The investigators design a large sample size study in the real-world to explore whether targeted therapy and immunotherapy can improve the survival, quality of life and drug safety of patients with advanced hepatobiliary tumors, and analyze the correlation between genetic variation and the effectiveness of therapy.

This trial is a multicenter, non-random, open and observational real-world study. It is estimated that 2000 patients with advanced hepatobiliary tumors will be enrolled in about 20 research centers. And it is planned to complete the enrollment within 2 years and it is expected that all enrolled subjects will reach the observation end point in 5 years.

After primary screening of all the patients, the investigators will further collect next-generation sequence(NGS) data and immunohistochemical data from the subjects, and enroll patients with any type of the following three treatment program: 1. Monotherapy or combination therapy with the targeted drug related to genetic variation of the subject; 2. Treatment with pan-target anti-angiogenic drugs, such as sorafenib, regorafenib, lenvatinib, apatinib, etc; 3. Immunotherapy or immunotherapy combined with targeted therapy.

The investigators will collect subjects' data from assessment centers each month and the efficacy, quality of life, and safety of treatment will be evaluated.

This trial plans to conduct an interim analysis and final analysis after collecting 500 cases, 1000 cases, and 2000 subjects, 3000 subjects,and explore the clinical application value of targeted therapy and immunotherapy in advanced hepatobiliary tumors in real world.

Inclusion Criteria:

Subjects must meet all of the following criteria：

1. ≥18 years old, gender is not limited, and life expectancy is at least 6 months.

2. Diagnosed as primary liver cancer or biliary malignant tumor by histopathology or confirmed by imaging as HCC (by the American Association for the Study of Liver Diseases or standard for the diagnosis and treatment of primary liver cancer 2017 in China).

3. The Barcelona staging classification: class B-C.

4. Child-Pugh classification: class A-B.

5. At least one measurable lesion (RECIST v1.1)

6. Unable to perform radical surgery or patient refuse surgery.

7. Subjects need palliative treatment, and have received or are undergoing any of the following three treatments:

   • Monotherapy or combination therapy with targeted drug associated with genetic variation in the subject.
   • Or, treat with pan-target anti-vascular drugs, such as sorafenib, regorafenib, lenvatinib, apatinib.
   • Or, immunotherapy or immunotherapy combined with targeted therapy or (and) classical chemotherapy.

8. Subjects volunteer to participate in the study and sign informed consent.

Exclusion Criteria:

Patients with one or more of the following criteria should be excluded:

1. Patients with early hepatobiliary tumor.
2. The Barcelona staging classification: class A.
3. Child-Pugh classification: class C.
4. Radical surgical resection.
5. CT or MRI shows unclear tumor boundary or no measurable lesions (RECIST v1.1).
6. Drug abuse, or any medical, psychological, or social condition that may affect the study, patient compliance, or even compromise the safety of the patient.
7. Conduct other experimental drug treatments other than this test within 4 weeks before the start of the study; or participate in another clinical study that has an impact on the results of this study.
8. Mental or medical instability makes patients unable or unwilling to sign informed consent.
9. Patients after comprehensive assessment are considered by the investigators to be unsuitable for participating in the study.

Patients With Advanced Hepatobilary Tumors.