Following this application, Wasenang et al. [25] developed a different approach to discriminate between CCA and non-tumoral biliary disease (i.e. chronic cholecystitis, cholangitis, cholelithiasis) relying on the methylation level of opioid binding protein cell adhesion molecule-like (OPCML) and 5’-Hoxd genes (HOXD9) as determined in cfDNA; the combined assessment showed high specificity and positive predictive value, suggesting that it could prevent misdiagnosis of CCA, thus potentially sparing unnecessary surgical procedures. The gene discussed is OPCML; the disease is cholangiocarcinoma.