A systematic review and meta-analysis: the diagnostic accuracy of methylated SEPTIN9 for the detection of hepatocellular carcinoma and the clinical evaluation of its use in combination with other surveillance modalities. (3rd April 2022)

• Record Type: Journal Article
• Authors: Chandrapalan, Subashini; Bannaga, Ayman; Weidner, Alice; Hitchins, Megan P.; Arasaradnam, Ramesh P.
• Is Part Of: Scandinavian journal of gastroenterology. Volume 57:Number 4(2022)
• Page Start: 473
• Page End: 480
• Publication Date: 2022-04-03
• Subjects: HCC -- methylated -- SEPTIN9 -- diagnosis -- surveillance; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; 616.33
• DOI: 10.1080/00365521.2021.2020331
• Languages: English
• ISSNs: 0036-5521

Abstract

Abstract: Background: Hepatocellular carcinoma (HCC) lacks a suitable biomarker for minimally-invasive disease detection. Methylated SEPTIN9 (mSEPT9) is an emerging liquid biopsy test. We aimed to investigate recent studies that applied mSEPT9 for HCC diagnosis. Furthermore, we evaluated the combinations of other surveillance modalities for the detection of HCC. Methods: A systematic review was performed on the diagnostic accuracy of mSEPT9 for the detection of HCC. Using a bivariate model, the pooled sensitivity and specificity were calculated. Additionally, Fagan's nomograms were used to calculate the pre-test and post-test probabilities of HCC for various combinations of surveillance modalities. Results: Six full texts were included in the meta-analysis. The pooled sensitivity and specificity of mSEPT9 for the detection of HCC, were 0.80 (95% CI, 0.67–0.89) and 0.90 (95% CI, 0.84–0.94). The area under the receiver operating curve was 0.92. The probability of having HCC for the combinations of mSEPT9+ ultrasound scan (USS) and mSEPT9+ Alpha fetoprotein (AFP) were 0.7% and 1.2% respectively if both tests were negative (in a population with 10% HCC prevalence). The combination of USS and AFP would miss relatively fewer cancers for 1000 patients in comparison to other combinations of two surveillance modalities. Conclusion: Test combinations have superior performance for the detection of HCC than any individual test. mSEPT9 has shown promise in the detection of HCC with higher estimates of performance accuracy. mSEPT9 has potential for use as an HCC surveillance modality in adjunct with other tests to improve detection rates. However, cost effectiveness of this approach needs further evaluation.