Conclusions: ANN identifies spontaneous HBsAg seroclearance in HBeAg-negative CHB patients with better accuracy, on the basis of easily available serum data. More useful predictors for HBsAg seroconversion are still needed to be explored in the future.
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. These authors contributed equally to this work.
In clinical practice, hepatitis B surface antigen (HBsAg)
seroclearance and seroconversion have been recommended as
the ideal outcomes in both the natural history of HBV infection
and as endpoint for the treatment of CHB [1]. Earlier HBsAg
seroclearance or seroconversion is likely resulted in a better
prognosis because of lower HBV replication as well as less liver
damage [1,2]. A few studies have explored the incidence of
spontaneous HBsAg seroclearance in CHB patients of both Asian
and European populations using long-term follow-up cohorts and
the annual incidence ranges from 0.62% to 2.26% [3,4,5,6,7,8].
Because of the more rarity of spontaneous HBsAg seroconversion,
compared to HBsAg seroclearance, the incidence and long-term
outcomes of CHB patients experiencing this event remain
disputed. Existing evidences indicate that HBsAg seroclearance
or seroconversion confers favorable long-term outcomes in
patients without hepatocellular carcinoma (HCC) or
decompensated liver cirrhosis [9,10,11,12].
Predictive factors for spontaneous HBsAg seroclearance or
seroconversion using various parameters have attracted much
attention recently. Previous studies had demonstrated that
lowering HBV DNA level was an important predictor for
spontaneous HBsAg seroclearance [5,6,8,13]. Furthermore, with
the technological advances of quantitative HBsAg (qHBsAg), it has
been suggested as a promising new marker in monitoring
immunological response in both treated and untreated CHB
patients, as well as a potential predictor of liver disease progression
[14]. Our previous study showed that low qHBsAg levels and an
increased reduction rate in qHBsAg levels were the most
significant predictors of spontaneous HBsAg seroclearance with
3 years of follow-up [15]. These findings have been further
validated by other studies [4,5,13,16,17]. However, our previous
study had several limitations. No specific time point was identified
where qHBsAg kinetics could have the highest predictive value.
Also the accuracy of qHBsAg levels in predicting HBsAg
seroclearance [area under receiver operating characteristic curve
(AUROC) 0.833] still warrants improvement [15]. In all currently
available studies [4,5,13,15,16,17], the predictability of qHBsAg
levels for (...truncated)