High serum gamma-glutamyltransferase level after hepatitis C virus elimination is a risk factor for the development of hepatocellular carcinoma

Miyako Murakawa¹, Mina Nakagawa^{1

2}, Hisaaki Nishimura³, Shun Kaneko¹, Masato Miyoshi¹, Fukiko Kawai-Kitahata¹, Sayuri Nitta¹, Jun Tsuchiya¹, Taro Shimizu¹, Keiya Watakabe¹, Tomohiro Mochida¹, Kento Inada¹, Yasuhiro Iizuka⁴, Hideki Sakai⁴, Yuki Sakurai⁵, Ayako Sato⁶, Seishin Azuma⁶, Takahiro Kawamura⁷, Chiaki Maeyashiki⁸, Masayuki Kurosaki⁸, Fumihiko Kusano⁹, Hideki Watanabe¹⁰, Hitoshi Kurata¹¹, Yuko Karakama¹², Takeo Fujiwara³, Yuki Nagata¹³, Toshihiro Tanaka¹³, Sei Kakinuma^{1

14}, Ryuichi Okamoto¹, Yasuhiro Asahina^{1

15}

Affiliations

¹ Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
² Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan.
³ Department of Public Health, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Gastroenterology and Hepatology, Kashiwa Municipal Hospital, Chiba, Japan.
⁵ Department of Gastroenterology and Hepatology, Showa General Hospital, Tokyo, Japan.
⁶ Department of Gastroenterology and Hepatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
⁷ Department of Gastroenterology and Hepatology, JA Toride Medical Center, Ibaraki, Japan.
⁸ Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
⁹ Department of Gastroenterology and Hepatology, Tsuchiura Kyodo General Hospital, Ibaraki, Japan.
¹⁰ Department of Gastroenterology and Hepatology, Yokosuka Kyosai Hospital, Kanagawa, Japan.
¹¹ Department of Gastroenterology and Hepatology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan.
¹² Department of Gastroenterology and Hepatology, Tokyo Kyosai Hospital, Tokyo, Japan.
¹³ Department of Human Genetics and Disease Diversity, Tokyo Medical Dental University, Tokyo, Japan.
¹⁴ Department of Clinical and Diagnostic Laboratory Science, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁵ Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 39073391
DOI: 10.1111/hepr.14094

High serum gamma-glutamyltransferase level after hepatitis C virus elimination is a risk factor for the development of hepatocellular carcinoma

Miyako Murakawa et al. Hepatol Res. 2024 Dec.

. 2024 Dec;54(12):1128-1138.

doi: 10.1111/hepr.14094. Epub 2024 Jul 29.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
² Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan.
³ Department of Public Health, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Gastroenterology and Hepatology, Kashiwa Municipal Hospital, Chiba, Japan.
⁵ Department of Gastroenterology and Hepatology, Showa General Hospital, Tokyo, Japan.
⁶ Department of Gastroenterology and Hepatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
⁷ Department of Gastroenterology and Hepatology, JA Toride Medical Center, Ibaraki, Japan.
⁸ Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
⁹ Department of Gastroenterology and Hepatology, Tsuchiura Kyodo General Hospital, Ibaraki, Japan.
¹⁰ Department of Gastroenterology and Hepatology, Yokosuka Kyosai Hospital, Kanagawa, Japan.
¹¹ Department of Gastroenterology and Hepatology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan.
¹² Department of Gastroenterology and Hepatology, Tokyo Kyosai Hospital, Tokyo, Japan.
¹³ Department of Human Genetics and Disease Diversity, Tokyo Medical Dental University, Tokyo, Japan.
¹⁴ Department of Clinical and Diagnostic Laboratory Science, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁵ Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 39073391
DOI: 10.1111/hepr.14094

Abstract

Aim: Gamma-glutamyltransferase (GGT) is known as an oxidative stress marker, induced by alcohol consumption and metabolic disorders, and is reported as a predictor of hepatocellular carcinoma (HCC) development after hepatitis C virus (HCV) elimination. However, it is not clear whether GGT serves simply as a surrogate marker for overlapping metabolic diseases or reflects HCV-specific carcinogenicity. We investigated the association between GGT and hepatocarcinogenesis after achieving a sustained viral response (SVR), accounting for drinking habits or diabetes, and examined predisposing factors associated with GGT levels after SVR.

Methods: This is a prospective, multicenter, and observational study using the database of 1001 patients after HCV eradication with direct-acting antiviral agents. The association of GGT at SVR with cumulative HCC development was examined in a multivariate analysis using Cox proportional hazard models after adjustment for covariates including alcohol and diabetes. The association between oxidative stress markers or genetic factors and GGT levels was analyzed.

Results: High GGT levels at SVR were associated with HCC development (HR] 2.38, 95% CI 1.10-5.17). This association was also significant when restricted to patients without alcohol consumption or diabetes (HR 8.38, 95% CI 2.87-24.47). GGT levels were correlated with serum growth differentiation factor 15 levels, a marker of mitochondrial dysfunction. Single-nucleotide polymorphisms of ZNF827 and GDF15 were associated with high GGT levels.

Conclusions: High GGT levels at SVR were associated with HCC development after accounting for alcohol consumption and diabetes. GGT levels are influenced by genetic predisposition and may reflect mitochondrial dysfunction after HCV eradication.

Keywords: GDF15; GGT; HCC; HCV; SVR.

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References

REFERENCES

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High serum gamma-glutamyltransferase level after hepatitis C virus elimination is a risk factor for the development of hepatocellular carcinoma

Affiliations

High serum gamma-glutamyltransferase level after hepatitis C virus elimination is a risk factor for the development of hepatocellular carcinoma

Authors

Affiliations

Abstract

References

REFERENCES

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous