{"title":"Finite nucleos(t)ide-analogue therapy for functional cure in HBeAg-negative chronic hepatitis B: recent development in the paradigm shift","authors":"Yun-Fan Liaw, George Papatheodoridis","doi":"10.1097/hep.0000000000001107","DOIUrl":null,"url":null,"abstract":"Long-term nucleos(t)ide analogue (Nuc) therapy in chronic hepatitis B (CHB) may lead to hepatitis B virus (HBV) suppression, alanine aminotransferase (ALT) normalization, improvement of histological lesions, and prevention of liver disease progression, but rarely achieve HBsAg loss, the hallmark of functional cure. HBeAg-negative CHB patients have often been recommended to continue Nuc therapy until HBsAg loss, which usually means indefinitely. However, long-term/life-long Nuc therapy is associated with increasing costs and concerns of adverse outcomes subsequent to poor adherence and/or self-cessation/loss-to-follow-up. Hence, 2012 Asian-Pacific guidelines recommended that HBeAg-negative CHB patients can stop Nuc therapy after ≥12 months of HBV DNA undetectability. Subsequent Asian and few European studies have found the strategy of finite Nuc therapy to be feasible and reasonably safe. In 2016-2017, stopping Nuc was also included as a conditional strategy for HBeAg-negative CHB patients in the American and European guidelines. Furthermore, progressively increasing HBsAg loss rates with prolongation of off-Nuc follow-up were documented, being higher in Caucasians and more apparent beyond years 4-5 in Asian patients. Recently, a large study in patients with HBV cirrhosis showed not only higher 10-year HBsAg loss rate (15.3 vs. 1.6%) but also ~50% lower 10-year hepatocellular carcinoma incidence (16.5 vs. 29.5%) and 60% lower liver-related mortality/transplantation rate (6.1 vs. 15.1%) after Nuc cessation, as compared with well-matched patients continuing Nuc therapy. Since novel drug development aiming for functional cure has not been satisfactory, the strategy of finite Nuc therapy in HBeAg-negative CHB seems to be the best realistic option for functional cure today.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":12.9000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/hep.0000000000001107","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Long-term nucleos(t)ide analogue (Nuc) therapy in chronic hepatitis B (CHB) may lead to hepatitis B virus (HBV) suppression, alanine aminotransferase (ALT) normalization, improvement of histological lesions, and prevention of liver disease progression, but rarely achieve HBsAg loss, the hallmark of functional cure. HBeAg-negative CHB patients have often been recommended to continue Nuc therapy until HBsAg loss, which usually means indefinitely. However, long-term/life-long Nuc therapy is associated with increasing costs and concerns of adverse outcomes subsequent to poor adherence and/or self-cessation/loss-to-follow-up. Hence, 2012 Asian-Pacific guidelines recommended that HBeAg-negative CHB patients can stop Nuc therapy after ≥12 months of HBV DNA undetectability. Subsequent Asian and few European studies have found the strategy of finite Nuc therapy to be feasible and reasonably safe. In 2016-2017, stopping Nuc was also included as a conditional strategy for HBeAg-negative CHB patients in the American and European guidelines. Furthermore, progressively increasing HBsAg loss rates with prolongation of off-Nuc follow-up were documented, being higher in Caucasians and more apparent beyond years 4-5 in Asian patients. Recently, a large study in patients with HBV cirrhosis showed not only higher 10-year HBsAg loss rate (15.3 vs. 1.6%) but also ~50% lower 10-year hepatocellular carcinoma incidence (16.5 vs. 29.5%) and 60% lower liver-related mortality/transplantation rate (6.1 vs. 15.1%) after Nuc cessation, as compared with well-matched patients continuing Nuc therapy. Since novel drug development aiming for functional cure has not been satisfactory, the strategy of finite Nuc therapy in HBeAg-negative CHB seems to be the best realistic option for functional cure today.
期刊介绍:
HEPATOLOGY is recognized as the leading publication in the field of liver disease. It features original, peer-reviewed articles covering various aspects of liver structure, function, and disease. The journal's distinguished Editorial Board carefully selects the best articles each month, focusing on topics including immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases, liver cancer, and drug metabolism.