Park 2017a.
| Study characteristics | |||
| Patient Sampling | The participant cohort consisted of 298 HCC cases from the Digestive Disease Center at the Soonchunhyang University Seoul Hospital, which were newly diagnosed between October 2013 and March 2016 by retrospective design. Among them, 79 HCC patients were selected for inclusion in this study after applying the following exclusion criteria: the baseline serum level of AFP, AFPL3, or PIVKA‐II was not obtained; presence of extrahepatic malignancy when HCC was diagnosed; previously treated for any type of malignancy before HCC was diagnosed; all other conditions with elevated AFP rather than liver disease; or fibrolamellar HCC which can show normal AFP. A further 77 patients with liver cirrhosis (LC) were selected in this study as a control group. LC was diagnosed based on a histological examination or clinical findings of portal hypertension. The LC patients in the control group had undergone imaging studies to exclude HCC. Age range: 48‐70. Males 85% |
||
| Patient characteristics and setting | |||
| Index tests | AFP: "alpha‐fetoprotein, AFP‐L3, and PIVKA‐II were measured in the same serum samples using microchip capillary electrophoresis and a liquid‐phase binding assay on an automatic analyser (mTAS Wako i30, Wako Pure Chemical Industries, Osaka, Japan). The measurement range was 0.3 to 2000ng/mL for AFP. All testing was conducted at the Soonchunhyang University Seoul Hospital by the same group of laboratory technicians, and none of the technicians was informed of the participant’s status before testing. We defined positivity for the 3 biomarkers alone as follows: AFP > 10ng/mL, PIVKA‐II > 40mAU/mL, and AFP‐L3 > 10%. The cut‐off value for serum AFP was 10 ng/mL since this is the setting used by our laboratory automatic analyser (Wako i30). Because the cut‐off value of other devices in our hospital is 20ng/ mL, we also determined whether the diagnostic performance of the biomarkers changed for a AFP cut‐off value of 20 ng/mL, and we also analysed the diagnostic performance of biomarkers for different cut‐off values of AFP‐L3 to verify the reproducibility of our study results." | ||
| Target condition and reference standard(s) | HCC: HCC was diagnosed based on histological findings or typical imaging characteristics as defined by the Korean Liver Cancer Study Group Guideline. Control group: the liver cirrhosis (LC) patients in the control group had undergone imaging studies to exclude HCC. |
||
| Flow and timing | No information on interval between index test and reference standard | ||
| Comparative | |||
| Notes | The authors reported no conflicts of interest. | ||
| Methodological quality | |||
| Item | Authors' judgement | Risk of bias | Applicability concerns |
| DOMAIN 1: Patient Selection | |||
| Was a consecutive or random sample of patients enrolled? | No | ||
| Was a case‐control design avoided? | No | ||
| Did the study avoid inappropriate exclusions? | No | ||
| Could the selection of patients have introduced bias? | High risk | ||
| Are there concerns that the included patients and setting do not match the review question? | High | ||
| DOMAIN 2: Index Test (AFP) | |||
| Were the index test results interpreted without knowledge of the results of the reference standard? | No | ||
| If a threshold was used, was it pre‐specified? | Yes | ||
| Could the conduct or interpretation of the index test have introduced bias? | High risk | ||
| Are there concerns that the index test, its conduct, or interpretation differ from the review question? | Low concern | ||
| DOMAIN 2: Index Test (US+AFP) | |||
| DOMAIN 2: Index Test (US) | |||
| DOMAIN 3: Reference Standard | |||
| Is the reference standards likely to correctly classify the target condition? | Yes | ||
| Were the reference standard results interpreted without knowledge of the results of the index tests? | Yes | ||
| Could the reference standard, its conduct, or its interpretation have introduced bias? | Low risk | ||
| Are there concerns that the target condition as defined by the reference standard does not match the question? | Low concern | ||
| DOMAIN 4: Flow and Timing | |||
| Was there an appropriate interval between index test and reference standard? | Unclear | ||
| Did all patients receive the same reference standard? | No | ||
| Were all patients included in the analysis? | Yes | ||
| Could the patient flow have introduced bias? | High risk | ||