TGF β1 negatively impacts liver regeneration under chemotherapy

Abstract Background: In the modern surgical and chemotherapy era metastatic liver disease is in the renaissance, enabling to extend patient's life with metastatic liver disease. However, the primary limiting factor to more radical surgical treatment is liver volume, particularly in patients with chemotherapy-induced liver damage. Since results regarding whether chemotherapy has an impact on liver volume regeneration are ambiguous, we have aimed to analyze liver regeneration and the factors influencing it. Methods: A prospective cohort study was performed. Patient inclusion criteria were as follows: patients between 18 and 90 years; liver resection of at least 2 segments either for benign or colorectal cancer metastasis; patients who underwent liver resection due to metastatic disease had to have previous chemotherapy treatment. All patients were divided into 2 groups – control and chemotherapy groups. Analysis of demographics, perioperative data, liver enzymes, liver stiffness, and liver volume was carried out, as well as the impact on regeneration marker expression in serum and liver tissue. Results: 34 patients in all were involved in this trial, and they were split into two groups: chemotherapy and control. The two groups were similar. Except for comorbidities, there were no variations between the perioperative and demographic data. In the chemotherapy group, regenerated liver volume was lower compared to control, 1240.5±69.6 vs 1525.3±106.6 ml p-0.039. Further analysis revealed that the chemotherapy group had increased anti-regenerative TGF β1 expression compared to control in serum and liver tissue, p-0.02 and p-0.034. Conclusions: The present study showed that chemotherapy is associated with lower regenerated volume in patients who received resection. Anti-regenerative TGFβ1 marker expression in liver tissue and serum might have an impact on regenerated liver volume, however, the exact mechanisms involved in decreased regeneration are further to be studied.