Nucleos(t)ide withdrawal in Hepatitis B virus infection (NUC-B)
Research type
Research Study
Full title
Nucleos(t)ide withdrawal in HBeAg negative hepatitis B virus infection to promote HBsAg clearance. (NUC-B)
IRAS ID
187932
Contact name
Mark Thursz
Contact email
Sponsor organisation
Imperial College London
Eudract number
2016-001010-17
Duration of Study in the UK
5 years, 5 months, 30 days
Research summary
Summary of Research
Hepatitis B virus (HBV) causes infection of the liver, either a severe infection with a shorter duration (acute) or a persistent longer term infection (chronic). Worldwide there are 350 million people with chronic HBV infection. Two types of treatment for chronic HBV infection are available: interferons or nucleoside/nucleotide analogues. Interferons are used for a finite period of time and treatment rarely results in elimination of the virus ie a cure. The majority of patients therefore choose to be treated instead with nucleos(t)ide analogues – tablets taken every day that cause no side effects, however, once started the majority of patients will need to continue taking them for the rest of their life.
There is evidence from a recent clinical trial that if treatment with nucleos(t)ide analogues is stopped after a few years of treatment/viral suppression some patients may be able to eliminate the virus. We therefore want to confirm the findings from this trial, following patients for at least three years after cessation of treatment and in addition use interferon in some of the patients at the time that the nucleos(t)ide analogue treatment is withdrawn to increase the immune response against the virus. Elimination of the virus is important because it represents cure of infection so all treatment can be safely discontinued.
We anticipate three outcomes for the trial patients. 1. Viral elimination (a cure), 2 A sustained virological response (their immune system can keep the virus at a low level) or 3. They might relapse and restart their nucleos(t)ide analogues. In future it will be important to be able to predict which patients have which outcome so as part of this trial we will measure a number of variables by testing patients’ liver and blood samples to predict which patients are most likely to benefit from which treatment.Summary of Results
Chronic hepatitis B is a long-term liver infection that can lead to serious complications, such as liver failure or cancer. A key goal of treatment is to achieve a “functional cure,” where the virus becomes undetectable in the bloodstream by the loss of a protein called HBsAg. Most people with hepatitis B take daily antiviral tablets, known as nucleos(t)ide analogues (NAs), to control the virus, but these rarely lead to a cure.
Our study, called NUC-B, tested whether adding a short course of a different medication - pegylated interferon (pIFN), which helps boost the immune system - could improve the chances of clearing the virus after stopping NA treatment.
The trial ran in the UK between 2017-2021 and included 156 adults with chronic hepatitis B who had no serious liver scarring and were a specific subtype known as HBeAg-negative. One group simply stopped taking their antiviral tablets. The other group also stopped treatment but then received weekly injections of pIFN for 16 weeks.
After three years, 14% of people who received pIFN cleared the virus (lost HBsAg), compared to only 3% in the group that stopped NA treatment alone. This shows that pIFN significantly increased the chance of a functional cure.
The group that received pIFN also had fewer severe flare-ups of hepatitis (13%) compared to the NA-only group (28%). About a third of patients in each group had to restart antiviral treatment, which is not unexpected.
Importantly, the number of serious side effects (called adverse events) was similar in both groups, suggesting that adding interferon was safe for most people in this setting.
This study suggests that a limited course of interferon after stopping antiviral pills could help some patients clear the hepatitis B virus more effectively, without adding significant safety risks.REC name
London - Central Research Ethics Committee
REC reference
16/LO/1318
Date of REC Opinion
26 Aug 2016
REC opinion
Further Information Favourable Opinion