The deep abdominal ultrasound transducer (DAX) increases the success rate and diagnostic accuracy of shear wave elastography for liver fibrosis assessment in patients with obesity-A prospective biopsy-controlled study.

BACKGROUND: Obesity impacts the diagnostic accuracy of shear wave elastography (SWE). A deep abdominal ultrasound transducer (DAX) capable of point (pSWE) and two-dimensional (2D)-SWE has recently been introduced to address this issue. METHODS: We performed a prospective study in a cohort of mostly patients with obesity undergoing liver biopsy with a high prevalence of metabolic dysfunction-associate steatotic liver disease (MASLD). Liver stiffness measurement (LSM) was measured using vibration-controlled transient elastography (VCTE), as well as pSWE and 2D SWE on the standard (5C1) and the DAX transducers. RESULTS: We included 129 patients with paired LSM and liver biopsy: median age 44.0 years, 82 (63.6%) women, median BMI: 43.2 kg/m2. Histologic fibrosis stages: F0: N = 55 (42.6%), F1: N = 14 (10.9%), F2: N = 50 (38.8%), F3: N = 2 (1.6%), F4: N = 8 (6.2%). VCTE-LSM failed (N = 13) or were unreliable (IQR/median ≤30% in ≥7.1 kPa, N = 14) in 20.9% of patients. The Pearson correlation of reliable VCTE-LSM with both pSWE and 2D SWE was strong (all >0.78). The diagnostic accuracy for all LSM techniques was poor for significant fibrosis (≥F2, AUC: 0.54-0.63); however, it was good to excellent for advanced fibrosis (≥F3, AUC: 0.87-0.99) and cirrhosis (F4, AUC: 0.86-1.00). In intention-to-diagnose analysis, pSWE on DAX was significantly superior to VCTE-LSM. CONCLUSIONS: pSWE- and 2D-SWE enable the non-invasive identification of advanced fibrosis and cirrhosis in patients with obese MASLD. The use of the DAX transducer for acoustic radiation force imaging (ARFI)-LSM avoids technical failures in an obese population and subsequently offers advantages over VCTE-LSM for the evaluation of fibrosis in an obese MASLD population at risk for fibrosis.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.

Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.

Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis.

BACKGROUND & AIMS: In individuals with compensated advanced chronic liver disease (cACLD), the severity of portal hypertension (PH) determines the risk of decompensation. Invasive measurement of the hepatic venous pressure gradient (HVPG) is the diagnostic gold standard for PH. We evaluated the utility of machine learning models (MLMs) based on standard laboratory parameters to predict the severity of PH in individuals with cACLD. METHODS: A detailed laboratory workup of individuals with cACLD recruited from the Vienna cohort (NCT03267615) was utilised to predict clinically significant portal hypertension (CSPH, i.e., HVPG ≥10 mmHg) and severe PH (i.e., HVPG ≥16 mmHg). The MLMs were then evaluated in individual external datasets and optimised in the merged cohort. RESULTS: Among 1,232 participants with cACLD, the prevalence of CSPH/severe PH was similar in the Vienna (n = 163, 67.4%/35.0%) and validation (n = 1,069, 70.3%/34.7%) cohorts. The MLMs were based on 3 (3P: platelet count, bilirubin, international normalised ratio) or 5 (5P: +cholinesterase, +gamma-glutamyl transferase, +activated partial thromboplastin time replacing international normalised ratio) laboratory parameters. The MLMs performed robustly in the Vienna cohort. 5P-MLM had the best AUCs for CSPH (0.813) and severe PH (0.887) and compared favourably to liver stiffness measurement (AUC: 0.808). Their performance in external validation datasets was heterogeneous (AUCs: 0.589-0.887). Training on the merged cohort optimised model performance for CSPH (AUCs for 3P and 5P: 0.775 and 0.789, respectively) and severe PH (0.737 and 0.828, respectively). CONCLUSIONS: Internally trained MLMs reliably predicted PH severity in the Vienna cACLD cohort but exhibited heterogeneous results on external validation. The proposed 3P/5P online tool can reliably identify individuals with CSPH or severe PH, who are thus at risk of hepatic decompensation. IMPACT AND IMPLICATIONS: We used machine learning models based on widely available laboratory parameters to develop a non-invasive model to predict the severity of portal hypertension in individuals with compensated cirrhosis, who currently require invasive measurement of hepatic venous pressure gradient. We validated our findings in a large multicentre cohort of individuals with advanced chronic liver disease (cACLD) of any cause. Finally, we provide a readily available online calculator, based on 3 (platelet count, bilirubin, international normalised ratio) or 5 (platelet count, bilirubin, activated partial thromboplastin time, gamma-glutamyltransferase, choline-esterase) widely available laboratory parameters, that clinicians can use to predict the likelihood of their patients with cACLD having clinically significant or severe portal hypertension.

Peripheral versus central venous blood sampling does not influence the assessment of platelet activation in cirrhosis.

Cirrhotic patients have an increased risk of bleeding and thromboembolic events, with platelets being involved as key players in both situations. The impact of peripheral versus central blood sampling on platelet activation remains unclear. In 33 cirrhotic patients, we thus analyzed platelet function in peripheral (P) and central (C) blood samples. Platelet surface expression of P-selectin, activated glycoprotein (GP) IIb/IIIa, and leukocyte-platelet aggregate formation were measured by flow cytometry in response to different agonists: thrombin receptor-activating peptide-6, adenosine diphosphate, collagen-related peptide (CrP), epinephrine, AYPGKF, Pam3CSK4, and lipopolysaccharide. Unstimulated platelet surface expression of P-selectin (p = .850) and activated GPIIb/IIIa (p = .625) were similar in peripheral and central blood samples. Stimulation with various agonists yielded similar results of platelet surface expression of P-selectin and activated GPIIb/IIIa in peripheral and central samples, except for CrP-inducible expression of activated GPIIb/IIIa (median fluorescence intensity, MFI in P: 7.61 [0.00-24.66] vs. C: 4.12 [0.00-19.04], p < .001). The formation of leukocyte-platelet aggregate was similar in central and peripheral blood samples, both unstimulated and after stimulation with all above-mentioned agonists. In conclusion, peripheral vs. central venous blood sampling does not influence the assessment of platelet activation by flow cytometry in cirrhosis.Abbreviations: ACLD: advanced chronic liver disease; ADP: adenosine diphosphate; ALD: alcoholic liver disease; AYPGKF: PAR-4 agonist AYPGKF; CrP: collagen related protein; EPI: epinephrine; FACS: fluorescence-activated cell sorting; GP: glycoprotein; HVPG: hepatic venous pressure gradient; IQR: interquartile range; LPS: lipopolysaccharide; LSM: liver stiffness measurement; MFI: median fluorescence intensity; NAFLD: nonalcoholic fatty liver disease; PAM: lipopeptide Pam3CSK4; PAR: protease-activated receptor; PBS: phosphate-buffered saline; PH: portal hypertension; TIPS: transjugular intrahepatic portosystemic stent shunt; TLR: toll-like receptor; TRAP-6: thrombin receptor-activator peptide-6; vWF: von Willebrand factor.

Point Shear Wave Elastography for Non-invasive Assessment of Liver Fibrosis in Patients with Viral Hepatitis.

Elastography point quantification (ElastPQ) is a new ultrasound-based shear wave elastography method for non-invasive assessment of liver fibrosis. We evaluated the diagnostic accuracy of ElastPQ in patients with chronic viral hepatitis. Fibrosis stage (F) was determined by transient elastography (F0/F1: <7.1 kPa, F2: 7.1-9.4 kPa, F3: 9.5-12.4 kPa, F4: ≥12.5 kPa). Area under the receiver operator characteristics curve (AUROC) analysis was performed to assess ElastPQ cutoffs for significant fibrosis (≥F2) and cirrhosis (F4). Paired transient elastography and ElastPQ measurements were obtained from 217 patients (mean age ± SEM: 49 ± 0.79 years, 68.2% male, F0/F1: n = 98 [45.0%], F2: 47 [21.6%], F3: 22 [10.1%], F4: 50 [22.9%]). AUROC for ≥F2 was 0.843 (95% confidence interval: 0.791-0.895), and for F4, 0.933 (95% confidence interval: 0.894-0.972). The optimal ElastPQ cutoff for F2 was 6.68 kPa (sensitivity: 80.7%, specificity: 70.4%, positive predictive value: 78.5%, negative predictive value: 72.3%), and for F4 11.28 kPa (sensitivity: 86.0%, specificity: 85.6%, positive predictive value: 60.52%, negative predictive value: 97.16%). In conclusion, ElastPQ represents an accurate tool for non-invasive staging of liver fibrosis in patients with viral hepatitis.

Adherence to quality criteria improves concordance between transient elastography and ElastPQ for liver stiffness assessment-A multicenter retrospective study.

BACKGROUND: Assessment of liver stiffness provides important diagnostic and prognostic information in patients with chronic liver disease. AIMS: To investigate whether the use of quality criteria (i) improves the concordance between transient elastography (TE) and a novel point shear wave elastography technique (ElastPQ®) and (ii) impacts on the performance of ElastPQ® for liver fibrosis staging using TE as the reference standard. METHODS: In this multicenter retrospective study, data of patients undergoing liver stiffness measurements (LSM) in five European centers were collected. TE was performed with FibroScan® (Echosens, France) and ElastPQ® with EPIQ® or Affiniti® systems (Philips, The Netherlands). The agreement between TE and ElastPQ® LSMs was assessed with Lin's concordance correlation coefficient (CCC). Diagnostic performance of ElastPQ® was assessed by the area under receiver operating characteristic (AUROC) curves. RESULTS: Overall, 664 patients were included: mean age: 54.8(13.5) years, main etiologies: viral hepatitis (83.1%) and NAFLD (7.5%). CCC increased significantly when LSMs with ElastPQ® were obtained with IQR/M ≤ 30% (p < 0.001). The diagnostic performance of ElastPQ® for fibrosis staging also increased if LSM values were obtained with IQR/M ≤ 30%. CONCLUSION: Quality criteria should be followed when using ElastPQ® for LSM, since the concordance with TE fibrosis staging was better at an ElastPQ® IQR/M ≤ 30.

Non-invasive liver fibrosis assessment and HCV treatment initiation within a systematic screening program in HIV/HCV coinfected patients.

BACKGROUND AND AIM: Hepatitis C virus (HCV) therapy should be considered without delay in all patients with significant (SIGFIB) or advanced liver fibrosis (ADVFIB). We aimed to investigate the rates of treatment initiation with interferon-free regimens within a screening program for SIGFIB/ADVFIB in human immunodeficiency virus/HCV coinfected patients (HIV/HCV). METHODS: The FIB-4 was calculated in all HIV/HCV from 2014-2016. HIV/HCV were counselled by the HIV clinic and referred to the Division of Gastroenterology and Hepatology for transient elastography (TE) and evaluation for HCV therapy. Patients were stratified by FIB-4 of 7.1 kPa/>9.5 kPa, respectively. RESULTS: Among 1348 HIV+ patients, 16% (210/1348) had detectable HCV-RNA. One hundred HIV/HCV had a FIB-4 ≥1.45. Among these, 57% (57/100) underwent TE. The majority of these patients had SIGFIB (75%; 43/57) or ADVFIB (37%; 21/57), however, interferon-free treatment was initiated in only 56% (24/43). In addition, fifty-two percent (57/110) of HIV/HCV with FIB-4 <1.45 underwent TE. Interestingly, 40% (23/57) and 18% (10/57) of these patients showed SIGFIB or even ADVFIB, respectively, and 78% (18/23) finally received interferon-free treatment. Overall, only 20% (42/210) of HIV/HCV received interferon-free treatment. CONCLUSION: FIB-4 was not useful for ruling out SIGFIB/ADVFIB in our cohort of HIV/HCV. Treatment was initiated only in a small proportion (20%) of HIV/HCV during the first 2 years of interferon-free treatment availability, although the observed proportion of patients with SIGFIB (assessed by TE) was considerably higher (58%). Thus, it requires the ongoing combined efforts of both HIV and HCV specialists to increase treatment uptake rates in this special population.

Assessment of response to beta-blockers by expression of ßArr2 and RhoA/ROCK2 in antrum mucosa in cirrhotic patients.

BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are first choice for prevention of variceal bleeding. But possible deleterious effects in refractory ascites and frequent non-response are clinical drawbacks. Since levels of vasoactive proteins in antrum mucosa reflect vascular dysfunction in cirrhosis, these expression levels might also reflect hemodynamic response to NSBB. METHODS: Biopsies from the gastric and duodenal mucosa of 25 patients with cirrhosis were collected and the hepatic venous pressure gradient (HVPG) was measured before and after an acute propranolol challenge. Transcription and protein expression of Ras homolog family member A (RhoA), Rho-kinase (ROCK)2, beta-arrestin2 (ßArr2), endothelial nitric oxide synthase (eNOS) and the phosphorylation of downstream effectors VASP and moesin were analyzed using PCR and Western blot. Further 21 patients on NSBB were evaluated on their follow up for events of variceal bleeding defined as non-response. RESULTS: Ten patients showed HVPG <10mmHg, further seven patients showed significant hemodynamic response to NSBB, whereas eight patients were non-responders. The mucosal transcription of vasoactive proteins was higher in antrum mucosa compared to corpus and duodenum. The transcriptional levels of vasoactive proteins were higher in patients with HVPG >10mmHg and HVPG >16mmHg. Interestingly, mRNA levels of RhoA and ROCK2 were lower in patients with large varices at endoscopy. Moreover, RhoA and ROCK2 transcription correlated with the decrease of HVPG after acute NSBB challenge. Finally, acute and long-term non-responders showed lower expression of ßArr2 in antrum mucosa. CONCLUSION: This study shows for the first time that the expression of ßArr2 in antrum mucosa biopsies might reflect the hemodynamic response to NSBB and their long-term protective effect. This finding might offer an easy approach at upper endoscopy to facilitate the decision to treat with NSBB if varices are present.

Performance of 2-D shear wave elastography in liver fibrosis assessment compared with serologic tests and transient elastography in clinical routine.

Liver stiffness values assessed with 2-D shear wave elastography (SWE), transient elastography (TE) and simple serologic tests were compared with respect to non-invasive assessment in a cohort of 127 consecutive patients with chronic liver diseases. The rate of reliable liver stiffness measurements was significantly higher with 2-D SWE than with TE: 99.2% versus 74.8%, p < 0.0001 (different reliability criteria used, according to current recommendations). In univariate analysis, liver stiffness measured with 2-D SWE correlated best with fibrosis stage estimated with TE (r = 0.699, p < 0.0001), followed by Forns score (r = 0.534, p < 0.0001) and King's score (r = 0.512, p < 0.0001). However, in multivariate analysis, only 2-D SWE-measured values remained correlated with fibrosis stage (p < 0.0001). The optimal 2-D SWE cutoff values for predicting significant fibrosis were 8.03 kPa for fibrosis stage ≥2 (area under the receiver operating characteristic curve = 0.832) and 13.1 kPa for fibrosis stage 4 (area under the receiver operating characteristic curve = 0.915), respectively. In conclusion, 2-D SWE can be used to obtain reliable liver stiffness measurements in almost all patients and performs very well in predicting the presence of liver cirrhosis.