Most hepatocellular carcinoma (HCC) cases were at advanced stage when diagnosis established. This study is intended to establish a clinical diagnostic model GAMAD for early-stage HCC and evaluate the diagnostic efficiency the same time. This study is a multicenter prospective study. Participants including healthy control,HCC, liver cirrhosis, hepatitis and benign tumor-like lesions are consecutively recruited into the cohort. All the blood samples are collected before any treatments and will be tested in single center in order to decrease bias.

GALAD score including age, sex, PIVKA-II(DCP), Alpha-fetoprotein (AFP) and alpha-fetoprotein L3 (AFP-L3), is a serum biomarker-based panel that can aid in early detection among patients with a high risk for liver cancer. While increasing studies showed the diagnostic accuracy of AFP-L3 was not as good as that of AFP or PIVKA-II, and AFP-L3 was not significant in the multivariable model. Thus, a model with better diagnostic accuracy and more suitable for Chinese patients is needed. Here, based on a multi-locus blood-based assay targeting circulating tumor DNA methylation, we aim to develop a novel diagnostic model--GAMAD (gender, age, methylation, AFP and DCP) and validate its performance among HCC patients and those at high risk of developing HCC,such as liver cirrhosis, hepatitis patients. This is a multicenter, observational, prospective study. After giving fully informed consent, the participants will undergo the regular treatment according to NCCN guidelines.

Inclusion Criteria:

• Age above 18
• Establishing Diagnosis according to the European Association for the Study of Liver(EASL) criteria
• High risk group of developing HCC including liver cirrhosis and hepatitis under the confirmed diagnosis
• Able to provide sufficient and qualified blood samples for study tests
• No prior or undergoing cancer treatment (local or systematic)
• Able to provide a written informed consent

Exclusion Criteria:

• Obstructive jaundice patients
• Medical history of taking warfarin
• With other known malignant tumors or multiple primary tumors
• Patients with autoimmune diseases, genetic diseases, mental diseases/ disabilities and other diseases considered unsuitable for the study by the investigator
• During pregnancy or lactation
• Recipient of blood transfusion within 3 months prior to study blood draw
• Insufficient qualified blood sample for study test

Patients must have baseline evaluations performed prior to the study and must meet all inclusion and exclusion criteria. In addition, the patient must be thoroughly informed about all aspects of the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent must be obtained from the patient prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).