bluuebunny/crossref_metadata_2025_split huggingface dataset:
1085 The Use of the Molecular Adsorbent Recirculating System (MARS) in Treatment of Cholestatic Drug Induced Liver Injury
Authors: Rapaka Babusai , Vora Ravi , Flynn Mary , Subramanian Ram 
Published: October 2019

INTRODUCTION:
Cholestatic drug induced liver injury (DILI) is a subtype of DILI defined by elevated alkaline phosphatase (ALP) or bilirubin levels from exposure to a drug causing cholestasis. It is a challenging diagnosis with limited treatment options. The molecular adsorbent recirculating system (MARS) allows for hemofiltration of albumin-bound substances that can improve cholestatic hepatitis, pruritus, and hepatic encephalopathy (HE). Here we report six cases of acute cholestatic DILI treated with MARS.

METHODS:
Patients with cholestatic DILI who underwent MARS were identified at a single institution. Pre-MARS, post-MARS and post hospitalization data on ALP, bilirubin, INR and HE were collected. Completion of MARS therapy was defined as continuous therapy for three to five days.

RESULTS:
Six cases were identified, one of which progressed to acute liver failure (ALF). Hepatotoxic medications included acetaminophen, phentermine, methimazole, OxyElite and two cases of the anabolic steroid Methyl-1-etiocholenololepietiocholanolone. Mean total bilirubin prior to MARS was 34.5 mg/dl. Over the course of therapy, patients had significant improvement with an average bilirubin of 13.4 mg/dl at completion of MARS and 2.4 mg/dl at follow up. Coagulopathy was seen in the case of ALF from acetaminophen with pre-MARS INR of 1.9 and post-MARS INR of 1.7. This patient also had grade 4 HE prior to MARS with improvement to grade 0 post-MARS. ALP levels were not abnormal and did not change. Clinical improvement in pruritis and jaundice was seen in all cases.

CONCLUSION:
This case series highlights six patients with cholestatic DILI who had significant improvement in bilirubin, pruritis and jaundice with MARS. This improvement in cholestasis was thought to be due to filtration of bilirubin. Removal of bilirubin also improved jaundice. In conjunction with medical therapy and withdrawal of the offending agent, there was sustained improvement in bilirubin that continued even on outpatient follow up. There was also improvement in pruritis that was refractory to maximal medical therapy. It is unclear which substance is the principal pruritogen associated with cholestasis. However, MARS provided significant symptomatic relief that persisted. In the one case of cholestatic DILI causing acute liver failure, MARS resulted in resolution of HE and served as a bridge to spontaneous hepatic recovery. Our case series shows that MARS is a viable option in treating acute cholestatic liver injury refractory to medical therapy.
1089 Hypophosphatemia in Patients With Alcoholic Hepatitis
Authors: Chiang Ryan S. , Farooq Ahmad , Parish Alice , Niedzwiecki Donna , Kappus Matthew R. , Patel Yuval , Liddle Rodger A. , Muir Andrew J. 
Published: October 2019

INTRODUCTION:
Patients with alcoholic hepatitis suffer from high rates of malnutrition and are at risk for hypophosphatemia due to poor dietary intake, renal wasting, and refeeding syndrome. The aim of this study was to assess phosphate monitoring and supplementation practices in patients with alcoholic hepatitis, and to determine if phosphorous levels are associated with increased risk of morbidity and mortality in patients with alcoholic hepatitis.

METHODS:
A retrospective analysis was performed on a cohort identified through the use of an electronic health record query tool for an academic health system. Study population was defined as 18 years or older with hospital admission 8/1/12 to 9/30/18. Alcoholic hepatitis was defined using ICD-9/10 codes 571.1, K70.10, or K70.11. Patients also met the National Institute on Alcohol Abuse and Alcoholism criteria for alcoholic hepatitis. Patients were excluded if other etiologies of liver disease were present.

RESULTS:
64 admissions met study criteria, and phosphate measurements occurred at least once during admission in 45/64 (70%). Patients with serum phosphorous data measured had higher serum creatinine. They also had higher Maddrey’s discriminant function and MELD scores, although not statistically significant (Table 1). Hypophosphatemia was noted in 18/45 (40%) patients at initial measurement, while 6/45 (13%) had hyperphosphatemia. Phosphate supplementation did not occur in 5/18 (28%) patients with hypophosphatemia. Of the 6 patients with hyperphosphatemia, 5 died with multi-system organ failure. There were 7 ICU admissions in the normal phosphate group, of which 6 had a reduction in phosphorous levels during the admission. Among the normal phosphorous group, phosphorous measurements were not repeated routinely during the admission. All 4 deaths in the normal phosphorous group experienced reduction in their phosphorous level during the admission; 2 did not receive any form of supplementation despite follow-up phosphorous levels below the normal range.

CONCLUSION:
Many patients with alcoholic hepatitis did not receive routine phosphorus measurement. Patients with phosphorus measurements had higher creatinine levels, suggesting that renal dysfunction prompted measurement. Among patients with normal initial phosphorous levels, all 4 deaths and 6 of 7 ICU admissions experienced evidence of refeeding syndrome. These findings reiterate the importance of phosphorus monitoring and supplementation for patients with alcoholic hepatitis.
1094 A Study of the Characteristics of Hepatic Blood Flow Ex Vivo Using a Cardio-Emulation Arterial Pump Perfusion System
Authors: Lake-Bakaar Gerond V. , Aardema Charles , Cronin David C. , Robertson John 
Published: October 2019

INTRODUCTION:
The CAVESWave® organ perfusion system provides cardio-emulated systolic and diastolic pressure waves to the hepatic artery HA, as well as variable pressure to the portal vein PV, replicating in vivo hepatic perfusion conditions. This allows a unique opportunity to study the interaction between HA and PV flow patterns in the autoregulation of hepatic venous HV outflow. The conditions exclude artefacts generated from cardiac pulsations.

METHODS:
Ten freshly procured porcine livers were perfused on the CAVESWave® system for four hours. At the two-hour midpoint, the temperature of the perfusate was increased from 15°C to 30°C and the flow variation associated with the temperature change documented. Flow rates in the HA, PV and HV were captured using flow sensors in the perfusion circuit. The distribution of perfusate was documented using Infra-red thermography (IRT), which measured surface liver temperature to a depth of 3 mm.

RESULTS:
Both IRT and the flow sensor measurements demonstrated stable, steady-state values after target perfusate temperatures were reached. Pulsatile waves reflecting cardio-emulated systolic and diastolic pressure waves were present in both HA (Figure 1) and PV (Figure 2). The only possible source of pulsations in the PV was transmission from the HA. Pulsatile waves were significantly attenuated or absent in the HV (Figure 3). The flow at 150 C in the HA (630.1 + 239.9; ml/min M + SD) was significantly greater than in the PV (316.2 + 90; P < 0.004). As expected, flow in the HV (904 + 292.8) approximated the sum of HA and PV flow. Increasing the temperature of the perfusate to 300 C significantly increased flow in all three circuits: HA (761.5 + 220; P < 0.014); PV flow (375.0 + 139.1; P < 0.007) and HV (1016.1 + 302.4; P < 0.007). The flow in the HA increased by 116.75 + 140.9 ml/min; the increase was 56.7 + 80.3 in the PV and 111.8 + 100.8 in the HV. The time for this change was significantly shorter for HA (18.9 + 13.5 mins) than for PV (26.4 + 18.1; P < 0.05). The significance of the delay in the PV flow is unclear. It likely reflects greater capacitance within the venous circuit. PV flow was inversely correlated with HA flow at all temperatures, correlation coefficient, -0.26. This suggests compensation or buffering between the arterial and venous circuits.

CONCLUSION:
Autoregulation of flow in response to temperature change is maintained in the ex vivo perfused liver. The inverse correlation between HA and PV flow, suggests a Hepatic Artery Buffering Response, HABR in this model.
1097 Are There Demographic Variations Between Obese and Non-Obese (Lean) Patients With Non-alcoholic Steatohepatitis?
Authors: Ismail Mohamed S. , Sanchez Javier , Hassan Manal , Abdullah Khalid , Jalal Prasun , Egwim Chukwuma , Ankomasey Victor 
Published: October 2019

INTRODUCTION:
Non-alcoholic steatohepatitis (NASH) in the absence of overweight and/or obesity is designated as non-obese (lean) NASH. Several studies suggested that lean NASH is a variant phenotype of NASH, where its features metabolically resemble obese NASH individuals with insulin resistance, and metabolic syndrome plays the pathogenetic role in both phenotypes. Limited data suggested that Asians have propensity to develop NASH at a comparatively lower BMI, mostly due to body composition and fat distribution. We aimed at assessing baseline demographic variations between obese and non-obese (lean) patients with NASH.

METHODS:
Based on fibroscan reports with CAP and fibrosis scores, 124 patients with NAFLD had been identified between 09/2018 and 05/2019 at the Liver Associates of Texas Hepatology Clinics in Houston. Standardized fibroscan report (steatosis, and fibrosis stage) was determined by expert clinicians. Demographic information, chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), baseline body mass index (BMI), presence of major comorbidities and metabolic syndrome were recorded for all patients. For continuous variables, we used the Student’s t test to compare differences in the mean values. The chi-squared test was used to compare the proportions of risk factors between groups.

RESULTS:
According to the baseline body mass index, patients were classified into obese (BMI ≥30) and non-obese (BMI < 30). With the consideration of presence and absence of NASH and obesity, participants were further classified into four groups as seen in Table 1. Our data indicated that Asians (47.1%) especially men (57.1%), P = .06 are more likely to be classified as non-obese/NASH. No significant variation between all groups, however, with respect to age at diagnosis or gender distribution.

CONCLUSION:
No significant difference between obese and lean patients with NASH regarding age, gender or ethnicity. NASH should be considered in the differential diagnosis of unexplained liver disease even in presence of normal BMI. Management strategy, and surveillance protocol for NASH should be evaluated and validated in non-obese (lean) NASH subjects.
1100 Outcomes of Cholecystostomy With and Without Follow-Up Cholecystectomy in Patients With Cirrhosis
Authors: Vedachalam Srikanth , Porter Kyle , Li Na , Kelly Sean , Conteh Lanla , Hanje James , Michaels Anthony , Black Sylvester , Mumtaz Khalid 
Published: October 2019

INTRODUCTION:
Cirrhotic patients are twice as likely as the general population to form gallstones and are therefore at increased risk for acute cholecystitis. Cholecystectomy (CCY) is currently the definitive therapy for cholecystitis, but cirrhotic patients have been shown to have dramatically higher mortality rates during CCY in previous studies. Percutaneous cholecystostomy tube (PCT) placement is therefore an alternative to CCY in cirrhosis. Subsequently these patients require CCY. However, data on PCT and subsequent CCY cirrhotics are not reported. We studied the trends and outcomes of PCT with and without follow-up CCY in cirrhotic patients.

METHODS:
The National Readmissions Database (NRD), using pre-validated ICD-9 codes was queried to study the patients with acute calculous cholecystitis between the years of 2010-2014 who underwent either CCY or PCT with or without follow-up CCY. Study groups included non-cirrhotics (NC), compensated cirrhotics (CC) and decompensated cirrhotics (DC). DC patients were classified using Baveno IV criteria. Variables included were patient and hospital characteristics, Elixhauser co-morbidities, rates of CCY, rates of PCT with or without follow-up CCY, and approach to CCY- open vs closed. Primary outcomes included 30-day readmission rates, plus index and calendar year mortality. Secondary outcomes were rates of PCT placement, rates of CCY after PCT, length of stay and cost.

RESULTS:
PCT are more commonly placed in cirrhotics (3.7%) compared to non-cirrhotics with acute cholecystitis (1.4%). Within cirrhotics, DC (7.7%) received far more PCT than CC (2.9%). Inversely, NC underwent more CCY vs CC and DC (98.9%, 97.4% and 92.9%, respectively). Predictors of PCT were DC (P < 0.001), but not CC (P = 0.23) compared to NC. PCT was followed by CCY less in cirrhotics than NC with DC having the lowest rates (NC: 39.9%, CC: 28.6%, and DC: 16.1%). Presence of CC and DC were predictors of not receiving CCY after PCT ((OR: 0.57; CI: 0.35-0.92) and (OR:0.29; CI:0.14-0.60), respectively). Finally, outcomes of CCY after PCT were shown to be similar between NC vs all cirrhotics with all comparisons not being statistically significant.

CONCLUSION:
Cirrhosis was seen as a risk factor for PCT without subsequent CCY with DC having the lowest rates. However, while CC and DC had lower rates of CCY after PCT, their outcomes were similar to NC. Allowing time for medical optimization with PCT tubes, especially in CC, may result in similar surgical outcomes to NC undergoing follow-up CCY.
1106 Impact of Splanchnic Vasoconstrictors on Sodium Level in Inpatient Cirrhotics With Hyponatremia: A Retrospective Cohort Study
Authors: Ismail Bahaaeldeen , Alkhairi Baker , Benrajab Karim , Ali Saad Emhmed , Castro Fernando 
Published: October 2019

INTRODUCTION:
Hyponatremia (hypoNa) in cirrhosis represents another consequence of splanchnic vasodilation. Splanchnic vasoconstrictors are currently used in hepatorenal syndrome (HRS) which has similar pathogenesis, however their role in hypoNa has not been fully investigated. Aim of the study is to evaluate the effect of octreotide ± midodrine on hypoNa in cirrhotics.

METHODS:
We retrospectively included adult cirrhotics admitted to the Cleveland Clinic hospitals between 10/1/2011 and 10/1/2015, who had Na < 133 at or during admission. We excluded subjects with less than 5 days of follow up, those who received potent vasoconstrictors as norepinephrine or received hypertonic saline, tolvaptan or renal replacement therapy during admission. Population was divided into those who received octreotide versus those who did not. Outcomes were Na level at days 5, 7 and 10 after starting octreotide. Secondary outcome was determination of predictors of change of Na at day 5 using a multivariate model that included variables with P < 0.1 on univariate analysis. We then performed a subgroup analysis for only those with baseline Na < 125 (as this is the correction threshold for many transplant centers).

RESULTS:
Patients in the octreotide group were younger, had higher Model for End-Stage Liver Disease score, more patients had ascites and varices compared to controls [Table 1]. The octreotide group had lower baseline Na, but the Na levels at 5,7 and 10 days after octreotide were significantly higher [Figure 1]. The two predictors of higher Na at 5 days were having a lower baseline Na and receiving both octreotide and midodrine Table 2]. When analysis was restricted to the subgroup with baseline Na < 125, 97% of those who received octreotide had Na ≥125 by day 5 (compared to 77% of controls, P = 0.03). In this subgroup, the only predictor of reaching Na ≥125 by day 5 (multivariate logistic regression model) was receiving octreotide; OR 11.2 (1.16- 109), P = 0.04.

CONCLUSION:
Cirrhotics with hypoNa that received octreotide had a significantly higher rise in Na. On a multivariate analysis accounting for the potential confounders, octreotide remained a significant predictor only when combined with midodrine, suggesting a synergistic effect (similar to HRS). To our knowledge, this is the largest study evaluating the effect of splanchnic vasoconstrictors on sodium level in cirrhotics with hypoNa compared to controls. Prospective studies are needed with matched controls and longer follow up.
1108 Alkaline Phosphatase Levels Are Negatively Correlated With the Severity of Hepatic Steatosis in Patients With Primary Sclerosing Cholangitis
Authors: Motowski Hayley , Senter-Zapata Michael , Ciorba Matthew A. , Deepak Parakkal , McHenry Scott 
Published: October 2019

INTRODUCTION:
Primary Sclerosing Cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease with a strong association with Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD). Our group has shown that patients with CD have twice the risk of hepatic steatosis compared to the general population. We have also shown that there is a robust protective effect of ileal-inflammation and hepatic steatosis in CD. Conversely, we found active perianal disease increases the risk of hepatic steatosis. These findings suggest that inflammation directed through the portal vein is protective against hepatic steatosis. In this study, we aimed to demonstrate if an analogous inflammatory marker in PSC, alkaline phosphatase, is protective against hepatic steatosis.

METHODS:
This is a single-center, retrospective cohort study between 1/1/2013 through 12/31/2018. Adult patients with a clinical diagnosis of PSC that had undergone magnetic resonance cholangiopancreatography (MRCP) were included. Patients with an alternative etiology of liver disease (e.g. chronic viral hepatitis, greater than moderate alcohol use) were excluded. All MRCP protocols had been modified to allow liver fat quantification by the proton density fat fraction (PDFF) method. The primary outcome was the nonparametric, Spearman’s correlation (Rs) between PDFF and alkaline phosphatase. Secondary analysis was performed using a linear regression model for the natural log (Ln) transformation of PDFF.

RESULTS:
There were 112 PSC patients (80% with Ulcerative colitis, median age at enrollment 48 years, median age at PSC diagnosis 39 years). The median PDFF was 2.3% and the median body-mass index (BMI) was 27 kg/m2. There was a negative-linear relationship between PDFF and alkaline phosphatase with a Rs = 0.4 (P < 0.001). This negative-linear relationship between alkaline phosphatase and PDFF persisted after adjusting for BMI in the linear regression model (P < 0.001).

CONCLUSION:
We demonstrated that alkaline phosphatase, the surrogate for PSC-associated cholestasis and hepatic inflammation, demonstrates a negative-linear relationship with liver fat even after adjusting for BMI. This supports the hypothesis that acute inflammation in the portal circulation is protective against hepatic steatosis. Future directions include clarifying the role of the enterohepatic circulation and non-immunologic enterokines in liver-fat handling.
1121 Impact of Weight Parameters on Colorectal Cancer Survival: A Systematic Review and Meta-Analysis
Authors: Jaspan Vita , Lin Kevin , Wilder Evan , Chang Steven , Popov Violeta 
Published: October 2019

INTRODUCTION:
Metabolic risk factors have been implicated in the incidence of colorectal cancer (CRC); however, less is known about the relationship between obesity and CRC outcomes. We hypothesized that obesity would be associated with worse outcomes compared to normal weight, but with better outcomes compared to underweight individuals.

METHODS:
A systematic review of electronic databases was performed through May 2019, including NCBI, Embase, Cochrane, and Web of Science. Screening was performed independently by two authors using Covidence. Inclusion criteria were retrospective and prospective cohort studies reporting CRC outcomes at least 60 months after CRC diagnosis. The primary outcome analyzed was CRC mortality in obese compared to normal body mass index (BMI). Secondary outcomes included overall mortality, disease free survival (DFS) and CRC mortality by BMI category (underweight, normal, overweight, and obese), and high vs. normal waist circumference (WC). Odds ratios (OR) and 95% confidence intervals (95% CI) are reported. Random effects analysis was performed for all outcomes, with heterogeneity assessed by the I2 statistic and meta-regression by area of origin (East vs. West).

RESULTS:
484 relevant citations were identified and 17 were included in the final analysis. Fifteen studies analyzed CRC outcome data in terms of BMI, and 2 in terms of WC. These studies comprised 251,347 patients, with a median age range of 61.8-71 years and follow-up time range of 60-192 months. Obesity was associated with significantly increased CRC-specific mortality compared to normal BMI (Figure 1). Interestingly, study origin (East vs. West) explained 53% of the heterogeneity in these results, R2 = 0.53 (Figure 2). Underweight patients had increased CRC mortality compared to both normal and overweight patients, but not significantly different from obese patients. High WC was also associated with increased CRC mortality compared to normal WC (Table 1). Obese and underweight patients both had increased OM compared to normal weight patients; underweight patients had increased OM compared to obese patients. Significant effects of BMI on DFS were only observed in Eastern studies, where underweight patients had worse DFS than normal weight and obese.

CONCLUSION:
Overweight and obesity as well as underweight are risk factors for CRC-specific mortality. Underweight patients had poorer prognosis than overweight patients, but not significantly different from obese patients.
1136 Weight to Height Ratio Is a Better Predictor of Non-Alcoholic Fatty Liver Disease in Both Genders in South Asian Population
Authors: Kumar Sandeep , Hanif Farina , Majid Zain , Luck Nasir Hassan , Khan Shoaib Ahmed , Laeeq Syed Mudassir , Mehmood Nasir 
Published: October 2019

INTRODUCTION:
Various obesity indices have been reported to predict non-alcoholic fatty liver disease (NAFLD). We aimed at evaluating these indices based upon anthropometric measures including waist to height ratio (WHtR), waist circumferences (WC), body mass index (BMI) and fatty liver index (FLI) and used it to determine the discriminatory ability of these indices in diagnosing NAFLD.

METHODS:
In this cross sectional study, NAFLD was diagnosed via abdominal ultrasound. Height (in), weight(cm), WC (cm), BMI, WHtR and FLI was calculated in all the participants .FLI comprising of BMI,WC, triglyceride and gamma glutamyl transferase was calculated by using an online scoring tool.1 The Receiver operating characteristic analysis was then conducted to determine the discriminatory ability and related cut-off points of indices. P value of ≤0.05 was taken as significant.

RESULTS:
In total of 300 participants, the prevalence of NAFLD was 44.8% in men and 54.8% in women. Univariate analysis reported statistical significant association of NAFLD with all of the applied indices (P = 0.00). The WHtR (AUC = 0.87, 95% CI:0.77-0.97) showed slight better performance as compared to FLI (AUC = 0.86, 95% CI:0.76-0.97) in diagnosing NAFLD. Regression analysis reported stronger association of WHtR (OR = 9.3, P = 0.00) compared to FLI (OR = 6.0, P = 0.02) with NAFLD. Moreover, the performance of WHtR was similar between men and women (AUC = 0.89) while different in FLI i.e., AUC of 0.88 in men and AUC of 0.85 in female.

CONCLUSION:
We reported a stronger association of WHtR in prediction of NAFLD and a similar discrimatory ability regardless of gender. WHtR is simple and easily performable modality for NAFLD prediction.