79 results on '"Grace L. Su"'
Search Results
2. Automated Measurements of Body Composition in Abdominal CT Scans Using Artificial Intelligence Can Predict Mortality in Patients With Cirrhosis
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Binu Enchakalody, Stewart C. Wang, Sameer D. Saini, Peng Zhang, Winnie Y. Zou, Nicholas C. Wang, Nidhi V. Shah, and Grace L. Su
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Male ,Cirrhosis ,Multivariate analysis ,Abdominal ct ,Abdominal Fat ,RC799-869 ,Proof of Concept Study ,Severity of Illness Index ,End Stage Liver Disease ,Deep Learning ,Artificial Intelligence ,Predictive Value of Tests ,Image Processing, Computer-Assisted ,medicine ,Humans ,In patient ,Prospective Studies ,Aged ,Hepatology ,business.industry ,Medical record ,Confusion matrix ,Original Articles ,Middle Aged ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,Test set ,Cohort ,Body Composition ,Original Article ,Female ,Artificial intelligence ,Tomography, X-Ray Computed ,business ,Algorithms - Abstract
Body composition measures derived from already available electronic medical records (computed tomography [CT] scans) can have significant value, but automation of measurements is needed for clinical implementation. We sought to use artificial intelligence to develop an automated method to measure body composition and test the algorithm on a clinical cohort to predict mortality. We constructed a deep learning algorithm using Google’s DeepLabv3+ on a cohort of de‐identified CT scans (n = 12,067). To test for the accuracy and clinical usefulness of the algorithm, we used a unique cohort of prospectively followed patients with cirrhosis (n = 238) who had CT scans performed. To assess model performance, we used the confusion matrix and calculated the mean accuracy of 0.977 ± 0.02 (0.975 ± 0.018 for the training and test sets, respectively). To assess for spatial overlap, we measured the mean intersection over union and mean boundary contour scores and found excellent overlap between the manual and automated methods with mean scores of 0.954 ± 0.030, 0.987 ± 0.009, and 0.948 ± 0.039 (0.983 ± 0.013 for the training and test set, respectively). Using these automated measurements, we found that body composition features were predictive of mortality in patients with cirrhosis. On multivariate analysis, the addition of body composition measures significantly improved prediction of mortality for patients with cirrhosis over Model for End‐Stage Liver Disease alone (P
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- 2021
3. Automated Measurements of Muscle Mass Using Deep Learning Can Predict Clinical Outcomes in Patients With Liver Disease
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Stewart C. Wang, Peng Zhang, Grace L. Su, Elliot B. Tapper, Nicholas C. Wang, and Sameer D. Saini
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Adult ,Male ,Michigan ,medicine.medical_specialty ,Cirrhosis ,Adolescent ,Intraclass correlation ,Population ,Article ,Cohort Studies ,Young Adult ,03 medical and health sciences ,Liver disease ,Deep Learning ,0302 clinical medicine ,Predictive Value of Tests ,Humans ,Medicine ,In patient ,Prospective Studies ,Muscle, Skeletal ,education ,Aged ,education.field_of_study ,Hepatology ,business.industry ,Deep learning ,Gastroenterology ,Middle Aged ,medicine.disease ,Fibrosis ,Confidence interval ,030220 oncology & carcinogenesis ,Cohort ,Female ,030211 gastroenterology & hepatology ,Artificial intelligence ,Radiology ,Tomography, X-Ray Computed ,business ,Algorithms - Abstract
INTRODUCTION There is increasing recognition of the central role of muscle mass in predicting clinical outcomes in patients with liver disease. Muscle size can be extracted from computed tomography (CT) scans, but clinical implementation will require increased automation. We hypothesize that we can achieve this by using artificial intelligence. METHODS Using deep convolutional neural networks, we trained an algorithm on the Reference Analytic Morphomics Population (n = 5,268) and validated the automated methodology in an external cohort of adult kidney donors with a noncontrast CT scan (n = 1,655). To test the clinical usefulness, we examined its ability to predict clinical outcomes in a prospectively followed cohort of patients with clinically diagnosed cirrhosis (n = 254). RESULTS Between the manual and automated methodologies, we found excellent inter-rater agreement with an intraclass correlation coefficient of 0.957 (confidence interval 0.953-0.961, P < 0.0001) in the adult kidney donor cohort. The calculated dice similarity coefficient was 0.932 ± 0.042, suggesting excellent spatial overlap between manual and automated methodologies. To assess the clinical usefulness, we examined its ability to predict clinical outcomes in a cirrhosis cohort and found that automated psoas muscle index was independently associated with mortality after adjusting for age, gender, and child's classification (P < 0.001). DISCUSSION We demonstrated that deep learning techniques can allow for automation of muscle measurements on clinical CT scans in a diseased cohort. These automated psoas size measurements were predictive of mortality in patients with cirrhosis showing proof of principal that this methodology may allow for wider implementation in the clinical arena.
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- 2020
4. Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients
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Peng Zhang, Chau-Ting Yeh, Hu Tsung-Hui, Kung-Hao Liang, Chih-Lang Lin, Stewart C. Wang, and Grace L. Su
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Liver Cirrhosis ,Male ,Michigan ,Cirrhosis ,Physiology ,Kaplan-Meier Estimate ,0302 clinical medicine ,Bone Density ,Image Processing, Computer-Assisted ,Cumulative incidence ,Prospective Studies ,Fascia ,Bone mineral ,education.field_of_study ,Incidence ,Liver Neoplasms ,Gastroenterology ,Middle Aged ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cohort ,Female ,030211 gastroenterology & hepatology ,alpha-Fetoproteins ,Radiology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Population ,Paraspinal Muscles ,Taiwan ,Risk Assessment ,Article ,Bone and Bones ,03 medical and health sciences ,Hepatitis B, Chronic ,Internal medicine ,medicine ,Humans ,Muscle, Skeletal ,education ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Proportional hazards model ,business.industry ,Reproducibility of Results ,Hepatitis C, Chronic ,Hepatology ,medicine.disease ,Tomography, X-Ray Computed ,business - Abstract
BACKGROUND & AIMS: Computed tomography (CT) provides scans of the human body from which digitized features can be extracted. The aim of this study was to examine the role of these digital biomarkers for predicting subsequent occurrence of hepatocellular carcinoma (HCC) in cirrhotic patients. METHODS: A cohort of 269 patients with cirrhosis were recruited and prospectively followed for the occurrence of HCC in Taiwan. CT scans were retrospectively retrieved and computationally processed using analytic morphomics. A predictive score was constructed using Cox regression and the generalized iterative modeling method, maximizing the log-likelihood of the time to HCC development. An independent cohort of 274 patients from University of Michigan was utilized to examine the predictive validity of this score in a Western population. RESULTS: Of the 27 digitized features at the 12th thoracic vertebral level, 6 features were significantly associated with HCC occurrence. Two digitized features (fascia eccentricity and the bone mineral density) was able to stratify patients into high and low-risk groups with distinct cumulative incidence of HCC in both the training and validation cohorts (P = 0.015 and 0.044 respectively). When the two digitized features were tested in the Michigan cohort, only bone mineral density remained an effective predictor. CONCLUSION: Digitized features derived from the CT were effective in predicting subsequent occurrence of HCC in cirrhosis patients. The bone mineral density measured on CT was an effective predictor for patients in both Taiwan and USA.
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- 2019
5. Systematic review: Radiomics for the Diagnosis and Prognosis of Hepatocellular Carcinoma
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Neehar D. Parikh, Amit G. Singal, Jeremy Louissaint, Grace L. Su, Bharat Maraj, Emily Harding-Theobald, Whitney Townsend, Mishal Mendiratta-Lala, Edward Cuaresma, and Anna S. Lok
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Hepatology ,Tumor biology ,business.industry ,Liver Neoplasms ,Gastroenterology ,Radiogenomics ,Gold standard (test) ,medicine.disease ,Prognosis ,Article ,Biomarker (cell) ,Data extraction ,Radiomics ,Hepatocellular carcinoma ,medicine ,Imaging technology ,Hepatectomy ,Humans ,Pharmacology (medical) ,Radiology ,business ,Retrospective Studies - Abstract
BACKGROUND: Advances in imaging technology have the potential to transform the early diagnosis and treatment of hepatocellular carcinoma (HCC) through quantitative image analysis. Computational ‘radiomic’ techniques extract biomarker information from images which can be used to improve diagnosis and predict tumor biology. AIMS: We performed a systematic review of literature on radiomic features in HCC diagnosis and prognosis, with a focus on reporting metrics and methodologic standardization. METHODS: A systematic review was performed of all full-text articles published from inception through December 1, 2019. Standardized data extraction and quality assessment metrics were applied to all studies. RESULTS: A total of 54 unique studies were included for analysis. Radiomic features demonstrated good discriminatory performance to differentiate HCC from other solid lesions (c-statistics 0.66–0.95), predict microvascular invasion (c-statistic 0.76–0.92), predict early recurrence after hepatectomy (c-statistics 0.71–0.86), and predict prognosis after locoregional or systemic therapies (c-statistics 0.74–0.81). Common stratifying features for diagnostic and prognostic radiomic tools included analyses of imaging skewness, analysis of the peritumoral region, and feature extraction from the arterial imaging phase. The overall quality of the included studies was low, with common deficiencies in both internal and external validation, standardized imaging segmentation, and lack of comparison to a gold standard. CONCLUSIONS: Quantitative image analysis demonstrates promise as a non-invasive biomarker to improve HCC diagnosis and management. However, standardization of protocols and outcome measurement, sharing of algorithms and analytic methods, and external validation are necessary prior to widespread application of radiomics to HCC diagnosis and prognosis in clinical practice.
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- 2021
6. Bedside Measures of Frailty and Cognitive Function Correlate with Sarcopenia in Patients with Cirrhosis
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Grace L. Su, Brian A. Derstine, Jad Baki, and Elliot B. Tapper
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medicine.medical_specialty ,Cirrhosis ,Physiology ,business.industry ,Gastroenterology ,Skeletal muscle ,Hepatology ,medicine.disease ,Cognitive test ,Correlation ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Sarcopenia ,Internal medicine ,medicine ,Cardiology ,030211 gastroenterology & hepatology ,Effects of sleep deprivation on cognitive performance ,business ,Hepatic encephalopathy - Abstract
Frailty and sarcopenia are associated with mortality and poor outcomes among patients with cirrhosis. Frailty is multifactorial but due in part to sarcopenia and cognitive dysfunction. Data are limited regarding the correlation of bedside frailty and cognitive function measures with sarcopenia. To evaluate the correlations between frailty measures and muscle indices from computed tomography (CT). We prospectively enrolled 106 patients with clinically compensated cirrhosis (and no prior hepatic encephalopathy). All patients underwent CT scan and cognitive testing (via inhibitory control test, ICT), and were subject to hand grip, 30-s chair stands, mid-arm muscle area (MAMA), and a four-question algorithm based on the Sickness Impact Profile (SIP) predictive of minimal HE. We evaluated Spearman correlations between all measures as well as the sensitivity and specificity of each measure for falls. In total, 106 (35.3%) patients (55 men) had CT scans to measure skeletal muscle area and quality. Hand grip correlated strongly with skeletal muscle area (correlation coefficient 0.64, p
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- 2019
7. Spotlight: Probiotics Guidelines
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Geoffrey A. Preidis, Grace L. Su, Cynthia W. Ko, Rebecca L. Morgan, Premysl Bercik, Adam V. Weizman, and Purna C. Kashyap
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Consensus ,Evidence-Based Medicine ,Hepatology ,Bacteria ,business.industry ,Gastrointestinal Diseases ,Probiotics ,MEDLINE ,Gastroenterology ,Article ,Gastrointestinal Microbiome ,World Wide Web ,Intestines ,Text mining ,Treatment Outcome ,Medicine ,Dysbiosis ,Humans ,business - Published
- 2020
8. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders
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Grace L. Su, Yngve Falck-Ytter, Adam V. Weizman, Shahnaz Sultan, Cynthia W. Ko, Premysl Bercik, and Rebecca L. Morgan
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medicine.medical_specialty ,Consensus ,Gastrointestinal Diseases ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Irritable bowel syndrome ,Evidence-Based Medicine ,Hepatology ,Bacteria ,business.industry ,Probiotics ,Gastrointestinal Microbiome ,Gastroenterology ,Odds ratio ,medicine.disease ,Confidence interval ,Intestines ,Treatment Outcome ,Relative risk ,Necrotizing enterocolitis ,Dysbiosis ,business - Published
- 2020
9. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis
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Ikuo Hirano, Edmond S. Chan, Matthew A. Rank, Rajiv N. Sharaf, Neil H. Stollman, David R. Stukus, Kenneth Wang, Matthew Greenhawt, Yngve T. Falck-Ytter, Karen A. Chachu, Lukejohn Day, Benjamin Lebwohl, Thiruvengadam Muniraj, Amit Patel, Anne F. Peery, Raj Shah, Harminder Singh, Siddharth Singh, Stuart J. Spechler, Shahnaz Sultan, Grace L. Su, Aaron P. Thrift, Jennifer M. Weiss, Adam V. Weizman, Jonathan A. Bernstein, Chitra Dinakar, David B.K. Golden, David A. Khan, Jay Lieberman, John Oppenheimer, Marcus Shaker, Dana V. Wallace, Julie Wang, Glenn Furuta, Evan Dellon, Jonathan Spergel, Seema Aceves, Yngve Falck-Ytter, and Rajiv Sharaf
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.drug_class ,Administration, Topical ,Immunology ,Advisory Committees ,MEDLINE ,Proton-pump inhibitor ,Article ,law.invention ,Randomized controlled trial ,law ,Adrenal Cortex Hormones ,Internal medicine ,Allergy and Immunology ,medicine ,Immunology and Allergy ,Humans ,Eosinophilic esophagitis ,Expert Testimony ,Societies, Medical ,Hepatology ,medicine.diagnostic_test ,Task force ,Extramural ,Esophagogastroduodenoscopy ,Allergy immunology ,business.industry ,Disease progression ,Gastroenterology ,Proton Pump Inhibitors ,Eosinophilic Esophagitis ,medicine.disease ,Confidence interval ,United States ,Phenotype ,Relative risk ,Practice Guidelines as Topic ,Disease Progression ,business - Published
- 2020
10. Body composition predicts mortality and decompensation in compensated cirrhosis patients: A prospective cohort study
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Venkat Krishnamurthy, Peng Zhang, Tori Nault, Kate Leary, Grace L. Su, Rohan Garg, and Elliot B. Tapper
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medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,Liver transplantation ,Gastroenterology ,HU, Hounsfield units ,MELD, model for end-stage liver disease ,sarcopenia ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Model for End-Stage Liver Disease ,Internal medicine ,Internal Medicine ,medicine ,Immunology and Allergy ,Decompensation ,lcsh:RC799-869 ,Prospective cohort study ,Hepatology ,business.industry ,Hazard ratio ,INR, international normalized ratio ,MELD score ,portal hypertension ,medicine.disease ,HR, hazard ratio ,HE, hepatic encephalopathy ,3. Good health ,NRI, net reclassification improvement ,liver transplant ,030220 oncology & carcinogenesis ,Cohort ,lcsh:Diseases of the digestive system. Gastroenterology ,030211 gastroenterology & hepatology ,business ,Research Article - Abstract
Background & Aims Body composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients. Methods A total of 274 patients with cirrhosis were followed prospectively for ≤5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort. Results Our cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C (vs. A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, p, Graphical abstract, Highlights • Features of body composition can predict clinical outcomes in patients with cirrhosis awaiting liver transplantation. • Data are lacking regarding long-term outcomes among patients with compensated disease. • We show that features of muscle and fat are associated with decompensation and risk of death across the spectrum of cirrhosis. • CT scans obtained for unrelated clinical purposes can be analyzed as a digital risk biomarker for patients with compensated cirrhosis.
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- 2019
11. A risk score to predict the development of hepatic encephalopathy in a population‐based cohort of patients with cirrhosis
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Neehar D. Parikh, Grace L. Su, Anna S.F. Lok, Jessica L. Mellinger, Neil Sengupta, Elliot B. Tapper, and David Ratz
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medicine.medical_specialty ,education.field_of_study ,Cirrhosis ,Framingham Risk Score ,Hepatology ,Proportional hazards model ,business.industry ,Population ,Retrospective cohort study ,Hepatitis C ,medicine.disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cohort ,medicine ,030211 gastroenterology & hepatology ,030212 general & internal medicine ,education ,business ,Cohort study - Abstract
Over 40% of patients with cirrhosis will develop hepatic encephalopathy (HE). HE is associated with decreased survival, falls, motor vehicle accidents, and frequent hospitalization. Accordingly, we aimed to develop a tool to risk-stratify patients for HE development. We studied a population-based cohort of all patients with cirrhosis without baseline HE (N=1,979) from the Veterans Administration from Michigan, Indiana, and Ohio (1/1/2005-12/31/10) using demographic, clinical, laboratory, and pharmacy data. The primary outcome was the development of HE. Risk-scores were constructed with both baseline and longitudinal data (annually updated parameters) and validated using bootstrapping. The cohort had mean age of 58.0±8.3 years, 36% had hepatitis C, 17% had ascites. Opiates, benzodiazepines, statins, and nonselective beta-blockers were taken at baseline by 24%, 13%, 17%, and 12%. Overall, 863(43.7%) developed HE within 5 years. In multivariable models, risk factors (HR, 95%CI) for HE included higher bilirubin (1.07, 1.05-1.09) and nonselective beta-blocker use (1.34, 1.09-1.64), while higher albumin (0.54, 0.48-0.59) and statin use (0.80, 0.65-0.98) were protective. Other clinical factors, including opiate and benzodiazepine use were not predictive. The AUROC for HE using the 4 significant variables in baseline and longitudinal models were 0.68 (0.66-0.70) and 0.73 (0.71-0.75), respectively. Model effects were validated and converted into a risk score. A score ≤0 in our longitudinal model assigns a 6% 1-year probability of HE while a score >20 assigns a 38% 1-year risk. Conclusion: Patients with cirrhosis can be stratified by a simple risk-score for HE that accounts for changing clinical data. Our data also highlight a role for statins in reducing cirrhosis complications including HE. This article is protected by copyright. All rights reserved.
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- 2018
12. Electronic Consultations: Delivering Specialty Care Anywhere
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Grace L. Su
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Editorial ,Hepatology ,business.industry ,Specialty ,Editorials ,Medicine ,lcsh:Diseases of the digestive system. Gastroenterology ,Medical emergency ,lcsh:RC799-869 ,business ,medicine.disease - Published
- 2019
13. AGA Clinical Practice Guideline on the Management of Coagulation Disorders in Patients With Cirrhosis
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Robert S. O’Shea, Perica Davitkov, Shahnaz Sultan, Yngve Falck-Ytter, Grace L. Su, Cynthia W. Ko, Alina M. Allen, and Anita Rajasekhar
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Liver Cirrhosis ,medicine.medical_specialty ,Consensus ,Cirrhosis ,medicine.drug_class ,Hemorrhage ,Risk Assessment ,law.invention ,Randomized controlled trial ,Predictive Value of Tests ,Risk Factors ,law ,Humans ,Medicine ,Intensive care medicine ,Blood Coagulation ,Coagulation Disorder ,Prothrombin time ,Evidence-Based Medicine ,Hepatology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Anticoagulants ,Guideline ,Blood Coagulation Disorders ,Vitamin K antagonist ,medicine.disease ,Portal vein thrombosis ,Treatment Outcome ,Blood Coagulation Tests ,Patient Safety ,Fresh frozen plasma ,business - Published
- 2021
14. Introducing the AASLD president: Anna S.F. Lok
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Grace L. Su and Robert J. Fontana
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Hepatology ,Political science ,Gastroenterology ,Hong Kong ,Humans ,Library science ,Female ,History, 20th Century ,United States - Published
- 2017
15. Fat Accumulation, Liver Fibrosis, and Metabolic Abnormalities in Chinese Patients With Moderate/Severe Versus Mild Hepatic Steatosis
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Rui Huang, Grace L. Su, Lai Wei, Yi Wang, Huiying Rao, Wei Zhang, and Anna S. Lok
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medicine.medical_specialty ,Waist ,Hepatology ,business.industry ,Liver fibrosis ,Original Articles ,medicine.disease ,Gastroenterology ,Liver disease ,Fat accumulation ,Hounsfield scale ,Internal medicine ,Nonalcoholic fatty liver disease ,Medicine ,lcsh:Diseases of the digestive system. Gastroenterology ,Original Article ,Metabolic syndrome ,Steatosis ,lcsh:RC799-869 ,business - Abstract
Several drugs in development for nonalcoholic fatty liver disease (NAFLD) aim to decrease the amount of fat in the liver. We compared quantity and quality of fat in subcutaneous, visceral and muscle compartments, liver fibrosis, and prevalence of metabolic abnormalities between Chinese patients with moderate/severe hepatic steatosis versus those with mild hepatic steatosis. NAFLD patients were prospectively recruited from Peking University People's Hospital in Beijing, China. All patients had baseline body composition measurements using computed tomography and analytic morphomics, clinical evaluation, labs and Fibroscan® controlled attenuation parameter and liver stiffness measurement. Moderate/severe hepatic steatosis was defined as computed tomography liver attenuation of 40 Hounsfield units or less. Calorie intake and physical activity were based on self‐report. A total of 160 NAFLD patients were included (46% men, median age 47 years): 50% had normal body mass index (BMI), 24% were diabetic, and 56% had metabolic syndrome (MS). Fifty‐three (33%) had moderate/severe steatosis, of whom 19 (35.8%) had normal BMI, and the rest had mild steatosis. Patients who had moderate/severe steatosis had significantly higher BMI, waist circumference, aminotransferases, controlled attenuation parameter, liver stiffness measurement, and prevalence of MS compared to those with mild steatosis. They also had larger visceral fat area, subcutaneous fat area, and low density dorsal muscle area. In addition, their calorie intake was higher and time spent on recreation activities was shorter. Conclusion: NAFLD patients with moderate/severe steatosis, including those with normal BMI, had higher prevalence of MS and more fat in visceral, subcutaneous, and muscle compartments than those with mild steatosis. They also had more advanced liver disease. Strategies to decrease hepatic fat may benefit both liver and metabolic diseases., NAFLD patients with moderate/severe hepatic steatosis had higher prevalence of metabolic syndrome and more fat in visceral, subcutaneous and muscle compartments than those with mild steatosis.
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- 2019
16. Limitations of the barcelona clinic liver cancer staging system with a focus on transarterial chemoembolization as a key modality for treatment of hepatocellular carcinoma
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Grace L. Su and Pranab Barman
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Oncology ,medicine.medical_specialty ,Modality (human–computer interaction) ,Hepatology ,business.industry ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Hepatocellular carcinoma ,medicine ,030211 gastroenterology & hepatology ,Radiology ,Liver cancer ,business ,Staging system - Published
- 2016
17. Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters
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John Oppenheimer, Jay Lieberman, Julie Wang, David R. Stukus, Dana V. Wallace, Adam V. Weizman, David B.K. Golden, Karen A. Chachu, Grace L. Su, Matthew Greenhawt, Anne F. Peery, Matthew A. Rank, Chitra Dinakar, Rajiv N. Sharaf, Jonathan A. Bernstein, Yngve T. Falck-Ytter, Stuart J. Spechler, Seema S. Aceves, Amit Patel, David A. Khan, Siddharth Singh, Shahnaz Sultan, Raj J. Shah, Jonathan M. Spergel, Aaron P. Thrift, Glenn T. Furuta, Evan S. Dellon, Harminder Singh, Lukejohn W. Day, Marcus Shaker, Jennifer M. Weiss, Benjamin Lebwohl, and Thiruvengadam Muniraj
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Administration, Topical ,law.invention ,0302 clinical medicine ,Maintenance therapy ,Randomized controlled trial ,law ,Immunology and Allergy ,Eosinophilia ,030212 general & internal medicine ,Child ,Grading (education) ,Societies, Medical ,Evidence-Based Medicine ,Age Factors ,Gastroenterology ,medicine.anatomical_structure ,Treatment Outcome ,Practice Guidelines as Topic ,Immunotherapy ,Esophagoscopy ,medicine.symptom ,Food Hypersensitivity ,medicine.drug ,Pulmonary and Respiratory Medicine ,Adult ,medicine.medical_specialty ,Immunology ,Advisory Committees ,MEDLINE ,Article ,03 medical and health sciences ,Internal medicine ,Allergy and Immunology ,Elimination diet ,medicine ,Humans ,Medical physics ,Esophagus ,Eosinophilic esophagitis ,Expert Testimony ,Glucocorticoids ,Montelukast ,Food, Formulated ,Hepatology ,Allergy immunology ,Task force ,business.industry ,Proton Pump Inhibitors ,Eosinophilic Esophagitis ,Guideline ,Eosinophil ,Allergens ,medicine.disease ,Dilatation ,United States ,Diet ,Eosinophils ,030228 respiratory system ,GERD ,Interdisciplinary Communication ,business - Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to
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- 2020
18. 325 ADAPTED TIME-VARYING COVARIATES COX MODEL PERFORMS WELL IN PREDICTING FUTURE CIRRHOSIS DEVELOPMENT AMONG HCV PATIENTS WITH AND WITHOUT ANTIVIRAL TREATMENT
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Akbar K. Waljee, Lauren A. Beste, Xuefei Zhang, Grace L. Su, Tony Van, Monica A. Tincopa, Boang Liu, Ji Zhu, and George N. Ioannou
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Time-varying covariate ,Oncology ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,Proportional hazards model ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Antiviral treatment ,medicine.disease ,business - Published
- 2020
19. Virtual Consultations Through the Veterans Administration SCAN-ECHO Project Improves Survival for Veterans With Liver Disease
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Grace L. Su, Tony Van, Anne E. Sales, Elliot B. Tapper, Lisa M. Glass, and Akbar K. Waljee
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Adult ,Male ,medicine.medical_specialty ,Specialty ,Context (language use) ,Cohort Studies ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Hepatology ,business.industry ,Proportional hazards model ,Mortality rate ,Liver Diseases ,Remote Consultation ,Hazard ratio ,Middle Aged ,medicine.disease ,United States ,United States Department of Veterans Affairs ,Emergency medicine ,Cohort ,Propensity score matching ,030211 gastroenterology & hepatology ,Female ,business - Abstract
Access to specialty care has been associated with improved survival in patients with liver disease but universal access is not always feasible. Methods of care delivery using virtual modalities including the SCAN-ECHO (Specialty Access Network-Extension of Community Healthcare Outcome) program were implemented by the Veterans Health Administration (VHA) to address this need but limited data are available on patient outcomes. We sought to evaluate the efficacy of a SCAN-ECHO visit within the context of a regional cohort of patients with liver disease in the VHA (n = 62,237) following implementation in the Ann Arbor SCAN-ECHO Liver Clinic from June 1, 2011, to March 31, 2015. The effect of a SCAN-ECHO visit on all-cause mortality was compared with patients with no liver clinic visit. To adjust for the differences among patients who had a SCAN-ECHO visit versus those with no visit, propensity score matching was performed on condition factors that affect the likelihood of a SCAN-ECHO visit: demographics, geographic location, liver disease diagnosis, severity, and comorbidities. During the study period, 513 patients who had a liver SCAN-ECHO visit were found within the cohort. Patients who had completed a virtual SCAN-ECHO visit were more likely younger, rural, with more significant liver disease, and evidence for cirrhosis. Propensity-adjusted mortality rates using the Cox Proportional Hazard Model showed that a SCAN-ECHO visit was associated with a hazard ratio of 0.54 (95% confidence interval 0.36-0.81, P = 0.003) compared with no visit. Conclusion: Improved survival in patients using SCAN-ECHO suggests that this approach may be an effective method to improve access for selected patients with liver disease, particularly in rural and underserved populations where access to specialty care is limited.
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- 2018
20. Reply
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Elliot B. Tapper, David Ratz, Anna S.‐F. Lok, and Grace L. Su
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Hepatology - Published
- 2018
21. Specialty Care Access Network-Extension of Community Healthcare Outcomes Model Program for Liver Disease Improves Specialty Care Access
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Grace L. Su, Heather McCurdy, Lisa M. Glass, Anne E. Sales, and Akbar K. Waljee
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medicine.medical_specialty ,Telemedicine ,Quality management ,Physiology ,Specialty ,Subspecialty ,Chronic liver disease ,Health Services Accessibility ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Internal medicine ,Health care ,medicine ,Humans ,030212 general & internal medicine ,Community Health Services ,Prospective Studies ,Referral and Consultation ,business.industry ,Liver Diseases ,Gastroenterology ,Hepatology ,medicine.disease ,Family medicine ,030211 gastroenterology & hepatology ,business - Abstract
To improve subspecialty access, VA Ann Arbor Healthcare System (VAAAHS) implemented the first Specialty Care Access Network (SCAN)-Extension of Community Healthcare Outcomes (ECHO) in chronic liver disease. SCAN-ECHO Liver links primary care providers (PCPs) to hepatologists via secure video-teleconferencing. We aim to describe characteristics of participants (PCPs) and patients (clinical question and diagnosis) in SCAN-ECHO Liver. This is a prospective study of the VAAAHS SCAN-ECHO Liver (June 10, 2011–March 31, 2015). This evaluation was carried out as a non-research activity under the guidance furnished by VHA Handbook 1058.05. It was approved through the Medicine Service at VAAAHS as noted in the attestation document which serves as documentation of approved non-research, quality improvement activities in VHA. In total, 106 PCPs from 23 sites participated. A total of 155 SCAN-ECHO sessions discussed 519 new and 49 return patients. 29.4% of Liver Clinic requests were completed in SCAN-ECHO Liver. SCAN-ECHO Liver consults were completed an average of 10 days sooner than in conventional clinic. Potential travel saving was 250 miles round-trip (median 255 (IQR 142–316) per patient. SCAN-ECHO Liver provided specialty care with increased efficiency and convenience for chronic liver disease patients. One of three of Liver Clinic consults was diverted to SCAN-ECHO Liver, reducing consult completion time by 20%.
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- 2017
22. Tu1482 – Application of Deep Learning Models to Predict Progression to Cirrhosis Among Veterans with Chronic Hepatitis C
- Author
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Grace L. Su, Ji Zhu, Akbar K. Waljee, Elliot B. Tapper, Lauren A. Beste, George N. Ioannou, Tony Van, Weijing Tang, Brahmajee K. Nallamothu, Sameer D. Saini, and Monica A. Konerman
- Subjects
medicine.medical_specialty ,Cirrhosis ,Hepatology ,Chronic hepatitis ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,medicine.disease ,business - Published
- 2019
23. Tu1496 – Democratic Deliberation to Assess Veteran Preferences on Allocation of Healthcare Resources for Chronic Hepatitis C Treatment
- Author
-
Maria Hughes, Raymond De Vries, George N. Ioannou, Pia Roman, Monica A. Konerman, Kerry A. Ryan, Akbar K. Waljee, Grace L. Su, Sameer D. Saini, Amanda Ellis, Lauren A. Beste, and Chris Krenz
- Subjects
Hepatology ,Nursing ,Chronic hepatitis ,business.industry ,Political science ,Health care ,Gastroenterology ,Democratic deliberation ,business - Published
- 2019
24. 498 – Deep Learning Models Accurately Predict Development of Hcc in 146,218 Patients with Chronic Hepatitis C
- Author
-
Monica A. Konerman, Weijing Tang, Grace L. Su, Akbar K. Waljee, Elliot B. Tapper, Lauren A. Beste, Tony Van, Amit G. Singal, George N. Ioannou, and Ji Zhu
- Subjects
Oncology ,medicine.medical_specialty ,Hepatology ,Chronic hepatitis ,business.industry ,Internal medicine ,Deep learning ,Gastroenterology ,Medicine ,Artificial intelligence ,business - Published
- 2019
25. Tu1817 – Increasing Subcutaneous Fat and Weight are Correlated with Reduced Adalimumab Drug Levels in Patients with Inflammatory Bowel Disease
- Author
-
Grace L. Su, Ryan W. Stidham, Stewart C. Wang, Brian A. Derstine, Peter D.R. Higgins, Sullivan A. June, Binu Enchakalody, and Akbar K. Waljee
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,medicine.disease ,Inflammatory bowel disease ,Subcutaneous fat ,Drug levels ,Internal medicine ,medicine ,Adalimumab ,In patient ,business ,medicine.drug - Published
- 2019
26. Does Karnofsky Performance Status of Patients With Cirrhosis on the Transplant Waitlist Meet the Eyeball Test?
- Author
-
Elliot B. Tapper and Grace L. Su
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,Karnofsky Performance Status ,business.industry ,Gastroenterology ,030230 surgery ,medicine.disease ,Article ,Test (assessment) ,End Stage Liver Disease ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,medicine ,Physical therapy ,Humans ,030211 gastroenterology & hepatology ,business - Published
- 2016
27. Access to Subspecialty Care And Survival Among Patients With Liver Disease
- Author
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Heather McCurdy, Grace L. Su, Michael L. Volk, Lisa M. Glass, Matheos Yosef, Deborah E. Welsh, Richard H. Moseley, Stephanie E. Moser, Mina O. Rakoski, Anne E. Sales, Jessica L. Mellinger, Akbar K. Waljee, and Tony Van
- Subjects
Male ,medicine.medical_specialty ,Comorbidity ,Subspecialty ,Article ,Health Services Accessibility ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Ambulatory care ,Liver Function Tests ,Internal medicine ,Ambulatory Care ,Medicine ,Outpatient clinic ,Humans ,030212 general & internal medicine ,Propensity Score ,Survival rate ,Veterans ,Hepatology ,medicine.diagnostic_test ,business.industry ,Liver Diseases ,Hazard ratio ,Gastroenterology ,Hepatitis C ,Middle Aged ,medicine.disease ,United States ,Survival Rate ,030211 gastroenterology & hepatology ,Female ,business ,Liver function tests ,Specialization - Abstract
OBJECTIVES: Access to subspecialty care may be difficult for patients with liver disease, but it is unknown whether access influences outcomes among this population. Our objectives were to determine rates and predictors of access to ambulatory gastrointestinal (GI) subspecialty care for patients with liver disease and to determine whether access to subspecialty GI care is associated with better survival. METHODS: We studied 28,861 patients within the Veterans Administration VISN 11 Liver Disease cohort who had an ICD-9-CM diagnosis code for liver disease from 1 January 2000 through 30 May 2011. Access was defined as a completed outpatient clinic visit with a gastroenterologist or hepatologist at any time after diagnosis. Multivariable logistic regression was used to determine predictors of access to a GI subspecialist. Survival curves were compared between those who did and those who did not see a specialist, with propensity score adjustment to account for other covariates that may affect access. RESULTS: Overall, 10,710 patients (37%) had a completed GI visit. On multivariable regression, older patients (odds ratio (OR) 0.98, P
- Published
- 2016
28. Mo1479 - using Longitudinal Prediction Models to Evaluate Disease Progression Among 156,588 Veterans with Hepatitis C
- Author
-
Tony Van, Lauren A. Beste, Ji Zhu, Monica A. Konerman, George N. Ioannou, Grace L. Su, Brahmajee K. Nallamothu, Sameer D. Saini, Xuefei Zhang, Akbar K. Waljee, and Boang Liu
- Subjects
Oncology ,medicine.medical_specialty ,Hepatology ,Longitudinal prediction ,business.industry ,Internal medicine ,Disease progression ,Gastroenterology ,medicine ,Hepatitis C ,medicine.disease ,business - Published
- 2018
29. Su1900 - Automated Image Analysis of CT Enterography Studies Predicts Future Surgery Similar to Experienced Radiologist Assessment in small Bowel Crohn's Disease
- Author
-
Peter D.R. Higgins, Mahmoud M. Al-Hawary, Stewart C. Wang, Grace L. Su, Ryan W. Stidham, Binu Enchakalody, Ashish P. Wasnik, and Akbar K. Waljee
- Subjects
Crohn's disease ,medicine.medical_specialty ,Hepatology ,CT enterography ,business.industry ,Gastroenterology ,Medicine ,Radiology ,business ,medicine.disease - Published
- 2018
30. Su1816 - Agreement of CT Imaging Features of Crohn's Disease Between Radiologists and Automated Machine Learning Image Analysis
- Author
-
Binu Enchakalody, Peter D.R. Higgins, Grace L. Su, Ryan W. Stidham, Akbar K. Waljee, Ashish P. Wasnik, Mahmoud M. Al-Hawary, and Stewart C. Wang
- Subjects
Crohn's disease ,medicine.medical_specialty ,Hepatology ,Computer science ,Gastroenterology ,medicine ,Radiology ,Ct imaging ,medicine.disease - Published
- 2018
31. Reply
- Author
-
Elliot B, Tapper, Anna S-F, Lok, and Grace L, Su
- Subjects
Hepatology - Published
- 2018
32. Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C
- Author
-
Richard K. Sterling, Herbert L. Bonkovsky, Jules L. Dienstag, Robert J. Fontana, Zachary Goodman, Grace L. Su, Elizabeth C. Wright, Mita Ghosh, and Deepa Naishadham
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Biopsy ,Gastroenterology ,Adipokines ,Fibrosis ,Lectins ,Internal medicine ,medicine ,Humans ,Chitinase-3-Like Protein 1 ,Hyaluronic Acid ,Glycoproteins ,Tissue Inhibitor of Metalloproteinase-1 ,Hepatology ,medicine.diagnostic_test ,Computers ,Platelet Count ,business.industry ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Peptide Fragments ,Procollagen peptidase ,Liver biopsy ,Female ,Collagen ,Hepatic fibrosis ,business ,Biomarkers ,Procollagen - Abstract
This study determined the utility of a panel of serum fibrosis markers along with routine laboratory tests in estimating the likelihood of histological cirrhosis in a cohort of prior nonresponders with chronic hepatitis C. The relationship between serum markers and quantitative hepatic collagen content was also determined. Liver biopsy samples from 513 subjects enrolled in the HALT-C trial were assigned Ishak fibrosis scores. The collagen content of 386 sirius-red stained, nonfragmented biopsy samples was quantified using computerized morphometry. Serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), amino-terminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA), and YKL-40 levels were determined using commercially available assays.Sixty-two percent of patients had noncirrhotic fibrosis (Ishak stage 2-4) whereas 38% had cirrhosis (Ishak stage 5,6). Multivariate analysis identified a 3-variable model (HA, TIMP-1, and platelet count) that had an area under the receiver operating curve (AUROC) of 0.81 for estimating the presence of cirrhosis. This model was significantly better than that derived from the cirrhosis discriminant score (AUROC 0.70), the AST-to-platelet ratio (AUROC 0.73), and a prior model developed in HALT-C patients (AUROC 0.79). Multivariate analysis demonstrated that the serum fibrosis markers correlated substantially better with Ishak fibrosis scores than with the log hepatic collagen content (AUROC 0.84 versus 0.72). Conclusion: A 3-variable model consisting of serum HA, TIMP-1, and platelet count was better than other published models in identifying cirrhosis in HALT-C Trial subjects. The stronger correlation of the serum markers with Ishak scores suggests that serum fibrosis markers reflect the pattern of fibrosis more closely than the quantity of hepatic collagen. (HEPATOLOGY 2008.)
- Published
- 2008
33. Sustained virologic response to therapy of recurrent hepatitis C after liver transplantation is related to early virologic response and dose adherence
- Author
-
Patricia Sullivan, Joel K. Greenson, Grace L. Su, Anna S.F. Lok, Frederick K. Askari, Pratima Sharma, Robert J. Fontana, Jorge A. Marrero, and Hari S. Conjeevaram
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Hepacivirus ,Liver transplantation ,Antiviral Agents ,Gastroenterology ,Virus ,Autoimmune Diseases ,Polyethylene Glycols ,chemistry.chemical_compound ,Pegylated interferon ,Internal medicine ,Ribavirin ,medicine ,Humans ,Recurrent hepatitis ,Adverse effect ,Transplantation ,Hepatology ,business.industry ,virus diseases ,Middle Aged ,Hepatitis C ,digestive system diseases ,Liver Transplantation ,chemistry ,Virologic response ,Immunology ,RNA, Viral ,Female ,Surgery ,Interferons ,business ,Immunosuppressive Agents ,medicine.drug ,Biomedical sciences - Abstract
Sustained virologic response (SVR) after antiviral therapy for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients is consistently lower than that achieved in non-LT patients. We evaluated efficacy and safety of pegylated interferon (IFN) and ribavirin (RBV) therapy in LT recipients with recurrent HCV and factors associated with SVR. All subjects with histologic evidence of recurrent HCV were intended to be treated for 48 weeks with full-dose pegylated IFN; target dose of RBV was 800 mg/day. Thirty-five LT recipients with recurrent HCV, median age 48.5 years, 77% genotype 1, and median pretreatment HCV RNA 6.4 log10 IU/mL were treated between January 2000 and February 2006. Antiviral therapy was discontinued prematurely in 15 subjects as a result of adverse events. Median overall treatment duration was 46 weeks. Early virologic response at week 12 was seen in 17 (49%) and an end-of-treatment virological response in 19 (54%) patients. SVR was achieved in 13 patients (37%), and all 9 patients followed for >1 year after treatment had durable response. Patients with SVR had significantly lower pretreatment HCV RNA (5.7 vs. 6.5 log10 IU/mL, P=0.003), more likely to have a week 12 virological response (85% vs. 27%, P=0.0009) and received higher cumulative doses of pegylated IFN (75% vs. 33%, P=0.029) and RBV (90% vs. 26%, P=0.016) compared with patients whose disease did not respond to therapy. In conclusion, SVR was achieved in 37% of patients with recurrent hepatitis C after LT. Similar to non-LT patients, those with lower pretreatment HCV RNA, a week 12 virological response, and pegylated IFN and RBV dose adherence were more likely to achieve SVR.
- Published
- 2007
34. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma
- Author
-
Sherry Fu, Grace L. Su, Anna S. Lok, Hari S. Conjeevaram, Jorge A. Marrero, and Robert J. Fontana
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Alcohol Drinking ,Liver disease ,Risk Factors ,Alcohol tobacco ,Internal medicine ,medicine ,Carcinoma ,Humans ,Obesity ,Risk factor ,Life Style ,neoplasms ,Hepatology ,business.industry ,Liver Neoplasms ,Smoking ,Case-control study ,Middle Aged ,medicine.disease ,digestive system diseases ,Surgery ,Case-Control Studies ,Hepatocellular carcinoma ,Female ,business - Abstract
Background/Aims Alcohol has been shown to be an important risk factor for hepatocellular carcinoma (HCC). The role of tobacco as a risk factor for HCC is controversial. Recently, obesity has been reported to be a risk factor for HCC. We investigated whether these factors increase the risk of HCC in American patients. Methods Consecutive patients with HCC, cirrhosis without HCC and, control patients without liver disease were enrolled and exposure to risk factors was assessed. Results When HCC cases were compared to cirrhotic controls, the risk of HCC increased 6-fold for alcohol (OR 5.7; 95% CI: 2.4–13.7), 5-fold for tobacco (OR 4.9; 95% CI: 2.2–10.6), and 4-fold with obesity (OR 4.3; 95% CI: 2.1–8.4). Using spline regression, a dose-dependent relationship between alcohol and tobacco exposure with risk of HCC was noted. There was significant interaction between alcohol, tobacco and obesity, with synergistic indices greater than 1. Conclusions Alcohol, tobacco and obesity are independent risk factors for HCC in our patient population, and they interact synergistically to increase the risk of HCC. Data from this study may allow us to stratify cirrhotics into low- and high-risk groups for the development of HCC surveillance strategies.
- Published
- 2005
35. Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice
- Author
-
William M. Kelley, Jian Min Sun, Saman Arbabi, Jason Hsieh, Mark R. Hemmila, Ming Hui Fan, Grace L. Su, Stewart C. Wang, Ke-Qin Gong, and Daniel G. Remick
- Subjects
medicine.medical_specialty ,Cellular immunity ,Necrosis ,Genetic Vectors ,Pharmacology ,Adenoviridae ,Mice ,Cytochrome P-450 Enzyme System ,Internal medicine ,medicine ,Animals ,Acetaminophen ,Mice, Knockout ,Liver injury ,Membrane Glycoproteins ,Hepatology ,biology ,business.industry ,Liver Diseases ,digestive, oral, and skin physiology ,Gene Transfer Techniques ,Acute-phase protein ,medicine.disease ,Glutathione ,Rats ,nervous system diseases ,Endotoxins ,Mice, Inbred C57BL ,Portal System ,Liver ,Toxicity ,Immunology ,biology.protein ,Cytokines ,Chemical and Drug Induced Liver Injury ,medicine.symptom ,Carrier Proteins ,business ,Lipopolysaccharide binding protein ,Acute-Phase Proteins ,medicine.drug - Abstract
Acetaminophen toxicity is the most common cause of acute liver failure in the United States and Europe. Although much is known about the metabolism of acetaminophen, many questions remain regarding the pathogenesis of liver injury. In this study, we examined the role of lipopolysaccharide-binding protein (LBP), a protein important in mediating cellular response to lipopolysaccharides, by using LBP wild-type and knockout (KO) mice. We found that LBP KO mice were protected from acetaminophen-induced hepatotoxicity. At 350 mg/kg of acetaminophen, LBP KO mice had significantly less liver injury and necrosis than wild-type mice. Repletion studies in LBP KO mice using an LBP-adenoviral construct resulted in significantly more hepatic injury and necrosis after acetaminophen exposure compared with mice receiving the control adenoviral construct. In conclusion, LBP KO mice are protected from toxicity with a decrease in hepatic necrosis following acetaminophen challenge. This suggests a novel role for LBP in modulating acetaminophen-induced liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/O270-9139/suppmat/index.html).
- Published
- 2005
36. Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort
- Author
-
Ashley Barrat, Robert J. Fontana, Grace L. Su, Frederick K. Askari, Hari S. Conjeevaram, Jorge A. Marrero, and Anna S. Lok
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Severity of Illness Index ,Gastroenterology ,Cohort Studies ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Survival analysis ,Neoplasm Staging ,Proportional Hazards Models ,Venous Thrombosis ,Hepatology ,Performance status ,Portal Vein ,business.industry ,Proportional hazards model ,Liver Neoplasms ,Hepatitis C ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Portal vein thrombosis ,Hepatocellular carcinoma ,Female ,Liver function ,Liver cancer ,business - Abstract
Currently there is no consensus as to which staging system is best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aims of this study were to identify independent predictors of survival and to compare 7 available prognostic staging systems in patients with HCC. A total of 239 consecutive patients with cirrhosis and HCC seen between January 1, 2000, and December 31, 2003, were included. Demographic, laboratory, and tumor characteristics and performance status were determined at diagnosis and before therapy. Predictors of survival were identified using the Kaplan-Meir test and the Cox model. Sixty-two percent of patients had hepatitis C, 56% had more than 1 tumor nodule, 24% had portal vein thrombosis, and 29% did not receive any cancer treatment. At the time of censorship, 153 (63%) patients had died. The 1- and 3-year survival of the entire cohort was 58% and 29%, respectively. The independent predictors of survival were performance status (P < .0001), MELD score greater than 10 (P = .001), portal vein thrombosis (P = .0001), and tumor diameter greater than 4 cm (P = .001). Treatment of HCC was related to overall survival. The Barcelona Clinic Liver Cancer (BCLC) staging system had the best independent predictive power for survival when compared with the other 6 prognostic systems. In conclusion, performance status, tumor extent, liver function, and treatment were independent predictors of survival mostly in patients with cirrhosis and HCC. The BCLC staging system includes aspects of all of these elements and provided the best prognostic stratification for our cohort of patients with HCC.
- Published
- 2005
37. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients
- Author
-
Jorge A. Marrero, Grace L. Su, Hari S. Conjeevaram, Dawn M. Emick, Robert J. Fontana, Anna S. Lok, and Wei Wei
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Chronic liver disease ,Sensitivity and Specificity ,Gastroenterology ,Diagnosis, Differential ,Liver disease ,Predictive Value of Tests ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,AFP-L3 ,Protein Precursors ,Prospective cohort study ,neoplasms ,Aged ,Hepatitis, Chronic ,Neoplasm Staging ,Des-gamma carboxyprothrombin ,Hepatology ,business.industry ,Liver Neoplasms ,Case-control study ,Middle Aged ,medicine.disease ,digestive system diseases ,Cross-Sectional Studies ,Hepatocellular carcinoma ,Female ,Prothrombin ,business ,Biomarkers - Abstract
Mortality due to hepatocellular carcinoma (HCC) has not improved over the last 20 years. This is in part due to the poor performance of available tumor markers leading to delays in diagnosis. Des-gamma carboxy-prothrombin (DCP) has been reported to be more sensitive and specific for the diagnosis of HCC in Japanese patients compared with α-fetoprotein (AFP). We conducted a cross-sectional case control study to evaluate whether DCP is more sensitive and specific than AFP for differentiating HCC from nonmalignant liver disease in a cohort of American patients from a single referral center. Four groups were studied: G1, normal healthy subjects; G2, patients with noncirrhotic chronic hepatitis; G3, patients with compensated cirrhosis; and G4, patients with histologically proven HCC. A total of 207 subjects were enrolled. Both DCP and AFP levels increased progressively from G1 to G4, but DCP values had less overlap among the groups than AFP. ROC curve indicated that a DCP value of 125 mAU/mL yielded the best sensitivity (89%; 95% CI, 77%-95%) and specificity (95%; 95% CI, 82%-96%) for differentiating patients with HCC from those with cirrhosis and chronic hepatitis. The optimal AFP cutoff value was 11 ng/mL and was inferior to the DCP value of 125 mAU/mL, the area under the ROC curves being 0.928 versus 0.810, respectively ( P = .002). In conclusion, DCP was more sensitive and specific than AFP for differentiating HCC from nonmalignant chronic liver disease. Prospective studies to evaluate the role of DCP in early HCC are underway. (H epatology 2003;37:1114-1121.)
- Published
- 2003
38. NAFLD may be a common underlying liver disease in patients with hepatocellular Carcinoma in the United States
- Author
-
Grace L. Su, Dawn M. Emick, Hari S. Conjeevaram, Robert J. Fontana, Jorge A. Marrero, and Anna S. Lok
- Subjects
Liver disease ,medicine.medical_specialty ,Hepatology ,business.industry ,Hepatocellular carcinoma ,Internal medicine ,medicine ,In patient ,medicine.disease ,business ,Gastroenterology - Published
- 2002
39. Selected Summary
- Author
-
Grace L. Su
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,General surgery ,Fatty liver ,Gastroenterology ,medicine ,Non alcoholic ,business ,medicine.disease ,Bench to bedside - Published
- 2017
40. Morphomics-Based Risk Stratification Model Predicts Complications after Pancreaticoduodenectomy for Pancreatic Cystic Neoplasms
- Author
-
Hari Nathan, Stewart C. Wang, Diane M. Simeone, Nicholas C. Wang, Grace L. Su, Alexander Larson, Clifford S. Cho, Binu Enchakalody, and Richard S. Kwon
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,General surgery ,medicine.medical_treatment ,Risk stratification ,Gastroenterology ,Medicine ,business ,Pancreaticoduodenectomy - Published
- 2017
41. Predictors of mortality in patients with hepatocellular carcinoma undergoing transarterial chemoembolization
- Author
-
Heather McCurdy, Pratima Sharma, Pranab Barman, Venkat Krishnamurthy, Richard H. Moseley, Jonathon M. Willatt, and Grace L. Su
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Physiology ,Article ,Cohort Studies ,Transplant surgery ,Risk Factors ,Internal medicine ,medicine ,Humans ,In patient ,Stage (cooking) ,Chemoembolization, Therapeutic ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Liver Neoplasms ,Gastroenterology ,Retrospective cohort study ,Hepatology ,Middle Aged ,medicine.disease ,Hepatocellular carcinoma ,Female ,business ,Cohort study - Abstract
Transarterial chemoembolization (TACE) is the recommended treatment for patients with Barcelona stage B hepatocellular carcinoma; however, community practice varies from these American Association for the Study of Liver Diseases guidelines. In this study, we sought to assess factors determining outcome after TACE and examine adherence to guidelines.From January 2006 to December 2012, 308 patients with newly diagnosed HCC were treated at the Veterans Affairs (VA) Ann Arbor Healthcare System. Of these, 109 patients underwent TACE. The primary outcome measured mortality. Kaplan-Meier analysis was used to determine the cumulative probability of death. Cox regression was used to assess the predictors of mortality.The median age of the 109 patients was 60 years (48-90), 97 % were males and 82 % had chronic HCV infection. The median size of the largest lesion was 4 cm, 51 % were multifocal, and portal vein thrombosis was present in 3.6 %. Sixty-two patients died after median 333 days from the index TACE treatment. Median overall survival from index TACE was 11.2 months. Unadjusted 1-, 2-, and 3-year survival was 64, 35, and 24 %, respectively. CTP score (B vs. A: HR 2.51, p = 0.002; C vs. A: HR 7.96, p 0.0001) and presence of complete response to TACE (HR 0.51, p = 0.004) were independent predictors of mortality. Barcelona stage (p = 0.88) and performance status as measured by ECOG (p = 0.98) were not associated with mortality after TACE.In this community based, single VA center study, we found a significant number of patients beyond Barcelona stage B were treated with TACE. Advanced TNM stage, poor liver synthetic function and achieving CR with TACE were better predictors of mortality than guideline-directed decisions based on Barcelona stage. These factors may be useful to guide future patient selection for TACE.
- Published
- 2014
42. Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines
- Author
-
Maryam Fotouhinia, Amin A. Nanji, Andrew J. Dannenberg, George L. Tipoe, Kalle Jokelainen, Grace L. Su, Amir Rahemtulla, and Peter Thomas
- Subjects
Male ,Chemokine ,Physiology ,medicine.medical_treatment ,Chemokine CXCL2 ,Weight Gain ,medicine.disease_cause ,Lipid peroxidation ,Pathogenesis ,chemistry.chemical_compound ,Chemokine CCL2 ,Liver injury ,Sex Characteristics ,NF-kappa B ,Gastroenterology ,Cytochrome P-450 CYP2E1 ,Isoenzymes ,Cytokine ,Liver ,Toxicity ,Female ,Chemokines ,medicine.symptom ,medicine.medical_specialty ,Iron ,Biology ,Lesion ,Fish Oils ,Dietary Fats, Unsaturated ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Liver Diseases, Alcoholic ,Ethanol ,Hepatology ,Tumor Necrosis Factor-alpha ,Membrane Proteins ,medicine.disease ,Endotoxemia ,Rats ,Endotoxins ,Oxidative Stress ,Endocrinology ,chemistry ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Cyclooxygenase 1 ,biology.protein ,Lipid Peroxidation ,Oxidative stress - Abstract
Alcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-kappa B (NF-kappa B) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-kappa B activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-alpha and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-kappa B activation and chemokine production, enhancing liver injury. TNF-alpha and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences.
- Published
- 2001
43. Outcome of liver transplantation for hepatitis B: Report of a single center's experience
- Author
-
Chi-Jen Chu, Robert M. Merion, Robert J. Fontana, Jeffrey D. Punch, John C. Magee, Douglas R. Armstrong, Anna S. Lok, Charles Moore, and Grace L. Su
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Immunoglobulins ,Liver transplantation ,Single Center ,Gastroenterology ,Liver disease ,Internal medicine ,Secondary Prevention ,medicine ,Humans ,Longitudinal Studies ,Retrospective Studies ,Transplantation ,Hepatitis B immune globulin ,Hepatology ,biology ,business.industry ,Lamivudine ,Retrospective cohort study ,Hepatitis B ,medicine.disease ,Liver Transplantation ,Surgery ,Treatment Outcome ,biology.protein ,Reverse Transcriptase Inhibitors ,Female ,Antibody ,business ,medicine.drug - Abstract
Results of liver transplantation (LT) for hepatitis B have improved significantly with the use of hepatitis B immune globulin (HBIG) and/or lamivudine. The aim of this study is to review the long-term outcome of patients who underwent LT for hepatitis B. Records of 41 patients who underwent LT for hepatitis B and survived 3 months or longer post-LT were reviewed. Twenty patients were administered no immunoprophylaxis or short-term intramuscular HBIG, whereas 21 patients were administered high-dose intravenous (IV) HBIG. Median post-LT follow-up in these 2 groups was 76 months (range, 4 to 155 months) and 25 months (range, 4 to 68 months), respectively. Hepatitis B recurred in 15 (75%) and 4 patients (19%) who underwent LT in the pre-HBIG and post-HBIG eras, respectively. Cumulative rates of recurrent hepatitis B at 1 and 3 years post-LT in these 2 groups were 66% and 77% and 20% and 20%, respectively (P < .001). Recurrent hepatitis B in the post-HBIG era correlated with antibody to hepatitis B surface antigen titer less than 100 IU/L. Nine patients with recurrent hepatitis B were administered lamivudine for 13 to 49 months (median, 28 months); 6 patients continued to have stable or improved liver disease, whereas 3 patients developed virological breakthrough with slow deterioration of liver disease. Long-term IV HBIG is effective in preventing recurrent hepatitis B. The risk for recurrent hepatitis B is negligible after the first year post-LT. Among patients with no virological breakthrough, lamivudine can stabilize or improve liver disease for up to 4 years in patients with recurrent hepatitis B post-LT. (Liver Transpl 2001;7:724-731.)
- Published
- 2001
44. Kupffer cell activation by lipopolysaccharide in rats: Role for lipopolysaccharide binding protein and toll-like receptor 4
- Author
-
Hong Y. Zhang, Richard D. Klein, Stewart C. Wang, Daniel G. Remick, Lars Steinstraesser, William H. Alarcon, Grace L. Su, and Alireza Aminlari
- Subjects
Lipopolysaccharides ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Kupffer Cells ,medicine.medical_treatment ,Molecular Sequence Data ,Receptors, Cell Surface ,Peripheral blood mononuclear cell ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Drosophila Proteins ,Amino Acid Sequence ,Receptor ,Mice, Inbred C3H ,Toll-like receptor ,Membrane Glycoproteins ,Base Sequence ,Hepatology ,biology ,business.industry ,Toll-Like Receptors ,Kupffer cell ,pathological conditions, signs and symptoms ,Macrophage Activation ,Rats ,nervous system diseases ,Cell biology ,Toll-Like Receptor 4 ,body regions ,Cytokine ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Cell culture ,biology.protein ,population characteristics ,lipids (amino acids, peptides, and proteins) ,Carrier Proteins ,business ,Lipopolysaccharide binding protein ,Acute-Phase Proteins - Abstract
Lipopolysaccharide (LPS) binding protein (LBP) is a key serum factor that mediates LPS activation of mononuclear cells. In the presence of LBP, 1/1,000 the concentration of LPS is sufficient to activate peripheral blood monocytes. Previous studies with Kupffer cells have shown a variable effect of serum on LPS activation of these cells and led to the conclusion that, unlike extrahepatic mononuclear cells, Kupffer cells do not respond to LPS in an LBP-dependent fashion. Because there are multiple components in serum other than LBP that might affect LPS activation, these reports with serum are difficult to interpret. To investigate the specific role of LBP in LPS activation of Kupffer cells, we produced a functional recombinant rat LBP using a baculovirus expression system, which we used to selectively examine the role of LBP's on Kupffer-cell function. Isolated Kupffer cells exposed to increasing concentrations of LPS (0, 1, 10 ng/mL) showed a dose-dependent increase in TNF-alpha production, which was augmented and accelerated by the presence of LBP. The effects of LBP on Kupffer cell activation by LPS are dependent on a functional Toll-like receptor 4 (Tlr 4) because Kupffer cells from C3H/HeJ mice failed to respond to LPS in the presence of LBP. LBP plays an important role in mediating Kupffer cell activation by LPS, and these effects are dependent on the presence of functioning Tlr 4.
- Published
- 2000
45. Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat
- Author
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Lili Miao, Amin A. Nanji, Grace L. Su, Kalle Jokelainen, Franz Fogt, Hiroshi Matsumoto, Amir Rahemtulla, and Steven R. Tahan
- Subjects
Male ,Lipid Peroxides ,medicine.medical_specialty ,Chemokine ,medicine.medical_treatment ,Biology ,Proinflammatory cytokine ,Lipid peroxidation ,Necrosis ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Liver Diseases, Alcoholic ,Macrophage inflammatory protein ,Hepatology ,Hepatitis, Alcoholic ,Monocyte ,Kupffer cell ,NF-kappa B ,Alanine Transaminase ,Rats ,DNA-Binding Proteins ,Endotoxins ,Endocrinology ,Cytokine ,medicine.anatomical_structure ,Liver ,chemistry ,Immunology ,biology.protein ,Cytokines ,I-kappa B Proteins ,Tumor necrosis factor alpha ,Chemokines ,Inflammation Mediators - Abstract
Inflammatory stimuli and lipid peroxidation activate nuclear factor kappa B (NF-kappaB) and upregulate proinflammatory cytokines and chemokines. The present study evaluated the relationship between pathological liver injury, endotoxemia, lipid peroxidation, and NF-kappaB activation and imbalance between pro- and anti-inflammatory cytokines. Rats (5 per group) were fed ethanol and a diet containing saturated fat, palm oil, corn oil, or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. Pathological analysis was performed and measurements of endotoxin were taken, lipid peroxidation, NF-kappaB, and messenger RNA (mRNA) levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNFalpha], interleukin-1 beta [IL-1beta], interferon-gamma, [IFN-gamma], and IL-12), C-C chemokines (regulated upon activation, normal T cell expressed and secreted [RANTES], monocyte chemotactic protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha), C-X-C chemokines (cytokine induced neutrophil chemoattractant (CINC), MIP-2, IP-10, and epithelial neutrophil activating protein [ENA]-78), and anti-inflammatory cytokines (IL-10, IL-4, and IL-13). Activation of NF-kappaB and increased expression of proinflammatory cytokines C-C and C-X-C chemokines was seen in the rats exhibiting necroinflammatory injury (fish oil-ethanol [FE] and corn oil-ethanol[CE]). These groups also had the highest levels of endotoxin and lipid peroxidation. Levels of IL-10 and IL-4 mRNA were lower in the group exhibiting inflammatory liver injury. Thus, activation of NF-kappaB occurs in the presence of proinflammatory stimuli and results in increased expression of proinflammatory cytokines and chemokines. The Kupffer cell is probably the major cell type showing activation of NF-kappaB although the contribution of endothelial cells and hepatocytes cannot be excluded. Downregulation of anti-inflammatory cytokines may additionally exacerbate liver injury.
- Published
- 1999
46. CD14 expression and production by human hepatocytes
- Author
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Andreas K. Nussler, Stewart C. Wang, Grace L. Su, Ken Dorko, and Stephen C. Strom
- Subjects
Lipopolysaccharides ,Hepatology ,medicine.diagnostic_test ,Metabolic Clearance Rate ,Liver cytology ,HL60 ,CD14 ,Monocyte ,Lipopolysaccharide Receptors ,Epithelial Cells ,Biology ,Molecular biology ,Cell Line ,chemistry.chemical_compound ,medicine.anatomical_structure ,Liver ,Solubility ,Biochemistry ,Western blot ,chemistry ,Hepatocyte ,medicine ,Humans ,Monocytic leukemia ,Northern blot - Abstract
Background/Aims: CD14 has been identified as a receptor for LPS and is present both in a membranebound and a soluble form. Membrane CD14 (mCD14) is predominantly expressed on monocytes, macrophages and granulocytes. The source of soluble CD14 (sCD14) is as yet unclear. Previous investigation using monocytes has shown that sCD14 can be derived either from the shedding of mCD14 or from direct secretion by monocytes. Whether the monocyte is the sole or even the major source of sCD14 is as yet uncertain. Clearance of LPS from the bloodstream is thought to be primarily mediated by the liver. Production of CD14 by hepatocytes would potentially provide a powerful mechanism by which the liver could clear LPS, and therefore we examined the ability of human hepatocytes to produce CD14. Methods: Human hepatocytes were isolated using collagenase perfusion. Results: Human hepatocytes were found to have CD14 mRNA by Northern blot analysis. Western blot analysis and immunohistochemical staining confirmed CD14 protein in primary hepatocyte cultures. Further studies showed that a liver epithelial-like cell line AKN-1 is capable of producing CD14. Comparisons of the size of hepatocyte-derived CD14 protein with the sCD14 protein from the human monocytic leukemia cell line HL60 suggested that a slightly larger form of CD14 is expressed by human liver cells. Conclusion: This is the first study to demonstrate production of CD14 by human hepatocytes.
- Published
- 1999
47. Obesity and IBD: are we tipping the scales toward an epidemic?
- Author
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Joshua B. Max, Grace L. Su, Ryan W. Stidham, and Akbar K. Waljee
- Subjects
Male ,Hepatology ,business.industry ,Gastroenterology ,MEDLINE ,medicine.disease ,Obesity ,Body Mass Index ,Crohn Disease ,Environmental health ,Medicine ,Humans ,Colitis, Ulcerative ,Female ,Colitis ,business ,Body mass index - Published
- 2013
48. Lipopolysaccharide binding protein is down-regulated during acute liver failure
- Author
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Jill Bayliss, Grace L. Su, Kartik Jinjuvadia, Robert J. Fontana, and Stewart C. Wang
- Subjects
Adult ,Lipopolysaccharides ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Physiology ,Down-Regulation ,Article ,chemistry.chemical_compound ,Mice ,Downregulation and upregulation ,Internal medicine ,medicine ,Animals ,Humans ,Serum amyloid P component ,Acetaminophen ,Membrane Glycoproteins ,biology ,business.industry ,digestive, oral, and skin physiology ,C-reactive protein ,Gastroenterology ,Acute-phase protein ,pathological conditions, signs and symptoms ,Hepatology ,Analgesics, Non-Narcotic ,Liver Failure, Acute ,nervous system diseases ,body regions ,Mice, Inbred C57BL ,Serum Amyloid P-Component ,Endocrinology ,C-Reactive Protein ,chemistry ,Liver ,biology.protein ,population characteristics ,Female ,business ,Carrier Proteins ,Lipopolysaccharide binding protein ,medicine.drug ,Acute-Phase Proteins - Abstract
Lipopolysaccharide binding protein (LBP) is involved in the modulation of acute liver injury and failure caused by acetaminophen (APAP). Although the biological activity of LBP is concentration dependent, little is known about its levels in acute liver failure.Serum and hepatic LBP were measured in acute APAP-induced liver injury in mice. Serum LBP was measured in patients with acute liver failure from APAP and non-APAP causes.Interestingly, contrary to other diseases, serum and hepatic LBP levels decreased significantly in mice within 24 h after being subjected to APAP-induced injury compared to the control (1.6 ± 0.1 vs. 3.5 ± 1.6 μg/ml, respectively; P0.05). Similar decreases were noted in another mouse model of acute liver injury due to carbon tetrachloride. Among patients with acute liver failure due to APAP (n = 5) and non-APAP (n = 5) causes, admission LBP levels were decreased compared to those of healthy controls (5.4 ± 1.4 vs. 3.2 ± 0.2 μg/ml, normal vs. acute liver failure; P = 0.07). However, the levels were not associated with the etiology of acute liver failure or 3-week outcome.Serum and hepatic LBP levels are significantly reduced early after the induction of severe acute liver injury/failure due to acetaminophen and other liver injuries. This reduction in LBP production is specific to acute liver failure and may be important in developing future diagnostic and therapeutic approaches for patients with acute liver failure.
- Published
- 2011
49. YKL-40 genetic polymorphisms and the risk of liver disease progression in patients with advanced fibrosis due to chronic hepatitis C
- Author
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Herbert L. Bonkovsky, Grace L. Su, Jules L. Dienstag, Richard K. Sterling, Heather J. Litman, Robert J. Fontana, and Anna S. Lok
- Subjects
musculoskeletal diseases ,Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Genotype ,Population ,Disease ,Gastroenterology ,Article ,Polyethylene Glycols ,Liver disease ,chemistry.chemical_compound ,Adipokines ,Fibrosis ,Internal medicine ,Lectins ,Ribavirin ,medicine ,Humans ,Genetic Predisposition to Disease ,Chitinase-3-Like Protein 1 ,education ,Promoter Regions, Genetic ,Genetic Association Studies ,education.field_of_study ,Polymorphism, Genetic ,Hepatology ,business.industry ,Interferon-alpha ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Recombinant Proteins ,chemistry ,Disease Progression ,Female ,business - Abstract
Background/Aims The aim of this study was to explore the association of a functional YKL-40 promoter polymorphism (rs4950928) with baseline disease stage, response to antiviral therapy and risk of liver disease progression in a group of patients with chronic hepatitis C (CHC). Methods YKL-40 promoter polymorphisms were determined in 456 Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial patients with bridging fibrosis or cirrhosis entering a prerandomization lead-in peginterferon/ribavirin 24-week treatment phase and in 462 patients followed for a mean of 3.8 years after randomization to maintenance peginterferon or observation. Results Mean patient age was 49.5 years, 70.4% were men and 71.2% were Caucasian. The 17% frequency of the YKL-40 minor allele (T) was similar to that reported in the general population. YKL-40 genotype was associated significantly with baseline serum YKL-40 levels but was not associated with the likelihood of a virological response following 24–48 weeks of peginterferon/ribavirin therapy. Serum YKL-40 levels remained significantly lower during follow-up in the randomized TT homozygotes compared with CT heterozygotes and CC homozygotes (P
- Published
- 2011
50. Lipopolysaccharide binding protein inhibitory peptide protects against acetaminophen-induced hepatotoxicity
- Author
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Mark R. Hemmila, Jill Bayliss, Stewart C. Wang, Grace L. Su, and L. M. Hoesel
- Subjects
Lipopolysaccharides ,Male ,Lipopolysaccharide ,Physiology ,Antidotes ,Peptide ,Pharmacology ,Cell Line ,Lesion ,chemistry.chemical_compound ,Mice ,Physiology (medical) ,medicine ,Animals ,Amino Acid Sequence ,Acetaminophen ,Liver injury ,chemistry.chemical_classification ,Hepatology ,biology ,Chemistry ,Binding protein ,Macrophages ,digestive, oral, and skin physiology ,Gastroenterology ,medicine.disease ,Glutathione ,Mice, Inbred C57BL ,Liver ,Knockout mouse ,Immunology ,biology.protein ,Cytokines ,medicine.symptom ,Chemical and Drug Induced Liver Injury ,Peptides ,Lipopolysaccharide binding protein ,medicine.drug - Abstract
Acetaminophen (APAP)-induced liver injury remains the main cause of acute liver failure in the United States. Our previous work demonstrated that LPS binding protein (LBP) knockout mice are protected from APAP-induced hepatotoxicity. LBP is known to bind avidly to LPS, facilitating cellular activation. In this study, we sought to specifically inhibit the interaction between LBP and LPS to define the role of this interaction in APAP-induced liver injury. The peptide LBPK95A was able to inhibit LBP-mediated LPS activation of RAW 267.4 cells in a dose-dependent manner in vitro. In vivo, C57Bl/6 mice were treated with either LBPK95A or vehicle control concurrently with the administration of APAP (350 mg/kg). Mice treated with LBPK95A had significantly lower serum aspartate aminotransferase and alanine aminotransferase levels. Morphometric analysis of the liver tissue showed significantly less liver injury in mice treated with LBPK95A. To assess whether the LBPK95A altered glutathione depletion and APAP metabolism, we measured total glutathione levels in the liver after APAP. We found no difference in the glutathione levels and APAP-adduct formation between LBPK95A vs. vehicle control both at baseline and after APAP. In conclusion, our results support the hypothesis that LBP-induced liver injury after APAP is due to its ability to mediate activation by endogenous LPS. Our results suggest that blocking LBP-LPS interactions is a potential therapeutic avenue for the treatment of APAP-induced liver injury.
- Published
- 2010
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