H. Aryafar

Magnetic resonance elastography is superior to acoustic radiation force impulse for the Diagnosis of fibrosis in patients with biopsy‐proven nonalcoholic fatty liver disease: A prospective study

Magnetic resonance elastography (MRE), an advanced magnetic resonance–based imaging technique, and acoustic radiation force impulse (ARFI), an ultrasound‐based imaging technique, are accurate for diagnosing nonalcoholic fatty liver disease (NAFLD) fibrosis. However, no head‐to‐head comparisons between MRE and ARFI for diagnosing NAFLD fibrosis have been performed. We compared MRE versus ARFI head‐to‐head for diagnosing fibrosis in well‐characterized patients with biopsy‐proven NAFLD. This cross‐sectional analysis of a prospective cohort involved 125 patients (54.4% female) who underwent MRE, ARFI, and contemporaneous liver biopsies scored using the Nonalcoholic Steatohepatitis Clinical Research Network histological scoring system. The performances of MRE versus ARFI for diagnosing fibrosis were evaluated using area under the receiver operating characteristic curves (AUROCs). The mean (± standard deviation) age and body mass index were 48.9 (±15.4) years and 31.8 (±7.0) kg/m2, respectively. For diagnosing any fibrosis (≥ stage 1), the MRE AUROC was 0.799 (95% confidence interval [CI] 0.723‐0.875), significantly (P = 0.012) higher than the ARFI AUROC of 0.664 (95% CI 0.568‐0.760). In stratified analysis by presence or absence of obesity, MRE was superior to ARFI for diagnosing any fibrosis in obese patients (P < 0.001) but not in nonobese patients (P = 0.722). The MRE AUROCs for diagnosing ≥stages 2, 3, and 4 fibrosis were 0.885 (95% CI 0.816‐0.953), 0.934 (95% CI 0.863‐1.000), and 0.882 (95% CI 0.729‐1.000); and the ARFI AUROCs were 0.848 (95% CI 0.776‐0.921), 0.896 (95% CI 0.824‐0.968), and 0.862 (95% CI 0.721‐1.000). MRE had higher AUROCs than ARFI for discriminating dichotomized fibrosis stages at all dichotomization cutoff points, but the AUROC differences decreased as the cutoff points (fibrosis stages) increased. Conclusion: MRE is more accurate than ARFI for diagnosing any fibrosis in NAFLD patients, especially those who are obese. (Hepatology 2016;63:453–461)

MRE is superior to ARFI for the diagnosis of fibrosis in patients with biopsy‐proven NAFLD: A prospective study

Magnetic resonance elastography (MRE), an advanced magnetic resonance–based imaging technique, and acoustic radiation force impulse (ARFI), an ultrasound‐based imaging technique, are accurate for diagnosing nonalcoholic fatty liver disease (NAFLD) fibrosis. However, no head‐to‐head comparisons between MRE and ARFI for diagnosing NAFLD fibrosis have been performed. We compared MRE versus ARFI head‐to‐head for diagnosing fibrosis in well‐characterized patients with biopsy‐proven NAFLD. This cross‐sectional analysis of a prospective cohort involved 125 patients (54.4% female) who underwent MRE, ARFI, and contemporaneous liver biopsies scored using the Nonalcoholic Steatohepatitis Clinical Research Network histological scoring system. The performances of MRE versus ARFI for diagnosing fibrosis were evaluated using area under the receiver operating characteristic curves (AUROCs). The mean (± standard deviation) age and body mass index were 48.9 (±15.4) years and 31.8 (±7.0) kg/m2, respectively. For diagnosing any fibrosis (≥ stage 1), the MRE AUROC was 0.799 (95% confidence interval [CI] 0.723‐0.875), significantly (P = 0.012) higher than the ARFI AUROC of 0.664 (95% CI 0.568‐0.760). In stratified analysis by presence or absence of obesity, MRE was superior to ARFI for diagnosing any fibrosis in obese patients (P < 0.001) but not in nonobese patients (P = 0.722). The MRE AUROCs for diagnosing ≥stages 2, 3, and 4 fibrosis were 0.885 (95% CI 0.816‐0.953), 0.934 (95% CI 0.863‐1.000), and 0.882 (95% CI 0.729‐1.000); and the ARFI AUROCs were 0.848 (95% CI 0.776‐0.921), 0.896 (95% CI 0.824‐0.968), and 0.862 (95% CI 0.721‐1.000). MRE had higher AUROCs than ARFI for discriminating dichotomized fibrosis stages at all dichotomization cutoff points, but the AUROC differences decreased as the cutoff points (fibrosis stages) increased. Conclusion: MRE is more accurate than ARFI for diagnosing any fibrosis in NAFLD patients, especially those who are obese. (Hepatology 2016;63:453–461)

Novel 3D Magnetic Resonance Elastography for the Noninvasive Diagnosis of Advanced Fibrosis in NAFLD: A Prospective Study.

OBJECTIVES:Recent studies show two-dimensional (2D)-magnetic resonance elastography (MRE) is accurate in diagnosing advanced fibrosis (stages 3 and 4) in nonalcoholic fatty liver disease (NAFLD) patients. Three-dimensional (3D)-MRE is a more advanced version of the technology that can image shear-wave fields in 3D of the entire liver. The aim of this study was to prospectively compare the diagnostic accuracy of 3D-MRE and 2D-MRE for diagnosing advanced fibrosis in patients with biopsy-proven NAFLD.METHODS:This cross-sectional analysis of a prospective study included 100 consecutive patients (56% women) with biopsy-proven NAFLD who also underwent MRE. Area under the receiver operating characteristic (AUROC) analysis was performed to assess the accuracy of 2D- and 3D-MRE in diagnosing advanced fibrosis.RESULTS:The mean (±s.d.) of age and body mass index were 50.2 (±13.6) years and 32.1 (±5.0) kg/m2, respectively. The AUROC for diagnosing advanced fibrosis was 0.981 for 3D-MRE at 40 Hz, 0.927 for 3D-MRE at 60 Hz (standard shear-wave frequency), and 0.921 for 2D-MRE at 60 Hz (standard shear-wave frequency). At a threshold of 2.43 kPa, 3D-MRE at 40 Hz had sensitivity 1.0, specificity 0.94, positive predictive value 0.72, and negative predictive value 1.0 for diagnosing advanced fibrosis. 3D-MRE at 40 Hz had significantly higher AUROC (P<0.05) than 2D-MRE at 60 Hz for diagnosing advanced fibrosis.CONCLUSIONS:Utilizing a prospective study design, we demonstrate that 3D MRE at 40 Hz has the highest diagnostic accuracy in diagnosing NAFLD advanced fibrosis. Both 2D- and 3D-MRE at 60 Hz, the standard shear-wave frequency, are also highly accurate in diagnosing NAFLD advanced fibrosis.

Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis

Background: Magnetic resonance imaging-estimated proton-density-fat-fraction (MRI-PDFF) has been shown to be a noninvasive, accurate and reproducible imaging-based biomarker for assessing steatosis and treatment response in nonalcoholic steatohepatitis (NASH) clinical trials. However, there are no data on the magnitude of MRI-PDFF reduction corresponding to histologic response in the setting of a NASH clinical trial. The aim of this study was to quantitatively compare the magnitude of MRI-PDFF reduction between histologic responders versus histologic nonresponders in NASH patients. Methods: This study is a secondary analysis of the MOZART trial, which included 50 patients with biopsy-proven NASH randomized to ezetimibe 10 mg/day orally or placebo for 24 weeks. The primary aim was to perform a head-to-head comparative analysis of histologic responders [defined as a ⩾2-point reduction in the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) without worsening fibrosis] versus nonresponders, and the corresponding quantitative change in liver fat content measured via MRI-PDFF. Results: Of the 35 patients who underwent paired liver biopsy and MRI-PDFF assessment at the beginning and end of treatment, 10 demonstrated a histologic response. Compared with histologic nonresponders, histologic responders had a statistically significant reduction in MRI-PDFF of −4.1% ± 4.9 versus −0.6 ± 4.1 (p < 0.04) with a mean relative percent change of −29.3% ± 33.0 versus +2.0% ± 24.0 (p < 0.004), respectively. Conclusions: Utilizing paired MRI-PDFF and liver histology data, we demonstrate that a relative reduction of 29% in liver fat on MRI-PDFF is associated with a histologic response in NASH. After external validation by independent research groups, these results can be incorporated into designing future NASH clinical trials, especially those utilizing change in hepatic fat quantified by MRI-PDFF, as a treatment endpoint.

Optional Inferior Vena Cava Filters in the Trauma Patient

Trauma patients are at exceedingly high risk of development of venous thromboembolism (VTE) including deep venous thrombosis and pulmonary embolism (PE). The epidemiology of VTE in trauma patients is reviewed. PE is thought to be the third major cause of death after trauma in those patients who survive longer than 24 hours after onset of injury. In fact, patients recovering from trauma have the highest rate of VTE among all subgroups of hospitalized patients. Various prophylactic and surveillance methods have been evaluated and found helpful in certain situations, but VTE complications can occur despite such measures. Therapeutic and prophylactic uses of inferior vena cava (IVC) filters in trauma patients are reviewed. Prophylactic IVC filter use is revealed to be a controversial subject with valid arguments on both sides of the issue. With the lack of prospective randomized trials of IVC filter use in trauma, it is impossible to make evidence-based recommendations. Unfortunately, two sets of guidelines are available for insertion of filters in trauma patients, with conflicting recommendations. The introduction of retrievable IVC filters seems to offer a unique solution for VTE protection in the trauma patient population, which often consists of younger members of our population. Lastly, current generations of FDA-approved retrieval filters are discussed.

Magnetic resonance elastography identifies fibrosis in adults with alpha-1 antitrypsin deficiency liver disease: a prospective study

Limited data exist on the clinical presentation and non‐invasive detection of liver fibrosis in adults with homozygous Z genotype alpha‐1 antitrypsin (AAT) deficiency.

Cardiovascular risk assessment in the treatment of nonalcoholic steatohepatitis: a secondary analysis of the MOZART trial

Background: Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular risk and mortality. No US Food and Drug Administration (FDA) approved therapies for NASH are available; clinical trials to date have not yet systematically assessed for changes in cardiovascular risk. This study examines the prospective utility of cardiovascular risk assessments, the Framingham risk score (FRS) and coronary artery calcium (CAC) score, as endpoints in a NASH randomized clinical trial, and assesses whether histologic improvements lead to lower cardiovascular risk. Methods: Secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial (MOZART) in which 50 biopsy-proven NASH patients received oral ezetimibe 10 mg daily (n = 25) versus placebo (n = 25). Biochemical profiling, FRS, CAC scores, liver biopsies were obtained at baseline and endpoint. Results: Ezetimibe improved FRS whereas placebo did not (4.4 ± 6.2 to 2.9 ± 4.8, p = 0.038; 3.0 ± 4.4 to 2.9 ± 4.2, p = 0.794). CAC scores did not change with ezetimibe or placebo (180.4 ± 577.2 to 194.1 ± 623.9, p = 0.293; 151.4 ± 448.9 to 183.3 ± 555.7, p = 0.256). Ezetimibe improved FRS and CAC scores in more patients than placebo (48% versus 23%, p = 0.079, and 21% versus 0%, p = 0.090, respectively), though not significantly. No differences were noted in cardiovascular risk scores among histologic responders versus nonresponders. Conclusions: Ezetimibe improved FRS whereas placebo did not. FRS and CAC scores improved in a greater proportion of patients with ezetimibe; this trend did not reach significance. These findings indicate the utility and feasibility of monitoring cardiovascular risk in a NASH trial. The utility of CAC scores may be higher in trials of longer duration (⩾52 weeks) and with older patients (age ⩾45). ClinicalTrials.gov registration: NCT01766713.

Intravascular Ultrasound in the Creation of Transhepatic Portosystemic Shunts Reduces Needle Passes, Radiation Dose, and Procedure Time: A Retrospective Study of a Single-Institution Experience

PURPOSE To assess whether intravascular ultrasound (US) guidance impacts number of needle passes, contrast usage, radiation dose, and procedure time during creation of transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS Intravascular US-guided creation of TIPS in 40 patients was retrospectively compared with conventional TIPS in 49 patients between February 2010 and November 2015 at a single tertiary care institution. Patient sex and age, etiology of liver disease (hepatitis C virus, alcohol abuse, nonalcoholic steatohepatitis), severity of liver disease (mean Model for End-Stage Liver Disease score), and indications for TIPS (variceal bleeding, refractory ascites, refractory hydrothorax) in conventional and intravascular US-guided cases were recorded. RESULTS The two groups were well matched by sex, age, etiology of liver disease, Child-Pugh class, Model for End-Stage Liver Disease scores, and indication for TIPS (P range = .19-.94). Fewer intrahepatic needle passes were required in intravascular US-guided TIPS creation compared with conventional TIPS (2 passes vs 6 passes, P < .01). Less iodinated contrast material was used in intravascular US cases (57 mL vs 140 mL, P < .01). Radiation exposure, as measured by cumulative dose, dose area product, and fluoroscopy time, was reduced with intravascular US (174 mGy vs 981 mGy, P < .01; 3,793 μGy * m(2) vs 21,414 μGy * m(2), P < .01; 19 min vs 34 min, P < .01). Procedure time was shortened with intravascular US (86 min vs 125 min, P < .01). CONCLUSIONS Intravascular US guidance resulted in fewer intrahepatic needle passes, decreased contrast medium usage, decreased radiation dosage, and shortened procedure time in TIPS creation.

Transjugular liver biopsy after transjugular intrahepatic portosystemic shunt (TIPS) or direct intrahepatic portocaval shunt (DIPS): Is it feasible, effective, and safe?

PURPOSE To evaluate our experience with transjugular liver biopsies (TJLB) in patients with previously placed transjugular intrahepatic portosystemic shunt (TIPS) or direct intrahepatic portocaval shunt (DIPS). MATERIAL AND METHODS A single-institution retrospective review was performed looking at all TJLBs in patients with previously placed TIPS or DIPS over the past seven years. There were six men and one woman (mean age 57.9±8.8 [SD] years; range: 47-71 years). Patient demographics, indications, procedural details, laboratory data, complications, and pathology were recorded. Patients with occluded TIPS were excluded from this study. RESULTS Seven TJLBs were performed, five in patients who had a TIPS and two who had a DIPS. Of the patients with TIPS, biopsies were performed from the same hepatic vein as TIPS in three procedures and from a different hepatic vein in two procedures. In DIPS patients, both biopsies were performed from the right hepatic vein. The reasons for the transjugular rather than the percutaneous approach to liver biopsy included ascites, coagulopathy, or need for concurrent TIPS/DIPS evaluation and/or revision. All procedures were technically successful with adequate samples obtained. There were no immediate or delayed complications. CONCLUSION Our results suggest that if needed a TJLB can safely and effectively be performed in patients with previously placed TIPS or DIPS.

Tu1706 Magnetic Resonance Elastography Identifies Fibrosis in Adults With Alpha-1 Antitrypsin Deficiency Liver Disease: A Pilot Prospective Study

Author(s): Kim, RG; Nguyen, P; Bettencourt, R; Dulai, PS; Haufe, W; Hooker, J; Minocha, J; Valasek, MA; Aryafar, H; Brenner, DA; Sirlin, CB; Loomba, R