IL28B, TLR7 SNPs, and cytomegalovirus infection are risk factors for advanced liver disease in chronic hepatitis C patients

ABSTRACT

BACKGROUND

Chronic hepatitis C (CHC) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). This study aimed to study the association of IL28B, toll-like receptor (TLR) 7, cytomegalovirus and advanced liver disease.

METHODS

Four groups were included; control (n = 125, 25.9%), CHC (n = 114, 23.6%), liver cirrhosis (n = 120, 24.8%), and HCC (n = 124, 25.7%).

RESULTS

In CHC group, patients were mainly F1 (60%) followed by F2. IL28B genotype CC percentage was higher in control group than the CHC and cirrhosis groups. CT and TT genotypes were higher in the CHC and cirrhosis groups than control group. The C allele was higher in the control group than the CHC, cirrhosis and HCC groups and the opposite with the T allele. Control and CHC had same TLR7 alleles. Cirrhosis patients and HCC had lower TLR 7 A allele and higher G allele than the control group. Both cirrhosis and HCC groups had statistically significant higher percentage of the AG and GG genotypes than the control group. Patients with HCC had higher cytomegalovirus infection percentage than cirrhosis and CHC group (38.7% vs 20% vs 16.7%), respectively.

CONCLUSION

IL28B, TLR7 SNPs and cytomegalovirus infection are risk factors for advanced liver disease in hepatitis C patients.

KEYWORDS:

• Hepatitis C virus
• cytomegalovirus
• toll-like receptor 7
• interleukin 28B
• hepatocellular carcinoma

Abbreviations

HCV, hepatitis C virus; CHC, chronic hepatitis C infection; HCC, hepatocellular carcinoma; PAMPs, pathogen-associated molecular patterns; PRRs, pattern recognition receptors; TLR, toll-like receptors; DAMPs, danger-associated molecular patterns; IFN, interferon; SNPs, single nucleotide polymorphisms; PEG/RBV, pegylated interferon/ribavirin; CMV, cytomegalovirus.

Expert Opinion

Hepatitis C virus infects the human liver in millions of patients worldwide. If viral eradication did not occur by using antiviral drugs, most patients will eventually progress to advanced disease, from chronic hepatitis, till cirrhosis and decompensation. The immune system recognizes viruses and bacteria released components (PAMPs) through receptors like the TLRs, that trigger an inflammatory cascade and release of interferons that help the viral clearance. In addition, IL28B gene encodes for INF-λ3 that hampers the viral replication. The SNPs C/C genotype favors spontaneous viral eradication in acute HCV infection and successful PEG/RBV antiviral therapy. The CMV virus may affect the liver causing acute hepatitis and poor graft survival post liver transplant. In our study, we postulated an association of IL28B, TLR7, CMV and the progression of the liver disease. Patients with advanced disease more CT/TT IL28B genotype and G allele TLR7. In patients with positive CMV infection, the development of liver cirrhosis and HCC was common.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

All authors shared in data collection, conception of the design, analysis, and paper writing. Final revision was approved by all authors. All authors agreed to be accountable for all aspects of the work.

Additional information

Funding

This paper was not funded.