entecavir
Sources réglementaires consultées
Indications approuvées
- Traitement de l’hépatite B chronique chez l’adulte avec maladie compensée ou décompensée et chez les patients pédiatriques autorisés avec maladie compensée.
Contre-indications
Absolues
- Hypersensibilité à l’entécavir.
Mises en garde cliniques
- L’arrêt peut provoquer une exacerbation sévère de l’hépatite B ; surveiller la fonction hépatique plusieurs mois. — CIMA/AEMPS, ficha técnica 06343003
- Confirmer le statut VIH avant l’instauration. En cas de coinfection non traitée, l’entécavir peut sélectionner une résistance du VIH. — CIMA/AEMPS, ficha técnica 06343003
Interactions médicamenteuses
- SévèreMédicaments altérant la fonction rénale ou concurrençant la sécrétion tubulaire
Mécanisme: Ils peuvent augmenter l’exposition à l’entécavir.
Recommandation: Surveiller la fonction rénale et la toxicité.
CIMA/AEMPS, ficha técnica 06343003
Effets indésirables
Communs (≥1%)
Céphalées, fatigue, vertiges et nausées
Rares mais graves
Acidose lactique, hépatomégalie avec stéatose et exacerbation sévère de l’hépatite B
Grossesse et allaitement
Ne l’utiliser pendant la grossesse qu’en cas de nécessité évidente. Décider d’interrompre l’allaitement ou le traitement selon le bénéfice clinique.
Bibliographie récente (PubMed)
Hepatitis D virus (HDV) infection occurs in association with hepatitis B virus (HBV) infection and affects approximately 12 million to 72 million people worldwide. HDV causes more rapid progression to cirrhosis and higher rates of hepatocellular carcinoma than HBV alone or hepatitis C virus. HDV requires HBV to enter hepatocytes and to assemble and secrete new virions. Acute HDV-HBV coinfection is followed by clearance of both viruses in approximately 95% of people, whereas HDV superinfection in an HBV-infected person results in chronic HDV-HBV infection in more than 90% of infected patients. Chronic hepatitis D causes more rapidly progressive liver disease than HBV alone. Approximately 30% to 70% of patients with chronic hepatitis D have cirrhosis at diagnosis and more than 50% die of liver disease within 10 years of diagnosis. However, recent studies suggested that progression is variable and that more than 50% of people may have an indolent course. Only approximately 20% to 50% of people infected by hepatitis D have been diagnosed due to lack of awareness and limited access to reliable diagnostic tests for the HDV antibody and HDV RNA. The HBV vaccine prevents HDV infection by preventing HBV infection, but no vaccines are available to protect those with established HBV infection against HDV. Interferon alfa inhibits HDV replication and reduces the incidence of liver-related events such as liver decompensation, hepatocellular carcinoma, liver transplant, or mortality from 8.5% per year to 3.3% per year. Adverse effects from interferon alfa such as fatigue, depression, and bone marrow suppression are common. HBV nucleos(t)ide analogues, such as entecavir or tenofovir, are ineffective against HDV. Phase 3 randomized clinical trials of bulevirtide, which blocks entry of HDV into hepatocytes, and lonafarnib, which interferes with HDV assembly, showed that compared with placebo or observation, these therapies attained virological and biochemical response in up to 56% o
Hepatitis B virus (HBV) infection affects an estimated 254 million people worldwide and causes approximately 1.1 million deaths annually. In 2022, there were approximately 1.2 million new HBV infections worldwide and 14 000 in the US. HBV is a DNA virus transmitted through percutaneous or mucosal exposure to infected blood, semen, or body fluids. Mother-to-child transmission, which is the principal cause of chronic HBV infection globally, occurs in 70% to 90% of infants born to mothers who are hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive and in 5% to 20% of those born to HBsAg-positive/HBeAg-negative mothers. However, HBV vaccination and administration of hepatitis B immune globulin within 12 to 24 hours of birth prevent approximately 94% of perinatal infections, and adding antiviral therapy in pregnant women with high HBV DNA reduces transmission to less than 1%. Although universal birth-dose HBV vaccination is the most effective strategy for eliminating HBV infection, global birth-dose HBV vaccine coverage was only 45% in 2024. The risk of developing chronic infection (HBsAg positive for more than 6 months) is 90% if HBV infection occurs during infancy, 30% in children aged 1 to 5 years, and less than or equal to 5% in immunocompetent adolescents and adults. HBV infection is diagnosed by serologic testing: HBsAg indicates ongoing infection, antibody to HBsAg indicates immunity, and antibody to hepatitis B core antigen indicates ongoing or past infection. Serum HBV DNA levels quantify virus-replication activity. Assessment of liver inflammation and fibrosis with alanine aminotransferase (ALT) and noninvasive tests such as Fibrosis-4 index and liver elastography guide treatment decisions. Chronic HBV infection may progress to cirrhosis and hepatocellular carcinoma (HCC); the 5-year cumulative risk of cirrhosis is 8% to 15% in untreated chronic HBV infection, and annual HCC incidence is 3% to 5% among patients with cirrhosis. Antivir
Functional cure of hepatitis B is defined as sustained undetectable circulating HBsAg and HBV DNA after a finite course of treatment. Barriers to HBV cure include the reservoirs for HBV replication and antigen production (covalently closed circular DNA [cccDNA] and integrated HBV DNA), the high viral burden (HBV DNA and HBsAg) and the impaired host innate and adaptive immune responses against HBV. Current HBV therapeutics, 1 year of pegylated-interferon-α (PEG-IFNα) and long-term nucleos(t)ide analogues (NUCs), rarely achieve HBV cure. Stopping NUC therapy may lead to functional cure in some Caucasian patients but rarely in Asian patients. Switching from a NUC to IFN after HBV DNA suppression increases the chance of HBsAg clearance mainly in those with low HBsAg levels. Novel antiviral strategies that inhibit viral entry, translation and secretion of HBsAg, modulate capsid assembly, or target cccDNA transcription/degradation have shown promise in clinical trials. Novel immunomodulatory approaches including checkpoint inhibitors, metabolic modulation of T cells, therapeutic vaccines, adoptive transfer of genetically engineered T cells, and stimulation of innate and B-cell immune responses are being explored. These novel approaches may be further combined with NUCs or PEG-IFNα in personalised strategies, according to virologic and disease characteristics, to maximise the chance of HBV cure. The development of curative HBV therapies should be coupled with the development of standardised and validated virologic and immunologic assays to confirm target engagement and to assess response. In addition to efficacy, curative therapies must be safe and affordable to meet the goal of global elimination of hepatitis B.
Despite the availability of vaccines, hepatitis B remains a significant cause of fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The increase in reported hepatitis B cases in Germany is attributed to factors such as immigration and the hepatitis B surface antigen (HBsAg) screening introduced in 2020 as part of health check-ups. The indication for treatment depends on various factors, including the level of hepatitis B virus (HBV) DNA and inflammatory activity. Nucleos(t)ide analogues are the preferred treatment option, but functional cure, defined as HBsAg loss, is rare. In principle, treatment with nucleos(t)ide analogues should usually be discontinued after loss of HBsAg, but can be stopped earlier under certain conditions and is currently the subject of ongoing research. Pregnancy and immunosuppression in the context of hepatitis B require special attention. In addition, a possible hepatitis D virus co-infection must always be taken into account, which is why every HBsAg-positive person should be tested for anti-HDV. Since 2020, the entry inhibitor bulevirtide has become a new treatment option alongside pegylated interferon alfa, which represents a significant advance in the treatment landscape. Trotz der Verfügbarkeit von Impfstoffen bleibt die Hepatitis B weltweit eine bedeutende Ursache für fulminante Hepatitis, Leberzirrhose und Leberzellkarzinom. Der Anstieg der gemeldeten Hepatitis-B-Fälle in Deutschland wird auf Faktoren wie Zuwanderung und das 2020 eingeführte Hepatitis-B-Oberflächenantigen(HBsAg)-Screening im Rahmen der Gesundheitsuntersuchungen zurückgeführt. Die Indikation zur Behandlung hängt von verschiedenen Faktoren ab, unter anderem von der Höhe der Hepatitis-B-Virus(HBV)-DNA und der Entzündungsaktivität. Nukleosid- bzw. Nukleotidanaloga sind die bevorzugte Behandlungsoption, aber funktionelle Heilungen, definiert als HBsAg-Verlust, sind selten. Im Prinzip kann die Behandlung mit Nukleosid- oder Nukleotidanaloga erst n