Optimal Cut-Off Value of PIVKA-II for the Diagnosis of Hepatocellular Carcinoma in Indian Patients: Interim Results from a Prospective Study

Background and Aim: Prothrombin induced by vitamin K absence-II (PIVKA-II) is an emerging biomarker for hepatocellular carcinoma (HCC) diagnosis. However, the recommended cut-off of 40 mAU/ml may not be applicable to Indian patients. This study aims to determine the optimal cut-off value for PIVKA-II in the diagnosis of HCC. Methods: This ongoing prospective observational study started in May 2022 at the Institute of Liver, Gastroenterology & Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi. Cirrhotic patients aged 18 years and above, excluding those on warfarin or with creatinine clearance <30 ml/min, were included. PIVKA-II levels were measured in all patients, followed by a triphasic CT scan of the liver. The optimal cut-off value for PIVKA-II was calculated using the receiver operating characteristic (ROC) curve. Results: Between May 2022 and April 2023, 100 cirrhotic patients were enrolled (mean age 58±11 years, 78% males). The etiologies of cirrhosis were non-alcoholic steatohepatitis (NASH) in 41% of cases, alcohol in 33%, viral causes in 20%, and other causes in 6%. HCC was present in 34% of patients. PIVKA-II levels 40 mAU/ml were found in 91% of HCC patients and 73% of non-HCC patients, resulting in a sensitivity of 91% and specificity of 27%. The area under the ROC curve for PIVKA-II in diagnosing HCC was 0.752 (95% CI 0.652, 0.853), with an optimal cut-off of 180 mAU/ml. At this cut-off, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 79%, 67%, 55%, 86%, and 71%, respectively. The sensitivity and specificity at various other cut-off levels were inferior to 180. Conclusion: The standard cut-off of PIVKA-II (40 mAU/ml) for diagnosing HCC is not suitable for Indian patients. Our study determined a more appropriate cut-off of 180 mAU/ml, which requires further validation in prospective studies conducted in India.