Serum hepatitis B virus RNA level is associated with biochemical relapse in patients with chronic hepatitis B infection who discontinue nucleos(t)ide analogue treatment

Summary Background Nucleos(t)ide analogue (NA) discontinuation may be attempted in carefully selected patients with chronic hepatitis B (CHB) infection. Aim To investigate whether a novel serum marker of quantitative hepatitis B virus (HBV) RNA levels could predict biochemical relapse after NA discontinuation. Methods We prospepctively followed non‐cirrhotic Asian patients with CHB who stopped NA according to pre‐specified stopping criteria. The primary endpoint was biochemical relapse (HBV DNA >2000 IU/mL and alanine transaminase >2x upper limit of normal), which were also the re‐treatment criteria. Results Biochemical relapse occurred in 50 patients (48.3% at year 6). Multivariable analysis showed that higher HBV RNA levels (HR 1.34; P < 0.001) at the time of NA discontinuation were associated with increased biochemical relapse risk. The area under the curve of HBV RNA at the time of NA discontinuation for the incidence of biochemical relapse was 0.760 at 6 years. Six years after treatment discontinuation, all patients with HBV RNA levels ≥20 000 copies/mL at the end of treatment developed a biochemical relapse compared with 23.8% of patients with HBV RNA levels<1000 copies/mL ( P < 0.001). More patients with HBV RNA levels <1000 copies/mL at end of treatment achieved loss of hepatitis B surface antigen than patients with higher levels (30.9% vs 1.6%; P = 0.027). Conclusions The HBV RNA level at end of treatment predicted biochemical relapse after treatment discontinuation and may be used to guide decisions on treatment discontinuation.