Michael Tröltzsch

Acoustic radiation force impulse imaging (ARFI) for non-invasive detection of liver fibrosis: examination standards and evaluation of interlobe differences in healthy subjects and chronic liver disease.

Abstract Objective. Acoustic radiation force impulse imaging (ARFI) is a non-invasive method for the quantification of liver stiffness. We aimed to develop standards for the measuring procedure and studied the impact of different measuring sites. Materials and Methods. ARFI was tested in a tissue phantom and in 50 healthy volunteers. In addition, 116 patients with chronic liver disease underwent ARFI. The results were compared with histological staging (non-viral liver disease) and transient elastography (hepatitis C). ARFI diagnostic performance was evaluated with receiver operating characteristic curves. Results. ARFI results were not normally distributed in >20% of cases. Deep inspiration significantly increased ARFI values by 13% (p < 0.05). The mean shear-wave velocity in healthy individuals was 1.28 ± 0.19 m/s in the left liver lobe and 1.15 ± 0.17 m/s in the right liver lobe (p < 0.001). Similarly, in 79/116 patients with chronic liver disease a significant difference of shear-wave velocity between both liver lobes was detected. The histological staging correlated with ARFI results of the biopsy site (r = 0.661, p < 0.001) in non-viral liver disease (n = 47). The mean shear-wave velocity in cases with F1 and F2 fibrosis was increased in the left compared with the right liver lobe (2.1 ± 0.73 m/s vs. 1.75 ± 0.89 m/s, p = 0.041). Similar results were obtained in patients with hepatitis C (n = 69). Conclusion. Our study strengthens the necessity for definition of examination standards and demonstrates the usefulness of ARFI in non-viral liver disease. Interlobe variations of liver stiffness demand further investigation.

Non-Invasive Assessment of Hepatic Steatosis in Patients with NAFLD Using Controlled Attenuation Parameter and 1H-MR Spectroscopy

Introduction Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). 1H-Magnetic resonance spectroscopy (1H-MRS) and the ultrasound-based controlled attenuation parameter (CAP) correlate with biopsy proven steatosis, but have not been correlated with each other so far. We therefore performed a head-to-head comparison between both methods. Methods Fifty patients with biopsy-proven NAFLD and 15 healthy volunteers were evaluated with 1H-MRS and transient elastography (TE) including CAP. Steatosis was defined according to the percentage of affected hepatocytes: S1 5-33%, S2 34–66%, S3 ≥67%. Results Steatosis grade in patients with NAFLD was S1 36%, S2 40% and S3 24%. CAP and 1H-MRS significantly correlated with histopathology and showed comparable accuracy for the detection of hepatic steatosis: areas under the receiver-operating characteristics curves were 0.93 vs. 0.88 for steatosis ≥S1 and 0.94 vs. 0.88 for ≥S2, respectively. Boot-strapping analysis revealed a CAP cut-off of 300 dB/m for detection of S2-3 steatosis, while retaining the lower cut-off of 215 dB/m for the definition of healthy individuals. Direct comparison between CAP and 1H-MRS revealed only modest correlation (total cohort: r = 0.63 [0.44, 0.76]; NAFLD cases: r = 0.56 [0.32, 0.74]). For detection of F2–4 fibrosis TE had sensitivity and specificity of 100% and 98.1% at a cut-off value of 8.85 kPa. Conclusion Our data suggest a comparable diagnostic value of CAP and 1H-MRS for hepatic steatosis quantification. Combined with the simultaneous TE fibrosis assessment, CAP represents an efficient method for non-invasive characterization of NAFLD. Limited correlation between CAP and 1H-MRS may be explained by different technical aspects, anthropometry, and presence of advanced liver fibrosis.

Acoustic radiation force impulse (ARFI) elastography in acute liver failure: necrosis mimics cirrhosis

Acoustic radiation force Impulse (ARFI) technology correlates shear-wave velocity with fibrosis. It can differentiate between advanced fibrosis and normal tissue in chronic liver disease. However, specificity is impaired by cholestasis, inflammation or oedema in acute hepatitis. In patients with acute liver failure (ALF) necessitating liver transplantation ARFI has not been evaluated yet. We investigated 3 patients with ALF and compared their ARFI results to those of healthy controls (n = 33) and cases with liver cirrhosis (n = 21). In the 3 ALF patients shear-wave velocities were 3.0, 2.5, and 2.7 m/s, respectively. These results were significantly increased compared to those of healthy controls (median: 1.13 m/s; p < 0.001) and similar to those of cirrhotic individuals (median: 2.93 m/s). Two individuals underwent liver transplantation. Explants showed massive necrosis, but no signs of chronic liver disease. Patient 3 recovered spontaneously and showed decreasing ARFI results during follow-up. In conclusion, hepatic necrosis can mimic liver cirrhosis at ARFI evaluation in ALF patients and this impairs the specificity of ARFI.

Estimating steatosis and fibrosis: Comparison of acoustic structure quantification with established techniques.

AIM To compare ultrasound-based acoustic structure quantification (ASQ) with established non-invasive techniques for grading and staging fatty liver disease. METHODS Type 2 diabetic patients at risk of non-alcoholic fatty liver disease (n = 50) and healthy volunteers (n = 20) were evaluated using laboratory analysis and anthropometric measurements, transient elastography (TE), controlled attenuation parameter (CAP), proton magnetic resonance spectroscopy ((1)H-MRS; only available for the diabetic cohort), and ASQ. ASQ parameters mode, average and focal disturbance (FD) ratio were compared with: (1) the extent of liver fibrosis estimated from TE and non-alcoholic fatty liver disease (NAFLD) fibrosis scores; and (2) the amount of steatosis, which was classified according to CAP values. RESULTS Forty-seven diabetic patients (age 67.0 ± 8.6 years; body mass index 29.4 ± 4.5 kg/m²) with reliable CAP measurements and all controls (age 26.5 ± 3.2 years; body mass index 22.0 ± 2.7 kg/m²) were included in the analysis. All ASQ parameters showed differences between healthy controls and diabetic patients (P < 0.001, respectively). The ASQ FD ratio (logarithmic) correlated with the CAP (r = -0.81, P < 0.001) and (1)H-MRS (r = -0.43, P = 0.004) results. The FD ratio [CAP < 250 dB/m: 107 (102-109), CAP between 250 and 300 dB/m: 106 (102-114); CAP between 300 and 350 dB/m: 105 (100-112), CAP ≥ 350 dB/m: 102 (99-108)] as well as mode and average parameters, were reduced in cases with advanced steatosis (ANOVA P < 0.05). However, none of the ASQ parameters showed a significant difference in patients with advanced fibrosis, as determined by TE and the NAFLD fibrosis score (P > 0.08, respectively). CONCLUSION ASQ parameters correlate with steatosis, but not with fibrosis in fatty liver disease. Steatosis estimation with ASQ should be further evaluated in biopsy-controlled studies.

Evaluation of Transient Elastography, Acoustic Radiation Force Impulse Imaging (ARFI), and Enhanced Liver Function (ELF) Score for Detection of Fibrosis in Morbidly Obese Patients.

Background Liver fibrosis induced by non-alcoholic fatty liver disease causes peri-interventional complications in morbidly obese patients. We determined the performance of transient elastography (TE), acoustic radiation force impulse (ARFI) imaging, and enhanced liver fibrosis (ELF) score for fibrosis detection in bariatric patients. Patients and Methods 41 patients (median BMI 47 kg/m2) underwent 14-day low-energy diets to improve conditions prior to bariatric surgery (day 0). TE (M and XL probe), ARFI, and ELF score were performed on days -15 and -1 and compared with intraoperative liver biopsies (NAS staging). Results Valid TE and ARFI results at day -15 and -1 were obtained in 49%/88% and 51%/90% of cases, respectively. High skin-to-liver-capsule distances correlated with invalid TE measurements. Fibrosis of liver biopsies was staged as F1 and F3 in n = 40 and n = 1 individuals. However, variations (median/range at d-15/-1) of TE (4.6/2.6–75 and 6.7/2.9–21.3 kPa) and ARFI (2.1/0.7–3.7 and 2.0/0.7–3.8 m/s) were high and associated with overestimation of fibrosis. The ELF score correctly classified 87.5% of patients. Conclusion In bariatric patients, performance of TE and ARFI was poor and did not improve after weight loss. The ELF score correctly classified the majority of cases and should be further evaluated.

Noninvasive characterization of graft steatosis after liver transplantation

Abstract Objective. Liver graft steatosis has not been noninvasively evaluated yet. We therefore characterized liver transplant recipients by transient elastography (TE) and controlled attenuation parameter (CAP) and correlated the results with clinical and genetic risk factors. Methods. A total of 204 patients (pretransplant disease: n = 102 nonalcoholic etiology, nonalcoholic liver cirrhosis (non-ALC); n = 102 alcoholic liver disease, ALC; 42% female; median age 57.8 years; median time since transplantation 66 months) underwent ultrasound, TE, CAP, and nonalcoholic fatty liver disease (NAFLD) fibrosis score. Recipient DNA samples were genotyped for patatin-like phospholipase domain-containing protein 3 (PNPLA3) (rs738409) and IL28B (rs8099917, rs12979860) polymorphisms. Results. Increased hepatic echogenicity at ultrasound was observed in 36% of patients, CAP values >252 and >300 dB/m indicated steatosis and advanced steatosis in 44% and 24% of individuals. Advanced fibrosis (TE >7.9 kPa) was associated with increased CAP results (266 vs. 229 dB/m, p = 0.012). PNPLA3 G-allele carriers had increased CAP values (257 vs. 222 dB/m, p = 0.032), higher liver stiffness (TE 6.4 vs. 5.5 kPa, p = 0.005), and prevalence of diabetes mellitus (40% vs. 22%, p = 0.016). No such association was observed for IL28B polymorphisms. ALC compared to non-ALC patients had higher body mass index (28.1 vs. 25.5 kg/m², p < 0.001), higher prevalence of diabetes mellitus (41% vs. 25%, p = 0.017), and PNPLA3 CG + GG genotype (73% vs. 47%, p = 0.006), and had elevated TE (6.3 vs. 5.4 kPa, p = 0.022), CAP (266 vs. 221 dB/m, p = 0.001), and NAFLD fibrosis score (score −0.5 vs. −1.3, p < 0.001). Conclusion. Modern noninvasive liver graft assessment frequently detects hepatic steatosis, which is associated with graft fibrosis, components of the metabolic syndrome and recipient PNPLA3 rs738409 genotype, especially in ALC patients.

Non-invasive evaluation of hepatic manifestation in Wilson disease with transient elastography, ARFI, and different fibrosis scores

Abstract Objective. Noninvasive investigation of liver fibrosis with ultrasound-based elastography and laboratory-based fibrosis indices have been established in various chronic liver diseases within the last years. We aimed to evaluate feasibility and diagnostic value of transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and different serologic fibrosis indices in Wilsons disease (WD). Materials and methods. TE and ARFI were performed in 50 Wilson patients. In addition, AST/Platelet Ratio Index (APRI), FIB-4, and Forns score were calculated. Hepatic fibrosis was classified by a clinical score. Results. Of the 50 Wilson patients 41 had hepatic manifestation of WD. TE results were significantly increased in advanced hepatic fibrosis (7.0 ± 2.2 kPa; p < 0.05) and cirrhosis (10.1 ± 6.73 kPa; p < 0.05) compared to individuals without hepatic manifestation (5.0 ± 1.4 kPa). Right liver lobe ARFI (R-ARFI) values were only increased in cirrhotic patients (1.43 ± 0.28 vs. 1.19 ± 0.14 m/s; p < 0.05). The cutoff values to best discriminate cirrhosis were 6.1 kPa for TE and 1.29 m/s for R-ARFI. Left lobe ARFI failed to provide additional diagnostic benefit. Elastography methods displayed a significant correlation with APRI, FIB-4, and Forns indices (Pearsons rho > 0.33; p < 0.03). Conclusions. TE displayed a gradual increase between different stages of hepatic manifestation in WD and could significantly discriminate cirrhosis. The TE cutoff for cirrhosis may be clinically more relevant than the R-ARFI value.

Interventionelle nichtchirurgische Therapie von Lebermetastasen

Der Goldstandard zur Behandlung von Lebermetastasen ist unverändert die komplette chirurgische Sanierung. Leider ist ein Groβteil der Betroffenen aufgrund der Zahl der Lebermetastasen nicht operabel und somit auf andere Behandlungsoptionen angewiesen. Neben der systemischen Chemotherapie mit Zytostatika und sogenannten «biologicals» gewinnen interventionell-internistische Ansätze wie die ultraschallgesteuerte Radiofrequenzablation, die Laser induzierte Thermotherapie, die perkutane Mikrowellen-Koagulationstherapie, hochintensiver fokussierter Ultraschall und die Kryoablation an Bedeutung. Die vorliegende Arbeit möchte einen Überblick über neue Entwicklungen dieser interventionellen Therapieformen von Lebermetastasen geben.