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Clin Infect Dis. 2018 Aug 31;67(6):869-877. doi: 10.1093/cid/ciy205.

Gut Dysbiosis Associated With Hepatitis C Virus Infection.

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Department of Clinical Laboratory Medicine, Nagoya City University Hospital.
Laboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka.
Third Department of Internal Medicine, Nara Medical University, Kashihara.
Department of Gastroenterology, Aichi Medical University School of Medicine, Nagakute.
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences.
Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Japan.



Little is known about the effect of hepatitis C virus (HCV) infection on gut microbiota and the relationship between alteration of gut microbiota and chronic hepatitis C (CHC) progression. We performed a comparative study of gut microbiota composition between CHC patients and healthy individuals.


Fecal samples from 166 CHC patients were compared with those from 23 healthy individuals; the gut microbiota community was analyzed using 16S ribosomal RNA gene sequencing. CHC patients were diagnosed with persistently normal serum alanine aminotransferase without evidence of liver cirrhosis (LC) (PNALT, n = 18), chronic hepatitis (CH, n = 84), LC (n = 40), and hepatocellular carcinoma in LC (n = 24).


Compared with healthy individuals, bacterial diversity was lower in persons with HCV infection, with a decrease in the order Clostridiales and an increase in Streptococcus and Lactobacillus. Microbiota dysbiosis already appeared in the PNALT stage with the transient increase in Bacteroides and Enterobacteriaceae. Predicted metagenomics of microbial communities showed an increase in the urease gene mainly encoded by viridans streptococci during CHC progression, consistent with a significantly higher fecal pH in CH and LC patients than in healthy individuals or those in the PNALT stage.


HCV infection is associated with gut dysbiosis, even in patients with mild liver disease. Additionally, overgrowth of viridans streptococci can account for hyperammonemia in CH and LC. Further studies would help to propose a novel treatment strategy because the gut microbiome can be therapeutically altered, potentially reducing the complications of chronic liver disease.


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