Step-down affordable treatment for chronic hepatitis B infection in Africa and India Acronym - STEP-HEP

Chronic infection with the hepatitis B virus is common in the developing world. Without therapy a large proportion of those who are infected will develop liver disease (cirrhosis and liver cancer) that will lead to premature death. Effective treatments for hepatitis B are available but they are too costly for wide spread use in the developing world.
We plan to investigate a new approach to treating chronic hepatitis B. We will initiate therapy with an expensive, but very powerful, drug - tenofovir - and, when the hepatitis B is controlled, we will step down to a weaker, but much cheaper drug - lamivudine. We will ensure that this approach is safe by checking that anyone who does not respond to lamivudine can be effectively treated by the re-introduction of tenofovir.
The best way to monitor treatment in people with chronic hepatitis B is to measure the amount of virus in the blood using very sophisticated, expensive test. These tests are often not available in the developing world and we will therefore determine whether or not we can use simple, cheap tests of liver inflammation to monitor patients receiving treatment for hepatitis B.

This is a randomised, multicentre, blinded clinical trial examining the hypothesis that in patients with chronic HBV infection and active liver inflammation, 48 weeks induction therapy with tenofovir can be followed by successful transfer to lamivudine therapy in patients with a 'normal' ALT and any relapse can be controlled by reintroduction of tenofovir.
The trial will examine the safety and cost effectiveness of this induction maintenance regime as well as evaluating the value of monitoring therapy by liver function tests rather than viral load measurements.

This pivotal trial has the potential to change the approach to chronic hepatitis B in the developing world. Given that current therapies are too expensive for wide spread use there is little incentive to screen for the disease and very poor awareness of chronic hepatitis B. The development of an affordable, practical, effective therapeutic regime is likely to lead to a step change in the approach to hepatitis B with many more patients receiving effective therapy leading to increased awareness and increased testing and treatment with a concomitant reduction in avoidable mortality.

At present lamivudine (the cheapest drug for treating chronic hepatitis B) is widely used as there are no affordable alternatives. The drug induces resistance in 70% of treated patients after 5 years and there is concern that the widespread use of this drug may lead to multidrug resistant hepatitis B and, potentially, vaccine resistant virus. If our approach is effective this significant risk can be avoided.

Although our study is aimed at developing nations the burden of chronic hepatitis B in the developed world is not inconsiderable and this cost effective strategy may become a global standard of care.