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Microbiology Research
Volume 17
Issue 7
10.3390/microbiolres17070120
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Article

A Cross-Sectional Study on the Association Between Hepatocellular Carcinoma and Gut Microbiota in Chronic Hepatitis B Virus Infection

by
Yusuke Tanaka
1,†,
Daiki Miki
1,*,†,
C. Nelson Hayes
1,
Yusuke Johira
1,
Ryoichi Miura
1,
Hatsue Fujino
1,
Atsushi Ono
1,
Eisuke Murakami
1,
Tomokazu Kawaoka
1,
Masataka Tsuge
1,2 and
Shiro Oka
1
1
Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
2
Liver Center, Hiroshima University Hospital, Hiroshima 734-8551, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work and share first authorship.
Microbiol. Res. 2026, 17(7), 120; https://doi.org/10.3390/microbiolres17070120 (registering DOI)
Submission received: 9 May 2026 / Revised: 12 June 2026 / Accepted: 22 June 2026 / Published: 23 June 2026
(This article belongs to the Special Issue Host–Microbe Interactions in Health and Disease)
Versions Notes

Abstract

There have been reports of an association between the gut microbiota and the development of chronic liver disease, fibrosis, and carcinogenesis; however, it is not yet possible to reach a definite conclusion. In this cross-sectional study, we examined the association between the presence or absence of hepatocellular carcinoma (HCC) and the gut microbiota in patients with chronic hepatitis B virus (HBV) infection. The study subjects consisted of 62 consecutive HBV patients admitted to our hospital who provided informed consent to participate in the study. We performed 16S rRNA analysis using DNA extracted from fecal pellets. The sequencing depth per sample was 80,000 to 90,000 reads. We calculated the proportion of each bacterial genus so that the total for each sample added up to 100%. The male-to-female ratio was 49/13, the median age was 67 years, and 46 of the patients had HCC. Twenty microbial phyla spanning 41 classes, 79 orders, 163 families, and 431 genera were identified. Receiver operating characteristic (ROC) analysis was performed on the identified bacterial taxa, from the level of phylum down to genus, to assess their ability to distinguish between patients with and without HCC. Several bacteria with an area under the curve (AUC) > 0.65 were identified as follows: TM7 phylum TM7-3 class (AUC = 0.700); Firmicutes phylum Clostridiales class Lachnobacterium genus, Dialister genus, Ruminococcus genus, and Roseburia genus (AUC = 0.670, 0.668, 0.667, and 0.660, respectively); and Firmicutes phylum Erysipelotrichi class (AUC = 0.656). Combining three of these taxa resulted in high discriminative power (p = 0.000585) with a sensitivity and specificity of 0.761 and 0.750, respectively. A similar trend was observed in the subgroup analysis based on liver reserve capacity. Even after adjusting for factors related to liver reserve capacity in the multivariate analysis, an association between these bacterial genera and HCC was confirmed. Our results suggest that gut microbiota may be associated with the prevalence of HCC in HBV patients.
Keywords: gut microbiota; hepatitis B virus; hepatocellular carcinoma gut microbiota; hepatitis B virus; hepatocellular carcinoma

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MDPI and ACS Style

Tanaka, Y.; Miki, D.; Hayes, C.N.; Johira, Y.; Miura, R.; Fujino, H.; Ono, A.; Murakami, E.; Kawaoka, T.; Tsuge, M.; et al. A Cross-Sectional Study on the Association Between Hepatocellular Carcinoma and Gut Microbiota in Chronic Hepatitis B Virus Infection. Microbiol. Res. 2026, 17, 120. https://doi.org/10.3390/microbiolres17070120

AMA Style

Tanaka Y, Miki D, Hayes CN, Johira Y, Miura R, Fujino H, Ono A, Murakami E, Kawaoka T, Tsuge M, et al. A Cross-Sectional Study on the Association Between Hepatocellular Carcinoma and Gut Microbiota in Chronic Hepatitis B Virus Infection. Microbiology Research. 2026; 17(7):120. https://doi.org/10.3390/microbiolres17070120

Chicago/Turabian Style

Tanaka, Yusuke, Daiki Miki, C. Nelson Hayes, Yusuke Johira, Ryoichi Miura, Hatsue Fujino, Atsushi Ono, Eisuke Murakami, Tomokazu Kawaoka, Masataka Tsuge, and et al. 2026. "A Cross-Sectional Study on the Association Between Hepatocellular Carcinoma and Gut Microbiota in Chronic Hepatitis B Virus Infection" Microbiology Research 17, no. 7: 120. https://doi.org/10.3390/microbiolres17070120

APA Style

Tanaka, Y., Miki, D., Hayes, C. N., Johira, Y., Miura, R., Fujino, H., Ono, A., Murakami, E., Kawaoka, T., Tsuge, M., & Oka, S. (2026). A Cross-Sectional Study on the Association Between Hepatocellular Carcinoma and Gut Microbiota in Chronic Hepatitis B Virus Infection. Microbiology Research, 17(7), 120. https://doi.org/10.3390/microbiolres17070120

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