bluuebunny/crossref_metadata_2025_split huggingface dataset:
947 Lusutrombopag for Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Who Are Undergoing Planned Invasive Procedures: Pooled Safety Analysis of Bleeding-Related Adverse Events
Authors: Giannini Edoardo G. , Kano Takeshi , Ochiai Toshimitsu , Bentley Roy , Shrestha Pomy 
Published: October 2019

INTRODUCTION:
Thrombocytopenia is a common complication in patients with chronic liver disease. A low platelet count in chronic liver disease patients who require an invasive procedure is a serious condition that may be associated with an increased risk of bleeding during or after the procedure. Lusutrombopag is a thrombopoietin receptor agonist approved in Japan (2015) and the US (2018) for treatment of thrombocytopenia, and in the EU (2019) for severe thrombocytopenia, associated with chronic liver disease in patients undergoing a planned invasive procedure. A pooled safety analysis was performed to assess differences in bleeding events following treatment with lusutrombopag without platelet transfusion or placebo with platelet transfusion.

METHODS:
Safety data were pooled from 3 double-blind, placebo-controlled studies, in patients with thrombocytopenia associated with chronic liver disease undergoing a planned invasive procedure (Phase 2b: M0626 [Japan; JapicCTI-121944]; Phase 3: L-PLUS 1 [Japan; JapicCTI-132323], L-PLUS 2 [global; NCT02389621]). Patients enrolled in these studies were randomized to lusutrombopag 3 mg or placebo for up to 7 days prior to procedure. Platelet transfusion was administered if platelet count was < 50 × 109/L no more than 2 days prior to procedure. Patients were classified into 1 of 4 subgroups: lusutrombopag alone or +platelet transfusion or placebo alone or +platelet transfusion. This analysis focused on patients in the lusutrombopag alone and placebo + platelet transfusion subgroups. Bleeding events were summarized pre-, during, and post-procedure.

RESULTS:
Lower bleeding event rates, regardless of severity and timing of onset, were observed for lusutrombopag alone vs placebo + platelet transfusion (Table 1). Percent of patients with bleeding events was numerically higher with placebo + platelet transfusion vs lusutrombopag alone, both during (4.8% vs 3.2%) and post-procedure (7.1% vs 4.0%). Percent of patients with procedural and post-procedural bleeding events in liver-related procedures was greater in the placebo + platelet transfusion (16.1%) vs lusutrombopag alone (11.1%) arm, and a larger difference was seen with gastrointestinal-related procedures in the placebo + platelet transfusion (8.9%) vs lusutrombopag alone (2.0%) arm.

CONCLUSION:
In this pooled analysis, a trend toward lower bleeding event rates was observed with lusutrombopag alone vs placebo + platelet transfusion, regardless of type of invasive procedure.
948 Trends of Hospital Admissions and Healthcare Burden From Patients Admitted With Hepatic Encephalopathy
Authors: Siddiqui Mohammad A. , Shabbir AImun , Shabbir Nawal , Haq Khwaja F. , Jafri Syed-Mohammed 
Published: October 2019

INTRODUCTION:
Hepatic encephalopathy (HE) develops in about 50% of patients with cirrhosis and is one of the features of decompensated cirrhosis. It causes substantial mortality and utilization of resources. We aimed to study the trends of admission rates and mortality rates over time of patient admitted with HE on a large national sample database.

METHODS:
The National Inpatient Sample database which is collected as part of Agency for Healthcare Cost and Utilization Project by Agency for Healthcare Research and Quality were utilized. Individuals aged over 18 were included. The hospitalizations with primary diagnosis of HE were captured by ICD-9 codes. Data on patient age, length of stay, cost of hospitalization and inpatient mortality was extracted. Descriptive statistics were then run using the online software at HCUPnet.

RESULTS:
The total number of patient with HE presenting to the ED has an upward trend, year after year, increasing from 42687 ED visits in 2006 to 57578 in 2014. Total number of these patient being admitted to the same hospital has also steadily increased from 37966 in 2006 to 49079 in 2014. The length of stay has ranged from 5.2 days to 5.5 days over these years. The increasing mean cost of hospital stay, from 28797 in 2006 to 40669 in 2014, has further added to the health care burden. The percentage of deaths during these hospitalizations from HE has declined from 7.4% in 2006 to 4.6% in 2014.

CONCLUSION:
In-patient admissions with HE represent a significant health care burden given increasing cost of hospitalization. Though the trend of mortality rate is decreasing over time, efforts need to be under taken to optimize outpatient care to avoid admissions.
960 Revised Lille Score for Predicting 90 Days Mortality in Severe Alcoholic Hepatitis
Authors: Majeed Muhammad , Agrawal Rohit , Attar Bashar M. , Wang Yuchen , Vohra Ishaan , Haque Zohaib , Gandhi Seema 
Published: October 2019

INTRODUCTION:
Iron is an essential micronutrient which circulates bound to transferrin for tissue distribution. Liver is the main site for transferrin synthesis and its dysfunction can alter iron homeostasis resulting in oxidative stress. Recent studies showed that transferrin saturation is an independent predictor of mortality in patients with decompensated cirrhosis. We aim to evaluate the prognostic efficacy of transferrin saturation and revised Lille score to predict 90-days mortality in patients with severe alcoholic hepatitis.

METHODS:
We retrospectively reviewed the electronic medical records of patients diagnosed with severe alcoholic hepatitis (SAH) who received prednisolone therapy. Demographic and biochemical data at diagnosis and day 4 was collected. Univariate logistic regression for all variables included in Lille score along with ferritin and transferrin percent was performed. A revised Lille score was created based on results of univariate analysis. The efficacy of revised Lille score was then tested against Lille score on day 4 with receiver operating characteristics (ROC) analysis and Kaplan-Meier survival analysis by dichotomization per optimal cut-offs.

RESULTS:
In our cohort of 80 patients with SAH, 12(13.3%) patients died within 90 days. Apart from all parameters included in the Lille score, transferrin saturation was identified as an independent predictor of 90-days mortality on univariate analysis (Table 1). Revised Lille score was generated by the formula mentioned below. The ROC analysis for the prediction of 90-day mortality of Day 4 revised Lille score revealed a higher AUC of 0.8419 in comparison to Day 4 Lille score that had a lower AUC of 0.6985 (Table 1). With the optimal cut-off value of 5, the revised Lille score sub-classified patients into low and high-risk (HR = 21.05, P < 0.004) groups (Figure 2). Revised Lille score = 2.15 × Lille score + 0.06 × Transferrin saturation

CONCLUSION:
In conclusion, revised Lille score at fourth day can be utilized to predict mortality at 90 days. When using a cut-off of 5, patients can be subclassified into low and high-risk groups with a sensitivity and specificity of 97.95% and 35.48 respectively. We propose that revised Lille score should be compared with Lille score in predicting outcomes in SAH. Moreover, patients with elevated transferrin saturation have a high mortality.
961 Striatal GABA Levels in Liver Cirrhosis Patients: Preliminary Results
Authors: Zupan Gasper , Stefanovic Sebastian , Jerovsek Marjanca Turk , Stabuc Borut , Oeltzschner Georg , Ropele Stefan , Vovk Andrej , Suput Dusan 
Published: October 2019

INTRODUCTION:
Liver cirrhosis (LC) is a worldwide public health problemthat represents an important cause of death in adults. One of the complications of LC is hepatic encephalopathy (HE). HE is sometimes challenging to detect as it can present as subtle cognitive impairment. Alterations of gamma-aminobutyric acid (GABA) levels in various brain regions were demonstrated in HE (1–3), however, changes of GABA levels in the striatum, a critical element of the motor, reward and executive systems, have not been yet reported. This pilot study focuses on the detection of GABA in the striata in LC patients with various degrees of cognitive impairment.

METHODS:
Six patients (2 females, mean age: 59.6 ± 8.4) with clinically diagnosed LC (all due to alcohol overconsumption) and seven (6 females, mean age: 53.9 ± 9.3) healthy subjects (HC) were included in this study. T1- and T2-weighted images were acquired to place two 35 × 25 × 25 mm voxels for MEGA-PRESS (4) MR spectroscopy in the left and right striatum. Data processing and quantitative analysis was performed in Gannet 3.0 (www.gabamrs.com). GABA levels were calculated with respect to the tissue water signal and corrected for tissue composition. Stroop test scores, psychometric hepatic encephalopathy score (PHES), Mini-Mental State Exam (MMSE) scores and venous blood ammonia levels were determined on the day of MR scanning.

RESULTS:
In left striatum, mean GABA levels were 3.5 ± 1.0 i.u. and 5.3 ± 0.8 i.u. in LC and HC group, respectively (P < 0.05). In right striatum, mean GABA levels were 4.8 ± 1.4 i.u. and 4.6 ± 0.81 i.u. in LC and HC group, respectively (P > 0.05). A negative correlation between the overall time needed for PHES completion and GABA levels in left striatum was demonstrated (r = -0.7, P < 0.05). No statistically significant correlations between response time of Stroop test, ammonia and GABA levels were noted for either voxel. MMSE did not significantly differ between groups.

CONCLUSION:
In this pilot study, decreased left striatal GABA levels were demonstrated in LC vs. HC group. This study was limited with number of enrolled subjects: continuation of this study and further stratification of patients in subgroups (accordingly to cognitive impairment) could potentially result in a model of predicting development of cognitive impairment in LC before presence of evident clinical signs.
963 Treatment Failure With Daclatasvir Plus Sofosbuvir With or Without Ribavirin in Treatment Naïve Patients With Chronic Hepatitis C Without Cirrhosis
Authors: Afzal Muhammad , Tarar Shahida Husain , Ali Shah Syed Muhammad , Butt Zamir , Ajmal Muhammad , Younis Irfan , Talat Syed Usama , Akhtar Hina , Ali Javeria 
Published: October 2019

INTRODUCTION:
Chronic hepatitis C treatment has been transformed by advent of DAAs. Pakistan is one of worst affected country with hepatitis C with recent suggested prevalence of 4.9%. Current AASLD guidelines recommend treatment with daily sofosbuvir plus daclatasvir with or without addition of weight based ribavirin. However this regimen is not first line recommendation. These drugs are available free of cost in government run setups. However it has raised questions about treatment failure with them and need for other DAAs.

METHODS:
This cross-sectional study is being conducted at ABSTH Gujrat from Oct. 2018 after approval of IRB and informed consent of patients using non-probability consecutive sampling. No genotyping is being done. Cirrhosis is considered when abdominal ultrasound shows coarse echotexture of liver as either Shear Wave Elastography or Fibroscan are not available. Treatment naive chronic hepatitis C patients without cirrhosis are being included. Patients on PCR testing having viral load of <400000 IU/L are being considered to have low viral load and are being given 12 weeks regimen of daclatasvir plus sofosbuvir. Patients with having viral load of >400000 IU/L are being considered to have high viral load and are being prescribed 24 weeks regimen of daclatasvir plus sofosbuvir with weight based ribavirin. ETR and SVR24 at 24 weeks are being noted. Patients who fail to achieve SVR24 after achieving ETR are being declared as treatment failure. Data analysis is being done using SPSS 20.0.

RESULTS:
1073 patients have been included this study till now. Mean age is 46.01 + 11.50 years. 712(66.4%) are female and 361(33.6%) are male. 729(67.9%) patients with low viral load received daclatasvir plus sofosbuvir for 12 weeks while 344(32.1%) patients with high viral load received daclatasvir, sofosbuvir and weight based ribavirin for 24 weeks. ETR and SVR24 have been reported of 163(15.2%) patients till now. All these patients achieved ETR however only 161 patients achieved SVR24. One patients had high viral load while other had low. Treatment failure rate is 1.23% till now but exact figure can only be predicted after completion of study as more results are awaited.

CONCLUSION:
Treatment failure rate in treatment naive chronic hepatitis C patients without cirrhosis with daclatasvir plus sofosbuvir with or without ribavirin is low. Similar results have been reported previously. However these preliminary results show that there is need to investigate the factors leading to treatment failures.
964 Patient Flow Across Physician Specialties Over the Course of the Hepatitis C Care Cascade: A Real World Analysis From the United States
Authors: Rege Sanika , Gonzalez Yuri Sanchez , Marx Steven , Reau Nancy 
Published: October 2019

INTRODUCTION:
Hepatitis C virus (HCV) infection is a major cause of hepatic and extrahepatic morbidity and mortality. In spite of recommendations for HCV screening, diagnosis, linkage to care and treatment, significant gaps remain in the cascade of care for HCV. As the role of physician specialties for closing these gaps is poorly understood, this study assesses the flow of HCV patients across physician specialties in the US, over the course of the care cascade.

METHODS:
This retrospective real-world study used two large de-identified national laboratory datasets (2013–2016). Screened patients had a HCV antibody (AB) test and/or HCV RNA viral load test. Diagnosed patients had a positive HCV RNA viral load test, and among this group, fibrosis assessment, genotype test and treatment were evaluated. Treatment was inferred with an algorithm based on changes in viral load. The number/proportion of patients at each step in the care cascade was calculated by physician specialty. Patient flow by physician specialty over the course of care cascade was assessed using Sankey Diagrams.

RESULTS:
Approximately 17 million patients received HCV screening, and 913,529 were diagnosed. Over the course of the care cascade, there was an increase in the proportion of patients switching to HCV specialists (gastroenterologist, hepatologist, and infectious disease specialist). Generalists (primary care, family practice, internal medicine) ordered 37% of the AB tests, and 15% initiated treatment. HCV specialists ordered 3% of screening tests and 37% initiated treatment. Most of the fibrosis assessment (30%) and genotype tests (29%) were ordered by HCV specialists. Obstetricians/gynecologists ordered 11% of screening tests but only 0.3% initiated treatment. Among 974,277 patients who received a positive AB test, 46% did not receive a confirmatory RNA test. Among diagnosed patients, 57% did not receive fibrosis assessment, 47% did not receive genotype test and 90% did not receive treatment.

CONCLUSION:
Generalists account for more than one third of all HCV screening tests, however, HCV specialists play a more prominent role in patient assessment (fibrosis status, genotype testing) and treatment. Significant gaps remain in all stages of the cascade of care for HCV, and improved efforts are needed for every physician specialty to address them. Timely screening, monitoring and linkage to care by generalists coupled with early treatment by specialists could effectively reduce the hepatic and extrahepatic burden of HCV.
966 Minimal Hepatic Encephalopathy and Driving
Authors: Dwivedi Sankalp , Balagoni Harika , Putrus Alan , Tapper Elliot , Piper Marc 
Published: October 2019

INTRODUCTION:
Minimal hepatic encephalopathy (MHE) is a well-known complication of cirrhosis that is difficult to detect. Patients with MHE have deficits in multiple domains that may lead to motor vehicle accidents (MVAs). Clinicians have little guidance on how to manage driving recommendations in this setting. We conducted a systematic review to find studies that indicated the prevalence of MVAs in patients with MHE, testing available to identify such patients, and interventions that may improve the surrogate measures of driving in patients with MHE.

METHODS:
A systematic review of full-text studies reporting the prevalence of MVAs in patients with MHE, along with testing and treatment options in this setting. Two librarians searched PubMed from inception to January 2018 using the keywords liver cirrhosis, hepatic encephalopathy (HE), automobile driving and accidents along with related synonyms. Studies were excluded if the patients had overt HE, non-liver related HE, and non-automobile accidents. Three reviewers independently extracted data from each study including study design, year of data collection, location, exclusion criteria, prevalence, diagnosis and treatment options.

RESULTS:
162 studies were identified, of which 15 met the inclusion criteria, comprising of 1379 patients. Studies were from US(8), Germany(3), Sri Lanka(1), Egypt(1), Japan(1) and Spain(1). Seven articles discussed how often patients with MHE had MVAs, which were conducted as either prospective(5) or survey studies(2) that relied on self-reported and transportation data. These studies suggest that 13–50% of patients with MHE had MVAs. Regarding testing, 10 studies discussed the diagnostic modalities available, including driving simulators(3), inhibitory control tests (ICT)(2), driving instructor(2), smartphone app(1) and Psychometric HE Reliability Score(1). Of these, ICT test was the most predictive. Two studies discussed the treatment modalities. Rifaximin showed improvement in avoiding total driving errors (76%vs31%; P = .01) and branched chain amino acid (BCAAs) significantly improved driving capacity vs placebo (median score of 2 vs 4, P < 0.01) with lower scores indicating the fitness to drive.

CONCLUSION:
Patients with MHE are at significant risk for MVAs. There are several testing modalities to assess driving fitness in patients with MHE. Rifaximin and BCAAs improved fitness to drive in MHE patients. Future studies are needed to help guide clinicians on how to best provide driving recommendations in patients with MHE.
967 Sex Differences in the Utilization of Bariatric Operation for NAFLD
Authors: Gupta Kamesh , Khan Ahmad , Goyal Hemant 
Published: October 2019

INTRODUCTION:
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in the developed world. Bariatric surgery is the most validated method for achieving significant, sustained weight loss and has shown to decrease the grade of steatosis.

METHODS:
We utilized the Nationwide Inpatient Sample database from 2004 to 2014 to identify all hospitalized adult patients with a history of NAFLD and patients who underwent bariatric surgery. We excluded NAFLD patients who had a diagnosis code for cirrhosis, alcoholism, viral hepatitis, or metabolic liver disorders. Age, race, insurance, and hospital characters were computed on the basis of sex.

RESULTS:
Our study included 92,293 NAFLD‐related hospitalizations, of which 36787 patients (39.8%) were female. A total of 710 bariatric surgeries were performed from 2004–2014 on patients with NAFLD. Of these, 590 (83.1%) were women. In the general population without NAFLD too, the procedure was more common in females (76.09%, n = 956,186) than males (23.91%, n = 300,500). In the patient population of NAFLD patients undergoing the surgery, females were less likely to have coexisting weight-related illnesses such as hyperlipidemia (46.5% vs 49.0%, P = 0.02), hypertension (49.2% vs 63.7%, P = 0.00), sleep apnea (46.1% vs 53.0%, P = 0.00), hypertension (51.7% vs 44.6%, P = 0.486). Demographic data showed that the female subgroup was significantly younger (43.0 vs 49.7 years, P = 0.01), and more commonly admitted in Midwest (21.5% vs 16.8%) and Western states (29.3% vs 15.2%). No significant differences were noted in the race, income quartile or insurance of the patients. The odds ratio for being a female NAFLD patient versus a male undergoing the procedure was +5.84 (P = 0.00). In the whole study period, only 5 patients died during the hospitalization for bariatric surgery.

CONCLUSION:
Results from our study show that bariatric surgery is more popular amongst females with NAFLD versus males with NAFLD when adjusted for other factors. This discrepancy is even starker than the general bariatric population without NAFLD, where females are more prevalent too. Female patients with NAFLD were more likely to be younger and having lesser weight-related comorbidities than males at the time of the surgery. The increased utilization of bariatric surgery in the female NAFLD population could be driven by cultural factors and self-consciousness. Bariatric surgery has low mortality in NAFLD patients.
970 Thrombolytic Therapy for Acute Non-Malignant Portal Vein Thrombosis: A Systematic Review and Meta-Analysis
Authors: Doherty Bryan , Palmer William , Zhang Allison , Briggs William M. , Marks Lisa A. , Mohanty Smruti R. 
Published: October 2019

INTRODUCTION:
Acute portal vein thrombosis (PVT) is a rare diagnosis frequently associated with cirrhosis. Clinical presentation is typically nonspecific with potentially catastrophic short-term complications including sepsis, bowel infarction, and death. Management strategies differ for acute and chronic PVT. Guidelines for treating acute PVT recommend immediate initiation of systemic anticoagulation. Direct and indirect thrombolytic therapy (mechanical thrombectomy and fibrinolytic therapy) may be used in combination with systemic anticoagulation in the setting of bowel ischemia or as an adjunct in patients with a contraindication to systemic anticoagulation. We aimed to assess the success of thrombolytic therapy for non-malignant acute PVT and to compare the success of direct versus indirect thrombolytic therapy.

METHODS:
This was a systematic review and meta-analysis in which two independent librarians searched the following databases from the date of inception to March 2019: Ovid Medline, Ovid Embase, Scopus and Web of Science. All included studies provided technical and clinical success data, as well as adverse events, and technique(s) used for the intervention of non-malignant acute PVT.

RESULTS:
The two independent database searches yielded 143 citations, of which 79 duplicates were removed leaving a total of 64 references and 11 were included in our analyses. The overall success rate of thrombolytic therapy using the random effects model was 83% (95%CI: 0.67, 0.92; P = <0.01; I 2 = 61%). The overall clinical improvement rate of thrombolytic therapy using the fixed effects model was 95% (95%CI: 0.88, 0.98; P = 0.73; I 2 = 0%). The overall mortality of thrombolytic therapy using the fixed effects model was 5% (95%CI: 0.03, 0.11; P = 0.92; I 2 = 0%). In the direct and indirect thrombolytic groups, the rate of technical success was 84% and 52%, respectively, with an odds ratio of 3.37 (95%CI (0.96, 7.67), P-value = 0.127).

CONCLUSION:
Our analysis demonstrates that thrombolytic therapy successfully eliminates non-malignant acute PVTs with low rates of mortality. Direct thrombolysis may produce increased efficacy compared to indirect thrombolytic therapy. Larger prospective randomized trials comparing these interventions are warranted.