Abstract

Direct-acting antiviral agents achieve a high cure rate, resulting in early hepatic necroinflammatory resolution and sustained fibrosis regression. This study aimed to obtain longitudinal, concurrent within-subject measurements of liver stiffness (LS) and spleen stiffness (SS) and their correlates over time. Participants with hepatitis C (n=592) receiving direct-acting antiviral-based therapy were monitored through point shear-wave elastography from the treatment baseline (TW0) across follow-up visits in terms of LS and SS. Generalized linear mixed modeling indicated that all LS values (2301 visits) were negatively correlated with the follow-up times (all P < .05) from TW0 to 24 weeks (PW24) after the end of treatment (EOT) and positively correlated with baseline LS values (P < .001). The slopes of declines (preceding minus next) differed significantly (P < .001) between TW0-TW4 (treatment week 4) (0.060 [-0.050 to 0.225] meter/second/month [m/s/mo]) and TW4-EOT (0.010 [-0.030 to 0.075] m/s/mo). All SS values (1704 visits) were negatively correlated with time only at PW24 (P < .001) and positively correlated with baseline SS values (P < .001). The slopes of the SS values differed significantly (P < .001) only between EOT-PW12 (-0.010 [-0.110 to 0.083] m/s/mo) and PW12-PW24 (0.043 [-0.063 to 0.160] m/s/mo). The biphasic fast-to-slow decline in LS occurred early in the on-treatment phase, which is consistent with the resolution of hepatic necroinflammation. The slow-to-fast decline in SS occurred off treatment. Future studies should investigate the association with regressions in liver fibrosis and portal hypertension.

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