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Discussion
The natural history of the disease was divided into five different phases in the EASL Clinical Practice Guidelines for CHB. It is not always easy to make an accurate distinction between these phases. It is especially quite difficult to make a definite distinction between IC and HBeAg-negative CHB patients. Today, non-invasive tests (ALT and HBV-DNA level) and liver histopathology are used for this distinction.[10] However, ALT and serum HBV-DNA levels are insufficient for identifying each phase, whereas liver biopsy is an impractical invasive procedure. In this regard, we need tests and/or tests with high sensitivity and specificity, which can reflect liver histopathology, be used in disease follow-up and enable us to better evaluate the phases of chronic hepatitis.
In this study, serum qHBsAg levels in IC and CHB patients, and the correlation between ALT, HBV-DNA, HAI severity, and the stage of fibrosis were examined. No correlation was noted between serum qHBsAg levels and ALT, HBV-DNA, HAI severity, and the stage of fibrosis in IC. A moderate and positive correlation was observed between serum qHBsAg level and HBV-DNA in HBeAg-positive hepatitis B patients. However, no correlation was found between serum qHBsAg levels and ALT, severity of HAI, and fibrosis in CHB patients. In the study of Chan et al.,[6] where the relationship between HBV-DNA and qHBsAg was investigated, and samples were taken from 49 HBeAg-positive and 68 HBeAg-negative patients at different times, a moderate relationship between qHBsAg levels and HBV-DNA was determined (r = 0.61, P < 0.001). In this study, a moderate positive correlation was determined between serum qHBsAg levels and HBV-DNA in the HBeAg-positive CHB patients (rho = 0.435, P = 0.009); however, no correlation was noted between the serum qHBsAg levels and HBV-DNA in HBeAg-negative CHB patients (rho = 0.087, P = 0.500). Thompson et al.[11] found that quantitative HBeAg and qHBsAg levels may be used as markers in deciding about the initiation of the treatment as well as in the follow-up of treatment. In this study, it is suggested that the relationship between quantitative serum HBsAg and HBeAg titers and serum HBV-DNA is complex and probably reflects an interaction between virologic and host immunologic factors. This explanation also defines results of the correlation analysis of this study.
In a recent study on this subject, the relation between the qHBsAg level and clinical and viral dynamics in patients with CHB infection was investigated. The qHBsAg levels were found to be significantly different among groups consisting of a total of 434 CHB patients including 62 immunotolerant patients, 103 HBeAg-positive CHB patients, 151 HBeAg-negative CHB patients and 218 IC. Following evaluation of the qHBsAg level together with HBV-DNA level, it suggested that they could be used as markers for distinguishing HBeAg-negative CHB and IC groups.[7]
In this study, the qHBsAg level of 204 patients with CHB infection was investigated in addition to the routine laboratory examination and liver histopathology. Apart from diagnosis, the efficiency of qHBsAg in distinguishing HBeAg-negative CHB patients from IC was examined. Accordingly, the diagnostic efficacy of qHBsAg levels was found to be at moderate level and the cutoff value of qHBsAg in diagnosis was determined as 1625 IU/mL (specificity: 80%, sensitivity: 49%, positive likelihood rate: 1.65, negative likelihood rate: 0.38).
Wustorn et al.[12] and Chan et al.[6] demonstrated that cccDNA is strongly related to qHBsAg and they suggested that serial monitoring of qHBsAg during antiviral treatment can be an additional marker for evaluating treatment response. In these studies, qHBsAg values were determined to be less than 10,000 IU/mL in patients after PEG-IFN-LAM treatment. Sensitivity, specificity, positive predictive value, and negative predictive value for the qHBsAg value obtained with regard to virologic response were 86%, 56%, 43%, and 93%, respectively. It was suggested that when evaluating qHBsAg response to treatment, a 0.5 log or 1.0 log decrease in weeks 12 and weeks 24 had a high predictive value for sustained viral response (SVR). Based on previous experiences and long-term follow-up data, it was observed that most patients with SVR obtained in th first year tended to stay in remission.
In another recent study, 102 HBeAg-negative patients treated with PEG-IFN were examined, and an end point was demonstrated where HBV-DNA and qHBsAg levels concurrently declined from baseline by weeks 12 of treatment. The decline at week 24 was the best predictor of SVR. Serum qHBsAg levels did not decrease and serum HBV-DNA levels decreased for less than 2 logs. SVR was not observed in any of the 20 patients (20% of the study group).[13]
In a study where patients with different phases of the CHB infection were followed for eight years, the natural course of serum qHBsAg changes during different phases of the CHB infection was demonstrated. The qHBsAg levels were reported to be stable at a positive phase, whereas HBeAg tended to decrease in a negative phase, when the disease was not treated. Although a decrease of more than 1 log in qHBsAg seemed to indicate an immune control, further studies examining the use of decreased qHBsAg as a predictor of treatment response should be conducted.[12] The studies that contain particularly post-treatment qHBsAg results may help us to understand the value and the dynamics of this new parameter. Our study is not a prospective study and does not involve the long-term follow-up results of the patients. This is the major limitation of our study. In a Taiwanese study involving genotype B and C patients with chronic hepatitis B infection, it was found that low HBsAg levels alone or in conjunction with low HBV-DNA levels were able to predict HBsAg loss when used one year after HBeAg seroconversion.[14] In another study from the same country, combining low HBsAg (<1000 IU/mL) with low ALT and HBV-DNA levels were again found to be beneficial in defining “minimal risk” levels in inactive HBV carriers.[15]
All these studies indicate that investigating qHBsAg levels can be an important test in identifying different phases and in evaluating the treatment response in CHB patients.
In this study, the diagnostic efficacy of qHBsAg was found to be at a moderate level with regard to distinguishing HBeAg-negative CHB patients from HBsAg carriers. As the qHBsAg cutoff value is 1625 IU/mL, its sensitivity was found to be at a moderate level although the specificity was high. These results show that qHBsAg is quite useful as a test when used together with ALT and HBV-DNA levels in distinguishing IC from HBeAg-negative CHB patients.
Conclusion
These studies questioned the use of serum qHBsAg levels as a screening biomarker (screening test for identifying phases of the disease) and as a follow-up marker for the evaluation of response to treatment (especially for the determination of sustained viral response). However, further prospective studies with a larger population requiring a long-term follow-up are needed. |
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发表于 2016-5-17 17:58