De Weggheleire A, Buyze J, An S, Thai S, van Griensven J, Francque S, Lynen L. Development of a risk score to guide targeted hepatitis C testing among human immunodeficiency virus patients in Cambodia. World J Hepatol 2021; 13(9): 1167-1180 [PMID: 34630883 DOI: 10.4254/wjh.v13.i9.1167]
Corresponding Author of This Article
Anja De Weggheleire, MD, MSc, Doctor, Senior Researcher, Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Nationalestraat 155, Antwerp 2000, Belgium. adeweggheleire@itg.be
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Sep 27, 2021; 13(9): 1167-1180 Published online Sep 27, 2021. doi: 10.4254/wjh.v13.i9.1167
Development of a risk score to guide targeted hepatitis C testing among human immunodeficiency virus patients in Cambodia
Anja De Weggheleire, Jozefien Buyze, Sokkab An, Sopheak Thai, Johan van Griensven, Sven Francque, Lutgarde Lynen
Anja De Weggheleire, Jozefien Buyze, Johan van Griensven, Lutgarde Lynen, Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Antwerp 2000, Belgium
Sokkab An, Sopheak Thai, Infectious Diseases Department, Sihanouk Hospital Center of Hope, Phnom Penh 12101, Cambodia
Sven Francque, Department of Gastroenterology Hepatology, Antwerp University Hospital, Antwerp 2000, Belgium
Sven Francque, Laboratory of Experimental Medicine and Paediatrics, University of Antwerp, Antwerp 2000, Belgium
Author contributions: De Weggheleire A designed and coordinated the study, and drafted the initial manuscript; An S and Thai S participated in the acquisition and review of the data; Buyze J reviewed the statistical analysis plan and data analysis; van Griensven J, Francque S and Lynen L reviewed the study design and analysis plan; Lynen L was the guarantor of the study; all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Institute of Tropical Medicine Antwerp (Approval No. IRB 925/14), the Ethics Committee of the Antwerp University Hospital (Belgium) (Approval No. 14/39/405), and the Cambodian National Ethics Committee for Health Research (Approval No. 0309).
Clinical trial registration statement: This study was registered in ClinicalTrials.gov, identifier NCT02361541.
Informed consent statement: Written informed consent was provided for all participants.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The data underlying this study are available upon request because the applied informed consent did not inform participants about the possibility of non-restricted data sharing. Data are available from the corresponding author (adeweggheleire@itg.be) for researchers who meet the criteria for access to confidential anonymized data.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anja De Weggheleire, MD, MSc, Doctor, Senior Researcher, Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Nationalestraat 155, Antwerp 2000, Belgium. adeweggheleire@itg.be
Received: April 25, 2021 Peer-review started: April 25, 2021 First decision: June 4, 2021 Revised: June 27, 2021 Accepted: August 24, 2021 Article in press: August 24, 2021 Published online: September 27, 2021 Processing time: 149 Days and 17.7 Hours
Abstract
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.
Core Tip: We developed and internally validated a clinical prediction score to stratify human immunodeficiency virus (HIV) patients for risk of hepatitis C (HCV) coinfection, and derived a decision rule to guide prioritization of HCV testing. The score incorporates readily available clinical and laboratory predictors, and had, in the Cambodian derivation cohort, a good ability to discriminate between HCV/HIV coinfection and HIV mono-infection. Key populations were rare in the Cambodian HIV cohort.
