Development of a risk score to guide targeted hepatitis C testing among human immunodeficiency virus patients in Cambodia

ARTICLE HIGHLIGHTS

Research background

The advent of direct-acting antivirals has revolutionized hepatitis C (HCV) treatment and has generated interest in the global elimination of hepatitis C as a public health problem. To allow timely scale up of treatment, efficient HCV testing strategies are crucial. By the end of 2017, only about 20% of those living with hepatitis C knew their status, with significantly lower proportions in low and middle income countries (LMIC).

Research motivation

In the absence of funding initiatives dedicated to viral hepatitis, it is expected to remain difficult for LMIC to offer broad access to HCV testing. Depending on local resources and epidemiology, offering targeted HCV screening might be a more feasible option. However, easy-to-use tools to guide such targeted HCV testing, other than prioritization of key populations or older birth cohorts, do not exist.

Research objectives

To develop and internally validate a clinical prediction score for targeted HCV screening combining age and factors linked to liver disease severity, aiming to identify most of the chronic hepatitis C patients in low-risk human immunodeficiency virus (HIV) populations, but especially those in more urgent need of treatment.

Research methods

Score development relied on the Spiegelhalter and Knill-Jones method which was applied on a cross-sectional dataset from a large HIV cohort in Phnom Penh, Cambodia. Predictors independently associated with current HCV infection (HCV RNA detected) with likelihood ratio ≥ 1.5 or ≤ 0.67 were retained in the score. Performance of the score was estimated by the area-under-the-ROC curve and diagnostic accuracy at the different cut-offs. For the decision rule, HCV coinfection probability ≥ 1% was agreed as test-threshold.

Research results

We developed (and internally validated) a clinical prediction score to risk-stratify, primarily heterosexually-infected HIV patients for HCV coinfection, for use as first step in the identification of HIV patients to be prioritized for HCV testing when resources are insufficient to test all. The risk score uses elements from history taking, physical examination and laboratory test results which are readily available or easily obtainable in most HIV programs. In the Cambodian derivation cohort, the score would have enabled identifying 85% of the coinfected while reducing the need for testing by 70%. At the best-fitting threshold-to-screen (score ≥ 0), a negative predictive value of 99.2% was obtained, and no cases with advanced fibrosis were missed.

Research conclusions

The score for targeted HCV screening performed well in the derivation cohort and bears potential to substantially reduce the number needed to test without compromising access to testing and treatment for HIV patients with advanced HCV disease. Confirmation of these promising findings through external validation is required before recommendations on wider use can be made.

Research perspectives

The validity of the score should be tested in other HIV cohorts with low onward risk of transmission, starting from similar HIV cohorts in Cambodia but also in HIV populations in other settings.