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. 2023 Dec 7;12(24):7547.
doi: 10.3390/jcm12247547.

Shear Wave Elastography for Assessing Liver Stiffness in HCV-Infected Kidney Transplant Recipients after Direct-Acting Antiviral Treatment: A Comparative Study with Magnetic Resonance Elastography

Salma Almutawakel  1 , Fabian Halleck  2 , Michael Dürr  2 , Ulrike Grittner  3 , Eva Schrezenmeier  2 , Klemens Budde  2 , Christian E Althoff  1 , Bernd Hamm  1 , Ingolf Sack  1 , Thomas Fischer  1 , Stephan R Marticorena Garcia  1
Affiliations

Shear Wave Elastography for Assessing Liver Stiffness in HCV-Infected Kidney Transplant Recipients after Direct-Acting Antiviral Treatment: A Comparative Study with Magnetic Resonance Elastography

Salma Almutawakel et al. J Clin Med. .

Abstract

Hepatitis C virus (HCV) infection can lead to hepatic fibrosis. The advent of direct-acting antivirals (DAAs) has substantially improved sustained virological response (SVR) rates. In this context, kidney transplant recipients (KTRs) are of particular interest due to their higher HCV infection rates and uncertain renal excretion and bioavailability of DAAs. We investigated liver stiffness after DAA treatment in 15 HCV-infected KTRs using ultrasound shear wave elastography (SWE) in comparison with magnetic resonance elastography (MRE). KTRs were treated with DAAs (daclatasvir and sofosbuvir) for three months and underwent SWE at baseline, end of therapy (EOT), and 3 (EOT+3) and 12 months (EOT+12) after EOT. Fourteen patients achieved SVR12. Shear wave speed (SWS)-as a surrogate parameter for tissue stiffness-was substantially lower at all three post-therapeutic timepoints compared with baseline (EOT: -0.42 m/s, p < 0.01; CI = -0.75--0.09, EOT+3: -0.43 m/s, p < 0.01; CI = -0.75--0.11, and EOT+12: -0.52 m/s, p < 0.001; CI = -0.84--0.19), suggesting liver regeneration after viral eradication and end of inflammation. Baseline SWS correlated positively with histopathological fibrosis scores (r = 0.48; CI = -0.11-0.85). Longitudinal results correlated moderately with APRI (r = 0.41; CI = 0.12-0.64) but not with FIB-4 scores (r = 0.12; CI = -0.19-0.41). Although higher on average, SWE-derived measurements correlated strongly with MRE (r = 0.64). In conclusion, SWE is suitable for non-invasive therapy monitoring in KTRs with HCV infection.

Keywords: direct-acting antivirals; elastography; hepatitis C; kidney transplant recipients; liver stiffness; magnetic resonance elastography; shear wave elastography; ultrasound elastography.

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Conflict of interest statement

I.S. is a patent holder for a technical development related to MR elastography. K.B. reports on the receipt of grants from Bristol Myers Squibb during the study, and T.F. acknowledges receiving honoraria from Canon Medical. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. S.A., F.H., M.D., U.G., E.S., C.E.A., B.H. and S.R.M.G. declare no conflict of interest.

Figures

Figure 1
Figure 1
Study timeline. All participants were examined serially before treatment started (baseline), at the end of treatment (EOT), 3 months after EOT (EOT+3), and 12 months after EOT (EOT+12). Sustained virological response was achieved at EOT+3 (SVR12).
Figure 2
Figure 2
Representative ultrasound and shear wave elastography images at baseline and after 6 months (EOT+3). Shear wave speed decreased after treatment with direct-acting antivirals. The visualization of shear wave propagation in real-time allowed identification of areas with sufficient dynamic strain for precise elasticity reconstruction. The presence of a consistent and parallel wavefront pattern was considered indicative of a technically successful elastography examination.
Figure 3
Figure 3
Shear wave elastography results after antiviral treatment: decrease in liver shear wave speed at 3 months (end of treatment, EOT, n = 13, * p = 0.008), 6 months (EOT+3, n = 14, ** p = 0.004) and 15 months (EOT+12, n = 13, *** p < 0.001). Red dots: persistent high SWS values in a patient who experienced viral relapses after SVR. Blue dots: patients who were categorized as responders. All p-values are from linear-mixed models and adjusted for age.
Figure 4
Figure 4
Repeated measures correlation analysis between shear wave speed (SWS) and serological fibrosis scores based on 55 measures of 15 and 39 degrees of freedom. Distinctive colors are used to represent each participant in the graph. (A) SWS and APRI show moderate correlation (r = 0.41, CI = 0.12 to 0.64, p = 0.007). (B) FIB-4 and SWS do not correlate substantially (r = 0.12, CI = −0.193 to 0.414, p = 0.448).
Figure 5
Figure 5
Bland–Altman plots for comparison of the two methods: shear wave speed measurements using MRE vs. SWE. x-axis: mean of MRI and US measurements; y-axis: difference between MRE and SWE (negative values indicate higher SWE-derived stiffness compared with MRE values). Horizontal lines are placed at both the mean difference and the agreement boundaries, which were calculated by adding and subtracting 1.96 times the standard deviation of the differences from the mean difference. In general, SWE yielded higher stiffness values. (A) Baseline, n = 15; (B) EOT, n = 13; (C) EOT+3, n = 14; and (D) EOT+12, n = 13.
Figure 6
Figure 6
Repeated measures correlation analysis shows a substantial and positive correlation between SWE and MRE (r = 0.64; CI = 0.41 to 0.80) based on 55 measures of 15 individuals and 35 degrees of freedom. Distinctive colors are used to represent each participant in the graph.
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