Gut Dysbiosis May Be Alleviated After DAA Treatment for Hepatitis C Virus Infection

Gut dysbiosis was found to be alleviated in patients with hepatitis C virus (HCV) with or without HIV coinfection who achieved sustained virologic response (SVR) after 12 weeks of treatment with elbasvir/grazoprevir, particularly in patients with early-stage fibrosis, according to results of a Thai study published in The Journal of Infectious Diseases.

In this longitudinal study (ClinicalTrials.gov Identifier: NCT03037151) conducted at a hospital in Bangkok, Thailand, researchers assessed the influence of direct-acting antivirals on gut microbiota by analyzing and comparing microbial diversity and composition in 62 patients with HCV and 24 patients with HIV coinfection vs 20 adults with neither infection in a control group. Patients were treated with elbasvir/grazoprevir and were followed for 12 weeks to assess SVR12 as defined by HCV RNA level less than 12 IU/mL.

At baseline, there was no difference in biochemical parameters except for higher levels of aspartate aminotransferase and alanine aminotransferase among the patients with HCV monoinfection  and HCV/HIV coinfection compared with those in the control group (P =.001 and P =.002, respectively). Compared with the control group, patients with HCV and HCV/HIV coinfection combined had lower Chao1 and Shannon indices (P <.001 and P =.038, respectively). There was no difference in the Simpson index between the groups.

When considering bacterial composition in all patients at baseline, Lachnospiraceae and Coriobacteriaceae were significantly lower among patients with HCV and HCV/HIV coinfection, while Enterobacteriaceae was significantly lower among those in the control group. Patients with HCV/HIV coinfection also had a lower Firmicutes/Bacteroidetes ratio compared with those who had HCV monoinfection (adjusted P =.020) and those in the control group (adjusted P =.008).

At 12 weeks’ follow-up, SVR was achieved in 98.4% (61/62) of the patients with HCV and 95.8% (23/24) of those with HCV/HIV. Moreover, in both treatment groups there was no difference in Chao1, Shannon, and Simpson indices vs the control group. Compared with stage 2, 3, and 4 fibrosis, those with stage 1 fibrosis had better improvement in Chao1 index (P =.013).

Bacterial composition in patients who achieved SVR12 showed a significant increase in Parabacteroides (P =.044) and Subdoligranulum (P =.011) but a reduction in Eubacterium (P <.001). Eubacterium significantly decreased in patients with HCV monoinfection and in those with HCV/HIV coinfection (P <.001 for both). In addition, there was a significant increase in Lachnospira and Subdoligranulum among patients with HCV/HIV coinfection (P =.014 and P =.023, respectively).

When comparing different fibrosis stages in patients who achieved SVR, Eubacterium was found to be significantly decreased across all fibrosis stages. Patients with stage 1 fibrosis had a significant increase in Phascolarctobacterium (P =.029), and patients with stage 2, 3, and 4 fibrosis had a significant increase in Subdoligranulum (P =.014).

Limitations of this study included a short follow-up period and the relatively small number of individuals with HCV/HIV coinfection.

In the present study, “…we extend clinically significant evidence that early initiating treatment not only prevents liver disease progression over time but could also improve gut dysbiosis approaching healthy controls,” the researchers noted. Further research is needed to investigate whether gut microbiota improvement is linked with reducing long-term HCV-related complications, they added.

Disclosure: Yasuhito Tanaka is currently conducting research funded by Janssen Pharmaceutical K.K. and has received an honorarium from Gilead Sciences.

Reference

Chuaypen N, Jinato T, Avihingsanon A, et al. Improvement of gut diversity and composition after direct-acting antivirals in HCV-infected patients with or without HIV coinfection. J Infect Dis. Published online February 17, 2021. doi:10.1093/infdis/jiab094