How a functional cure for chronic hepatitis B can be achieved

Hepatitis B is an inflammation of the liver caused by the hepatitis B virus, which can lead to late effects such as liver cirrhosis or liver cancer. It is easily transmitted through body fluids. With around 350 million chronically infected people, it is one of the most common viral infections worldwide. People with chronic hepatitis B usually have to take lifelong medication to reduce the viral load and normalise the inflammation levels in the liver. Around half of those affected suffer from a so-called HBe antigen-negative form of the disease. Antiviral therapy consists of the administration of nucleoside or nucleotide analogues, which in almost all patients with an HBeAg-negative form leads to permanent immune control that allows treatment to be discontinued. This therapy is associated with high costs for the healthcare system and can cause side effects.

The results recently published in the Journal of Hepatology show in a multicentre, controlled randomised study with 166 HBeAg-negative patients from 20 clinics throughout Germany after 96 weeks of observation that discontinuation of at least four years of effective antiviral treatment led to immunological control of the disease in many patients. Immunological control was demonstrated in ten per cent of patients as a loss of previously detectable hepatitis B surface antigen (HBsAg) in the blood, an event that is considered a functional cure of hepatitis B. In 77 per cent of patients, no elevated liver inflammation values were detectable at the end of the study. In around 41 per cent, hepatitis B virus levels in the blood also fell below the 2,000 units per millilitre mark, which means that, according to international guidelines, there is no longer an indication for renewed antiviral therapy. In contrast, no HBsAg loss was observed in any patient who continued the therapy.

Study leader Professor Dr Florian van Bömmel, senior physician in the Department of Hepatology at Leipzig University Hospital, says: "We were able to show that interrupting long-term therapy with nucleoside or nucleotide analogues after at least four years is more effective for some patients than continuing it, and that many no longer need antiviral therapy after discontinuing it. Particularly in patients who have a low HBsAg level at the time of discontinuation, the chance of functional recovery after stopping long-term therapy is high.

After discontinuation of treatment, all patients initially experienced a resurgence of hepatitis B viruses and many also experienced temporary re-inflammation of the liver. In some patients with severe liver inflammation, antiviral therapy was then started again to prevent liver damage. Patients with liver cirrhosis were not allowed to be included in the study for safety reasons. No serious adverse events related to discontinuation of therapy occurred during the study.

In other studies, however, severe cases of liver inflammation have been observed in individual cases after discontinuation of antiviral therapy, which is why discontinuation should only take place under the supervision of an experienced doctor,

said the study leader.

Prof. Florian van Bömmel and Professor Thomas Berg, Head of the Department of Hepatology at Leipzig University Hospital, are certain that the results of the STOP-NUC study will have a major impact on the overall development of hepatitis B therapy: „We assume that international guidelines for the treatment of hepatitis B will refer to this study in the future. By the middle of this year, the results of the extension of the study will be evaluated, which will show whether the rate of patients with immunological control increases in the long-term course after discontinuation of antiviral treatment.

The STOP-NUC study (DRKS register number DRKS00006240) was funded by the German Federal Ministry of Education and Research (funding code: 01KG1308).

Press release of the "idw - Informationsdienst Wissenschaft" from 30 March 2023