Impending HCC diagnosis in patients with cirrhosis after HCV cure features a natural killer cell signature.
Hepatology
; 80(1): 202-222, 2024 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-38381525
ABSTRACT
BACKGROUND AND AIMS:
The risk of developing HCC in chronically infected patients with AQ2 HCV with liver cirrhosis is significantly elevated. This risk remains high even after a sustained virological response with direct-acting antivirals. To date, disease-associated signatures of NK cells indicating HCC development are unclear. APPROACH ANDRESULTS:
This study investigated NK cell signatures and functions in 8 cohorts covering the time span of HCC development, diagnosis, and onset. In-depth analysis of NK cell profiles from patients with cirrhosis who developed HCC (HCV-HCC) after sustained virological response compared with those who remained tumor-free (HCV-noHCC) revealed increasingly dissimilar NK cell signatures over time. We identified expression patterns with persistently high frequencies of TIM-3 and CD38 on NK cells that were largely absent in healthy controls and were associated with a high probability of HCC development. Functional assays revealed that the NK cells had potent cytotoxic features. In contrast to HCV-HCC, the signature of HCV-noHCC converged with the signature found in healthy controls over time. Regarding tissue distribution, single-cell sequencing showed high frequencies of these cells in liver tissue and the invasive margin but markedly lower frequencies in tumors.CONCLUSIONS:
We show that HCV-related HCC development has profound effects on the imprint of NK cells. Persistent co-expression of TIM-3hi and CD38 + on NK cells is an early indicator for HCV-related HCC development. We propose that the profiling of NK cells may be a rapid and valuable tool to assess the risk of HCC development in a timely manner in patients with cirrhosis after HCV cure.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Killer Cells, Natural
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Carcinoma, Hepatocellular
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Hepatitis C, Chronic
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Liver Cirrhosis
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Liver Neoplasms
Limits:
Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Hepatology
Year:
2024
Document type:
Article
Affiliation country: