Earlier treatment for young patients with chronic hepatitis B more effective in clearing virus

Scientists from A*STAR's Singapore Institute for Clinical Sciences (SICS), together with clinical collaborators from London , discovered for the first time that children and young patients with chronic Hepatitis B Virus infection (HBV carriers) do have a protective immune response, contrary to current belief, and hence can be more suitable treatment candidates than previously considered.

This discovery by the team of scientists led by Professor Antonio Bertoletti, programme director and research director of the infection and immunity programme at SICS, could lead to a paradigm shift in the current treatment of patients with chronic HBV. The findings were published in Gastroenterology on 1st September.

Current guidelines from international liver associations recommend delaying therapy until HBV carriers show clear signs of active liver disease, which generally appear after the age of 30 . This is based on two assumptions. One, young patients are unable to react to treatment because they are immune-tolerant to the virus. This means that there is no protective immune response in their body to help them get rid of the virus, and therefore, they will not run the risk of liver damage or inflammation. Two, HBV infection is largely harmless in HBV carriers until active liver disease is apparent.

However, Professor Bertoletti and his team showed that young patients are not immune tolerant as they posses HBV-specific T cells with the ability to produce distinct antiviral cytokines that help the body fight against HBV. They also showed that the longer a patient is left untreated, the less effective their immune system becomes against HBV and the less able the patient will be able to clear the virus from their body even when they receive treatment.

The scientists demonstrated that the presence of HBV in the body over a long period of time is harmful to the patient due to repeated activation of T-cells which induces a progressive state of T-cell exhaustion, a state of immune system dysfunction that prevents optimal control of the infection and clearance of the virus from the body. Thus, young patients produce an immune response against HBV which is less compromised than that in older patients.

Professor Bertoletti said, "Young patients infected with HBV are most at risk of developing chronic HBV but current guidelines mean that they are also the least likely to be treated. However, our findings suggest that it might be better to start treatment early as young people with their stronger immune system, respond better to treatment and are more able to clear the virus."

Prof Judith Swain, Executive Director of SICS, said, "These findings may change the way treatment is applied to patients with HBV in hospitals in Singapore and throughout the world. This is a fine example of how clinicians, physician scientists, and scientists work together to improve healthcare for the public."

HBV infection affects 400 million people worldwide, 75% of whom reside in Asia. In Singapore, one in every 35 adult is a Hepatitis B carrier. Hepatitis B is the most common infection of the liver that is spread by direct contact with the blood or body fluids of an infected person. Not all HBV carriers display symptoms but lifelong infection carries the risk of serious health complications including cirrhosis, hepatocellular carcinoma, and liver failure.

The research findings described in this news release can be found in the volume 143 N 3 issue of Gastroenterology under the title "Preserved T-Cell Function in Children and Young Adults With Immune-Tolerant Chronic Hepatitis B", by Patrick Kennedy, Elena Sandalova, Juandy Jo, Upkar Gill, Ines Ushiro-Lumb, Anthony Tan, Sandhia Naik, Graham Foster, and Antonoio Bertoletti.

The paper can be accessed at http://www.gastrojournal.org/article/S0016-5085(12)00840-2/abstract.

AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR)

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Established in 2007, the Singapore Institute for Clinical Sciences (SICS) is a research institute within the Agency for Science, Technology and Research (A*STAR), and its mission is to develop disease-oriented clinical and translational research programmes in key disease areas.

SICS is distinguished by its focus on clinical sciences and the use of innovative approaches and technologies that enable the efficient and effective study of human health and diseases. The clinical scientists in SICS conduct the full spectrum of "bench to bedside" research activities in metabolic diseases (including diabetes, obesity and insulin resistance), pathways to normal growth and development (including cognitive and behavioural development), nutritional sciences as well as in certain viral infectious diseases such as chronic viral diseases.

The institute aims to attract, train and nurture clinician-scientists and to develop joint programs with universities, academic medical centres, government hospitals and research institutes.

For more information on SICS, please visit: www.sics.a-star.edu.sg

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy.

In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.

A*STAR oversees 20 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories.

Please visit www.a-star.edu.sg for more information about A*STAR.