Factors associated with recurrence of chronic hepatitis B after nucleoside analogs withdrawal: a meta–analysis

Abstract

Objective To evaluate the factors associated with recurrence of chronic hepatitis B (CHB) after nucleoside analogs (NAs) withdrawal. Methods A literature search from PubMed, Wanfang data, CQVIP, CNKI, Duxiu and SinoMed was conducted to identify studies on the recurrence of CHB after NAs withdrawal. Meta–analysis was performed using RevMan 5.3. Random–effects or fixed–effects model was performed based on the heterogeneity. Weighted mean difference (WMD) was used to assess the continuous data, and odds ratio (OR) was used to assess the dichotomous data. Publication bias was evaluated with Egger's regression test using Stata SE 11.0. Results A total of 20 case–control studies were included in this analysis. The recurrence rates were 21.0%, 30.4%, 33.2% in HBeAg–positive CHB patients, and 26.5%, 34.1%, 50.1% in HBeAg–negative patients after NAs withdrawal for 3 months, 6 months and 1 year, respectively. For patients treated with lamivudine, the recurrence rates of CHB were 21.0%, 28.0%, 34.3% at 3–, 6– and 12–month after NAs withdrawal. Meta analysis demonstrated that among HBeAg–positive CHB patients, the average age (WMD=7.36, 95%CI: 5.72–9.00, Z=8.81, P<0.01) and baseline HBV DNA level (WMD=0.26, 95%CI: 0.05–0.46, Z=2.44, P=0.01) were higher in recurrence group, while antiviral treatment duration was shorter in recurrence group (WMD=–3.12, 95%CI: –4.56––1.68, Z=4.26, P<0.01), and the rate of recurrence was higher in patients with liver cirrhosis (OR=2.59, 95%CI: 1.33–5.04, Z=2.79, P<0.01). Among HBeAg negative patients, the average age of patients in recurrence group was higher than that in non–recurrence group (WMD=5.90, 95%CI: 1.57–10.23, Z=2.67, P<0.01), and no difference was observed in other factors between recurrence and non–recurrence patients. Among patients treated with lamivudine, the average age (WMD=7.68, 95%CI: 5.02–10.34, Z=5.66, P<0.01) and baseline HBV DNA level (WMD=0.26, 95%CI: 0.05–0.46, Z=2.44, P=0.01) were higher, while antiviral treatment duration was shorter in recurrence group (WMD=–2.11, 95%CI: –3.85––0.38, Z=2.39, P<0.01), and the rate of recurrence was higher in patients with liver cirrhosis (OR=2.59, 95%CI: 1.33–5.04, Z=2.79, P<0.05). Conclusion Among HBeAg–positive and lamivudine–treated patients, age, baseline HBV DNA level, antiviral treatment duration and liver cirrhosis are associated with the recurrence of CHB after NAs withdrawal; while for HBeAg–negative patients, age is the only risk factor. Key words: Hepatitis B, chronic; Nucleotides; Lamivudine; Recurrence; Meta–analysis