Table 2.

Summary of key points from additional studies included in the External Assessment Centre systematic review (n = 7)

Study	Patient population and country	Intervention and/or comparator	Study design	Main findings
Chen et al. [40]	Patients with hepatitis C (n = 127) Taiwan/China	VTq, liver biopsy	Prospective, observational, operator-blind study. Liver biopsy within 1 h of ARFI measurements (Acuson S2000™). No follow-up	Found a statistically significant correlation (r = 0.70, p < 0.001) (with all AUROC values above 0.83) between ARFI and liver biopsy. However, the degree of concurrent hepatic necro-inflammatory activity significantly affected the measurements of liver fibrosis using ARFI
Kuroda et al. [41]	n = 30 patients with hepatitis C, n = 30 patients with liver cirrhosis, and n = 10 healthy subjects (controls) Japan	VTq, biochemical tests, liver biopsy	Prospective, diagnostic accuracy study. Biochemical tests performed on the same day as ARFI measurements. Timing of liver biopsy unclear	Diagnosis of liver cirrhosis using ARFI (AUROC: 0.930 [no CI]). The most appropriate cut-off value for shear wave velocity values was 1.59 (sensitivity 95 %, specificity 83 %)
Liu et al. [38]	Patients with hepatitis B (n = 95) and 16 healthy volunteers China	VTq, liver biopsy, TE	Prospective, diagnostic accuracy, ARFI measurement with Siemens Acuson S2000™ within 1 day of liver biopsy. No follow-up	Both ARFI and TE had similar AUROC values for both the intermediate (F2) and advanced (F4) fibrosis stages
Nishikawa et al. [42]	Patients with hepatitis C (n = 108) Japan	VTq, liver biopsy	Prospective diagnostic accuracy, ARFI measurement with Siemens Acuson S2000™ within 1 week of liver biopsy. Patients underwent a liver biopsy before starting treatment with interferon. No follow-up	Found that ARFI correlated significantly with liver fibrosis stage in all patients. Additionally, ARFI correlated significantly with BMI, GTP and hyaluronic acid blood levels in fibrosis stages F0–1, F2 and F3–4, respectively. ARFI measurements did not correlate with inflammation
Rizzo et al. [43]	Patients with hepatitis C (n = 139) Italy	VTq, liver biopsy, TE	Prospective, diagnostic accuracy, percutaneous liver biopsy and ARFI/TE measurements (Acuson S2000™) within 6 months. No follow-up	Found that ARFI imaging was reproducible and accurate for staging of both intermediate (>F2) and advanced (F3–4) liver fibrosis. The AUROC results for these stages were comparable with the performance of TE
Yamada et al. [39]	Patients with hepatitis C (n = 124) Japan	VTq, peg-IFN plus ribavirin combination therapy. Liver fibrosis assessed histologically by liver biopsy, response to treatment measured with serum hepatitis C RNA levels and ARFI	Diagnostic accuracy and prediction of response to treatment, prospective status not clear, ARFI measurement (Acuson S2000™) was performed within 1 week preceding liver biopsy. Follow-up was at weeks 4, 12, 24, 36, and 48, end of treatment and week 24 after the treatment for genotype 1. For genotype 2, follow-up was at weeks 4, 12 and 24, and week 24 after the treatment	The shear velocity value increased with the progression of the histological fibrosis stage, as assessed using the Metavir scoring system, and a significant correlation was found between the two variables (Pearson product–moment correlation coefficient = 0.764 (p < 0.001). The AUROCs were F ≥ 2 (0.890) and F ≥ 3 (0.943). The shear velocity value measured by ARFI could not predict the treatment response for patients with hepatitis C genotype 2 but showed some benefit for patients with genotype 1
Ye et al. [44]	Patients with hepatitis B (n = 204) and healthy volunteers (n = 60). Only 66 of 204 patients underwent liver biopsy for comparison with ARFI China	VTq, ultrasound-guided liver biopsy	Prospective diagnostic accuracy, ARFI measurement with Siemens Acuson S2000™ within 3 days of liver biopsy. No follow-up	Found that ARFI liver stiffness measurements showed good correlation with the fibrosis stage (p = 0.87, p < 0.001), and a high diagnostic accuracy between early/intermediate and advanced fibrosis stages (F0–2 vs. F3 = 0.99, F0–2 vs. F4 = 0.97)

ARFI acoustic radiation force impulse, AUROC area under receiver operating characteristic, BMI body mass index, CI confidence interval, GTP γ-glutamyltranspeptidase, IFN interferon, LB liver biopsy, TE transient elastography, VTq Virtual Touch™ Quantification