Predicting hepatitis C treatment success

A combined therapy using interferons and ribavirin is often used to treat chronic hepatitis C, but around half of patients are unresponsive and suffer relapse. Previous research has shown that variations in a gene called interleukin 28B (IL28B) render a patient either sensitive to treatment or completely resistant to it.

However, the mechanisms relating the IL28B gene to the treatment are not well understood.

Now, Shuichi Kaneko and colleagues at Kanazawa University have discovered that, in therapy-resistant patients, interferon-stimulated gene (ISG) expression is up-regulated in the liver but down-regulated in the blood – a significantly different pattern of ISG expression to therapy-responsive patients. 

The team analyzed liver and blood samples from hepatitis C patients taken before treatment, and found that fewer immune cells reached the livers of patients with the therapy-resistant genotype. 

The team believe this lack of immune cells may induce higher levels of other inflammatory proteins, such as WNT5A. Higher WNT5A levels in the therapy-resistant patients both enhanced the expression of ISGs in the liver and increased hepatitis C viral replication. The researchers hope that further research will clarify these mechanisms with regard to treatment response. 

In the meantime, measuring ISG expression patterns in blood and liver samples could provide a useful way of predicting a patient’s response to interferon / ribavirin therapy. 

Further information:
Organization of Frontier Science and Innovation
Kanazawa University
Kakuma, Kanazawa, Ishikawa 920-1192, Japan
E-mail: fsojimu@adm.kanazawa-u.ac.jp

Website: http://www.o-fsi.kanazawa-u.ac.jp/en   

About Kanazawa University

Kanazawa University, Japan publishes the May 2014 issue of its online newsletter, Kanazawa University Research Bulletin: http://www.kanazawa-u.ac.jp/research_bulletin/index.html

Kanazawa University Research Bulletin highlights the latest research from one of Japan's leading comprehensive universities with its three colleges and 16 schools offering courses in subjects that include medicine, computer engineering, and humanities.

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 16 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa—a city rich in history and culture. The city of Kanazawa has cultivated a highly respected intellectual profile since the time of the Kaga fiefdom (1598–1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 12,200 students including 500 from overseas.

Kanazawa University website: http://www.kanazawa-u.ac.jp/e/index.html

Associated links

• Kanazawa University Research Bulletin
• Kanazawa University

Journal information

M. Honda1,2, T. Shirasaki2, T. Shimakami1, A. Sakai1, R.Horii1, K. Arai1, T. Yamashita1, Y. Sakai1, T. Yamashita1, H. Okada1, K. Murai1, M. Nakamura2, E. Mizukoshi1 & S. Kaneko1. Hepatic interferon-stimulated genes are differentially regulated in the liver of chronic hepatitis C patients with different interleukin-28B genotypes. Hepatology (2014).
DOI: 10.1002/hep.26788

1 Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
2 Department of Advanced Medical Technology, Kanazawa University Graduate School of Health Medicine, Kanazawa, Japan.

* Corresponding author email: Shuichi Kaneko: skaneko@m-kanazawa.jp