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Meta-Analysis
. 2020 Feb 13;15(2):e0228857.
doi: 10.1371/journal.pone.0228857. eCollection 2020.

The threshold of alpha-fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

Jiaxin Zhang  1   2 , Guang Chen  1   2 , Peng Zhang  1   2 , Jiaying Zhang  3 , Xiaoke Li  1   2 , Da'nan Gan  1   2 , Xu Cao  1   2 , Mei Han  4 , Hongbo Du  1   2 , Yong'an Ye  1   2
Affiliations
Meta-Analysis

The threshold of alpha-fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

Jiaxin Zhang et al. PLoS One. .

Abstract

Objective: Hepatocellular carcinoma (HCC) has become a pressing health problem facing the world today due to its high morbidity, high mortality, and late discovery. As a diagnostic criteria of HCC, the exact threshold of Alpha-fetoprotein (AFP) is controversial. Therefore, this study was aimed to systematically estimate the performance of AFP in diagnosing HCC and to clarify its optimal threshold.

Methods: Medline and Embase databases were searched for articles indexed up to November 2019. English language studies were included if both the sensitivity and specificity of AFP in the diagnosis of HCC were provided. The basic information and accuracy data included in the studies were extracted. Combined estimates for sensitivity and specificity were statistically analyzed by random-effects model using MetaDisc 1.4 and Stata 15.0 software at the prespecified threshold of 400 ng/mL, 200 ng/mL, and the range of 20-100 ng/mL. The optimal threshold was evaluated by the area under curve (AUC) of the summary receiver operating characteristic (SROC).

Results: We retrieved 29,828 articles and included 59 studies and 1 review with a total of 11,731 HCC cases confirmed by histomorphology and 21,972 control cases without HCC. The included studies showed an overall judgment of at risk of bias. Four studies with AFP threshold of 400 ng/mL showed the summary sensitivity and specificity of 0.32 (95%CI 0.31-0.34) and 0.99 (95%CI 0.98-0.99), respectively. Four studies with AFP threshold of 200 ng/mL showed the summary sensitivity and specificity of 0.49 (95%CI 0.47-0.50) and 0.98 (95%CI 0.97-0.99), respectively. Forty-six studies with AFP threshold of 20-100 ng/mL showed the summary sensitivity and specificity of 0.61 (95%CI 0.60-0.62) and 0.86 (95%CI 0.86-0.87), respectively. The AUC of SROC and Q index of 400 ng/mL threshold were 0.9368 and 0.8734, respectively, which were significantly higher than those in 200 ng/mL threshold (0.9311 and 0.8664, respectively) and higher than those in 20-100 ng/mL threshold (0.8330 and 0.7654, respectively). Furthermore, similar result that favored 400 ng/mL were shown in the threshold in terms of AFP combined with ultrasound.

Conclusion: AFP levels in serum showed good accuracy in HCC diagnosis, and the threshold of AFP with 400 ng/mL was better than that of 200 ng/mL in terms of sensitivity and specificity no matter AFP is used alone or combined with ultrasound.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram of study selection.
Fig 2
Fig 2. Forest plots of the estimates for AFP in HCC diagnosis (20–100 ng/mL).
(A) Pooled sensitivity. (B) Pooled specificity. (C) Pooled positive LR. (D) Pooled negative LR.
Fig 3
Fig 3. Forest plots of the estimates for AFP in HCC diagnosis (200 ng/mL).
(A) Pooled sensitivity. (B) Pooled specificity. (C) Pooled positive LR. (D) Pooled negative LR.
Fig 4
Fig 4. Forest plots of the estimates for AFP in HCC diagnosis (400 ng/mL).
(A) Pooled sensitivity. (B) Pooled specificity. (C) Pooled positive LR. (D) Pooled negative LR.
Fig 5
Fig 5. Summary receiver operating characteristic curves (SROC).
(A). SROC curve for AFP in 20–100 ng/mL. (B). SROC curve for AFP in 200 ng/mL. (C). SROC curve for AFP in 400 ng/mL. (D) SROC curve for AFP in 20–100 ng/mL combined with ultrasound. (E) SROC curve for AFP in 200 ng/mL combined with ultrasound. (F) SROC curve for AFP in 400 ng/mL combined with ultrasound.
See this image and copyright information in PMC

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