CD4/CD8 Ratio could be predictor of burden hepatocellular carcinoma in Egyptian chronic hepatitis C after combined sofosbuvir and daclatasvir therapy

Afr Health Sci. 2023 Mar;23(1):198-212. doi: 10.4314/ahs.v23i1.22.

Abstract

Background: During the first years of the use of direct acting Hepatitis C antiviral drugs (DAAS), several studies reported a possible correlation between this new era of treatment and an increased risk of Hepatocellular carcinoma (HCC). Its development could possibly be favored by the changes in the immunological milieu and the different cellular behavior after eradication of HCV infection with them. For this reason, this study aimed to address the immunological effect of DAAS.

Subject & methods: Prospective paired -sample design, carried out on 90 naïve chronically infected HCV patients before and after receiving a combination therapy of sofosbuvir; at a dose of 400 mg once daily and daclatasvir; at a dose of 60 mg once daily for 12 weeks and follow up for one year. immunological tests including: total T cell count, T helper cell count, T cytotoxic cell count and natural killer cell count in peripheral blood through (CD3, CD3/CD4, CD3/CD8 and CD56 respectively) by Fluorochrome monoclonal antibodies labelled with specific dyes through Multiparameter, FACSCanto ™ II flow cytometer (Becton Dickinson, USA).

Result: Concerning the immunological changes, total T cells (CD3+), Natural killer cells showed non-significant decrease at end of therapy while significant decrease in T helper cells (CD3+CD4+) T cytotoxic cells (CD3+CD8+) compared to pre-treatment value. Long follow up revealed 26.6% developed focal HCC, in more addition, multivariate analysis show CD4/CD8 ratio could be predictor as well as sex for early development of HCC after combined DAAS therapy.

Conclusion: HCV treatment by DAAS produces significant decrease in T helper, T cytotoxic cells in CHC patients at the end of therapy. 26.6% developed focal HCC with independent CD4/CD8 predictor for burden malignancy. Further large extended population study is needed for clarify this concern.

Keywords: DAAS Therapy; HCV; T Cytotoxic; T helper; hepatocellular carcinoma; natural killer cells.

MeSH terms

  • Antiviral Agents / therapeutic use
  • CD8-Positive T-Lymphocytes
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Egypt / epidemiology
  • Hepacivirus
  • Hepatitis C, Chronic* / complications
  • Hepatitis C, Chronic* / drug therapy
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Prospective Studies
  • Sofosbuvir / pharmacology
  • Sofosbuvir / therapeutic use

Substances

  • Antiviral Agents
  • daclatasvir
  • Sofosbuvir