Tauroursodeoxycholic Acid Combined With PD-1/PD-L1 Immunotherapy in Advanced Hepatocellular Carcinoma: A Prospective Study

This is a clinical trial that aims to evaluate whether adding a bile acid called tauroursodeoxycholic acid (TUDCA) can improve the effects of immunotherapy in patients with advanced liver cancer (hepatocellular carcinoma). Immunotherapy has shown promise in treating this type of cancer, but not all patients respond well. TUDCA is known to help protect liver cells and may improve the liver's immune environment, potentially making immunotherapy more effective. In this study, 300 patients with advanced liver cancer will be randomly assigned to receive either immunotherapy alone or immunotherapy combined with TUDCA. Researchers will look at how well the cancer responds, whether the treatment helps more patients become eligible for surgery, and how safe the combination is. The goal is to find a more effective and better tolerated treatment for patients with liver cancer.

Sex

All

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of primary hepatocellular carcinoma (HCC).

Unresectable advanced HCC classified as Barcelona Clinic Liver Cancer (BCLC) stage C.

Age ≥ 18 years.

No prior systemic anti-tumor therapy for HCC before first dose of study treatment.

At least one measurable lesion according to RECIST v1.1, or a measurable lesion with clear progression after local treatment based on RECIST v1.1.

Adequate organ and bone marrow function within 7 days prior to enrollment, with no blood products, growth factors, albumin, or other intravenous/subcutaneous corrective treatment within 14 days prior to laboratory assessment:

Hematology:

Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelet count (PLT) ≥ 75 × 10⁹/L Hemoglobin (Hb) ≥ 9.0 g/dL

Liver function:

Total bilirubin (TBil) ≤ 2 × ULN ALT and AST ≤ 5 × ULN Serum albumin ≥ 28 g/L

Alkaline phosphatase (ALP) ≤ 5 × ULN

Renal function:

Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50 mL/min (calculated by Cockcroft-Gault formula) Urinalysis shows urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine collection must show protein \< 1g/24h

Coagulation:

International Normalized Ratio (INR) ≤ 2.3 or prothrombin time (PT) prolongation ≤ 6 seconds

Estimated life expectancy of ≥ 12 weeks.

Exclusion Criteria:

History of hepatic encephalopathy or liver transplantation.

Acute cholecystitis, acute cholangitis, patients with frequent biliary colic attacks, complete biliary obstruction, or gallbladder dysfunction (inability to contract and empty).

Patients with Child-Pugh class C or decompensated cirrhosis, including those with a history of severe hepatic encephalopathy or refractory ascites due to liver disease.

Patients with a previous diagnosis of biliary atresia without adequate biliary drainage (e.g., failed biliary-enteric anastomosis).

Pregnant or breastfeeding women.

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