MR Elastography for Classification of Focal Liver Lesions Using Viscoelastic Parameters: A Pilot Study Based on Intrinsic and Extrinsic Activations.

BACKGROUND: Intrinsic activation MR elastography (iMRE) uses cardiovascular pulsations to assess tissue viscoelastic properties. Applying it to focal liver lesions extends its capabilities. PURPOSE: To assess the viscoelastic parameters of focal liver lesions measured by iMRE and compare its diagnostic performance with extrinsic MRE (eMRE) for differentiating malignant and benign lesions. STUDY TYPE: Prospective. POPULATION: A total of 55 participants underwent MRI with research MRE sequences; 32 participants with 17 malignant and 15 benign lesions underwent both iMRE and eMRE. FIELD STRENGTH/SEQUENCE: iMRE at ~1 Hz heart rate used a 3 T scanner with a modified four-dimensional (4D)-quantitative flow gradient-echo phase contrast and low-velocity encoding cardiac-triggered technique. eMRE employed a gradient-echo sequence at 30, 40, and 60 Hz. ASSESSMENT: Liver displacements were measured using 4D-phase contrast and reconstructed via a nonlinear inversion algorithm to determine shear stiffness (SS) and damping ratio (DR). iMRE parameters were normalized to the corresponding values from the spleen. Lesions were manually segmented, and image quality was reviewed. STATISTICAL TESTS: Kruskal-Wallis, Mann-Whitney, Dunn's test, and areas under receiver operating characteristic curves (AUC) were assessed. RESULTS: SS was significantly higher in malignant than benign lesions with iMRE at 1 Hz (3.69 ± 1.31 vs. 1.63 ± 0.45) and eMRE at 30 Hz (3.76 ± 1.12 vs. 2.60 ± 1.26 kPa), 40 Hz (3.76 ± 1.12 vs. 2.60 ± 1.26 kPa), and 60 Hz (7.32 ± 2.87 vs. 2.48 ± 1.12 kPa). DR was also significantly higher in malignant than benign lesions at 40 Hz (0.36 ± 0.11 vs. 0.21 ± 0.01) and 60 Hz (0.89 ± 0.86 vs. 0.22 ± 0.09). The AUC were 0.86 for iMRE SS, 0.87-0.98 for eMRE SS, 0.47 for iMRE DR, and 0.62-0.86 for eMRE DR. DATA CONCLUSION: Cardiac-activated iMRE can characterize liver lesions and differentiate malignant from benign lesions through normalized SS maps. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Between-Visit Reproducibility of Shear Wave Viscoelastography in Volunteers and Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

OBJECTIVE: To assess the reproducibility of six ultrasound (US)-determined shear wave (SW) viscoelastography parameters for assessment of mechanical properties of the liver in volunteers and patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH). METHODS: This prospective, cross-sectional, institutional review board-approved study included 10 volunteers and 20 patients with MASLD or MASH who underwent liver US elastography twice, at least 2 weeks apart. SW speed (SWS), Young's modulus (E), shear modulus (G), SW attenuation (SWA), SW dispersion (SWD), and viscosity were computed from radiofrequency data recorded on a research US scanner. Linear mixed models were used to consider the sonographer on duty as a confounder. The reproducibility of measurements was assessed by intraclass correlation coefficient (ICC), coefficient of variation (CV), reproducibility coefficient (RDC), and Bland-Altman analyses. RESULTS: The sonographer performing the exam had no impact on viscoelastic parameters (P > .05). ICCs of SWS, E, G, SWA, SWD, and viscosity were, respectively, 0.89 (95% confidence intervals [CI]: 0.79-0.95), 0.81 (95% CI: 0.79-0.95), 0.90 (95% CI: 0.80-0.95), 0.96 (95% CI: 0.93-0.98), 0.78 (95% CI: 0.60-0.89), and 0.90 (95% CI: 0.80-0.95); CVs were 11.9, 23.3, 24.2, 10.1, 29.0, and 32.2%; RDCs were 33.0, 64.5, 66.9, 27.7, 80.3, and 89.2%, and Bland-Altman mean biases and 95% limits of agreement were -0.05 (-0.45, 0.35) m/s, -0.61 (-5.33, 4.10) kPa, -0.25 (-2.06, 1.56) kPa, -0.01 (-0.27, 0.26) Np/m/Hz, -0.09 (-7.09, 6.91) m/s/kHz, and -0.33 (-2.60, 1.94) Pa/s, between the two visits. CONCLUSION: US-determined viscoelastography parameters can be measured with high reproducibility and consistency between two visits 2 weeks apart on the same ultrasound machine.

Inter-visit and inter-reader reproducibility of multi-parametric diffusion-weighted MR imaging in longitudinally imaged patients with metabolic dysfunction-associated fatty liver disease and healthy volunteers.

BACKGROUND: Despite the widespread use of diffusion-weighted imaging (DWI) in metabolic dysfunction-associated fatty liver disease (MAFLD), MRI acquisition and quantification techniques vary in the literature suggesting the need for established and reproducible protocols. The goal of this study was to assess inter-visit and inter-reader reproducibility of DWI- and IVIM-derived parameters in patients with MAFLD and healthy volunteers using extensive sampling of the "fast" compartment, non-rigid registration, and exclusion voxels with poor fit quality. METHODS: From June 2019 to April 2023, 31 subjects (20 patients with biopsy-proven MAFLD and 11 healthy volunteers) were included in this IRB-approved study. Subjects underwent MRI examinations twice within 40 days. 3.0 T DWI was acquired using a respiratory-triggered spin-echo diffusion-weighted echo-planar imaging sequence (b-values of 0, 10, 20, 30, 40, 50, 100, 200, 400, 800 s/mm2). DWI series were co-registered prior to voxel-wise non-linear regression of the IVIM model and voxels with poor fit quality were excluded (normalized root mean squared error ≥ 0.05). IVIM parameters (perfusion fraction, f; diffusion coefficient, D; and pseudo-diffusion coefficient, D*), and apparent diffusion coefficients (ADC) were computed from manual segmentation of the right liver lobe performed by two analysts on two MRI examinations. RESULTS: All results are reported for f, D, D*, and ADC respectively. For inter-reader agreement on the first visit, ICC were of 0.985, 0.994, 0.986, and 0.993 respectively. For intra-reader agreement of analyst 1 assessed on both imaging examinations, ICC between visits were of 0.805, 0.759, 0.511, and 0.850 respectively. For inter-reader agreement on the first visit, mean bias and 95 % limits of agreement were (0.00 ± 0.03), (-0.01 ± 0.03) × 10-3 mm2/s, (0.70 ± 10.40) × 10-3 mm2/s, and (-0.02 ± 0.04) × 10-3 mm2/s respectively. For intra-reader agreement of analyst 1, mean bias and 95 % limits of agreement were (0.01 ± 0.09) × 10-3 mm2/s, (-0.01 ± 0.21) × 10-3 mm2/s, (-13.37 ± 56.19) × 10-3 mm2/s, and (-0.01 ± 0.16) × 10-3 mm2/s respectively. Except for parameter D* that was associated with between-subjects parameter variability (P = 0.009), there was no significant variability between subjects, examinations, or readers. CONCLUSION: With our approach, IVIM parameters f, D, D*, and ADC provided excellent inter-reader agreement and good to very good inter-visit or intra-reader agreement, thus showing the reproducibility of IVIM-DWI of the liver in MAFLD patients and volunteers.

Risk Factors for Hospitalization Duration Longer Than 24 Hours Following Percutaneous Radiofrequency Ablation of Liver Tumours.

PURPOSE: Prior studies have described complications of radiofrequency ablation (RFA) of liver tumours. The aim of this study was to identify risk factors for hospitalization duration longer than 24 hours following RFA of liver tumours. METHODS: This retrospective, single-centre study included patients with liver tumours undergoing RFA between October 2017 and July 2020. Medical records were reviewed to collect patient, tumours, and procedure characteristics for each RFA session. The association between potential risk factors and duration of hospitalization (less than or more than 24 hours) was analyzed using univariate and multivariate logistic regressions. RESULTS: Our study included 291 patients (mean age: 65.2 ± 11.2 [standard deviation]; 201 men) undergoing 324 RFA sessions. Sixty-eight sessions (21.0%) resulted in hospitalization of more than 24 hours. Multivariate analysis identified each additional needle insertion per session (OR 1.4; 95% CI [1.1-1.9]; P = .02), RFA performed in segment V (OR 2.8; 95% CI [1.4-5.7]; P = .004), and use of artificial pneumothorax (OR 14.5; 95% CI [1.4-146.0]; P = .02) as potential risk factors. A history of hepatic encephalopathy (OR 2.6; 95% CI [1.1-6.0]; P = .03) was only significant in univariate analysis. Post-hoc, subgroup analysis of patients with hepatocellular carcinoma (69.8%) did not identify other risk factors. CONCLUSION: Risk factors for a hospitalization duration longer than 24 hours include a higher number of needle insertions per session, radiofrequency ablation in segment V, and use of an artificial pneumothorax.

IL-6 Trans-Signaling Is Increased in Diabetes, Impacted by Glucolipotoxicity, and Associated With Liver Stiffness and Fibrosis in Fatty Liver Disease.

Many people living with diabetes also have nonalcoholic fatty liver disease (NAFLD). Interleukin-6 (IL-6) is involved in both diseases, interacting with both membrane-bound (classical) and circulating (trans-signaling) soluble receptors. We investigated whether secretion of IL-6 trans-signaling coreceptors are altered in NAFLD by diabetes and whether this might associate with the severity of fatty liver disease. Secretion patterns were investigated with use of human hepatocyte, stellate, and monocyte cell lines. Associations with liver pathology were investigated in two patient cohorts: 1) biopsy-confirmed steatohepatitis and 2) class 3 obesity. We found that exposure of stellate cells to high glucose and palmitate increased IL-6 and soluble gp130 (sgp130) secretion. In line with this, plasma sgp130 in both patient cohorts positively correlated with HbA1c, and subjects with diabetes had higher circulating levels of IL-6 and trans-signaling coreceptors. Plasma sgp130 strongly correlated with liver stiffness and was significantly increased in subjects with F4 fibrosis stage. Monocyte activation was associated with reduced sIL-6R secretion. These data suggest that hyperglycemia and hyperlipidemia can directly impact IL-6 trans-signaling and that this may be linked to enhanced severity of NAFLD in patients with concomitant diabetes. ARTICLE HIGHLIGHTS: IL-6 and its circulating coreceptor sgp130 are increased in people with fatty liver disease and steatohepatitis. High glucose and lipids stimulated IL-6 and sgp130 secretion from hepatic stellate cells. sgp130 levels correlated with HbA1c, and diabetes concurrent with steatohepatitis further increased circulating levels of all IL-6 trans-signaling mediators. Circulating sgp130 positively correlated with liver stiffness and hepatic fibrosis. Metabolic stress to liver associated with fatty liver disease might shift the balance of IL-6 classical versus trans-signaling, promoting liver fibrosis that is accelerated by diabetes.

Ultrasound Shear Wave Attenuation Imaging for Grading Liver Steatosis in Volunteers and Patients With Non-alcoholic Fatty Liver Disease: A Pilot Study.

OBJECTIVE: The aims of the work described here were to assess shear wave attenuation (SWA) in volunteers and patients with non-alcoholic fatty liver disease (NAFLD) and compare its diagnostic performance with that of shear wave dispersion (SWD), magnetic resonance imaging (MRI) proton density fat fraction (PDFF) and biopsy. METHODS: Forty-nine participants (13 volunteers and 36 NAFLD patients) were enrolled. Ultrasound and MRI examinations were performed in all participants. Biopsy was also performed in patients. SWA was used to assess histopathology grades as potential confounders. The areas under curves (AUCs) of SWA, SWD and MRI-PDFF were assessed in different steatosis grades by biopsy. Youden's thresholds of SWA were obtained for steatosis grading while using biopsy or MRI-PDFF as the reference standard. RESULTS: Spearman's correlations of SWA with histopathology (steatosis, inflammation, ballooning and fibrosis) were 0.89, 0.73, 0.62 and 0.31, respectively. Multiple linear regressions of SWA confirmed the correlation with steatosis grades (adjusted R2 = 0.77, p < 0.001). The AUCs of MRI-PDFF, SWA and SWD were respectively 0.97, 0.99 and 0.94 for S0 versus ≥S1 (p > 0.05); 0.94, 0.98 and 0.78 for ≤S1 versus ≥S2 (both MRI-PDFF and SWA were higher than SWD, p < 0.05); and 0.90, 0.93 and 0.68 for ≤S2 versus S3 (both SWA and MRI-PDFF were higher than SWD, p < 0.05). SWA's Youden thresholds (Np/m/Hz) (sensitivity, specificity) for S0 versus ≥S1, ≤S1 versus ≥S2 and ≤S2 versus S3 were 1.05 (1.00, 0.92), 1.37 (0.96, 0.96) and 1.51 (0.83, 0.87), respectively. These values were 1.16 (1.00, 0.81), 1.49 (0.91, 0.82) and 1.67 (0.87, 0.92) when considering MRI-PDFF as the reference standard. CONCLUSION: In this pilot study, SWA increased with increasing steatosis grades, and its diagnostic performance was higher than that of SWD but equivalent to that of MRI-PDFF.

Perioperative clinical practice in liver transplantation: a cross-sectional survey.

PURPOSE: The objective of this study was to describe some components of the perioperative practice in liver transplantation as reported by clinicians. METHODS: We conducted a cross-sectional clinical practice survey using an online instrument containing questions on selected themes related to the perioperative care of liver transplant recipients. We sent email invitations to Canadian anesthesiologists, Canadian surgeons, and French anesthesiologists specialized in liver transplantation. We used five-point Likert-type scales (from "never" to "always") and numerical or categorical answers. Results are presented as medians or proportions. RESULTS: We obtained answers from 130 participants (estimated response rate of 71% in Canada and 26% in France). Respondents reported rarely using transesophageal echocardiography routinely but often using it for hemodynamic instability, often using an intraoperative goal-directed hemodynamic management strategy, and never using a phlebotomy (medians from ordinal scales). Fifty-nine percent of respondents reported using a restrictive fluid management strategy to manage hemodynamic instability during the dissection phase. Forty-two percent and 15% of respondents reported using viscoelastic tests to guide intraoperative and postoperative transfusions, respectively. Fifty-four percent of respondents reported not pre-emptively treating preoperative coagulations disturbances, and 91% reported treating them intraoperatively only when bleeding was significant. Most respondents (48-64%) did not have an opinion on the maximal graft ischemic times. Forty-seven percent of respondents reported that a piggyback technique was the preferred vena cava anastomosis approach. CONCLUSION: Different interventions were reported to be used regarding most components of perioperative care in liver transplantation. Our results suggest that significant equipoise exists on the optimal perioperative management of this population.

RéSUMé: OBJECTIF: L'objectif de cette étude était de décrire certaines composantes de la pratique périopératoire en transplantation hépatique telles que rapportées par les cliniciens. MéTHODE: Nous avons mené un sondage transversal sur la pratique clinique à l'aide d'un instrument en ligne comportant des questions sur des thèmes sélectionnés liés aux soins périopératoires des receveurs de greffe du foie. Nous avons envoyé des invitations par courriel à des anesthésiologistes canadiens, des chirurgiens canadiens et des anesthésiologistes français spécialisés en transplantation hépatique. Nous avons utilisé des échelles de type Likert à cinq points (de « jamais ¼ à « toujours ¼) et des réponses numériques ou catégorielles. Les résultats sont présentés sous forme de médianes ou de proportions. RéSULTATS: Nous avons obtenu des réponses de 130 participants (taux de réponse estimé à 71 % au Canada et à 26 % en France). Les répondants ont déclaré utiliser rarement l'échocardiographie transœsophagienne de routine, mais l'utiliser fréquemment pour l'instabilité hémodynamique, souvent en utilisant une stratégie de prise en charge hémodynamique peropératoire axée sur les objectifs, et jamais en utilisant une phlébotomie (médianes des échelles ordinales). Cinquante-neuf pour cent des répondants ont déclaré utiliser une stratégie restrictive de gestion liquidienne pour prendre en charge l'instabilité hémodynamique pendant la phase de dissection. Quarante-deux pour cent et 15 % des répondants ont déclaré utiliser des tests viscoélastiques pour guider les transfusions peropératoires et postopératoires, respectivement. Cinquante-quatre pour cent des répondants ont déclaré ne pas traiter préventivement les troubles préopératoires de la coagulation, et 91 % ont déclaré les traiter en peropératoire uniquement lorsque les saignements étaient importants. La plupart des répondants (48-64 %) n'avaient pas d'opinion sur les temps ischémiques maximaux du greffon. Quarante-sept pour cent des répondants ont déclaré qu'une technique de 'piggyback' (anastomose latéroterminale) était l'approche préférée pour l'anastomose de la veine cave. CONCLUSION: Différentes interventions ont été signalées pour la plupart des composantes des soins périopératoires dans la transplantation hépatique. Nos résultats suggèrent qu'il existe une incertitude significative concernant la prise en charge périopératoire optimale de cette population.

EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B.

BACKGROUND: Chronic hepatitis B (CHB) remains a major cause of morbidity and mortality. EDP-514 is a potent core inhibitor of hepatitis B virus (HBV) that reduces viral load reduction in HBV-infected chimeric mice. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics (PK) of EDP-514 in healthy subjects and antiviral activity in patients with CHB. METHODS: In Part 1, 82 subjects received placebo or EDP-514 in fed or fasted state as single ascending doses of 50-800 mg and multiple ascending doses of 200-800 mg for 14 days. In Part 2, 24 HBV DNA-suppressed, nucleos(t)ide (NUC)-treated (i.e., NUC-suppressed) CHB patients received EDP-514 200-800 mg or placebo for 28 days. RESULTS: EDP-514 was well tolerated in healthy subjects and CHB patients with most adverse events of mild intensity. In Part 1, EDP-514 exposure increased in an approximately dose proportional manner up to 600 mg after single doses and up to 400 mg after 14-day dosing. In Part 2, EDP-514 exposure increased linearly with dose on Day 1 and Day 28, with some accumulation for Day 28 and median trough concentrations (Ctrough) approximately 20-fold above the protein-adjusted 50% effective concentration (EC50) for the dose range. Mean change in HBV RNA from baseline to Day 28 was -2.03, -1.67, -1.87, and -0.58 log U/mL in the 200 mg, 400 mg, 800 mg, and placebo CHB groups, respectively. CONCLUSIONS: EDP-514 was well tolerated, had a PK profile supporting once daily dosing, and reduced HBV RNA levels in NUC-suppressed CHB patients.

Quantitative ultrasound, elastography, and machine learning for assessment of steatosis, inflammation, and fibrosis in chronic liver disease.

OBJECTIVE: To develop a quantitative ultrasound (QUS)- and elastography-based model to improve classification of steatosis grade, inflammation grade, and fibrosis stage in patients with chronic liver disease in comparison with shear wave elastography alone, using histopathology as the reference standard. METHODS: This ancillary study to a prospective institutional review-board approved study included 82 patients with non-alcoholic fatty liver disease, chronic hepatitis B or C virus, or autoimmune hepatitis. Elastography measurements, homodyned K-distribution parametric maps, and total attenuation coefficient slope were recorded. Random forests classification and bootstrapping were used to identify combinations of parameters that provided the highest diagnostic accuracy. Receiver operating characteristic (ROC) curves were computed. RESULTS: For classification of steatosis grade S0 vs. S1-3, S0-1 vs. S2-3, S0-2 vs. S3, area under the receiver operating characteristic curve (AUC) were respectively 0.60, 0.63, and 0.62 with elasticity alone, and 0.90, 0.81, and 0.78 with the best tested model combining QUS and elastography features. For classification of inflammation grade A0 vs. A1-3, A0-1 vs. A2-3, A0-2 vs. A3, AUCs were respectively 0.56, 0.62, and 0.64 with elasticity alone, and 0.75, 0.68, and 0.69 with the best model. For classification of liver fibrosis stage F0 vs. F1-4, F0-1 vs. F2-4, F0-2 vs. F3-4, F0-3 vs. F4, AUCs were respectively 0.66, 0.77, 0.72, and 0.74 with elasticity alone, and 0.72, 0.77, 0.77, and 0.75 with the best model. CONCLUSION: Random forest models incorporating QUS and shear wave elastography increased the classification accuracy of liver steatosis, inflammation, and fibrosis when compared to shear wave elastography alone.

Association between intraoperative fluid balance, vasopressors and graft complications in liver transplantation: A cohort study.

INTRODUCTION: Biliary complications following liver transplantation are common. The effect of intraoperative fluid balance and vasopressors on these complications is unknown. MATERIALS AND METHODS: We conducted a cohort study between July 2008 and December 2017. Our exposure variables were the total intraoperative fluid balance and the use of vasopressors on ICU admission. Our primary outcome was any biliary complication (anastomotic and non-anastomotic strictures) up to one year after transplantation. Our secondary outcomes were vascular complications, primary graft non-function and survival. RESULTS: We included 562 consecutive liver transplantations. 192 (34%) transplants had a biliary complication, 167 (30%) had an anastomotic stricture and 56 had a non-anastomotic stricture (10%). We did not observe any effect of intraoperative fluid balance or vasopressor on biliary complications (HR = 0.97; 95% CI, 0.93 to 1.02). A higher intraoperative fluid balance was associated with an increased risk of primary graft non-function (non-linear) and a lower survival (HR = 1.40, 95% CI, 1.14 to 1.71) in multivariable analyses. CONCLUSION: Intraoperative fluid balance and vasopressors upon ICU admission were not associated with biliary complications after liver transplantation but may be associated with other adverse events. Intraoperative hemodynamic management must be prospectively studied to further assess their impact on liver recipients' outcomes.

A real-world experience of SARS-CoV-2 infection in a tertiary referral centre of Montréal: Unexpected low prevalence and low mortality.

BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre Centre hospitalier de l'Université de Montréal (CHUM) during the first wave of the SARS-CoV-2 pandemic. METHODS: This real-world, retrospective cohort included all patients admitted to our liver unit and/or seen as an outpatient with CLD with or without cirrhosis and/or LT recipients who tested positive to SARS-CoV-2 infection. Cases were considered positive as defined by the detection of SARS-CoV-2 by reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. RESULTS: Between April 1 and July 31, 2020, 5,637 were admitted to our liver unit and/or seen as outpatient. Among them, 42 were positive for SARS-CoV-2. Twenty-two patients had CLD without cirrhosis while 16 patients had cirrhosis at the time of the infection (13, 2, and 1 with Child-Pugh A, B, and C scores, respectively). Four were LT recipients. Overall, 15 of 42 patients (35.7%) were hospitalized; among them, 7 of 42 (16.7%) required respiratory support and 4 of 42 (9.5%) were transferred to the intensive care unit. Only 4 of 42 (9.5%) patients died: 2 with CLD without cirrhosis and 2 with CLD with cirrhosis. Overall survival was 90.5%. CONCLUSION: This real-world study demonstrates an unexpectedly low prevalence and low mortality in the context of SARS-CoV-2 infection among patients with CLD with or without cirrhosis and LT recipients.

Acute Severe Liver Injury Related to Long-Term Garcinia cambogia Intake.

Herbal and dietary supplements are frequently used as weight loss supplements. However, they account for 20% of drug-induced liver injury. Garcinia cambogia's (GC) active compound, hydroxycitric acid, can be found among those supplements. We report a 26-year-old woman who had been taking GC for 7 months when she presented with subacute liver failure and ultimately required a liver transplantation. This report highlights the risk of liver injury after long-term use of GC and demonstrates the importance of considering a close and prolonged monitoring of patients in a tertiary liver transplant center.

Prospective comparison of transient, point shear wave, and magnetic resonance elastography for staging liver fibrosis.

OBJECTIVES: To perform head-to-head comparisons of the feasibility and diagnostic performance of transient elastography (TE), point shear-wave elastography (pSWE), and magnetic resonance elastography (MRE). METHODS: This prospective, cross-sectional, dual-center imaging study included 100 patients with known or suspected chronic liver disease caused by hepatitis B or C virus, nonalcoholic fatty liver disease, or autoimmune hepatitis identified between 2014 and 2018. Liver stiffness measured with the three elastographic techniques was obtained within 6 weeks of a liver biopsy. Confounding effects of inflammation and steatosis on association between fibrosis and liver stiffness were assessed. Obuchowski scores and AUCs for staging fibrosis were evaluated and the latter were compared using the DeLong method. RESULTS: TE, pSWE, and MRE were technically feasible and reliable in 92%, 79%, and 91% subjects, respectively. At univariate analysis, liver stiffness measured by all techniques increased with fibrosis stages and inflammation and decreased with steatosis. For classification of dichotomized fibrosis stages, the AUCs were significantly higher for distinguishing stages F0 vs. ≥ F1 with MRE than with TE (0.88 vs. 0.71; p < 0.05) or pSWE (0.88 vs. 0.73; p < 0.05), and for distinguishing stages ≤ F1 vs. ≥ F2 with MRE than with TE (0.85 vs. 0.75; p < 0.05). TE, pSWE, and MRE Obuchowski scores for staging fibrosis stages were respectively 0.89 (95% CI 0.85-0.93), 0.90 (95% CI 0.85-0.94), and 0.94 (95% CI 0.91-0.96). CONCLUSION: MRE provided a higher diagnostic performance than TE and pSWE for staging early stages of liver fibrosis. TRIAL REGISTRATION: NCT02044523 KEY POINTS: • The technical failure rate was similar between MRE and US-based elastography techniques. • Liver stiffness measured by MRE and US-based elastography techniques increased with fibrosis stages and inflammation and decreased with steatosis. • MRE provided a diagnostic accuracy higher than US-based elastography techniques for staging of early stages of histology-determined liver fibrosis.

Superior Wait-List Outcomes in Patients with Alcohol-Associated Liver Disease Compared With Other Indications for Liver Transplantation.

Alcohol-associated liver disease (ALD) is the most common indication for liver transplantation (LT) in the United States and Europe. A 6-month alcohol abstinence period has been required by many transplant programs prior to listing, which may influence wait-list (WL) outcomes. Therefore, we examined WL events in patients with ALD versus non-ALD with a special interest in whether these outcomes differed by sex. All US adults listed for LT from January 2002 to December 2016 were eligible except status 1 patients, Model for End-Stage Liver Disease exceptions, retransplants and those with acute alcoholic hepatitis. The outcomes of interest were cumulative WL death or being too sick and WL removal for improvement within 2 years of listing. Competing risk regression models were used to evaluate recipient factors associated with the outcomes. Among the 83,348 eligible WL patients, 23% had ALD. Unadjusted cumulative WL removal within 2 years was 19.0% for ALD versus 21.1% for non-ALD (P < 0.001). In fully adjusted models, ALD was associated with a significantly lower risk of WL removal for death or being too sick (subhazard ratio [SHR], 0.84; 95% confidence interval [CI], 0.81-0.87; P < 0.001) and a higher risk of removal for improvement (SHR, 2.91; 95% CI, 2.35-3.61; P < 0.001) versus non-ALD patients. After adjusting for potential confounders, women with ALD had a higher risk of removal for death or being too sick (SHR, 1.09; 95% CI, 1.00-1.08; P < 0.001) and a higher chance for improvement (SHR, 2.91; 95% CI, 2.35-3.61; P < 0.001) than men with ALD. In conclusion, WL candidates with ALD have more favorable WL outcomes than non-ALD patients with a 16% lower risk of removal for deterioration and 191% higher risk of removal for improvement. This result likely reflects the benefits of alcohol abstinence, but it suggests that listing criteria for ALD may be too restrictive, with patients who might derive benefit from LT not being listed.

Cost-Utility Analysis of Imaging for Surveillance and Diagnosis of Hepatocellular Carcinoma.

OBJECTIVE. The purpose of this study is to compare imaging-based surveillance and diagnostic strategies in patients at risk for hepatocellular carcinoma (HCC) while taking into account technically inadequate examinations and patient compliance. MATERIALS AND METHODS. A Markov model simulated seven strategies for HCC surveillance and diagnosis in patients with cirrhosis: strategy A, ultrasound (US) for surveillance and CT for diagnosis; strategy B, US for surveillance and complete MRI for diagnosis; strategy C, US for surveillance and CT for inadequate or positive surveillance; strategy D, US for surveillance and complete MRI for inadequate or positive surveillance; strategy E, surveillance and diagnosis with CT followed by complete MRI for inadequate surveillance; strategy F, surveillance and diagnosis with complete MRI followed by CT for inadequate surveillance; and strategy G, surveillance with abbreviated MRI followed by CT for inadequate surveillance or complete MRI for positive surveillance. Two compliance scenarios were evaluated: optimal and conservative. For each scenario, the most cost-effective strategy was based on a willingness-to-pay threshold of $50,000 (Canadian) per quality-adjusted life year (QALY). Sensitivity analyses were performed. RESULTS. Base-case analysis revealed that strategy E was the most cost-effective when compliance was optimal ($13,631/QALY), and strategy G was the most cost-effective when compliance was conservative ($39,681/QALY). Sensitivity analyses supported the base-case analysis in the optimal compliance scenario, but several parameters altered the most cost-effective strategy in the conservative compliance scenario. CONCLUSION. In an optimal compliance scenario, CT for HCC surveillance and diagnosis and complete MRI for inadequate CT was most cost-effective. In a conservative compliance scenario, abbreviated MRI may be an alternative to US-based surveillance.

Gastric antral vascular ectasia is more frequent in patients with non-alcoholic steatohepatitis-induced cirrhosis.

Background: Gastric antral vascular ectasia (GAVE) is an uncommon cause of occult gastrointestinal (GI) bleeding. Based on clinical observations, we hypothesized that GAVE was more common in patients with non-alcoholic steatohepatitis (NASH) cirrhosis. Methods: We performed this retrospective study at Centre Hospitalier de l'Université de Montréal (CHUM). We included all cirrhotic patients who had undergone an esophagogastroduodenoscopy (EGD) between 2009 and 2011. GAVE was diagnosed based on a typical endoscopic appearance. NASH cirrhosis was diagnosed in patients with a metabolic syndrome after excluding other causes of liver disease. GAVE was considered symptomatic if it required treatment. Results: We included 855 cirrhotic patients in the study. The median age was 58 (range 19-88) years. The etiology of cirrhosis was as follows: NASH in 18% (n = 154), autoimmune diseases in 15.1% (n = 129), hepatitis B virus (HBV) in 6.3% (n = 54), hepatitis C virus (HCV) in 19.4% (n = 166), alcohol in 25.7% (n = 220), alcohol plus HCV in 7.8% (n = 67), cryptogenic in 2.8% (n = 24), and other etiologies in 4.8% (n = 41). GAVE was more frequently observed among patients with NASH cirrhosis than in cirrhosis of other etiologies (29.2% vs. 9.4%, respectively; p < 0.001). In multivariate analysis, NASH was strongly associated with GAVE with an odds ratio (OR) of 3.73 (95% CI 2.36 to 5.90, p < 0.001), and the association was stronger with symptomatic GAVE (OR 5.77, 95% CI 2.93 to 11.38). Conclusions: NASH cirrhosis is a major risk factor for GAVE and symptomatic GAVE.

Alpha-Fetoprotein Slope >7.5 ng/mL per Month Predicts Microvascular Invasion and Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Rising alpha-fetoprotein (AFP) is a potential marker of worse prognosis after liver transplant (LT) for hepatocellular carcinoma (HCC), but prior studies relied on only 2 data points and were imprecise in assessing AFP slope. The aim of this study was to examine the association between AFP slope and post-LT HCC recurrence, with AFP slope estimated from multiple data points over time. METHODS: Our cohort included 336 patients undergoing LT with Model for End Stage Liver Disease exception for HCC within Milan criteria from 2003 to 2013. Most (98%) had pre-LT locoregional therapy. AFP slope was estimated by fitting a regression line to the AFP levels over time. RESULTS: The 1- and 5-year post-LT survivals were 94% and 77% and 1- and 5-year recurrence-free probabilities were 95% and 86%, respectively. In univariate analysis, HCC recurrence was significantly associated with microvascular invasion (hazard ratio [HR], 13.1; P<0.001), tumor grade (HR, 1.8; P<0.001), pathologic stage >Milan criteria (HR, 8.9; P<0.001), 3 tumor nodules (HR, 5.5; P=0.002), AFP slope greater than 7.5 ng/mL per month (HR, 3.9; P=0.005), and female sex (HR, 2.3; P=0.01). In multivariable analysis of factors known before LT, 3 tumor nodules (HR, 7.6; P<0.001), female sex (HR, 2.5; P=0.01), and AFP slope >7.5 (HR, 3.0; P=0.03) were significantly associated with HCC recurrence. AFP slope greater than 7.5 was also associated with microvascular invasion (odds ratio, 6.8; P=0.008). CONCLUSIONS: AFP slope increasing greater than 7.5 ng/mL per month despite locoregional therapy is associated with post-LT HCC recurrence and may serve as a surrogate for microvascular invasion. These findings support incorporating changes in the AFP into candidate selection for LT.

Alcoholic liver disease is a strong predictor of colorectal polyps in liver transplant recipients.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is associated with a significantly reduced survival rate in transplant recipients. The prevalence and risk factors of CRC and of colorectal polyps after orthotopic liver transplant (OLT) remain unclear. The study aim was to determine the prevalence of colorectal polyps in OLT recipients. A secondary objective was to explore possible risk factors of polyps. PATIENTS AND MATERIALS: This was a retrospective single center study of all OLT recipients transplanted between 2007 and 2009. All patients who underwent a colonoscopy 5 ±â€Š5 years after OLT were included. The outcome was colorectal polyps, as identified on colonoscopy. A logistic regression model was performed to identify potential predictors of polyps. RESULTS: Of 164 OLT recipients, 80 were included in this study. Polyps were diagnosed in 37 % of patients before transplant and in 33 % afterwards. With regard to post-transplant lesions, 22 % were advanced adenomas or cancerous. In the regression analysis, the odds of post-transplant polyps were 11 times higher in patients with alcoholic liver disease (OR 11.3, 95 %CI 3.2 - 39.4; P  < 0.001). CONCLUSION: Patients with end-stage liver disease may be at high risk of colorectal polyps before and after liver transplant, and screening should be continued in both contexts. Those with alcoholic liver disease are particularly at risk for post-OLT polyps and may benefit from more intensive screening.