Professor Ed Gane
Australia and New Zealand need to step up their support of hepatitis B control programs in the Asia Pacific region.
Delivering the Trans-Tasman Lecture at Australian Gastroenterology Week 2018 in Brisbane, Professor Ed Gane said a coordinated regional and global approach was required to eradicate hepatitis B.
High-income countries would need to assist lower income countries that carry the highest burden of disease.
Professor Gane, from the University of Auckland, told the meeting that 3.9% of the world’s population was living with chronic hep B with the highest prevalence countries in Asia and sub-Saharan Africa.
He said the WHO hepatitis elimination strategy had very ambitious targets including a 90% reduction in incidence and a 65% reduction in deaths by 2030.
“For this to be global, you need political will and public support as the countries which carry the highest burden are the low-income countries. They need funding and treatment needs to be affordable.”
But hepatitis B was a ‘harder nut to crack than hepatitis C’, he said.
“I think this can be achieved for chronic hepatitis B. We have superb vaccination that is very effective in preventing hepatitis B and we also have good antivirals which prevent progression to complications, cirrhosis and deaths from liver cancer.”
Vaccination highs and lows
A recent study in Taiwan, the first country in the world to introduce universal neonatal vaccination, had shown a drop off in hepatitis B prevalence from 9.7% prior to the program to less than 1%.
“But we are still seeing people in high endemic areas contracting hepatitis B at birth or during childhood.”
Recent modelling showed while most regions of the world were meeting targets for the three doses of childhood vaccine (87% overall), there was less success with timely birth doses of prophylaxis (46%) and with antiviral treatment of pregnant women with a high viral load in their third trimester (<1%).
He said the birth dose, which was probably the most important dose to prevent transmission, should be given within 12 hours.
“Overall less than half of infants are getting this and although we are doing well here, we are not doing so well in other regions. We still have high rates of hepatitis B in children because of the lack of birth dose vaccination.”
Professor Gane said while New Zealand had ‘pretty much stopped childhood transmission – a great achievement’, the number of adults with hepatitis B was continuing to rise by about 1,000 each year.
The situation reflected migration from Southeast Asia, China and Pacific island nations such as Samoa and Tonga.
“With current trends, over half our population will be either Polynesian or Asian in the next 20 years. The same thing is happening here in Australia,” he said.
“If you roll out the three infant doses, it has some effect in a large European population. But what you have to do to reduce the prevalence of hepatitis B in this country, as in New Zealand, is to reach out to where the people are coming from and in our region that is the Asia Pacific. If you do so, you will have a dramatic effect on the number of people living in this country with hepatitis B.”
It was possible to reduce the rates of carriage in new immigrants to Australia and New Zealand by 50% within five years, according to Professor Gane.
He said New Zealand was involved in setting up a hepatitis B testing and surveillance program in Samoa, which would hopefully roll out to Tonga. Australians were doing similar work in Kiribati.
“Hepatitis B will be eradicated through vaccination but it is going to take a very long time. Even with birth dosing of all infants it is going to take 90 years with vaccination alone to eradicate hepatitis B and during that time you are going to have 80 million deaths related to HBV and the vast majority are going to be from liver cancer.”
Treatment advances
Currently only 5-10% of people infected with hepatitis B received long-term anti-viral therapy, Professor Gane told the conference.
“We have great treatments but they are not perfect. They do prevent progression, they do halt decompensation but treatment is life-long. It has a cost, which is prohibitive even with generics, and there is the risk of toxicity in older patients and huge risks of non-compliance and failure. Even in those people we put on life-long treatment, many still go on to develop liver cancer.”
“Hepatitis B is not hepatitis C; hepatitis C was easy. With hepatitis B you have a cccDNA and integrated DNA so you need lifelong suppression. That is the problem. What we need is a complete cure – getting ride of the reservoir in the nucleus.”
He said there had an explosion of knowledge about the virology and immunology of the disease, which had created a number of targets for small molecules and the potential for curative treatment.
New kids on the block included core inhibitors, siRNAs, nucleic acid polymers, gene editing and transcription inhibition.
“We are going to need combinations which turn off transcription and then we need immunostimulants such as checkpoint inhibitors. Next year there are ten combination studies – combining different classes of drugs – aimed at a hepatitis B cure, so we are going to get results very quickly.”
Professor Gane concluded with a message to pharma companies calling for new treatments to be of short duration – ‘it can’t be five years’, convenient – ‘it can’t be intravenous’, and affordable especially for the countries which carry the highest burden of disease.
“If you are going to design a cure it has to be a cure for everyone,” he concluded.