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. 2022 May-Jun;12(3):735-744.
doi: 10.1016/j.jceh.2021.12.011. Epub 2022 Jan 4.

A Prospective Five-Year Follow-up After peg-Interferon Plus Nucleotide Analogue Treatment or no Treatment in HBeAg Negative Chronic Hepatitis B Patients

Robin Erken  1 , Vladimir V Loukachov  2 , Annikki de Niet  3 , Louis Jansen  3 , Femke Stelma  3 , Jeltje T Helder  3 , Martine W Peters  3 , Hans L Zaaijer  4 , Neeltje A Kootstra  5 , Sophie B Willemse  1 , Hendrik W Reesink  1
Affiliations

A Prospective Five-Year Follow-up After peg-Interferon Plus Nucleotide Analogue Treatment or no Treatment in HBeAg Negative Chronic Hepatitis B Patients

Robin Erken et al. J Clin Exp Hepatol. 2022 May-Jun.

Abstract

Background: Currently available treatment options for chronic hepatitis B (CHB) are not recommended for HBeAg-negative patients with a low viral load. These patients may however benefit from treatment by achieving a functional cure, defined by HBsAg-loss and undetectable HBV DNA. This study evaluated the long-term effect of combination treatment with peg-interferon-alpha-2a (peg-IFN) and adefovir or tenofovir compared to no treatment in these patients.

Methods: HBeAg-negative CHB patients with HBV-DNA levels < 20,000 IU/mL (n = 151) were previously randomised 1:1:1 for peg-IFN 180 μg/week plus either adefovir 10 mg/day or tenofovir 245 mg/day, or no treatment and treated for 48 weeks in an open-label study. In this prospective long-term follow-up study, patients were monitored yearly up to five years after end of treatment (week 308). The primary outcome was sustained HBsAg-loss and secondary outcome the dynamics of HBsAg and HBV-DNA levels over time.

Results: Of the 131 followed patients, the HBsAg-status was known for 118 patients after five-year follow-up. HBsAg-loss occurred similarly (P = 0.703) in all arms: 8/43 (18.6%) peg-IFN + adefovir, 4/34 (11.7%) peg-IFN + tenofovir, and 6/41 (14.6%) among the untreated patients. The time to HBsAg-loss did not differ between groups (P = 0.641). Low baseline HBsAg levels and genotype A were independently associated with HBsAg-loss irrespective of allocation. HBsAg and HBV-DNA levels declined similarly during follow-up in all patient groups.

Conclusions: This prospective randomised controlled study showed that HBsAg-loss overtime was not influenced by treatment with a combination of nucleotide analogue and Peg-IFN. Low baseline HBsAg levels can predict HBsAg-loss irrespective of treatment allocation.

Keywords: ADV, Adefovir dipivoxil; ALT, Alanine aminotransferase; CHB, Chronic hepatitis B; EOT, End of treatment; GZ, Grey zone; HBeAg, Hepatitis B e antigen; HBsAg, Hepatitis B surface antigen; HCC, Hepatocellular Carcinoma; HNCH, HBeAg-negative chronic infection; NA, Nucleot(s)ide analogue; ROC, Receiver operating characteristic; TAF, Tenofovir alafenamide fumarateor; TDF, Tenofovir disoproxil fumarate; ULN, Upper limit of normal; UMC, University Medical Centers; combination therapy; functional cure; hepatitis B virus; inactive carrier; low viral load; peg-IFN, Pegylated-interferon.

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Figures

Figure 1
Figure 1
Summarising flow diagram of inclusion and follow-up. EOT, end of treatment; HBsAg, hepatitis B surface antigen; LTFU, long term follow-up; Peg-IFN, pegylated interferon.
Figure 2
Figure 2
Kaplan Meier curve of HBsAg-loss events over time. Proportion of HBsAg-positive patients shown over time for each treatment group. The top 20% of events are displayed in the middle of the figure. HBsAg, hepatitis B surface antigen; no, no treatment arm; Peg-IFN + ADV, pegylated interferon plus adefovir; Peg-IFN + TDF, pegylated interferon plus tenofovir.
Figure 3
Figure 3
A-B, dynamics virology marker in different treatment groups. HBsAg (A) and HBV DNA (B) change compared to baseline, over time, standard deviation. Symbols; ▼ black downward triangle, interferon + adefovir; ▲ grey upward triangle, interferon + tenofovir; ○ circle, no-treatment group. HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus.
Figure 4
Figure 4
Individual HBsAg dynamics of patients achieving FC. HBsAg, hepatitis B surface antigen; Peg-IFN + ADV, pegylated interferon plus adefovir; Peg-IFN + TDF, pegylated interferon plus tenofovir.
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