4.7 Article

Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus-Infected Patients With or Without Human Immunodeficiency Virus Coinfection

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 224, Issue 8, Pages 1410-1421

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab094

Keywords

gut microbiota; DAAs; SVR; HCV; HIV; 16S rRNA

Funding

  1. Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University [RA62-033]
  2. Thailand Research Fund [RTA6280004]
  3. Center of Excellence in Hepatitis and Liver Cancer, Chulalongkorn University
  4. National Research Council of Thailand (NRCT)-Research Grants for Talented Young Researchers [NRCT5-RGJ63001-007]
  5. Second Century Fund (C2F), Chulalongkorn University
  6. National Institute of General Medical Sciences, National Institutes of Health [P20GM125503]

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The study found that direct-acting antivirals can improve gut microbiota dysbiosis in HCV-infected patients, with reduced microbial diversity and Firmicutes-Bacteroidetes ratio in those with HIV coinfection. Responders achieving sustained virological response showed better recovery of gut microbiota after treatment.
Background: The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)-infected patients with or without human immunodeficiency virus (HIV) is unclear. Methods: We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. Results: Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. Conclusions: This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

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