Background The accuracy of alpha‐fetoprotein (AFP) as a diagnostic marker for hepatocellular carcinoma (HCC) is insufficient, and the application of abnormal prothrombin (PIVKA‐II) in HCC is still controversial. Methods Serum AFP and PIVKA‐II levels were analyzed in 145 cases of HCC, 57 of benign liver disease, 55 of cholangiocarcinoma and gallbladder carcinoma, 112 of other gastrointestinal tumors with liver metastasis, and 101 healthy controls. Receiver operating characteristic curve and area under the curve were used to evaluate the diagnostic value of AFP and PIVKA‐II for HCC. The changes in serum AFP and PIVKA‐II levels before and after treatment in 47 HCC patients who underwent surgery and 77 who received interventional treatment were used to evaluate treatment efficacy and prognosis in HCC. Results The concentrations of AFP and PIVKA‐II in the HCC group were significantly higher than those in other groups (p < 0.01). The diagnostic value of PIVKA‐II in HCC was better than that of AFP, and combined detection improved the diagnostic sensitivity and specificity. The levels of AFP and PIVKA‐II after liver cancer surgery were significantly lower than those before surgery. Elevated levels of PIVKA‐II before surgery predicted disease progression, and patients who remained positive for PIVKA‐II after surgery had worse prognosis than those who became negative after surgery. Conclusions Combined detection of AFP and PIVKA‐II is superior to both tests alone. We found that higher serum level of PIVKA‐II indicates more severe HCC, with worse prognosis, while the level of AFP had no correlation with the prognosis.
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