Predictive Factors for not Undergoing RNA Testing in Patients Found to Have Hepatitis C Serology and Impact of an Automatic Alert

Dalia Morales-Arraez; Ana Alonso-Larruga; Felicitas Diaz-Flores; Jose A. García Dopico; Antonia de Vera; Enrique Quintero; Manuel Hernández-Guerra


J Viral Hepat. 2019;26(9):1117-1123. 

In This Article


Our results show that a significant proportion of patients with a positive anti-HCV test did not undergo RNA testing despite an acceptable and reasonable period of time for obtaining the test. This is in clear disagreement with the recommendations of HCV clinical guidelines.[8] Furthermore, most of the patients were young and had no significant comorbidities, thus lacking overt limitations for a full investigation into their HCV infection. Our strategy based on the automatic alert message promoted better care for these patients.

Over one-third of the patients testing positive for HCV antibodies did not receive RNA testing. Previous studies have shown similar results regarding the inadequate diagnosis of HCV infection, indicating that around 50%-75% of HCV-infected patients remain unaware of their infection status.[7,23]

Our study is the first to evaluate in the setting of a public health system predictive factors for not undergoing RNA testing after a positive HCV test. The independent predictive factors for not undergoing RNA testing were no history of drug use, lack of social support and a diagnosis of positive HCV serology in primary care setting. The first factor is anticipated because drug users are well known as a high-risk population for active HCV infection[8] and full assessment is mandatory to provide treatment and reduce transmission and reinfection rates among them.[24] The lack of social support is another expected predictor for not undergoing RNA testing since this group of patients is traditionally considered difficult to complete assessment and refer to specialist care.[25] In fact, in our nonreferred group of patients there was a greater percentage of patients lacking social support. It is worth to note that this group of patients could benefit the most from current direct-acting antiviral regimens given their scarce contraindications, drug interactions, side effects and their shorter treatment duration.[26,27]

The majority of patients without RNA testing were diagnosed after undergoing an HCV test requested in a primary care setting. Given that primary care has a major role in the process of screening, diagnosis and referral of HCV patients to specialist care,[28,29] studies such as ours are mandatory to improve the correct evaluation of patients in primary care according to clinical guidelines.[30,31]

Another interesting result of our study is that HCV patients without RNA testing had a greater percentage of normal values of transaminases. It may be that the attending physician did not request RNA tests, because they wrongly assume that transaminase levels correlate with the presence of active infection and liver damage.[32,33]

Overall, we should keep in mind that identifying these and other predictive factors for not undergoing RNA testing could guide us to improve the management of HCV. To control HCV infection, it is necessary to improve the diagnosis and referral process based on case findings using targeted interventions. In this regard, educational efforts at different levels should be planned and implemented among health providers, especially in the primary care setting because it is the most accessible area for screening and decreasing gaps in the diagnosis process.[26,31]

Besides the broad diffusion of guidelines and recommendations related to HCV infection, the implementation of alert systems is a more specific action to improve the rate of appropriate evaluation of HCV patients. More recently, electronic alert systems were implemented in primary care to increase HCV screening among baby boomers, which achieved a significant increase in the percentage of patients diagnosed.[34,35] However, our study is the first one to approach the effectiveness of implementing an electronic alert to improve full evaluation among known HCV-positive patients.

Our study showed an overall HCV seroprevalence of 1.96%, which is in accordance with population seroprevalence in recent published studies in our country[36] and Western Europe.[37] Not surprisingly, a lower prevalence was detected in the post-alert cohort. However, it is consistent with the fact that the HCV seroprevalence decreases in time[38] and that an increase in the number of unselected HCV serology requests after the recent emergence of direct-acting antivirals and its immense pull effect may have decreased seroprevalence in the post-alert cohort. However, this difference in the prevalence rate of both cohorts should not influence the results.

In the present study, the alert intervention increased RNA requests by 15%, even after a shorter follow-up period in the post-alert cohort. This rate is expected to increase with longer follow-up time since the awareness about this type of initiative is crucial.[35] Moreover, in the pre-alert cohort there was a higher percentage of patients with drug use and lack of social support, which could have had a negative effect on assessing the effectiveness of the alert as both factors are a predictor for requesting RNA tests. Nevertheless, the alert showed to be of benefit in the group of patients with and without drug use and with good and lacking social support.

The introduction of recommendations increased not only the rate of RNA requests but also the percentage of anti-HCV-positive patients with detectable RNA, suggesting a positive influence of the alert on diagnosing active infection. Thus, these patients would directly benefit from treatment prescriptions. In addition, the alert reduced the time until the first determination of RNA, which may contribute to reducing waiting times until the start of treatment. In addition, a trend to increase the percentage of patients sent to specialist care was observed after the implementation of the alert. This data can be explained in part by the more favourable characteristics among patients referred to specialists including social support, perceived need for treatment due to higher levels of transaminases, and higher comorbidity.

Reflex RNA testing is a novel strategy that facilitates the diagnosis and linkage to care since it reduces the process to one step. However, it is not available in many hospitals, mainly due to the low seroprevalence of HCV and RNA positivity rate in certain health areas or to technical difficulties.[39] The computerized alert system is a more simple, feasible and economic alternative to this more complicated strategy. In addition, is also a generalizable strategy in both public and private health, where the effectiveness of alert systems had also been demonstrated.[40] It remains to be studied if both strategies increase the opportunities to improve follow-up to specialty care.

Our study has some limitations. Firstly, because of the retrospective design of the study, the clinical and laboratory data were limited, although the majority of variables associated with a lack of diagnosis were included.[41,42] Second, patients without a confirmatory RNA test in the laboratory registry may have received HCV-related care independently of the public health system. However, the percentage of the population in our setting with a private insurance or both is reported to be very low. In addition, to reduce this bias, we excluded patients lacking subsequent visits to primary care physicians or blood tests after the HCV antibody determination. Moreover, we used a long follow-up for searching appointment with the specialist because the mandatory hospital pharmacy dispensation of the therapy. Finally, there were differences regarding the age, drug use and social support between cohorts, which is inherent to the design of the study. Nevertheless, both cohorts were close in time to avoid other factors that could influence RNA requests and multivariable analysis was performed.

In conclusion, more than one-third of new diagnoses of HCV are not fully evaluated after a positive HCV antibody test. The simple action of implementing a computerized alert system after the detection of a positive anti-HCV antibody seems to be effective in decreasing the rate of patients without RNA test, reducing the time for RNA testing and increasing the rate of referrals to specialist care. Our study may guide other centres to improve the rates of full diagnosis and linkage to care among HCV patients.