Impact of Interferon Lambda 4 Genotype on Interferon‐Stimulated Gene Expression During Direct‐Acting Antiviral Therapy for Hepatitis C

• Published in: Hepatology (Baltimore, Md.) Vol. 68; no. 3; pp. 859 - 871
• Main Authors: Ramamurthy, Narayan, Marchi, Emanuele, Ansari, M. Azim, Pedergnana, Vincent, Mclean, Angela, Hudson, Emma, Bowden, Rory, Spencer, Chris C.A., Barnes, Eleanor, Klenerman, Paul
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health, Inc 01.09.2018; Wiley-Blackwell; John Wiley and Sons Inc
• Subjects: Antiviral Agents; Antiviral Agents - therapeutic use; Antiviral drugs; Cirrhosis; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genotype; Genotype & phenotype; Genotypes; Hepatitis; Hepatitis C; Hepatitis C - blood; Hepatitis C - drug therapy; Hepatitis C - genetics; Hepatology; Human health and pathology; Humans; Interferon; Interleukins; Interleukins - genetics; Life Sciences; Liver; Liver - metabolism; Liver Cirrhosis; Liver Cirrhosis - virology; Original; Peripheral blood; Phenotypes; Ribavirin; Ribavirin - therapeutic use; Sofosbuvir; Sofosbuvir - therapeutic use; Sustained Virologic Response
• ISSN: 0270-9139; 1527-3350; 1527-3350
• DOI: 10.1002/hep.29877

New directly acting antivirals (DAAs) provide very high cure rates in most patients infected by hepatitis C virus (HCV). However, some patient groups have been relatively harder to treat, including those with cirrhosis or infected with HCV genotype 3. In the recent BOSON trial, genotype 3, patients with cirrhosis receiving a 16‐week course of sofosbuvir and ribavirin had a sustained virological response (SVR) rate of around 50%. In patients with cirrhosis, interferon lambda 4 (IFNL4) CC genotype was significantly associated with SVR. This genotype was also associated with a lower interferon‐stimulated gene (ISG) signature in peripheral blood and in liver at baseline. Unexpectedly, patients with the CC genotype showed a dynamic increase in ISG expression between weeks 4 and 16 of DAA therapy, whereas the reverse was true for non‐CC patients. Conclusion: These data provide an important dynamic link between host genotype and phenotype in HCV therapy also potentially relevant to naturally acquired infection. (Hepatology 2018; 00:000‐000).