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Hepatocyte expression of TRAIL pathway regulators correlates with histopathological and clinical parameters in

Sylvia Brost1, Anna Zimmermann1, Ronald Koschny1

  • 1Department of Gastroenterology, University Hospital Heidelberg, Germany.

Pathology, Research and Practice
|November 26, 2013
PubMed
Abstract

Insights

Hepatitis C virus (HCV) therapy involves pegylated interferon-alpha (PEG-IFN) and ribavirin. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression in HCV patients predicts treatment success.

Area of Science:

  • Hepatology
  • Immunology
  • Molecular Biology

Background:

  • Hepatitis C virus (HCV) infection is treated with pegylated interferon-alpha (PEG-IFN) and ribavirin, but mechanisms remain unclear.
  • The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) system, involved in immune responses and apoptosis, may play a role in HCV infection and treatment.
  • Investigating the TRAIL/TRAIL-receptor system, caspase-8, and cFLIP is crucial for understanding HCV pathogenesis and therapy response.

Purpose of the Study:

  • To analyze the expression of the TRAIL/TRAIL-receptor system, caspase-8, and cFLIP in HCV patients.
  • To determine the prognostic and predictive value of these molecules in HCV infection and antiviral therapy.

Main Methods:

  • Immunohistochemical analysis of liver biopsies from 116 therapy-naive HCV patients and healthy controls.
  • Correlation of TRAIL, TRAIL-R1 to TRAIL-R4, caspase-8, and cFLIP expression with sustained virologic response (SVR), HCV genotype, and liver disease stage.

Main Results:

  • Caspase-8, cFLIP, TRAIL-R2, and TRAIL-R4 were upregulated in HCV patients; TRAIL-R3 was downregulated.
  • High expression of TRAIL and pro-apoptotic TRAIL-R2 on hepatocytes correlated with sustained virologic response (SVR).

Conclusions:

  • The TRAIL system appears to have a pathophysiological role in both HCV infection and its treatment.
  • TRAIL-related pathways may represent potential therapeutic targets for future clinical applications in HCV management.
Keywords:
ApoptosisCMVCaspase-8DREBVEVREpstein–Barr virusFADDFAS-associated via death domainHCCHepatitis CIFNNF-κBPEG-IFNPLADRBVRVRSVRTNFTNF-related apoptosis inducing ligandTRAILTRAIL-R1TRAIL-R2TRAIL-R3TRAIL-R4TRAIL-receptorTRAIL-receptor 1TRAIL-receptor 2TRAIL-receptor 3TRAIL-receptor 4cEVRcFLIPcellular FLICE/caspase-8-inhibitory proteincomplete early viral responsecytomegalovirusdeath receptorearly virologic responsehepatocellular carcinomainterferonmIgGmouse IgGnuclear factor kappa BpEVRpartial early virologic responsepegylated interferon alphapreligand assembly domainrapid virologic responseribavirinsustained virologic responsetumor necrosis factor

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