Serology for the diagnosis of human hepatic cystic echinococcosis and its relation with cyst staging: A systematic review of the literature with meta-analysis

Abstract

Background: The diagnosis of cystic echinococcosis (CE) is primarily based on imaging, while serology should be applied when imaging is inconclusive. CE cyst stage has been reported among the most important factors influencing the outcome of serodiagnosis. We performed a systematic review and meta-analysis of the relation between cyst stage of hepatic CE and diagnostic sensitivity of serological tests, to evaluate whether their relation is a consistent finding and provide guidance for the interpretation of results of serological tests.

Methodology/principal findings: MEDLINE, EMBASE, CENTRAL, and Lilacs databases were searched on December 1st 2019. Original studies published after 2003 (year of publication of the CE cyst classification), reporting sensitivity of serological tests applied to the diagnosis of human hepatic CE, as diagnosed and staged by imaging, were included. The quality of studies was assessed using the Newcastle-Ottawa Scale. Data from 14 studies were included in the meta-analysis. Summary estimates of sensitivities and 95% confidence intervals were obtained using random effects meta-analysis. Overall, test sensitivity was highest in the presence of CE2 and CE3 (CE3a and/or CE3b), and lowest in the presence of CE5 and CE4 cysts. ELISA, ICT and WB showed the highest sensitivities, while IHA performed worst.

Conclusions/significance: The results of our study confirm the presence of a clear and consistent relation between cyst stage and serological tests results. Limitations of evidence included the heterogeneity of the antigenic preparations used, which prevented to determine whether the relation between cyst stage and sensitivity was influenced by the type of antigenic preparation, the paucity of studies testing the same panel of sera with different assays, and the lack of studies assessing the performance of the same assay in both field and hospital-based settings. Our results indicate the absolute need to consider cyst staging when evaluating serological results of patients with hepatic CE.

Fig 1. Flow diagram of the literature search.

Fig 2. Sensitivity (%) of different serology tests for the diagnosis of untreated hepatic CE cysts according to cyst stage.

“CE3 all” = data from CE3a + CE3b + CE3 not divided into CE3a and CE3b. “CE inactive” = data from CE4 + CE5 + CE4 and CE5 not divided into CE4 and CE5. LQS = Low Quality Studies. Data from papers referring to the field or to the hospital/lab setting were included. In case more than one assay per type was investigated in the same paper (e.g. more than one ELISA test), the one with the best sensitivity was used for the meta-analysis. Error bars represent 95% CI.

Fig 3. Sensitivity (%) of ELISA tests for the diagnosis of untreated hepatic CE cysts according to cyst stage and setting (field vs lab and/or hospital).

“CE3 all” = data from CE3a + CE3b + CE3 not divided into CE3a and CE3b. “CE inactive” = data from CE4 + CE5 + CE4 and CE5 not divided into CE4 and CE5. LQS = Low Quality Studies. In case more than one assay per type was investigated in the same paper (e.g. more than one ELISA test), the one with the best sensitivity was used for the meta-analysis. Error bars represent 95% CI.

Fig 4. Sensitivity (%) of ELISA tests for the diagnosis of hepatic CE cysts, irrespective of previous treatment and setting.

“CE3 all” = data from CE3a + CE3b + CE3 not divided into CE3a and CE3b. “CE inactive” = data from CE4 + CE5 + CE4 and CE5 not divided into CE4 and CE5. LQS = Low Quality Studies. In case more than one assay per type was investigated in the same paper (e.g. more than one ELISA test), the one with the best sensitivity was used for the meta-analysis. Error bars represent 95% CI.

Fig 5. Sensitivity (%) of different assays using a variety of antigenic preparations, as reported by three example recent studies, showing the same pattern according to cyst stage.