Lipoprotein Z, a hepatotoxic lipoprotein, predicts outcome in alcohol-associated hepatitis.

BACKGROUND AND AIMS: Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation. APPROACH AND RESULTS: We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay. Serum levels of LP-Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z-index, calculated by the ratio of LP-Z to total apolipoprotein B-containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z-index was associated with 90-day mortality independent from the Model for End-Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z-index ≤ 0.6 and a decline of Z-index by ≥0.1 in 2 weeks predicted 90-day survival. RNA-sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP-Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP-Z particles caused direct toxicity to human hepatocytes in a concentration-dependent manner, supporting a pathogenic role of FC in LP-Z. CONCLUSIONS: Impaired lipoprotein metabolism in AH leads to the accumulation of LP-Z in the circulation, which is hepatotoxic from excessive FC. A Z-index ≤ 0.6 predicts 90-day survival independent from conventional biomarkers for disease prognostication.

The Impact of Race and Sex on the Clinical Outcomes of Homeless Patients With Alcoholic Liver Disease: Propensity Score Matched Analysis of US Hospitals.

BACKGROUND: Among patients with alcoholic liver disease (ALD), homelessness poses significant medical and psychosocial risks; however, less is known about the effects of race and sex on the hospital outcomes of admitted homeless patients with ALD. METHODS: The National Inpatient Sample database from 2012 to 2017 was used to isolate homeless patients with ALD, and the cohort was further stratified by race and sex for comparisons. Propensity score matching was utilized to minimize covariate confounding. The primary endpoints of this study include mortality, hospital length of stay, and hospital costs; secondary endpoints included the incidence of liver complications. RESULTS: There were 3972 females/males postmatch, as well as 2224 Blacks/Whites and 4575 Hispanics/Whites postmatch. In multivariate, there were no significant differences observed in mortality rate, length of stay, and costs between sexes. Comparing liver outcomes, females had a higher incidence of hepatic encephalopathy [adjusted odds ratio (aOR) 1.02, 95% CI: 1.01-1.04, P<0.001]. In comparing Blacks versus Whites, Black patients had higher hospitalization costs (aOR 1.13, 95% CI: 1.03-1.24, P=0.01); however, there were no significant differences in mortality, length of stay, or liver complications. In comparing Hispanics versus Whites, Hispanic patients had longer length of hospital stay (aOR 1.12, 95% CI: 1.06-1.19, P<0.001), greater costs (aOR 1.15, 95% CI: 1.09-1.22, P<0.001), as well as higher prevalence of liver complications including varices (aOR 1.04, 95% CI: 1.02-1.06, P<0.001), hepatic encephalopathy (aOR 1.03, 95% CI: 1.02-1.04, P<0.001), and hepatorenal syndrome (aOR 1.01, 95% CI 1.00-1.01, P=0.03). However, there was no difference in mortality between White and Hispanic patients. CONCLUSIONS: Black and Hispanic ALD patients experiencing homelessness were found to incur higher hospital charges; furthermore, Hispanic patients also had greater length of stay and higher incidence of liver-related complications compared with White counterparts.

The Trends in Health Care Utilization and Costs Associated With Primary Liver Cancer: An Analysis of United States Hospitals Between 2016 and 2019.

BACKGROUND: Primary liver cancer (PLC) has placed an increasing economic and resource burden on the health care system of the United States. We attempted to quantify its epidemiology and associated costs using a national inpatient database. METHODS: Hospital discharge and insurance claims data from the National Inpatient Sample were used to conduct this analysis. Patients diagnosed with PLC (hepatocellular carcinoma or cholangiocarcinoma) were included in the study population, which was then stratified using patient demographics, comorbidities, degree of cancer spread, liver disease complications, and other descriptors. Trends were analyzed via regression curves for each of these strata from the years 2016 to 2019, with special attention to patterns in hospitalization incidence, inpatient mortality rate, total costs, and average per-capita costs. The resulting curves were evaluated using goodness-of-fit statistics and P-values. RESULTS: Aggregate hospitalization incidence, inpatient mortality rates, and total costs were found to significantly increase throughout the study period (P=0.002, 0.002, and 0.02, respectively). Relative to their demographic counterparts, males, White Americans, and those older than 65 years of age contributed the largest proportions of total costs. These population segments also experienced significant increases in total expenditure (P=0.04, 0.03, and 0.02, respectively). Admissions deemed to have multiple comorbidities were associated with progressively higher total costs throughout the study period (P=0.01). Of the categorized underlying liver diseases, only admissions diagnosed with alcoholic liver disease or nonalcoholic fatty liver disease saw significantly increasing total costs (P=0.006 and 0.01), although hepatitis C was found to be the largest contributor to total expenses. CONCLUSIONS: From 2016 to 2019, total costs, admission incidence, and inpatient mortality rates associated with PLC hospitalization increased. Strata-specific findings may be reflective of demographic shifts in the PLC patient populations, as well as changes in underlying chronic liver disease etiologies.

Demographic inequities exist and influence transplant outcomes in liver transplantation for acute alcohol-associated hepatitis.

BACKGROUND: Liver transplantation has inherent disparities but data is scarce in liver transplant (LT) candidates with acute alcohol-associated hepatitis (AAH). We aimed to investigate demographic inequities and its impact on survival outcomes among AAH LT candidates. METHODS: A retrospective analysis using the United Network of Organ Sharing database was conducted between 2000 and 2021. 25 981 LT recipients with alcohol-associated liver cirrhosis and 662 recipients with AAH were included. Waitlisted candidates were also evaluated. RESULTS: In comparison with alcohol-associated liver cirrhosis, AAH LT recipients were more likely Asian or "other" race and younger. Hispanics demonstrated better graft and patient survival (p < 0.05) but were less likely to be waitlisted and transplanted for AAH than for liver cirrhosis. Women with AAH were more likely to be waitlisted and transplanted. Pre-existing diabetes and male sex were associated with higher graft failure (25% and 8% respectively). Increasing recipient age were 2% more likely to experience negative outcomes. Chronicity of liver disease did not impact graft (p = 0.137) or patient survival (p = 0.145). CONCLUSION: Our results revealed demographic factors have a significant impact on transplant listing, organ allocation and survival outcomes. Further investigations are imperative to minimize disparities in LT evaluation and provide equity in healthcare.

Yttrium-90 radioembolization using MIRD dosimetry with resin microspheres.

OBJECTIVE: To review the technical feasibility of resin microsphere (SIR-Spheres®) yttrium-90 radioembolization prescribed using the medical internal radiation dose (MIRD) model. METHODS: All radioembolization procedures for hepatic malignancies using resin microspheres with MIRD model between November 2015 and February 2019 were included in this IRB-approved study (n = 60). Student's T test was used to compare prescribed activity based on MIRD and BSA models. Adverse events were assessed immediately, 30 days, and 6 months post-treatment. RESULTS: Sixty radioembolizations were performed in 54 patients (age 68 ± 9 years, 48-87 years, 35% female). Mean prescribed activity calculated by the MIRD model (target absorbed dose 120-200 Gy for primary and 80-200 Gy for metastatic liver cancers) was 1.7 GBq (0.3-6.4) compared with 0.6 GBq (0.12-2.1) if BSA had been used (p < 0.0001). The prescribed activity was successfully delivered in 93% (56/60) treatments. Prophylactic embolization and anti-reflux catheters were used in 20% (12/60) and 5% (3/60) treatments, respectively. No immediate post-procedural complications occurred. Abdominal pain was the most common clinical Grade 3 CTCAE in 30 days (10%) and 6 months (12%). Radiation pneumonitis occurred in 3 (5%) patients but no radiation-induced gastric ulcer or radiation-induced liver disease occurred. CONCLUSION: MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry with resin microspheres. MIRD prescribed activity with target absorbed doses up to 200 Gy can be successfully administered without prophylactic embolization in selected patients. KEY POINTS: •MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry for radioembolization. •MIRD dosimetry can be used for yttrium-90 resin microsphere radioembolization with acceptable safety profile.

Efficacy of TIPS Reduction for Refractory Hepatic Encephalopathy, Right Heart Failure, and Liver Dysfunction.

OBJECTIVE. The purpose of this study was to determine clinical outcomes of patients undergoing TIPS reduction. MATERIALS AND METHODS. In this institutional review board-approved, HIPAA-compliant study, all TIPS reductions performed at two institutions from January 1, 2008 to January 31, 2016, were retrospectively identified. Patients were divided into two groups according to pre-TIPS symptoms: volume overload due to ascites or hydrothorax (VO; n = 14) or variceal bleeding (VB; n = 12). Patient demographics, pre-TIPS model for end-stage liver disease score, pre- and post-TIPS portosystemic gradients, and clinical parameters were recorded. The primary endpoint was change in symptoms of hepatic encephalopathy (HE; West Haven criteria), right heart failure, or liver dysfunction. Secondary endpoints included paracentesis rate for the VO group and rebleeding for the VB group. RESULTS. The degree of HE increased in 24 of 26 patients (92%) after TIPS placement and decreased in 24 of 26 patients (92%) after TIPS reduction. Mean West Haven scores for the VO group decreased after TIPS reduction (from 2.57 ± 0.97 [SD] to 1.07 ± 0.70; p < .001). Mean West Haven scores for the VB group also decreased after TIPS reduction (from 2.45 ± 0.89 to 1.27 ± 0.86; p = .007). Right heart failure improved in two of three patients (67%), and total bilirubin improved in one of three patients (33%). Follow-up data were available up to median of 134 days (interquartile range, 44-286). TIPS reduction led to an increased paracentesis rate compared with before TIPS placement in four of 14 patients with VO (29%). One patient had a stable paracentesis rate after TIPS reduction compared with before TIPS placement. Variceal rebleeding did not occur in any patients with VB after TIPS reduction. At 54 days after TIPS reduction, one of the 12 patients with VB (9%) experienced hematemesis due to an endoscopically proven band-related ulcer. CONCLUSION. TIPS reduction successfully resolved HE and refractory right heart failure in most patients. In patients with VB, TIPS reduction with variceal embolization results in a low risk of short-term recurrent VB. However, in patients with VO, ascites may return or worsen after TIPS reduction despite improvement in HE.

Hemorrhagic Complications of Invasive Intracranial Pressure Monitor Placement in Acute Liver Failure: Outcomes of a Single-Center Protocol and Comprehensive Literature Review.

BACKGROUND: Elevated intracranial pressure due to cerebral edema is associated with very poor survival in patients with acute liver failure (ALF). Placing an intracranial pressure monitor (ICPm) aids in management of intracranial hypertension, but is associated with potentially fatal hemorrhagic complications related to the severe coagulopathy associated with ALF. METHODS: An institutional Acute Liver Failure Clinical Protocol (ALF-CP) was created to correct ALF coagulopathy prior to placing parenchymal ICP monitoring bolts. We aimed to investigate the frequency, severity, and clinical significance of hemorrhagic complications associated with ICPm bolt placement in the setting of an ALF-CP. All assessed patients were managed with the ALF-CP and had rigorous radiologic follow-up allowing assessment of the occurrence and chronology of hemorrhagic complications. We also aimed to compare our outcomes to other studies that were identified through a comprehensive review of the literature. RESULTS: Fourteen ALF patients were included in our analysis. There was no symptomatic hemorrhage after ICP monitor placement though four patients were found to have minor intraparenchymal asymptomatic hemorrhages after liver transplant when the ICP monitor had been removed, making the rate of radiographically identified clinically asymptomatic hemorrhage 28.6%. These results compare favorably to those found in a comprehensive review of the literature which revealed rates as high as 17.5% for symptomatic hemorrhages and 30.4% for asymptomatic hemorrhage. CONCLUSION: This study suggests that an intraparenchymal ICPm can be placed safely in tertiary referral centers which utilize a protocol such as the ALF-CP that aggressively corrects coagulopathy. The ALF-CP led to advantageous outcomes for ICPm placement with a 0% rate of symptomatic and low rate of asymptomatic hemorrhagic complications, which compares well to results reported in other series. A strict ICPm placement protocol in this setting facilitates management of ALF patients with cerebral edema during the wait time to transplantation or spontaneous recovery.

Causes and Rates of 30-Day Readmissions After Transjugular Intrahepatic Portosystemic Shunts.

OBJECTIVE. The purpose of this study was to investigate the causes and rates of 30-day readmission after transjugular intrahepatic portosystemic shunt (TIPS) at a single liver transplant center. MATERIALS AND METHODS. We reviewed 165 TIPS procedures performed between 2003 and 2013. After excluding patients who died during the index admission (n = 16), any readmission within 30 days of discharge was identified, and cause of readmission was determined. Causes were categorized as planned or unplanned and interventional radiology (IR)-related or IR-unrelated. Unplanned readmissions were independently categorized as preventable or unpreventable by two interventional radiologists. Discrepant opinions were resolved by consensus. Factors predictive of 30-day readmission were identified by univariate and multivariate analysis. RESULTS. The reviewed TIPS procedures were performed in 165 patients (mean age ± SD, 56 ± 11 years; 69% male, 31% female). TIPS were placed for ascites or hydrothorax in 82 patients (50%) and variceal bleeding in 83 patients (50%). The 30-day readmission rate was 21% (31/149). The most common causes for readmissions were ascites or hydrothorax (23%, 7/31) and hepatic encephalopathy (23%, 7/31). All 30-day readmissions were unplanned; 17 (55%) of them were potentially preventable. Of the 17 potentially preventable readmissions, five (29%) were IR-related and 12 (71%) were IR-unrelated. In IR-related readmissions, all patients presented with a recurrence of symptoms (rebleeding or ascites) and were found to have TIPS stenosis or occlusion. Mortality rates were similar between patients who were and were not readmitted (p = 0.23). On multivariate analysis, spontaneous bacterial peritonitis during the index admission was the only variable associated with 30-day readmission (odds ratio = 4.81, p = 0.02). CONCLUSION. Over half of 30-day readmissions after TIPS could have been prevented by early outpatient follow-up and intraprocedural technique to optimize stent landing zones.

Identifying Barriers to the Treatment of Chronic Hepatitis C Infection.

BACKGROUND AND AIMS: Chronic hepatitis C (CHC) viral infection has a major impact on our health care system. The emergence of direct-acting antiviral agents (DAA) has made treatment simple (oral), efficacious, and safe. However, treatment is expensive and access is variable. Despite great treatment outcomes, only a minority of patients with CHC receive antiviral therapy. This study identifies the barriers to treatment in CHC infection. METHODS: Study recruited all hepatitis C antibody-positive patients between 2012 and 2016 from a large academic teaching hospital in New York City. Demographic information, clinical data, and insurance information were reviewed. Statistical analysis performed with OR and p < 0.05 reported. RESULT: A total of 1,548 patients with hepatitis C antibody-positive titer were included in the initial analysis. One thousand and twenty-four patients were forwarded to the final analysis after exclusion of 524 patients (for distant resolved hepatitis C viral [HCV] infection [n = 42], patients cured with interferon-based regimens [n = 94], patients with comorbid conditions [n = 176], and patients with an incomplete medical chart [n = 212]). In the intention to treat cohort of 1,024 patients, 204 patients achieved a sustained virological response after receiving DAAs (n = 204/1,024 - 20%). The majority of patients had not received DAAs (n = 816/1,024 patients - 80%). Multiple factors resulted in hepatitis C viral infection (HCV) patients not receiving DAAs including the following primary factors: (a) lost to follow-up clinic visits and poor adherence to clinic appointments (n = 548 [67%]; p value <0.0001), (b) active substance abuse (alcoholism and IV drug abuse; n = 165 [20%]; p value 0.22), (c) patients with significant psychiatric illness (n = 103 [12.7%]; p value 0.015), and subgroup analysis revealed that 188 (188/1,024 - 12%) patients had human immunodeficiency virus-1 (HIV-1) and HCV coinfection. Majority of HCV/HIV coinfected patients had not received DAAs (n = 176 [97%]; p value <0.0001, OR 4.46). The etiology of nontreatment in coinfected HIV/HCV patients was 73.3% poor adherence, 11.5% active substance abuse including alcohol and IV drug use, and 9% significant psychiatric illness and 6.2% multiple reasons for not receiving HCV treatment. CONCLUSION: Multifactorial barriers are preventing hepatitis C patients from receiving effective DAA therapy. Primary factors include poor compliance, substance abuse, and significant psychiatric illness, with significant overlap between these groups. Subgroup analysis showed a substantial number of high-risk patients with HIV/HCV coinfection did not receive DAA therapy. A multidisciplinary clinic approach with a hepatologist, ID physicians, social worker, and behavioral health psychologist and case manager should provide a solution to improve diagnosis and treatment with DAA.

Arm crank ergometer "spin" training improves seated balance and aerobic capacity in people with spinal cord injury.

BACKGROUND: There is some evidence that upper-body training modalities can improve not only aerobic capacity but also seated balance in people with spinal cord injury (SCI), even in those classified with motor-complete paralysis above T6. Here, we evaluated the effect of arm crank ergometry (ACE) "spin" training on trunk muscle recruitment and its effects on seated balance and aerobic capacity. METHODS: Eight individuals with high-level complete and 6 with either a low-level complete or a motor-incomplete SCI participated in this study. Participants completed 5 weeks of a group ACE "spin" training protocol which featured modulations in cadence and resistance as well as back-supported and unsupported bouts. Surface electromyography was used to confirm trunk muscle recruitment during unsupported ACE. Changes in aerobic capacity (peak oxygen consumption) and seated balance control (center of pressure parameters) were assessed at pre- and post-intervention. RESULTS: Unsupported ACE was effective for eliciting trunk muscle activity (P < .05). Following training, peak oxygen consumption significantly improved by an average of 16% (P = .005). Static sitting balance significantly improved from pre- to post-intervention, but only when tested with eyes closed as measured by a reduction in area (P = .047) and velocity of center of pressure (P = .013). No significant changes were observed in static sitting balance with eyes open or in dynamic sitting balance. CONCLUSION: Group ACE "spin" classes may benefit not only aerobic fitness but also static seated balance control in people with SCI.

Hospital volume and mortality after transjugular intrahepatic portosystemic shunt creation in the United States.

The link between higher procedure volume and better outcomes for surgical procedures is well established. We aimed to determine whether procedure volume affected inpatient mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). An epidemiological analysis of an all-payer database recording hospitalizations during 2013 in the United States (Nationwide Readmissions Database) was performed. All patients ≥ 18 years old undergoing TIPS during a hospital admission (n = 5529) without concurrent or prior liver transplantation were selected. All-cause inpatient mortality was assessed. Risk-adjusted mortality was assessed for hospitals categorized into quintiles based on annual TIPS volume (very low, 1-4/year; low, 5-9/year; medium, 10-19/year; high, 20-29/year; and very high, ≥ 30/year). TIPS were placed in all 5529 patients (mean age, 57 years [standard deviation, ± 10.9 years]; women, n = 2071; men, n = 3458). Mortality decreased with rising annual TIPS volume (13% for very low to 6% for very high volume hospitals; P < 0.01). Elective admissions were more common in hospitals with higher annual TIPS volume (20.3% for very low to 30.8% for very high; P < 0.01). On multivariate analysis, compared with hospitals performing ≥30 TIPS per year, only hospitals performing 1-4/year (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.21-3.01; P = 0.01), 5-9/year (aOR, 2.0; 95% CI, 1.25-3.17; P < 0.01), and 10-19/year (aOR, 1.9; 95% CI, 1.17-3.00; P = 0.01) had higher inpatient mortality (20-29/year: aOR, 1.4; 95% CI, 0.84-2.84; P = 0.19). The absolute difference between risk-adjusted mortality rate for very low volume and very high volume hospitals was 6.1% (13.9% versus 7.8%). TIPS volume of ≤ 20 TIPS/year, variceal bleeding, and nosocomial infections were independent risk factors for inpatient mortality in patients with both elective and emergent admissions. Conclusion: The risk of inpatient mortality is lower in hospitals performing ≥20 TIPS per year. Future research exploring preventable factors for higher mortality and benefits of patient transfer to higher volume centers is warranted. (Hepatology 2018;67:690-699).

Improvements in skilled walking associated with kinematic adaptations in people with spinal cord injury.

INTRODUCTION: Individuals with motor-incomplete SCI (m-iSCI) remain limited community ambulators, partly because they have difficulty with the skilled walking requirements of everyday life that require adaptations in inter-joint coordination and range of motion of the lower limbs. Following locomotor training, individuals with SCI show improvements in skilled walking and walking speed, however there is limited understanding of how adaptations in lower limb kinematics following training contribute to improvements in walking. OBJECTIVE: To determine the relationship between changes in lower limb kinematics (range of motion and inter-joint coordination) and improvements in walking function (walking speed and skilled walking) following locomotor training. METHODS: Lower limb kinematics were recorded from 8 individuals with chronic m-iSCI during treadmill walking before and after a 3-month locomotor training program. Data were also collected from 5 able-bodied individuals to provide normative values. In individuals with SCI, muscle strength was used to define the stronger and weaker limb. Motion analysis was used to determine, hip, knee and ankle angles. Joint angle-angle plots (cyclograms) were used to quantify inter-joint coordination. Shape differences between pre-and post-training cyclograms were used to assess the changes in coordination and their relation to improvements in walking function. Walking function was assessed using the 10MWT for walking speed and the SCI-FAP for skilled walking. Comparing pre- and post-training cyclograms to the able-bodied pattern was used to understand the extent to which changes in coordination involved the recovery of normative motor patterns. RESULTS: Following training, improvements in skilled walking were significantly related to changes in hip-ankle coordination (ρ = - .833, p = 0.010) and knee range of motion (ρ = .833, p = 0.010) of the weaker limb. Inter-joint coordination tended to revert towards normative patterns, but not completely. No relationships were observed with walking speed. CONCLUSION: Larger changes in hip-ankle coordination and a decrease in knee range of motion in the weaker limb during treadmill walking were related to improvements in skilled walking following locomotor training in individuals with SCI. The changes in coordination seem to reflect some restoration of normative patterns and the adoption of compensatory strategies, depending on the participant.

Primary Stent Placement for Hepatic Artery Stenosis After Liver Transplantation: Improving Primary Patency and Reintervention Rates.

Recent studies have reported high rates of reintervention after primary stenting for hepatic artery stenosis (HAS) due to the loss of primary patency. The aims of this study were to evaluate the outcomes of primary stenting after HAS in a large cohort with longterm follow-up. After institutional review board approval, all patients undergoing liver transplantation between 2003 and 2017 at a single institution were evaluated for occurrence of hepatic artery complications. HAS occurred in 37/454 (8%) of patients. HAS was defined as >50% stenosis on computed tomography or digital subtraction angiography. Hepatic arterial patency and graft survival were evaluated at annual intervals. Primary patency was defined as the time from revascularization to imaging evidence of new HAS or reaching a censored event (retransplantation, death, loss to follow-up, or end of study period). Primary stenting was attempted in 30 patients (17 female, 57%; median age, 51 years; range, 24-68 years). Surgical repair of HAS prior to stenting was attempted in 5/30 (17%) patients. Endovascular treatment was performed within 1 week of the primary anastomosis in 5/30 (17%) of patients. Technical success was accomplished in 97% (29/30) of patients. Primary patency was 90% at 1 year and remained unchanged throughout the remaining follow-up period (median, 41 months; interquartile range [IQR], 25-86 months). Reintervention was required in 3 patients to maintain stent patency. The median time period between primary stenting and retreatment was 5.9 months (IQR, 4.4-11.1 months). There were no major complications, and no patient developed hepatic arterial thrombosis or required listing for retransplantation or retransplantation during the follow-up period. In conclusion, primary stenting for HAS has excellent longterm primary patency and low reintervention rates.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD.

Sensorimotor integration of vision and proprioception for obstacle crossing in ambulatory individuals with spinal cord injury.

Skilled walking, such as obstacle crossing, is an essential component of functional mobility. Sensorimotor integration of visual and proprioceptive inputs is important for successful obstacle crossing. The objective of this study was to understand how proprioceptive deficits affect obstacle-crossing strategies when controlling for variations in motor deficits in ambulatory individuals with spinal cord injury (SCI). Fifteen ambulatory individuals with SCI and 15 able-bodied controls were asked to step over an obstacle scaled to their motor abilities under full and obstructed vision conditions. An eye tracker was used to determine gaze behaviour and motion capture analysis was used to determine toe kinematics relative to the obstacle. Combined, bilateral hip and knee proprioceptive sense (joint position sense and movement detection sense) was assessed using the Lokomat and customized software controls. Combined, bilateral hip and knee proprioceptive sense in subjects with SCI varied and was significantly different from able-bodied subjects. Subjects with greater proprioceptive deficits stepped higher over the obstacle with their lead and trail limbs in the obstructed vision condition compared with full vision. Subjects with SCI also glanced at the obstacle more frequently and with longer fixation times compared with controls, but this was not related to proprioceptive sense. This study indicates that ambulatory individuals with SCI rely more heavily on vision to cross obstacles and show impairments in key gait parameters required for successful obstacle crossing. Our data suggest that proprioceptive deficits need to be considered in rehabilitation programs aimed at improving functional mobility in ambulatory individuals with SCI. NEW & NOTEWORTHY: This work is unique since it examines the contribution of combined, bilateral hip and knee proprioceptive sense on the recovery of skilled walking function, in addition to characterizing gaze behavior during a skilled walking task in people with motor-incomplete spinal cord injury.

Comparison of Vascular Plugs and Pushable Coils for Variceal Embolization After TIPS.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) with variceal embolization is routinely performed to treat variceal bleeding. Embolization using vascular plugs is reported, but outcomes are not known. Outcomes and material costs of embolization using vascular plugs and coils are compared. MATERIALS AND METHODS: A single center's medical records of TIPS procedures (May 2003-December 2014) with variceal embolization were reviewed. Twenty patients with vascular plug embolization (age [± SD], 50 ± 10 years; seven men and 13 women; median Model for End-Stage Liver Disease [MELD], 20; interquartile range [IQR], 14-23) were compared with an age-, sex-, and MELD-matched cohort who underwent coil embolization (age, 50 ± 9 years; seven men and 13 women; median MELD, 17; IQR, 15-19; p = 0.52). Procedure details, primary outcome (rebleeding), secondary outcome (mortality), and costs were compared. RESULTS: Vascular plug use was associated with a lower fluoroscopy time (49.05 minutes [IQR, 36-62] vs 68 minutes [IQR, 49-76]; p = 0.006) and total procedure time (255 minutes [IQR, 205-290] for vascular plugs vs 275 minutes [IQR, 230-330]; p = 0.05). Total volume of contrast agent used was similar (180 mL [IQR, 155-234] for vascular plugs vs 210 mL [IQR, 185-261]; p = 0.14). In patients with at least a 30-day follow-up, rebleeding rates (2/17 [12%] for vascular plugs vs 4/15 [27%]; p = 0.40) and mortality (2/17 [12%] for vascular plugs vs 4/15 [27%]; p = 0.66) were similar. Per procedure, vascular plugs cost significantly more than coils ($1292 ± $676 vs $228 ± $292, p < 0.0001). CONCLUSION: The use of vascular plugs or coils has similar outcomes for variceal embolization after TIPS. The advantages of vascular plug use (i.e., reduced fluoroscopy or procedure time) may be offset by increased material cost, a trade-off that merits further study given current cost concerns in health care.

A Standardized Assessment of Functional Disability Predicts 1-year Mortality in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt for Refractory Ascites.

GOALS: To determine the association between functional disability and mortality after transjugular intrahepatic portosystemic shunt (TIPS). BACKGROUND: TIPS is a common therapeutic procedure for cirrhotic patients with refractory ascites. The conventional metric for periprocedure risk stratification is the model for end-stage liver disease (MELD), which uses biochemical parameters to predict post-TIPS mortality. It does not account for functional disability. STUDY: This is a retrospective cohort study of 83 patients admitted at an academic liver transplant center with cirrhosis and refractory ascites for the purpose of TIPS placement. We assessed the association of patients' reported activities of daily living (ADL) on a scale of 1 to 21 before TIPS with a primary outcome of 1-year mortality. Multivariable regression to adjust for MELD and Child class was performed. RESULTS: A higher ADL score or functional independence, was associated with decreased 1-year mortality when modeled as both a continuous variable [odds ratio (OR), 0.80; 95% confidence interval (CI), 0.66-0.97; P=0.02) and a dichotomous variable (ADL 21 vs. <21; OR, 0.21; 95% CI, 0.05-0.70; P=0.01). After adjusting for MELD and Child class, functional independence was associated with decreased 1-year transplant-free mortality (OR, 0.22; 95% CI, 0.05-0.77; P=0.02). An ADL score consistent with dependence (<21) was significantly associated with a 3.40-day (95% CI, 1.76-5.04) longer hospital stay, adjusting for MELD and Child class (P<0.0001). CONCLUSIONS: Functional disability is a predictor of post-TIPS mortality and length of stay after controlling for MELD.

Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis.

BACKGROUND & AIMS: Bacterial infections, particularly repeated infections, are significant causes of morbidity and mortality among patients with cirrhosis. We investigated and characterized risk factors for repeat infections in these patients. METHODS: In a prospective study, we collected data from 188 patients hospitalized with cirrhosis and infections and enrolled in the North American Consortium for the Study of End-Stage Liver Disease (12 centers). Patients were followed up for 6 months after hospital discharge and data were analyzed on type of infections and factors associated with subsequent infections. RESULTS: Six months after hospital discharge, 14% of subjects had received liver transplants, 27% died, and 59% were alive without liver transplantation. After discharge, 45% had subsequent infections, but only 26% of the subsequent infections occurred at the same site. Compared with patients not re-infected, patients with repeat infections were older and a higher proportion used proton pump inhibitors (PPIs) (P = .006), rifaximin (P < .001), or prophylactic therapy for spontaneous bacterial peritonitis (SBP) (P < .001). Logistic regression showed that SBP prophylaxis (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.56-7.63), PPI use (OR, 2.94; 95% CI, 1.39-6.20), SBP at hospital admission (OR, 0.37; 95% CI, 0.15-0.91), and age (OR, 1.06; 95% CI, 1.02-1.11) were independent predictors of subsequent infections. CONCLUSIONS: Patients hospitalized with cirrhosis and infections are at high risk for subsequent infections, mostly at different sites, within 6 months of index infection resolution. Those at highest risk include previously infected older patients receiving PPIs and/or SBP prophylaxis, although these associations do not prove that these factors cause the infections. New strategies are needed to prevent infections in patients with cirrhosis.

Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures.

UNLABELLED: Infections worsen survival in cirrhosis; however, simple predictors of survival in infection-related acute-on-chronic liver failure (I-ACLF) derived from multicenter studies are required in order to improve prognostication and resource allocation. Using the North American Consortium for Study of End-stage Liver Disease (NACSELD) database, data from 18 centers were collected for survival analysis of prospectively enrolled cirrhosis patients hospitalized with an infection. We defined organ failures as 1) shock, 2) grade III/IV hepatic encephalopathy (HE), 3) need for dialysis and mechanical ventilation. Determinants of survival with these organ failures were analyzed. In all, 507 patients were included (55 years, 52% hepatitis C virus [HCV], 15.8% nosocomial infection, 96% Child score ≥ 7) and 30-day evaluations were available in 453 patients. Urinary tract infection (UTI) (28.5%), and spontaneous bacterial peritonitis (SBP) (22.5%) were the most prevalent infections. During hospitalization, 55.7% developed HE, 17.6% shock, 15.1% required renal replacement, and 15.8% needed ventilation; 23% died within 30 days and 21.6% developed second infections. Admitted patients developed none (38.4%), one (37.3%), two (10.4%), three (10%), or four (4%) organ failures. The 30-day survival worsened with a higher number of extrahepatic organ failures, none (92%), one (72.6%), two (51.3%), three (36%), and all four (23%). I-ACLF was defined as ≥ 2 organ failures given the significant change in survival probability associated at this cutoff. Baseline independent predictors for development of ACLF were nosocomial infections, Model for Endstage Liver Disease (MELD) score, low mean arterial pressure (MAP), and non-SBP infections. Independent predictors of poor 30-day survival were I-ACLF, second infections, and admission values of high MELD, low MAP, high white blood count, and low albumin. CONCLUSION: Using multicenter study data in hospitalized decompensated infected cirrhosis patients, I-ACLF defined by the presence of two or more organ failures using simple definitions is predictive of poor survival.

New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection.

BACKGROUND & AIMS: Participants at a consensus conference proposed defining cirrhosis-associated acute kidney injury (AKI) based on a >50% increase in serum creatinine level from the stable baseline value in <6 months or an increase of ≥ 0.3 mg/dL in <48 hours. We performed a prospective study to evaluate the ability of these criteria to predict mortality within 30 days of hospitalization among patients with cirrhosis and infection. METHODS: We followed up 337 patients with cirrhosis who were admitted to the hospital with an infection or developed an infection during hospitalization (56% men; 56 ± 10 years of age; Model for End-Stage Liver Disease [MELD] score, 20 ± 8) at 12 centers in North America. We compared data on 30-day mortality, length of stay in the hospital, and organ failure between patients with and without AKI. RESULTS: In total, based on the consensus criteria, 166 patients (49%) developed AKI during hospitalization. Patients who developed AKI were admitted with higher Child-Pugh scores than those who did not develop AKI (11.0 ± 2.1 vs 9.6 ± 2.1; P < .0001) as well as higher MELD scores (23 ± 8 vs 17 ± 7; P < .0001) and lower mean arterial pressure (81 ± 16 vs 85 ± 15 mm Hg; P < .01). Higher percentages of patients with AKI died within 30 days of hospitalization (34% vs 7%), were transferred to the intensive care unit (46% vs 20%), required ventilation (27% vs 6%), or went into shock (31% vs 8%); patients with AKI also had longer stays in the hospital (17.8 ± 19.8 vs 13.3 ± 31.8 days) (all P < .001). Of the AKI episodes, 56% were transient, 28% were persistent, and 16% resulted in dialysis. Mortality was higher among those without renal recovery (80%) compared with partial (40%) or complete recovery (15%) or those who did not develop AKI (7%; P < .0001). CONCLUSIONS: Among patients with cirrhosis, 30-day mortality is 10-fold higher among those with irreversible AKI than those without AKI. The consensus definition of AKI accurately predicts 30-day mortality, length of hospital stay, and organ failure.