Gut Dysbiosis Associated with HCV Infection

Takako Inoue, MD, PhD

New research finds patients with chronic hepatitis C (HCV) infection have lower bacterial diversity in their gut microbiota, even when their liver disease is less severe.

A team of researchers in Japan wanted to know more about the gut microbiota of patients with HCV, and what effect, if any, progression of HCV had on gut bacteria.

Takako Inoue, MD, PhD, vice director of the Department of Clinical Laboratory Medicine at Nagoya City University Hospital, told MD Magazine there were a number of reasons she and colleagues initially became interested in the topic of HCV’s effect on the gut microbiota.

For one, it was already known that HIV infection was associated with dysbiosis, and HCV was already known to cause general viremia. Therefore, she wondered if HCV might cause gut dysbiosis.

“Second, due to the anatomical location, the liver is exposed to gut-derived bacterial components,” Inoue said. “The gut microbial community is closely associated with the progression of liver diseases because of gut-liver circulation via the gut-microbiota-liver axis.”

Earlier research has shown that dysbiosis affects liver disease in a number of ways, including nonalcoholic fatty liver and nonalcoholic steatohepatitis.

“We guessed that to elucidate the relationship between gut microbiota and chronic hepatitis C (would be) valuable to know about bacterial ecology in the body,” Inoue said.

To investigate the relationship, the researchers looked at fecal samples from 166 chronic HCV patients and compared those samples to samples from 23 healthy patients. Those samples were examined via analyzed using 16S ribosomal RNA gene sequencing.

Among the HCV-infected patients, researchers noted lower bacterial diversity compared to the healthy control patients. HCV patients’ gut microbiota showed a decrease in the order Clostridiales and an increase in Streptococcus and Lactobacillus. Even patients in the persistently normal serum alanine aminotransferase (PNALT) phase of the disease showed evidence of dysbiosis. Inoue said that suggests dysbiosis is a result of HCV, rather than a pre-existing factor.

“PNALT patients show a significant increase in Enterobacteriaceae and genus Bacteroides compared with healthy individuals, a characteristic observed only in PNALT, not in advanced stages,” she said. “Based on these findings, I think that the altered gut microbiota is a result of HCV infection.”

As a caveat, however, Inoue noted that the study also found aging and/or high Fib-4 indexes also were correlated with changes in gut microbiota. Administration of proton pump inhibitors also had a marginal, though not statistically significant, effect on gut microbiota.

“Of course, advance of chronic hepatitis C (cirrhosis or hepatocellular carcinoma) can make gut microbiota altered,” Inoue added.

Further research is needed to find out what treatment options might be possible to alter the gut microbiota. In theory, Inoue and colleagues said it’s possible that treating the gut dysbiosis might lessen the severity of the underlying liver condition.

“If we can normalize the gut microbiota in patients with HCV infection, we think we can avoid endotoxemia and/or hyperammonemia,” Inoue said. “Therefore, we think normalization of the gut microbiota can be an innovative treatment.”

The study, “Gut Dysbiosis Associated With Hepatitis C Virus Infection,” was published online in Clinical Infectious Diseases.