Background
Chronic hepatitis C virus (HCV) infection is a high risk factor for the development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma [
1]. According to the World Health Organization, approximately 185 million people worldwide become infected with HCV, and about 350,000 deaths are caused by HCV infection each year [
2,
3]. In 1992, a sero-epidemiological survey of viral hepatitis in China showed that the prevalence of anti-HCV detected in samples was 3.2%, leading to an estimate of approximately 40 million people infected with HCV in China [
4]. In 2006, the China Center for Disease Control and Prevention reported that the prevalence of anti-HCV in central China (0.67%) was slightly higher than that in eastern and western China (0.37 and 0.31%, respectively), whereas the prevalence in northern China (0.53%) was significantly higher than that in southern China (0.29%). These data suggested that only 5.6 million people are infected with HCV in China with a prevalence of about 1% [
5].
With the successful development of direct antiviral agents (DAAs) for HCV and their excellent clinical therapeutic efficacy, HCV infection has now become a clinically curable disease [
6‐
8]. Therefore, it is essential to identify patients in need of antiviral treatment in a timely and effective manner to provide proper therapy. Such effective screening and intervention can not only help to eliminate the active replication of HCV and prevent disease progression, but could also reduce the overall rate of infection and prevalence of HCV in the population by minimizing the chance of transmission [
9,
10].
Although the majority of investigations on the prevalence of HCV infection are based on a positive result for serum antibodies against the virus (anti-HCV) [
4,
5,
11,
12], the main criterion to provide antiviral treatment for HCV infection clinically is the detection of HCV RNA. Therefore, it is necessary to further evaluate the prevalence of HCV RNA to reassess the population that is most in need of antiviral treatment on the basis of the current epidemiological survey of HCV infection.
To improve the screening of HCV infection, serum anti-HCV examination was required in outpatients scheduled to undergo invasive examinations and/or treatments, along with patients at the emergency department and all inpatient departments of Shengjing Hospital of China Medical University (hereafter referred to as Shengjing Hospital), which is the largest public hospital in Shenyang and has been one of the top 20 largest public hospitals in China since 2016. Individuals that tested positive for anti-HCV were automatically informed through the clinical warning system based on the hospital information system (HIS), and the patients were recruited for further HCV RNA detection.
Clinically, we found significant differences in serum anti-HCV levels among the patients, and patients with low anti-HCV levels tended to be negative for serum HCV RNA. This general finding led us to wonder about the relationship between the serum anti-HCV level and the positivity of HCV RNA. Therefore, we sought to explore whether we could predict the status of serum HCV RNA according to the result of anti-HCV testing. A review of the relevant literature showed that there have been few systematic comparisons and assessments of the correlation between serum anti-HCV level and HCV RNA [
13,
14]. However, all of these studies only focused on the level of anti HCV in viremia-positive and negative patients. Moreover, all of these studies were conducted outside China, and thus clinical data for Chinese patients have not been reported. Therefore, we conducted the present retrospective analysis to evaluate the prevalence of anti-HCV and HCV RNA among patients who were tested for serum anti-HCV production at Shengjing Hospital in 2018 with follow-up for HCV RNA detection.
Discussion
Chronic hepatitis C has become a clinically curable disease with the successful application of DAAs, offering the potential for the eradication of HCV. However, effective screening and timely treatment of patients with HCV infection play key roles in controlling the prevalence of HCV infection. In particular, appropriate and accurate screening methods are important during this process [
17,
18].
Both serum anti-HCV and HCV RNA are common indicators for HCV infection. Anti-HCV detection is sensitive and convenient, and is therefore often used for screening of HCV infection, whereas HCV RNA detection is considered the “gold standard” for the clinical diagnosis of HCV infection and is the main criterion for antiviral therapy [
9]. A positive result for anti-HCV will activate the screening and warning feedback network for HCV infection. That is, the system will remind the doctor to carry out a follow-up HCV RNA examination for anti-HCV-positive patients or to transfer the patients to the department of infectious disease for further evaluation. Based on this system, the anti-HCV screening rate of inpatients and outpatients has reached up to 68.06 and 0.94%, respectively, at Shengjing Hospital since 2016 [
19]. Despite this relatively low screening rate for outpatients, majority of the population of childbearing age has undergone this test. Our results showed that more than 60% of anti-HCV-positive patients also underwent HCV RNA testing, making it possible to investigate the correlation between these results.
The Shengjing hospital includes all major clinical departments along with a large number of pediatric patients. The majority of patients reside in Liaoning Province and surrounding areas. Therefore, although our data were obtained from the HIS system of a single institute, the sample can provide a good representation of the prevalence of HCV infection in Liaoning Province. Overall, we found an anti-HCV-positive rate of 1.04%, which is higher than the rate of 0.53% reported previously in northern China in 2006 [
4,
5]. We speculate that this increased anti-HCV-positive rate may not reflect an actual increase in the incidence of HCV infection in recent years, but is rather most likely related to the increased awareness of the importance of screening for HCV infection along with the increased sensitivity of anti-HCV detection methods. This is supported by the fact that the anti-HCV-positive population was mainly over 40 years old, and the prevalence was quite low in younger patients in the current study, consistent with previous reports [
20,
21].
In line with previous reports showing a difference in anti-HCV-positive rates between sexes [
22‐
25], the positive rates of both serum anti-HCV and HCV RNA in male patients were significantly higher than those in female patients in the current study. Although the precise reasons for this difference in prevalence of HCV infection according to sex are not yet clear, it may be related to different life styles, such as male homosexuality, sharing of equipment used for drug injection, and tattoo, and thus men may have a higher chance of being infected by HCV [
26].
The prevalence of HCV infection among different age groups has rarely been reported. Here, we showed a significant difference in the serum anti-HCV-positive rate among different age groups, which increased with increasing age and was significantly higher in patients older than 40 years than in those below 40 years old. This result is consistent with previous studies [
18,
27,
28] indicating that the infection rate of HCV in younger people is reducing, which is attributed to the increasingly more strict and standardized inspection and management of blood and blood products [
29]. Moreover, there was an interaction between age and sex in that there was no sex difference in anti-HCV-positive prevalence among patients younger than 20 years, whereas males had a higher prevalence in patients older than 20 years. This result further indicated that the difference in the HCV infection rate might not be related to sex itself, but rather to the fact that men have a higher chance of infection due to unhealthy behavior.
Only patients positive for HCV RNA require antiviral therapy; however, not all patients that are positive for anti-HCV harbor detectable levels of HCV RNA in the serum. Nevertheless, we found a significant correlation between the serum anti-HCV level and HCV RNA positivity; the positive rate of HCV RNA was significantly lower in patients with a low anti-HCV level than in patients with a high anti-HCV level. When all of the anti-HCV-positive patients were stratified for age and sex, the positive rate of serum HCV RNA was consistent with the prevalence of anti-HCV overall and within different age groups. HCV RNA positivity also gradually increased with age among the anti-HCV-positive patients, at below 20% in patients under 40 years old but more than 50% in patients over 40 years old. This result further suggested that patients over 40 years are the main target population for HCV infection and treatment.
In the training group, we determined the cut-off values of anti-HCV levels for predicting a serum HCV RNA-positive status at 9.19 s/co and 10.18 s/co in male and female patients, respectively, with high AUC values, sensitivity, and specificity, indicating the good predictive value of the anti-HCV level for serum HCV RNA positivity. These results were confirmed in the validation group. Serum anti-HCV detection is widely used for screening HCV infection worldwide owing to the simple and easy process, with relatively high sensitivity, availability of standardized commercial kits, and no requirement of specialized experimental instruments. Based on our results, serum HCV RNA positivity can be accurately predicted according to the simple measurement of anti-HCV levels in most anti-HCV-positive patients, which can facilitate timely screening and intervention in contexts where HCV RNA detection is inconvenient or unavailable.
The main advantage of this study is that we provide data based on a rare systematic analysis of the prevalence of anti-HCV and HCV RNA in the population of Liaoning Province in the northeast of China. At present, the prevalence of HCV infection reported in the literature is mostly based on anti-HCV detection [
4,
5,
11,
12]. We found that Only 42.9% of all anti-HCV positive patients were positive for HCV RNA, indicating that more than half of the anti-HCV-positive patients do not need antiviral therapy; thus, the number of patients who actually require antiviral therapy may have been overestimated previously [
30]. This study further revealed a correlation between serum anti-HCV levels and HCV RNA, with a lower positive rate of HCV RNA in patients with a low level of serum anti-HCV. This correlation could offer a solution to practical problems in clinical laboratories to improve the screening and identification of chronic hepatitis C patients.
However, there are still some shortcomings of this study. First, the patient information was obtained from the records of a general hospital. Although the patients are widely distributed across the region, they still cannot fully represent the characteristics of the local population. Moreover, our data were derived from a single hospital excluding data from other hospitals in the region, which could introduce bias. In addition, this study employed a cross-sectional design, and the proportion of female patients was relatively higher, which may have impacted the results.
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