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HBsAg seroclearance with NUCs: rare but important
  1. Markus Cornberg,
  2. Christoph Höner zu Siederdissen
  1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
  1. Correspondence to Dr Markus Cornberg, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover 30623, Germany; cornberg.markus{at}

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A major breakthrough in the treatment of chronic hepatitis B virus (HBV) infection had been the approval of nucleoside and nucleotide analogues (NUCs), which inhibit the reverse transcriptase and, thereby, dramatically suppress HBV DNA. To date, five NUCs are approved for the treatment of hepatitis B, with tenofovir and entecavir considered as first-line therapy.1 Treatment with tenofovir or entecavir leads to viral suppression below the limit of detection in almost 100% of adherent patients.1 This is associated with regression of fibrosis or even cirrhosis.2 ,3 Furthermore, some studies suggest a lowered incidence of hepatocellular carcinoma (HCC) with long-term NUC treatment. However, a significant risk for HCC development remains despite low HBV DNA, especially in patients with cirrhosis.4 Data from the REVEAL study suggest that higher HBsAg in low viremic patients is associated with an increased risk for HCC, underlining the importance of HBsAg as a complement to HBV DNA in risk stratification.5 One important limitation of NUC therapy is that treatment duration is indefinite in most cases. Guidelines suggest that NUCs can only safely be stopped 12 months after anti-HBe seroconversion in HBeAg-positive patients, or if HBsAg seroclearance is achieved.1 However, relapse after anti-HBe seroconversion can be frequent, and limited data exist if NUC-induced HBsAg seroclearance is stable and associated with an improved outcome.1 So far, only reports on spontaneous or interferon α (IFN)-induced HBsAg …

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