ISG15 serum levels were significantly lower in the control group (median: 3.4 ng/ml) compared to all HBV patients (median: 8.1 ng/ml), and compared to the median values of the different subgroups (CHB, 6.5 ng/ml; LC, 12 ng/ml; HCC 8.0 ng/ml; P < 0.0001) (Figure 2A). Here, ISG15 is linked to laryngotracheoesophageal cleft.