HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients

J Biomed Sci. 2021 Mar 30;28(1):23. doi: 10.1186/s12929-021-00718-6.


Objective: To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients.

Methods: We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) ≥ 1.5 (in either direction) and false discovery rate (FDR) ≤ 0.05 were identified as significantly differentially expressed (SDE).

Results: HIV/HCV-b showed six SDE genes compared to HIV-mono group, but no significantly enriched pathways were observed. For HIV/HCV-f vs. HIV/HCV-b, we found 58 SDE genes, 34 upregulated and 24 downregulated in the HIV/HCV-f group. Of these, the most overexpressed were CXCL2, PDCD6IP, ATP5B, IGSF9, RAB26, and CSRNP1, and the most downregulated were IFI44 and IFI44L. These 58 SDE genes revealed two significantly enriched pathways (FDR < 0.05), one linked to Epstein-Barr virus infection and another related to p53 signaling. For HIV/HCV-f vs. HIV-mono group, we found 44 SDE genes that revealed 31 enriched pathways (FDR < 0.05) related to inflammation, cancer/cell cycle alteration, viral and bacterial infection, and comorbidities associated with HIV/HCV-coinfection. Five genes were overrepresented in most pathways (JUN, NFKBIA, PIK3R2, CDC42, and STAT3).

Conclusion: HIV/HCV-coinfected patients who eradicated hepatitis C with IFN-based therapy showed profound gene expression changes after achieving sustained virological response. The altered pathways were related to inflammation and liver-related complications, such as non-alcoholic fatty liver disease and hepatocellular carcinoma, underscoring the need for active surveillance for these patients.

Keywords: Gene expression; HCV clearance; HIV/HCV coinfection; Immune system; Interferon therapy; PBMCs.

MeSH terms

  • Adult
  • Coinfection / prevention & control*
  • Female
  • Gene Expression*
  • HIV / drug effects
  • HIV Infections / prevention & control*
  • Hepacivirus / drug effects
  • Hepatitis C / prevention & control*
  • Humans
  • Interferons / therapeutic use*
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged


  • Interferons