The Performance of GALAD Score for Diagnosing Hepatocellular Carcinoma in Patients with Chronic Liver Diseases: A Systematic Review and Meta-Analysis

Abstract

Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the Web of Science, PubMed, Scopus, Ovid, Cochrane Library, and Embase databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78–0.85), 0.89 (95%CI: 0.85–0.91), and 0.92 (95%CI: 0.89–0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66–0.79)) and a high specificity (0.87 (95%CI: 0.81–0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66–0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66–0.87), 0.80 (95%CI: 0.72–0.87), and 0.86 (95%CI: 0.83–0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.

A Statistical Approach to the Diagnosis and Prediction of HCC Using CK19 and Glypican 3 Biomarkers

“…In a recent paper, Li et al validated the GALAD score and compared it with other scores and biomarker combinations, demonstrating the superiority of GALAD (AUC 0.925, 0.945) [ 37 ]. Furthermore, a systematic review published by Guan et al supports the robust power of GALAD as an HCC screening or diagnostic tool [ 52 ]. However, a phase 3 biomarker study from the United States showed that GALAD’s performance was modest and not different from AFP-L3 alone or carcinoma early detection screening (HES) [ 53 ].…”

“…However, a phase 3 biomarker study from the United States showed that GALAD’s performance was modest and not different from AFP-L3 alone or carcinoma early detection screening (HES) [ 53 ]. GALAD’s performance is also influenced by the etiology of the chronic liver disease of the patient at high risk for HCC, with decreased performance in HBV etiology and higher pooled sensitivities and AUC values seen in HCV and non-viral liver disease patients [ 52 ]. However, the number of HCV cirrhotic patients is decreasing due to direct-acting antivirals (DAA), while NAFLD is increasing.…”

“…GALAD’s sensitivity and AUC are associated with the BCLC stage [ 52 ]. Considering that approximately half of our cohort is outside the Milan criteria, this may explain the high AUC and sensitivity of GALAD in our cohort.…”

Systematic review: Glycomics as diagnostic markers for hepatocellular carcinoma

“…However, it has been reported that protein biomarkers possess suboptimal diagnostic values 73,74 . To improve these values, the GALAD score was developed by the combination of clinical variables (age and gender) and protein markers (AFP, AFP‐L3, and DCP) 70,71,75 . Furthermore, the methylation patterns of circulating tumour DNA (ctDNA) has been investigated as diagnostic markers for HCC.…”

“…Recently, the development of the GALAD score has improved the detection rate of early HCC. However, the threshold values of this score for the detection of early‐stage HCC have to be validated 70,71 . In this systematic review, several glycomics tests (DA Plus, glycosylated AFP, AFP‐fuc%, and GP73+Fuc‐Kin + AFP) show promising results for the early diagnosis of HCC.…”