Low-level, interventional, biological and non-pharmacological study prospective intervention for the preparation of organotypic human liver slice cultures Liver Slice Culture (hLSC) applying the protocol described by Jiang and collaborators.

Human liver slice culture hLSCs will be used from non-tumor liver tissue collected by biopsy from patients undergoing abdominal surgery, who have signed informed consent and agree to perform a liver biopsy for the specific research protocol.

The study is "low level interventional" when a small portion (approximately 10 mm in diameter) of liver tissue macroscopically free from parenchymal alterations obtained in the open at the site of surgery for primary or secondary liver tumors will be taken (hepatic metastases from colorectal, pancreatic or breast cancer). The goal is to create organotypic liver cultures (hLSC) derived from liver biopsies taken from patients undergoing abdominal surgery.

for primary or secondary liver tumors for the molecular characterization of liver fibrosis.

Use hLSC to study the liver microenvironment and molecular determinants involved in fibrosis through single cell sequencing; compare the sequencing data obtained with hLSC with that obtained via characterization of a GEMM whose generation is foreseen in the same project financed by the MoS.

To generate this GEMM, the pro-fibrotic Hipk2 gene was specifically deleted in the tissue liver (HIPK2-liver knock-out, HIPK2-LKO) and liver fibrosis will be induced through a high-fat, low-choline diet.

Inclusion Criteria:

• age over 18 years old;
• patients for whom it is indicated to undergo abdominal surgery for tumors primary or secondary liver diseases;
• patients who express informed consent to the study.

Exclusion Criteria:

• medical contraindication to performing a liver biopsy;
• liver cirrhosis;
• macroscopic signs of chronic liver disease;
• moderate or severe steatosis;
• cholestasis;
• hepatic necrosis.

Biopsy sample in an area of liver macroscopically free from parenchymal alterations