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Development of a risk score to guide targeted hepatitis C testing among human immunodeficiency virus patients in
Anja De Weggheleire1, Jozefien Buyze2, Sokkab An3
1Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Antwerp 2000, Belgium. adeweggheleire@itg.be.
Insights
A new clinical prediction score (CPS) effectively identifies human immunodeficiency virus (HIV) patients at high risk for hepatitis C virus (HCV) coinfection, aiding targeted testing in resource-limited settings.
Area of Science:
- Infectious Diseases
- Hepatology
- Public Health
Background:
- The World Health Organization (WHO) recommends universal hepatitis C virus (HCV) screening for all human immunodeficiency virus (HIV) patients.
- In resource-constrained settings with low-to-intermediate HCV prevalence, such as Cambodia, targeted testing may be more feasible and cost-effective than universal screening.
- Prioritizing HCV testing is crucial where resources limit universal screening recommendations.
Purpose of the Study:
- To develop a clinical prediction score (CPS) for risk-stratifying HIV patients for HCV coinfection.
- To create a decision rule for prioritizing HCV testing in settings where universal testing is not feasible.
- To guide cost-effective HCV screening strategies in HIV cohorts.
Main Methods:
- Utilized data from a cross-sectional HCV diagnostic study in an HIV cohort in Phnom Penh, Cambodia.
- Employed the Spiegelhalter and Knill-Jones method for score development, retaining predictors with adjusted likelihood ratios ≥ 1.5 or ≤ 0.67.
- Evaluated CPS performance using area-under-the-ROC curve (AUROC) and diagnostic accuracy at various cut-offs.
Main Results:
- Seven predictors were identified: age ≥ 50, diabetes mellitus, partner with liver disease, generalized pruritus, platelets < 200 × 10^9/L, AST < 30 IU/L, and APRI status.
- The developed CPS demonstrated good discrimination with an AUROC of 0.84 (95% CI: 0.80-0.89).
- A CPS threshold of ≥0 achieved a negative predictive value of 99.2%, enabling testing of 30% of patients while missing 15% of coinfections (none with advanced fibrosis).
Conclusions:
- The clinical prediction score (CPS) shows promise for identifying HIV patients needing HCV testing in low-prevalence settings with limited resources.
- The CPS can aid in risk-stratifying patients for HCV coinfection, optimizing testing strategies.
- External validation of the CPS in diverse patient cohorts is recommended before widespread implementation.
Background:
The World Health Organization recommends testing all human immunodeficiency virus (HIV) patients for hepatitis C virus (HCV). In resource-constrained contexts with low-to-intermediate HCV prevalence among HIV patients, as in Cambodia, targeted testing is, in the short-term, potentially more feasible and cost-effective.
Aim:
To develop a clinical prediction score (CPS) to risk-stratify HIV patients for HCV coinfection (HCV RNA detected), and derive a decision rule to guide prioritization of HCV testing in settings where 'testing all' is not feasible or unaffordable in the short term.
Methods:
We used data of a cross-sectional HCV diagnostic study in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh. Key populations were very rare in this cohort. Score development relied on the Spiegelhalter and Knill-Jones method. Predictors with an adjusted likelihood ratio ≥ 1.5 or ≤ 0.67 were retained, transformed to natural logarithms, and rounded to integers as score items. CPS performance was evaluated by the area-under-the-ROC curve (AUROC) with 95% confidence intervals (CI), and diagnostic accuracy at the different cut-offs. For the decision rule, HCV coinfection probability ≥1% was agreed as test-threshold.
Results:
Among the 3045 enrolled HIV patients, 106 had an HCV coinfection. Of the 11 candidate predictors (from history-taking, laboratory testing), seven had an adjusted likelihood ratio ≥ 1.5 or ≤ 0.67: ≥ 50 years (+1 point), diabetes mellitus (+1), partner/household member with liver disease (+1), generalized pruritus (+1), platelets < 200 × 109/L (+1), aspartate transaminase (AST) < 30 IU/L (-1), AST-to-platelet ratio index (APRI) ≥ 0.45 (+1), and APRI < 0.45 (-1). The AUROC was 0.84 (95%CI: 0.80-0.89), indicating good discrimination of HCV/HIV coinfection and HIV mono-infection. The CPS result ≥0 best fits the test-threshold (negative predictive value: 99.2%, 95%CI: 98.8-99.6). Applying this threshold, 30% (n = 926) would be tested. Sixteen coinfections (15%) would have been missed, none with advanced fibrosis.
Conclusion:
The CPS performed well in the derivation cohort, and bears potential for other contexts of low-to-intermediate prevalence and little onward risk of transmission(i.e. cohorts without major risk factors as injecting drug use, men having sex with men), and where available resources do not allow to test all HIV patients as recommended by WHO. However, the score requires external validation in other patient cohorts before any wider use can be considered.
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