Elevated expression of serum soluble ST2 in clinical relapse after stopping long-term Nucleos(t)ide analogue therapy for chronic hepatitis B

Abstract

Background The virological or clinical relapse is common in chronic hepatitis B (CHB) patients after stopping long-term nucleos(t)ide analogue (NA) therapy. Soluble growth stimulation expressed gene 2 (sST2), one of the Toll-like/interleukin-1 receptor members, is involved in a variety of inflammatory processes and immune responses. However, the expression and function of serum sST2 in CHB patients after stopping NA treatment remains unknown. Methods A total of 91 non-cirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed up to 240 weeks. All patients were divided into clinical relapse group and non-clinical relapse (including sustained virological response and only virological relapse) group according HBV DNA and ALT levels. The serum levels of sST2 of all participants were determined by ELISA and compared between each two groups. Results Clinical relapse occurred in 26 patients and virological relapse occurred in 57 patients. We found that there was a positive correlation between sST2 expression and HBsAg, ALT, HBV DNA, and anti-HBc levels in CHB patients after discontinuation of NA treatment. Levels of serum sST2 in clinical relapse patients showed a rising trend and most patients showed peak sST2 levels at the point of clinical relapse. Moreover, the sST2 levels of clinical relapse group at week 12, week 24 and week 48 were relatively higher than non-clinical relapse group. However, the level of sST2 at the end of treatment was not an effective biological marker for the early prediction of clinical relapse after discontinuation of long-term NA therapy. Conclusions In conclusion, we found that an increase in sST2 in clinical relapse patients might be associated with an inflammation-related immune response after discontinuation of NA treatment. Trial registration The trial was retrospectively registered at Chinese Clinical Trial Registry: ChiCTR-OOC-17013970 . Registration date: December 15, 2017.

Cessation of nucleos(t)ide analogues therapy in chronic hepatitis B: a systematic review and meta-analysis

“…Male gender was associated with off-NAs VR only in one study [24]. In addition, older age was associated with off-NAs VR in seven studies (all with both HBeAg-positive and HBeAg-negative patients) [19,23,33,[39][40][41]43], and two of these studies found that higher rates of off-NAs VR in patients >35 years old than patients ≤35 years old [33,44]. They did not found off-NAs VR was association with alcohol consumption in one [36], diabetes and hypertension in one [28], and body mass index (BMI) in two studies [29,36].…”

“…The rate of VR after NAs cessation was not related to the type of NAs in six studies using rst-line (tenofovir or entecavir) and second-line NAs (adefovir, lamivudine or telbivudine) involving 683 patients (330 HBeAgpositive, 353 HBeAg-negative) [33,36,37,39,40,44]. Whereas, the rate of VR was higher in 22 tenofovir-treated than 113 entecavir-treated HBeAg-negative CHB patients in one study [41].…”

“…At baseline, 337 (13.9%) of the 2433 patients with cirrhosis (information of cirrhosis was not reported in two studies [24,27], including 140 off-NAs patients), which was diagnosed by histology ndings and/or imaging studies. [32], entecavir in three [23,24,28], tenofovir in two [20,34], several NAs in fteen [19,21,22,26,30,31,33,[35][36][37][38][39][40][41]44], and NAs was not reported in the remaining ve studies [25,27,29,42,43] ( Table 1).…”

“…The de nition of VR after NAs cessation was based on HBV DNA levels >20 IU/mL in one [22], >120 IU/mL in one [21], >2000 IU/mL (or 10,000 copies/mL) in 19 [19,20,[22][23][24][25][26][28][29][30][31][33][34][35][38][39][40]43,44], and >20,000 IU/mL (or 100,000 copies/mL) in one study [27]. One study provided two de nitions of VR which were based on HBV DNA levels >2000 IU/mL and >20,000 IU/mL [32].…”

“…As to the three studies [32,36,37] provided more than one de nition of VR, when calculating the overall pooled rates of VR, we adopted the de nition of VR based on HBV DNA level >2000 IU/mL. BR after NAs cessation was de ned as ALT above the upper limit of normal (ULN) in three [24,31,41], >1.2 ULN in one [20], and >2 ULN in fteen studies [19,22,[25][26][27][28][29][32][33][34][35]38,39,43,44]. One study speci ed two de nitions of BR which were based on ALT >ULN and > 2 ULN [36].…”