An EAS was developed to remind physicians of the need for HBV and HCV testing in certain patients. The EAS was linked to the hospital’s prescription software and requested HBsAg, anti-HBc, and anti-HCV results when specific haematological drugs were prescribed. The physician was informed about the potential risk of HBV reactivation and the need to refer the patient to a hepatologist according to the scheme summarized in Fig. 2. In patients testing HBsAg or antiHBc positive and those with unknown status, the system automatically sends an e-mail to the Hepatology Department with the patient’s coded data. Furthermore, to facilitate the physicians’ work and achieve relevant data, 3 preconfigured blood tests were created: one to complete the study of HBsAg-positive individuals (Code 520, which included a haemogram, biochemistry, clotting, quantitative HBsAg, HBV DNA, HBeAg, anti-HBe, anti-hepatitis D virus, human immunodeficiency virus (HIV) serology, and anti-HCV), another for anti-HBc positive or unknown serological status (Code 527, including HBsAg, anti-HBc, HBV DNA, and anti-HBs titers), and a third for those with detectable HCV RNA (Code 528, haemogram, biochemistry, clotting, HIV serology, and HCV genotype). Whenever a new treatment schedule was prescribed, the computerized system requested the patient’s viral hepatitis status if it had not been previously introduced. If data were lacking and viral hepatitis screening had not been performed within the first 3 months after the therapy prescription, the viral hepatitis panel was added to the patient’s next scheduled blood test.
Prior to implementation of the EAS, Haematology Department physicians underwent training sessions to highlight the importance of hepatitis B and C screening, the rationale to set up this system and to inform about the functioning of the EAS. During the first year of the system, this prospective, observational study was carried out to evaluate the performance of the EAS according to the following items:
Number of patients whose viral hepatitis status was checked after the EAS warning. All patients lacking data at the first prescription were checked for later viral hepatitis screening requests from the Haematology Department.
Number of patients with newly diagnosed viral hepatitis markers.
Number of HBV prophylaxis therapies initiated as a result of the EAS (newly diagnosed HBsAg- or anti-HBc-positive patients) and estimation of the number of HBV reactivations avoided because of the EAS.
Number of HBV reactivations within the first year of the EAS.
This study was approved by the Vall d’Hebron Hospital ethics committee and was conducted in compliance with the principles of the Declaration of Helsinki, Good Clinical Practice guidelines, and local regulatory requirements. Since screening of viral hepatitis markers is considered within recommended daily clinical practice, no informed consent was requested in agreement with the Hospital ethics committee.
Definition of HBV reactivation
HBV reactivation was defined according to the AASLD guidelines as a ≥ 2 log increase in baseline HBV DNA in HBsAg-positive patients, or reappearance of HBsAg or detectable HBV DNA in patients who had been previously HBsAg-negative/anti-HBc-positive (reverse seroconversion)28.
All haematological patients receiving specific treatment (including monoclonal antibodies in monotherapy) from 1 March, 2017, the date the EAS was launched, to 1 March, 2018, were included.
In all cases, epidemiological (race, date of birth, sex), clinical (malignancy, treatment regimen, previously known viral hepatitis infection, prior treatment for viral hepatitis, antiviral therapy), and serological (HBsAg, anti-HBc, anti-HCV, and HIV if available) data were recorded, as well as antiviral treatment for chronic hepatitis C and nucleos(t)ide analogue prophylaxis for HBsAg- or anti-HBc-positive patients. These treatments were prescribed at the discretion of the haematologist, except for patients referred to the Hepatology Department and those with chronic hepatitis B, who were treated in all cases.
Serological markers for HBV (HBsAg, anti-HBc, and anti-HBs) and HCV (anti-HCV) were analysed by commercial enzyme immunoassays. The lower limit of quantification of anti-HBs was 10 mIU/mL and the upper limit, 500 mIU/mL. Serum HBV DNA was quantified by PCR with a COBAS 6800 HBV test (Roche Diagnostics, Mannheim, Germany): lower limit of quantification, 20 IU/mL and lower limit of detection, 10 IU/mL.
Normally-distributed quantitative variables were compared with the Student t test and expressed as the mean ± standard deviation (SD). Variables with a non-normal distribution were analysed with the Mann-Whitney U test and expressed as the median and interquartile range. Categorical variables were compared using the chi-square or Fisher exact test, as appropriate, and expressed as frequencies and percentages. P values < 0.05 were considered statistically significant. The impact of the EAS was estimated using the number needed to treat (NNT), based on the number of patients who initiated antiviral prophylaxis, and the 95% confidence interval was calculated using the Newcombe method29. All analyses were carried out using IBM SPSS, 20 (SPSS Inc., Armonk, NY, USA).