Portosystemic shunt placement reveals blood signatures for the development of hepatic encephalopathy through mass spectrometry.

Elective transjugular intrahepatic portosystemic shunt (TIPS) placement can worsen cognitive dysfunction in hepatic encephalopathy (HE) patients due to toxins, including possible microbial metabolites, entering the systemic circulation. We conducted untargeted metabolomics on a prospective cohort of 22 patients with cirrhosis undergoing elective TIPS placement and followed them up to one year post TIPS for HE development. Here we suggest that pre-existing intrahepatic shunting predicts HE severity post-TIPS. Bile acid levels decrease in the peripheral vein post-TIPS, and the abundances of three specific conjugated di- and tri-hydroxylated bile acids are inversely correlated with HE grade. Bilirubins and glycerophosphocholines undergo chemical modifications pre- to post-TIPS and based on HE grade. Our results suggest that TIPS-induced metabolome changes can impact HE development, and that pre-existing intrahepatic shunting could be used to predict HE severity post-TIPS.

Pre- and Post-Portosystemic Shunt Placement Metabolomics Reveal Molecular Signatures for the Development of Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a common complication of advanced liver disease causing brain dysfunction. This is likely due to the accumulation of unfiltered toxins within the bloodstream. A known risk factor for developing or worsening HE is the placement of a transjugular intrahepatic portosystemic shunt (TIPS), which connects the pre-hepatic and post-hepatic circulation allowing some blood to bypass the dysfunctional liver and decreases portal hypertension. To better understand the pathophysiology of post-TIPS HE, we conducted a multi-center prospective cohort study employing metabolomic analyses on hepatic vein and peripheral vein blood samples from participants with cirrhosis undergoing elective TIPS placement, measuring chemical modifications and changes in concentrations of metabolites resulting from TIPS placement. In doing so, we identified numerous alterations in metabolites, including bile acids, glycerophosphocholines, and bilirubins possibly implicated in the development and severity of HE.

Intravascular Ultrasound Guidance for TIPS Procedures: A Review.

The most challenging and time-consuming step of TIPS procedures is obtaining appropriate portal vein (PV) access. Given the lack of real-time direct target visualization, conventional fluoroscopic guidance requires multiple passes, contributing to complications. In comparison, intravascular ultrasound (IVUS) guidance during TIPS procedures provides direct visualization of hepatic structures and real-time guidance for PV puncture. IVUS guidance during TIPS creation improves procedural metrics such as radiation dose, contrast agent volume, procedure time, and technical success rate and is particularly beneficial in technically challenging cases (e.g., in patients portal vein thrombosis, small or variant portal vein anatomy, Budd-Chiari syndrome, or liver masses). The purpose of this review is to summarize current IVUS technology, describe the technical aspects of IVUS-guided TIPS creation, and discuss the clinical indications for and benefits of using IVUS for TIPS creation, while presenting available evidence supporting the technique's use. Given the improved safety profile and overall success rate in comparison with conventional guidance methods, IVUS guidance has the future potential to become the standard practice for TIPS placement.

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.

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.

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/m(2), 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.

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.

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.

UNLABELLED: 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/m(2) , 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.

Transjugular intrahepatic portosystemic shunt for treatment of cirrhosis-related chylothorax and chylous ascites: single-institution retrospective experience.

PURPOSE: To investigate the efficacy and safety of the use of transjugular intrahepatic portosystemic shunt (TIPS) creation to treat cirrhosis-related chylous collections (chylothorax and chylous ascites). METHODS: We retrospectively reviewed data from four patients treated for refractory cirrhosis-related chylous collections with TIPS at our institution over an 8 year period. RESULTS: One patient had chylothorax, and three patients had concomitant chylothorax and chylous ascites. There were no major complications, and the only procedure-related complications occurred in two patients who had mild, treatable hepatic encephalopathy. All patients had improvement as defined by decreased need for thoracentesis or paracentesis, with postprocedure follow-up ranging from 19 to 491 days. CONCLUSION: TIPS is a safe procedure that is effective in the treatment of cirrhosis-related chylous collections.

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.

Coronary artery disease in South Asians: an emerging risk group.

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide and was responsible for 7.2 million deaths in 2003. Various studies have pointed out that South Asians have a higher prevalence of CAD as compared with other ethnicities. South Asians may have a genetic predisposition to CAD; however, environmental, nutritional, and lifestyle factors may also be responsible. South Asians have a much higher prevalence of metabolic syndrome, diabetes, insulin resistance (and resultant hyperinsulinemia), central obesity, dyslipidemias (lower high-density lipoprotein, increased lipoprotein[a], higher triglyceride levels), increased thrombotic tendency (increased plasminogen activator inhibitor-1 and decreased tissue plasminogen activator levels), decreased levels of physical activity, and low birth weights ("fetal origins hypothesis"). In addition, the dietary indiscretions and sedentary lifestyle practiced by most South Asians puts them at a higher risk. A multidisciplinary approach involving the population at risk, healthcare personnel, and the government is required to diminish the incidence. Educational programs regarding the genetic predisposition as well as risk factors for CAD, physical activity, and dietary modifications need to be encouraged. There is a need for implementation of newer guidelines as well as a lower threshold for initiating therapeutic interventions in this population. Mass media should be involved to bring about behavioral changes, and these changes should be reinforced at the physician's level.