Clinical utility of serum fucosylated fraction of alpha-fetoprotein in the diagnostic of hepatocellular carcinoma: a comprehensive analysis with large sample size

We conducted a comprehensive meta-analysis of the utility of AFP-L3 for the diagnosis of hepatocellular carcinoma, to provide a more accurate estimation for the clinical utility of AFP-L3. We performed online searches in five databases (PubMed, China National Knowledge Infrastructure, Wanfang, Web of Science, and Embase), from inception to December 31, 2021. Pooled sensitivity, specificity, and area under the curve (AUC) with the matching 95% confidence intervals (95% CIs) were calculated to estimate the diagnostic value of AFP-L3. Thirty-four studies were included in the meta-analysis. The pooled sensitivity was 0.70 [95% confidence interval (CI): 0.63–0.77], and the specificity was 0.91 (95% CI: 0.88–0.94). The estimated area under the curve (AUC) was 0.90 (95% CI: 0.87–0.92). The positive likelihood ratio and negative likelihood ratio were 7.78 (95% CI: 5.7–10.7) and 0.33 (95% CI: 0.26–0.41), respectively. The diagnostic odds ratio was 24 (95% CI: 16–37). The subgroup analysis indicated moderate sensitivity (0.79) and high specificity (0.89) for the Asian population (AUC = 0.89), and similar specificity (0.95) but lower sensitivity (0.35) for Caucasians (AUC = 0.80). Deeks’ funnel plot asymmetry test detected no publication bias (P = 0.460). The sensitivity analysis showed that the pooled results were stable. Taken together, our results indicated that AFP-L3 demonstrates high diagnostic ability for HCC, especially among Asian populations. AFP-L3 is a useful means for high-volume screening, which can help doctors optimize diagnosis workflow, reduce workload, and improve detection sensitivity. The combination of multiple biomarkers may provide more accurate diagnostic tools for HCC in the future.


Rationale
3 Describe the rationale for the review in the context of what is already known.
Introduction (P3) Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

Protocol and registration 5
Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.
Unpublished document circulated to collaborators (P5) Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

Methods (P6)
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

Methods (P5)
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

Methods (P5)
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

Methods (P5)
Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

Methods (P6)
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

Methods (P7)
Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means).

Methods (P7)
Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.

Risk of bias across studies 15
Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

Results (P7)
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection 17
Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

Figure 1 (P8)
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

Summary of evidence 24
Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

Limitations 25
Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

Conclusions 26
Provide a general interpretation of the results in the context of other evidence, and implications for future research.

Funding 27
Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.