{'fraction_non_alphanumeric': 0.02155992390615092, 'fraction_numerical': 0.006975269499048827, 'mean_word_length': 5.297405189620759, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Editorial: the role for PIVKA‐II measurement after HCV elimination by direct‐acting anti‐virals in terms of prediction of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth leading cause of malignancy and the third most common cause of cancerrelated death worldwide.1 The main causes of HCC continue to be hepatitis B virus and hepatitis C virus (HCV). HCV cure by directacting antivirals (DAAs) leads to an improved outcome, irrespective of the stage of liver disease, with a favourable safety profile and a sustained virological response rate exceeding 90% in clinical practice.2 However, the risk of the development of HCC remains significant after HCV cure, especially for patients with cirrhosis. Various background factors related to the development of HCC after HCV cure include age, alcohol abuse, serum albumin and FIB4 index.3,4 Degasperi et al in a singlecentre, retrospective study evaluated the potential of protein induced by vitamin K absence or antagonistII (PIVKAII) to predict which patients with cirrhosis will develop HCC after DAA treatment.5 They reported, using baseline and end of treatment (EOT) data, that EOTPIVKAII would be useful as a predictive biomarker. Liebman et al first reported PIVKAII,6 also known as desγcarboxy prothrombin, to be a highly specific marker for HCC, with a commonly used cutoff level of 40 mAU/ml.7 In general, PIVKAII promotes proliferation and migration8 and induces the overexpression of epithelial growth factor receptor and vascular endothelial growth factor.9 Accordingly, the production of PIVKAII by HCC cells could induce angiogenesis in surrounding liver tissue and thus promote vascular invasion. According to the Degasperi group's report, approximately one third of their patients who had PIVKAII>100 mAU/ ml at baseline developed HCC during the shortterm followup period. However, given the high specificity of PIVKAII measurement for HCC, it is possibile that HCC nodules already existed at the time of DAA initiation. A sensitivity analysis focused on patients without high level of PIVKAII and/or alphafetoprotein (AFP) at baseline would enhance understanding. AFP is currently the most frequently used method for HCC surveillance worldwide. However, even with the most efficient cutoff value, its diagnostic sensitivity for HCC is only 60%10 because pathological elevation of AFP is seen not only in hepatocarcinogenesis but also in hepatocyte regeneration within a fibrotic liver.7 In fact, the authors showed a significant decline in the total AFP level after DAA treatment, which was not found for the longitudinal PIVKAII level. Therefore, many studies, including the current study, have shown the utility of EOTAFP level as a surveillance tool for predicting HCC. The early diagnosis of HCC is essential to ensure that curative treatment can be implemented in a timely manner to improve the survival of patients with cirrhosis. Unless further research shows new evidence of a role for PIVKAII measurement as a predictor of HCC after HCV cure, its value will continue to be as a diagnostic tool for monitoring the progress of patients after DAA administration.