Mutations in the NS5A gene predict response to interferon therapy in Japanese patients with chronic hepatitis C and cirrhosis
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Published on: June 9, 2022
S Murashima1, T Ide, I Miyajima
1Kurume University Research Center for Innovative Cancer Therapy, Japan.
Abstract:
The virus genotype, serum HCV-RNA level and liver histology are reported to be important factors in the response to interferon therapy. Recent studies have revealed that HCV NS5A 2209-2248 amino acid changes affect the response to interferon therapy of genotype 1b chronic hepatitis C. In contrast, some studies done in western countries have reported no such correlation. In the present study, interferon therapy was given to 58 Japanese patients, including 15 liver cirrhosis patients. NS5A 2209-2248 changes, the serum HCV level, ALT level, age and histology were examined in relation to the interferon effect. Twenty-four of the 58 patients (41%) showed a sustained virological response to the therapy. The responses to interferon therapy were significantly correlated with NS5A 2209-2248 changes (p < 0.0001), the HCV-RNA level (p < 0.0001) and histology (p < 0.0060). Among 15 liver cirrhosis patients, 3 of 6 mutant type patients showed a sustained virological response; 5 intermediate and 4 with wild type virus infected patients showed no responses. In conclusion, NS5A 2209-2248 changes may be a useful predictive marker of response to interferon therapy in addition to the serum HCV RNA level even in histologically advanced patients.
Insights
Hepatitis C virus (HCV) NS5A amino acid changes, along with viral load and liver histology, predict interferon therapy response in Japanese patients. These factors offer valuable insights for treatment efficacy, especially in advanced liver disease.
Area of Science:
- Hepatology
- Virology
- Genetics
Background:
- Interferon therapy response in chronic hepatitis C is influenced by virus genotype, serum HCV-RNA levels, and liver histology.
- Recent research indicates that specific amino acid changes in the Hepatitis C virus (HCV) NS5A protein (residues 2209-2248) may impact treatment outcomes for genotype 1b infections.
- Contrasting findings exist, with some Western studies reporting no correlation between these NS5A changes and interferon response.
Purpose of the Study:
- To investigate the correlation between HCV NS5A 2209-2248 amino acid changes, serum HCV-RNA levels, liver histology, and the effectiveness of interferon therapy in Japanese patients.
- To evaluate the predictive value of these factors, including in patients with liver cirrhosis.
Main Methods:
- A cohort of 58 Japanese patients, including 15 with liver cirrhosis, received interferon therapy.
- Analysis included examination of NS5A 2209-2248 amino acid variations, serum HCV-RNA levels, ALT levels, patient age, and liver histology.
- Sustained virological response (SVR) was assessed as the primary outcome measure.
Main Results:
- Twenty-four out of 58 patients (41%) achieved a sustained virological response to interferon therapy.
- Significant correlations were found between SVR and NS5A 2209-2248 changes (p < 0.0001), serum HCV-RNA levels (p < 0.0001), and liver histology (p < 0.0060).
- In liver cirrhosis patients, mutant NS5A types showed a higher SVR rate (3/6) compared to intermediate and wild-type infections (0/5 and 0/4, respectively).
Conclusions:
- HCV NS5A 2209-2248 amino acid changes represent a potential predictive marker for interferon therapy response.
- These genetic variations, alongside serum HCV RNA levels, may improve treatment outcome prediction, even in patients with advanced liver histology.
- The findings highlight the importance of considering viral genetic factors in tailoring hepatitis C treatment strategies.
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