ABSTRACT
Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in developed countries. The liver is the most prevalent site of metastasis from CRC. Currently, the gold-standard treatment for colorectal liver metastases (CLMs) is surgical resection. However, depending on the pattern of the disease, a significant number of patients may require different approaches alone or in combination with surgery, including thermal ablation (radiofrequency (RFA) or microwave (MWA) ablation) or transarterial liver-directed therapies, although the latter is not yet part of the standard treatment for CRC liver metastases. Methods and Results: We present the case of a 63-yearold man with bilobar CLM who was treated with transarterial embolization (TAE) and RFA followed by chemotherapy. A post-RFA study of immune parameters revealed the downregulation of CD39 expression in the circulating CD4+ T cell population and a reduction of the serum levels of cytokines IL-10, TGF-ß, IFN-gamma and IL-17, which positively correlated with the diminished serum level of gamma-glutamyl transferase (GGT) and the subdued inflammatory markers: the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). Later, the patient underwent chemotherapy. Liver failure developed within two years and nine months following tumour ablation, leading to the death of the patient. Conclusions: However, the denial of adjuvant chemotherapy by the patient gave us the opportunity to assess the immunomodulatory changes following RFA in the absence of any other therapeutic modalities.
ABSTRACT
BACKGROUND: T cell-mediated immune responses contribute to the hepatocellular injury during autoimmune hepatitis, viral infection, and hepatotoxins. Pharmacological compounds regulating immune responses are suitable candidates for prevention/treatment of this pathology. Therefore, the main aim of this study was to define the effects of antioxidant, anti-inflammatory mixture of citrus peel extract (CPE) on the immune-mediated liver injury. METHODS: The influence of CPE on liver injury was determined by the activity of transaminases in plasma and the histological changes. Anti-inflammatory and antioxidant effects were studied by measuring frequency of T regulatory cells (Tregs), cytokines (TNF-α, IL-10, and IFN-γ), and nitric oxide levels. RESULTS: The CPE application notably prevents development of liver injury through decreasing levels of both cytokines (TNF-alpha, INF) and regulatory T cells and increasing levels of IL-10. CPE injection also diminished the serum NO, which in turn resulted in evident reduction of the liver damage. CONCLUSION: Our findings represent the primary preclinical data indicating that the CPE in vivo could ameliorate Con A induced hepatitis. The low dose of CPE most likely can be used for the treatment of the T cell-mediated liver injury as in autoimmune hepatitis, alcoholic hepatitis, and chronic viral hepatitis.