Beyond virological cure: A meta-analysis of liver stiffness reduction after DAA treatment for HCV

Direct-acting antiviral (DAA) therapy has transformed HCV treatment by achieving high cure rates and showing promise in reversing liver fibrosis. However, comprehensive evaluation of its effects on fibrosis-related outcomes is essential to inform future clinical strategies. This systematic review and meta-analysis evaluates the changes in non-invasive liver stiffness and fibrosis markers following DAA therapy and investigates key determinants influencing these elastography-based outcomes across diverse patient populations. PubMed, Google Scholar, Scopus, and Science Direct databases were searched for studies published from January 2011 to March 2026 for this study (PROSPERO ID: CRD42025642274). Studies assessing liver fibrosis in HCV patients treated with DAAs were included if they used tools like VCTE, SWE, MRI, APRI, FIB-4, or biopsy at baseline and follow-up. Standardized mean change (SMC) was calculated and pooled using random-effects models in RStudio. DAA therapy was associated with significant reductions in liver stiffness, with pooled SMCs of 0.53(95% CI: 0.38–0.69; p < 0.0001, I 2 99.1%) at SVR12, 0. 542 (95%CI: 0.22–0.8635; p = 0.001; I 2 = 99.05%) at SVR24, and 0.46 (95%CI: 0.37–0.55, p < 0.0001, I 2 = 92.2%) at SVR48 for TE and 0.82(95% CI: 0.22–1.42, p = 0.007) for point shear wave elastography (pSWE). Albumin increased significantly (SMC = −0.26, 95% CI: −0.45 to −0.07; p = 0.007), reflecting improved hepatic synthetic function. Haemoglobin change was not statistically significant (SMC = 0.13; p = 0.13). Sensitivity analyses restricted to uniform HCV mono-infected populations and to peer-reviewed articles only yielded SVR12 estimates (SMC range: 0.49–0.53) similar to the primary estimate. In case of SVR24 estimates, removal of one influential study, Elkhayat et al. substantially reduced the SVR24 estimates to 0.359 (0.294–0.423). DAA therapy is associated with significant reductions in liver stiffness measurements and improvement in non-invasive fibrosis markers in HCV patients within 12–24 weeks post-SVR. The observed reductions in liver stiffness likely reflect a combination of resolution of hepatic necroinflammation and, in some patients, genuine structural fibrosis change, although histological confirmation is required to establish true fibrosis regression.