Elevated pre-treatment IL-18 level is associated with HBeAg seroconversion in HIV–HBV coinfection

Background: In HBV-infected patients, hepatitis B e antigen (HBeAg) seroconversion is associated with better outcomes. Interleukin-18 (IL-18) controls hepatitis B replication in a mouse model. However, its role in treatment response in HIV–HBV-coinfected patients is unknown. Methods: We enrolled 35 treatment-naive, HBeAg-positive, HIV–HBV-coinfected patients. HBV DNA, HIV RNA, CD4⁺ T-cell count, HBV surface antigen (HBsAg) quantification (qHBsAg), HBeAg quantification (qHBeAg) and IL-18 levels were measured prior to, at 24 and 48 weeks of HBV-active combination antiretroviral therapy (cART). Multivariate Poisson regression models with robust standard errors were used to determine factors associated with HBeAg seroconversion. Results: Twenty-one patients received tenofovir (TDF) + lamivudine (3TC) based cART while 14 patients received 3TC-based cART. After 48 weeks of treatment, 10 patients experienced HBeAg seroconversion. Compared with non-seroconverters, seroconverters had higher median HIV RNA (5.22 versus 4.58 log copies/ ml; P=0.030), lower median qHBsAg (3.97 versus 4.76 log IU/ml; P=0.011), lower median qHBeAg (1.61 versus 3.01 log PEIU/ml; P=0.004) and marginally higher median IL-18 (2.70 versus 2.53 log pg/ml; P=0.068) prior to ART. In the multivariate regression, higher baseline IL-18 (adjusted relative risk [aRR] 2.99 per 1 log pg/ml increase; P=0.035), high HIV RNA (aRR 1.84 per 1 log copies/ml; P=0.029) and low qHBeAg (aRR 0.71 per 1 log PEIU/ml; P=0.029) were significantly associated with HBeAg seroconversion. Conclusions: In HIV–HBV-coinfected patients with HBeAg positivity, higher IL-18 levels, HIV RNA load, as well as low qHBeAg prior to cART were associated with HBeAg seroconversion.