Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant...

Area of Science:

• Hepatology
• Virology
• Genomics

Background:

• Chronic hepatitis C virus (HCV) infection is a leading cause of liver failure and liver transplantation.
• Recurrent HCV infection post-transplant universally impacts grafts, rapidly causing severe fibrosis and end-stage liver disease in a significant portion of patients.
• Current clinical variables are insufficient for accurately predicting hepatic decompensation risk in transplant recipients.

Purpose of the Study:

• To identify a molecular signature predicting severe fibrosis development in HCV-infected liver transplant recipients.
• To determine if gene expression alterations precede histological evidence of liver disease progression.
• To uncover a common precursor state for diverse severe clinical outcomes.

Main Methods:

• Longitudinal analysis of transcriptomes from 111 liver biopsy specimens.
• Dimensionality reduction and categorical analysis of gene expression data from 57 HCV-infected patients.
• Correlation of molecular signatures with clinical and histological outcomes over time.

Main Results:

• A molecular signature of gene expression was identified in patients at risk of developing severe fibrosis.
• Significant alterations in gene expression were observed before histological evidence of liver disease progression.
• A common precursor molecular state was identified for different severe clinical outcomes.

Conclusions:

• Severe liver disease following HCV infection in transplant recipients is initiated early after donor organ infection.
• The study identified and characterized the probable cellular network underlying the initial transition to severe liver disease.