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Gene & Protein in Disease                                       PIVKA-II in differential diagnosis of AFP-NHCC



            lymphocytes using blood cell analyzer, and PIVKA-II   the benign lesion group, with the healthy control group
            by means of chemiluminescent particle immunoassay.   recording the lowest levels; the differences were statistically
            Afterward, the NLR was calculated.                 significant (P < 0.05) (Table 2).

            2.5. Observation index                             3.3. Performance analysis of different diagnostic
            The laboratory test results of the three groups were   methods
            compared to analyze the diagnostic efficacy of the   The diagnostic sensitivity and specificity of PIVKA-II were
            inflammatory index combined with PIVKA-II, and     84.40% and 73.80% for AFP-NHCC, 56.70% and 68.87%
            PIVKA-II alone, for AFP-NHCC.                      for hs-CRP, and 78.10% and 56.90% for PA, respectively.
                                                               The sensitivity and specificity of NLR were 75.00% and
            2.6. Statistical analysis                          47.80%, respectively. The sensitivity and specificity of
            All the data were input into Statistical Package for Social   combined diagnosis were 84.40% and 82.80%, and the area
            Sciences (SPSS) 22.0 software (IBM SPSS Statistics, United   under the curve (AUC) of combined diagnosis was larger
            States  of  America)  for  processing.  The  whole  variance   (Figures 1 and 2, Table 3).
            homogeneity test and normal distribution test were
            performed on continuous data. Normally distributed   4. Discussion
            data that meet homogeneous variance requirements are   AFP is a typical and most widely used tumor marker for
            expressed as mean ± standard deviation. One-way analysis   all kinds of liver cancers, which is of great significance for
            of variance was used for comparison among multiple   disease diagnosis and prognosis monitoring.  However,
                                                                                                    23
            groups, and the LSD-t test was used for comparison   not all HCC patients will show increased AFP levels, and
            between two  groups.  The non-normally distributed data   it is worth noting that other types of liver injury (hepatitis,
            are presented as median (M) and interquartile range (P25   cirrhosis, etc.) and even gastric cancer, teratoma, ovarian
            and P75), and the comparison was performed using a non-  tumor, and other diseases are accompanied by increased
            parametric test. The diagnostic efficiency was analyzed   AFP levels; this lack of disease specificity greatly limits
            using the receiver operating characteristics (ROC) curve.   the diagnostic value of AFP in HCC. Furthermore, the
            P < 0.05 was considered statistically significant.  application of AFP alone cannot meet the actual clinical

            3. Result                                          needs for HCC diagnosis. AFP-NHCC is a clinically special
                                                               type of HCC, which loses the expression of AFP during the
            3.1. Comparison of baseline information            early stage. 24
            The  age,  gender,  and  living  habits  of  the  three  groups   The prognosis of HCC depends on the  stage of the
            of patients were found to  be comparable  (P  >0.05).  In   tumor. In the Barcelona stage of liver cancer, liver cancer is
            addition, there were no significant differences in the size of   divided into very early stage, early stage, middle stage, late
            the tumor, normal liver function, and presence or absence   stage, and terminal stage. Patients with early-stage HCC
            of liver cirrhosis between the AFP-NHCC group and the   have a 5-year survival rate of more than 70%, whereas
            benign lesion group (P > 0.05) (Table 1).          symptomatic advanced patients have a median survival of
                                                               1.0 – 1.5 years after systemic therapy. In the very early stage,
            3.2. Comparison of laboratory indexes              patients usually have no related symptoms and signs, and
            The levels of all inflammatory indexes and PIVKA-II   only a single lesion of ≤2 cm is present at this time, with
            were  the  highest  in  the  AFP-NHCC group,  followed by   minimal liver function damage; therefore, early diagnosis

            Table 2. Comparison of laboratory indexes
            Group                       hs‑CRP (mg/L)         PA (mg/L)          NLR          PIVKA‑\ (mAU/mL)
            AFP-NHCC group (n=32)     74.65 (56.36, 129.43) a,b  45.71 (26.57, 67.46) a,b  3.59±1.58 a,b  814.27 (654.64, 978.46) a,b
            Benign lesion group (n=58)  37.26 (28.67, 63.24) a  92.01 (55.67, 130.35) a  2.82±1.04 a  424.84 (316.65, 532.54) a
            Healthy control group (n=45)  0.12 (0.06, 0.18)  241.15 (189.54, 290.67)  1.79±0.81  48.60 (20.04, 78.57)
            χ 2                            8.567               7.366             5.577            12.245
            P                              <0.001              0.000             0.001             0.000
            Notes: Data are expressed as either M (P25, P75) or mean±SD.  P<0.05 compared with the healthy control group;  P<0.05 compared with the benign
                                                                                    b
                                                    a
            lesion group.
            Abbreviations: AFP-NHCC: Alpha-fetoprotein-negative hepatocellular carcinoma; hs-CRP: High-sensitivity C-reactive protein; NLR: Neutrophil–
            lymphocyte ratio; PA: Prealbumin.
            Volume 3 Issue 4 (2024)                         4                               doi: 10.36922/gpd.4269
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