Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin

Figure 1 Forest plots of factors associated with abnormally elevated protein induced by vitamin K absence or antagonist-II by univariate and multivariate logistic analysis in patients with non-hepatocellular carcinoma and hepatocellular carcinoma. A: In non- hepatocellular carcinoma (HCC) patients; B: In HCC patients. HBV: Hepatitis B virus; HCV: Hepatitis C virus; NAFLD: Nonalcoholic fatty liver disease; ALD: Alcohol-related liver disease; AILD: Autoimmune liver disease; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; ULN: Upper limit of normal; TBIL: Total bilirubin; PLT: Platelet; LLN: Lower limit of normal; 95%CI: 95% confidence interval; OR: Odds ratio.

Figure 2 Distributions and comparisons of serum protein induced by vitamin K absence or antagonist-II in different subgroups. A: Different etiologies of hepatitis B virus (HBV), HCV, nonalcoholic fatty liver disease, alcohol-related liver disease (ALD), autoimmune liver disease; B: Different tumor sizes of ≤ 2 cm (n = 60), > 2 cm and ≤ 5 cm (n = 88), > 5 cm and ≤ 10 cm (n = 65), > 10 cm (n = 54); C: Subgroups between viral and nonviral liver diseases; D: Subgroups between alkaline phosphatase (ALP) ≤ 1 × upper limit of normal (ULN) and ALP > 1 × ULN; E: Subgroups between total bilirubin (TBIL) ≤ 1 × ULN and TBIL > 1 × ULN; F: Subgroups between aspartate aminotransferase (AST) ≤ 1 × ULN and AST > 1 × ULN. HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus; HCV: Hepatitis C virus; NAFLD: Nonalcoholic fatty liver disease; ALD: Alcohol-related liver disease; AILD: Autoimmune liver disease; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; ULN: Upper limit of normal; TBIL: Total bilirubin.

Figure 3 Comparisons of receiver operating characteristic curves of serum protein induced by vitamin K absence or antagonist-II for diagnosing early-stage hepatocellular carcinoma in different subgroups. A: For all early-stage patients; B: Between viral and nonviral subgroups; C: Between alkaline phosphatase ≤ 1 × upper limit of normal (ULN) and alkaline phosphatase > 1 × ULN subgroups; D: Between total bilirubin (TBIL) ≤ 1 × ULN and TBIL > 1 × ULN subgroups; E: Between aspartate aminotransferase (AST) ≤ 1 × ULN and AST > 1 × ULN subgroups. ULN: Upper limit of normal; TBIL: Total bilirubin; HCC: Hepatocellular carcinoma; AUC: Area under the receiver operating characteristic curve; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase.

Figure 4 Comparisons of receiver operating characteristic curves of serum protein induced by vitamin K absence or antagonist-II for diagnosing early-stage hepatocellular carcinoma in subgroups of alkaline phosphatase and total bilirubin for patients with viral etiology. A: Between alkaline phosphatase (ALP) ≤ 1 × upper limit of normal (ULN) and ALP > 1 × ULN subgroups; B: Between total bilirubin (TBIL) ≤ 1 × ULN and TBIL > 1 × ULN subgroups. ULN: Upper limit of normal; TBIL: Total bilirubin; ALP: Alkaline phosphatase; AUC: Area under the receiver operating characteristic curve.