Stopping oral antiviral treatment to cure chronic hepatitis B, is it in sight?
Rong Fan & Jinlin Hou
Hepatology International volume 14, pages302–304(2020)Cite this article
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The treatment of chronic hepatitis B (CHB) patients has evolved dramatically over the past two decades. Currently, oral nucleos(t)ide analogues (NA) with potent viral suppression and a high genetic barrier to resistance, i.e., entecavir, tenofovir disoproxil and tenofovir alafenamide, are recommended as first-line antivirals. Long-term NA treatment can suppress hepatitis B virus (HBV) replication, reverse liver fibrosis, and reduce the risk of hepatocellular carcinoma (HCC) [1].
In the era of oral antiviral treatment, functional cure and finite treatment are the few unmet needs left for clinicians to address. In 2012, Hadziyannis et al. linked stopping treatment to the functional cure of CHB [2]. Surprisingly, they found that treatment discontinuation could lead to as high as 40% HBsAg loss during up to 6-year post-treatment follow-up among 33 HBeAg-negative, genotype D-infected, NA-naive CHB patients who stopped adefovir monotherapy after 4–5 years of successful treatment. Non-re-treatment and higher ALT levels at the end of treatment (EOT) were associated with a higher incidence of HBsAg loss [2]. Thereafter, a growing number of studies showed that HBsAg could be cleared after stopping NA treatment due to the activation of the host immune response along with off-treatment relapse in Asian and Caucasian HBeAg-negative patients [3, 4]. In a randomized controlled trial (RCT) in Europe (FINITE study), 42 HBeAg-negative, mainly Caucasian patients stopped or continued NA therapy; 19% of the patients in the treatment cessation group achieved HBsAg loss by off-treatment week 144, whereas none of the patients in the continuation group cleared HBsAg [3]. A larger retrospective study from Taiwan also reported high HBsAg loss among 691 patients, with an annual incidence of 1.8% [4]. However, there is also strong opposition that claims that the few patients achieved HBsAg loss after treatment cessation [5, 6]. The HBsAg decline was similar between the treatment cessation and continuation groups (0.2 vs. 0.1 log10 IU/mL at off-treatment week 72) among 67 HBeAg negative, mainly Asian CHB patients in an RCT [5]. The opposite results among the above results may be explained by different ethnicities (Asian vs. Caucasian), pre-treatment HBeAg status (positive vs. negative), HBV genotypes (B and C vs. A and D) and retreatment criteria. Therefore, it is still unclear whether stopping NAs can improve the functional cure.作者: StephenW 时间: 2020-5-18 17:45