Published online Nov 27, 2020. doi: 10.4254/wjh.v12.i11.1076
Peer-review started: June 2, 2020
First decision: June 15, 2020
Revised: June 23, 2020
Accepted: September 4, 2020
Article in press: September 4, 2020
Published online: November 27, 2020
Processing time: 174 Days and 20.9 Hours
Functional cure of chronic hepatitis B (CHB), defined as the loss of hepatitis B surface antigen (HBsAg), is very unusual with current antiviral treatments in hepatitis B e antigen (HBeAg)-negative patients. HBsAg levels decline very slow in patients receiving nucleos(t)ids analogues (NAs). Therefore, they need long-term antiviral treatment.
The hypothesis that we wanted to answer with our study was that the addition of pegylated-interferon (Peg-IFN) could accelerate the decline of HBsAg levels in patients that were receiving NAs and that this therapeutic strategy could increase the HBsAg loss rate.
In our study we wanted to evaluate in patients under NAs therapy if the addition of Peg-IFN could decrease HBsAg and hepatitis B core-related antigen (HBcrAg) levels, and increase HBsAg loss rate. If HBeAg-negative patients could achieve low levels of HBsAg it could be a good strategy to shorten the antiviral treatment.
We have performed a prospective, non-randomized, open-label trial evaluating the combination of Peg-IFN 180 µg/wk plus NAs during forty-eight weeks vs NAs in monotherapy, in HBeAg-negative non-cirrhotic CHB patients after a minimum of two years of NA therapy and with virological response.
We have shown that the addition of Peg-IFN 180 µg/wk during forty-eight weeks to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy alone, especially in those patients with interleukin 28B polymorphism CC. However, the HBcrAg levels remained stable after adding Peg-IFN to NAs. We have also shown that, the low acceptance by the patients of this therapeutic strategy and the side effects of Peg-IFN can limit its use in clinical practice.
This study shows that the addition of Peg-IFN to NA therapy accelerates the decline of HBsAg, especially in patients with interleukin 28B polymorphism CC. Therefore, even Peg-IFN has several side effects, this treatment strategy could be offered to some selected patients in order to achieve the functional cure of CHB. On the other hand, our study shows that HBcrAg levels do not seem useful to monitor this kind of treatment, neither as a predictor of HBsAg loss.
It is well known that patients with HBeAg-negative CHB usually need a long-term therapy with NAs, even lifelong, to achieve HBsAg loss. However, it has been suggested that low levels of HBsAg are related to higher rates of HBsAg loss after NA discontinuation, being advisable to achieve low levels of HBsAg before stopping NA therapy.