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Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct-acting Antivirals

Journal of Clinical and Translational Hepatology 2017年第1期5卷 43-49页

作者： Kelvin Nguyen Melissa Jimenez Nima Moghadam Crystal Wu Alex Farid Jonathan Grotts David Elashoff Gina Choi Francisco A.Durazo Mohamed M.El-Kabany steven-huy b.han Sammy Saab Departments of Medicine the University of California at Los AngelesLos AngelesCAUSA Departments of Surgery the University of California at Los AngelesLos AngelesCAUSA Departments of biostatistics the University of California at Los AngelesLos AngelesCAUSA

background and Aims:The lack of specificity has limited the role of serum alpha-fetoprotein(AFP)for hepatocellular carcinoma(HCC)screening among patients with cirrhosis related to hepatitis C virus(HCV)*** sought to examine whether AFP may decrease after achieving a sustained virological response(SVR)in patients with HCV-related ***:We performed a retrospective study of patients with HCV-related cirrhosis who were cured with direct-acting antiviral(DAA)therapy at the University of California,Los *** values,including serum AFP,were measured before and after completing the DAA ***:Fifty-six patients met the inclusion criteria,with median(interquartile range[IQR])age of 67(58-69)years and with 51.8%being *** patients received DAA therapy without *** decreased from median(IQR)7.2(4.2-13.4)ng/mL before DAAs to 4.2(2.7-6.3)ng/mL at the end of treatment and 4.2(2.9-6.8)ng/mL at 12 weeks after treatment(Pbrosis-4(FIb4),and aspartate transaminase(AST)to platelet ratio index(APRI)scores at baseline were not significantly associated with AFP *** multivariate analysis,platelet count,AST and total bilirubin at baseline were significantly correlated to AFP reduction(P=0.04,0.009 and 0.04,respectively).The higher the baseline AFP,the greater the reduction in *** was no statistically significant correlation between baseline AFP and MELD,FIb4 or APRI ***:There was a significant decrease in AFP in patients with cirrhosis who achieved a SVR with *** a reduction in AFP after DAA treatment,AFP should be further studied as a screening modality for HCC in patients with cirrhosis.

关键词： Hepatitis C Hepatocellular carcinoma Screening Direct-acting antivirals

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Elimination of Hepatitis C in Liver Transplant Recipients

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Journal of Clinical and Translational Hepatology 2018年第3期6卷 247-250页

作者： Sammy Saab Youssef Challita Phillip H.Chen Melissa A.Jimenez Alex D.Lee Elena G.Saab Timothy Ahn Gina Choi Francisco A.Durazo Mohamed M.El-Kabany steven-huy b.han Jonathan Grotts Vatche G.Agopian Ronald W.busuttil Department of Medicine University of California at Los AngelesLos AngelesCaliforniaUSA Department of Surgery at the University of California at Los Angeles Los AngelesCaliforniaUSA

background and Aims:Recurrent hepatitis C(HCV)disease in liver transplant(LT)recipients is associated with significant morbidity and *** the availability of noninterferon-based therapy,eliminating HCV may be achievable in LT ***:We studied all consecutive recipients who underwent LT at the University of California Los Angeles be-tween January 2005 and June *** collected data on date of transplant and last follow-up,as well as laboratory *** also recorded type and timing of antiviral therapy relative to *** were performed to assess the proportion of LT recipi-ents who are viremic after ***:Six hundred thirty-four patients underwent LTwith a diagnosis of *** was a statistically significant trend for patients to be cured be-fore(pble for therapy,8%and 74%were treated within 12 months of transplant for the study periods 2005 to 2013 and 2014 to 2016,*** was a significant decrease between the two study periods in the proportion of patients undergoing re-LT 1 year after the original LT:5.5%(n=28/510)and 1.5%(n=2/124)respec-tively for study periods 2005 to 2013 and 2014 to 2016 respec-tively(p=0.011).Conclusions:The proportion of LTrecipients who are viremic has decreased over *** HCV in LT recipients is feasible after the introduction of direct-acting *** HCV should translate to improved clinical out-comes in LT recipients who were transplanted for HCV infection with longer *** results suggest the de-creased need for transplant in the direct-acting agents era.

关键词： Hepatitis C Direct-acting agents Liver transplant Elimination

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Limited Knowledge of Acetaminophen in Patients with Liver Disease

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Journal of Clinical and Translational Hepatology 2016年第4期4卷 281-287页

作者： Sarnrny Saab Peter G.Konyn Matthew R.Viramontes Melissa A.Jimenez Jonathan F.Grotts Wally Hamidzadah Veronica P.Dang Negin L.Esmailzadeh Gina Choi Francisco A.Durazo Mohamed M.El-Kabany steven-huy b.han Myron J.Tong Department of Medicine the University of California at Los Angeles Los Angeles CA USA Department of Surgery the University of California at Los Angeles Los Angeles CA USA Department of Surgery the University of California at Los Angeles Los Angeles CA USA Department of biostatistics the University of California at Los Angeles Los Angeles CA USA Department of Surgery the University of California at Los Angeles Los Angeles CA USA California and Huntington Medical Research Institutes Pasadena CA USA

background andAims:Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United *** with underlying liver disease are at higher risk of poor outcomes from acetaminophen *** knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver *** purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver ***:We performed a cross-sectional study of patients with liver disease at the Pfleger Liver Institute at the University of California,Los Angeles between June 2015 and August *** completed a demographic questionnaire and an acetaminophen knowledge *** information was obtained from the medical ***:Of 401 patients with liver disease,30 (15.7%) were able to correctly identify that people without liver disease can safely take up to 4 g/day of *** majority of patients (79.9%-86.8%) did not know that Norco(R) (hydrocone/acetaminophen),Vicodin(R) (hydrocone/acetaminophen) and Percocet(R) (oxycodone/acetaminophen) contained *** 45.3% of the patients knew that Tylenol(R) #3 contained ***:We conclude that patients with liver disease have critically low levels of knowledge of acetaminophen,putting them at risk both of acetaminophen overdose,as well as undermedication,and inadequate management of chronic *** recommend an increase in education efforts regarding acetaminophen dosage and its safety in the setting of liver *** education for those at risk of low acetaminophen knowledge is essential to minimizing acetaminophen overdose rates and optimizing pain management.

关键词： Acetaminophen Pain management Cirrhosis

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Effectiveness of Ledipasvir/Sofosbuvir with / without Ribavarin in Liver Transplant Recipients with Hepatitis C

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Journal of Clinical and Translational Hepatology 2017年第2期5卷 101-108页

作者： Sammy Saab Justin Rheem Melissa A.Jimenez Tiffany M.Fong Michelle H.Mai Caterina A.Kachadoorian Negin L.Esmailzadeh Sherona N.bau Susan Kang Samantha D.Ramirez Jonathan Grotts Gina Choi Francisco A.Durazo Mohammed M.El-Kabany steven-huy b.han Ronald W.busuttil Departments of Medicine at the University of California at Los Angeles Los Angeles California USA Departments of Surgery at the University of California at Los Angeles Los Angeles California USA Department of Medicine at Harbor-University of California at Los Angeles Medical Center Torrance California USA Departments of Surgery at the University of California at Los Angeles Los Angeles California USA Department of biostatistics at the University of California at Los Angeles Los Angeles California USA

background and Aims:Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and ***:We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis ***:Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 *** mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) *** mean (± SD) age of the cohort was 63 (±8.6) years *** recipients were male (70%).baseline alanine transaminase,total bilirubin,and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126)mg/dL,0.8 (±1.3) U/L,and 8,010,421.9 (±12,420,985)IU/mL,*** of 43 recipients who were treated with ribavirin required drug cessation due to side effects,with 4 of those being anemia *** recipient discontinued the ledipasvir/***-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy,and all recipients had complete viral suppression at the end of *** sustained viral response at 12 weeks after completion of therapy was 94%.Conclusion:Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after *** is not uncommon in LT recipients receiving ribavirin.

关键词： Liver transplantation Immunosuppressant Hepatitis C Direct-acting agents Sustained viral response

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Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c

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World Journal of Hepatology 2018年第9期10卷 612-621页

作者： Tien S Dong Elizabeth S Aby Jihane N benhammou Jenna Kawamoto steven-huy han Folasade P May Joseph R Pisegna the Vatche and Tamar Manoukian Division of Digestive Diseases University of California Los AngelesDepartment of MedicineUniversity of California David Geffen School of MedicineLos AngelesCA 90095United States Division of Gastroenterology Hepatology and Parenteral NutritionDepartment of MedicineVA Greater Los Angeles Healthcare SystemLos AngelesCA 90073United States the Pfleger Liver Institute Department of SurgeryUniversity of California David Geffen School of MedicineLos AngelesCA 90095United States VA Health Services Research and Development Center for the Study of Healthcare Innovation Center for the Study of Healthcare Innovation Implementation and Policy(CSHIIP)Los AngelesCA 90073United States Jonsson Comprehensive Cancer Center Los AngelesCA 90095United States

AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(SVR).METHODS We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment(SVR12).RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved SVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved SVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved SVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve SVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.

关键词： Hepatitis C virus Hemoglobin A1c Diabetes mellitus Direct-acting antivirals Metabolic syndrome

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Nationwide trends and predictors of inpatient mortality in 83884 transjugular intrahepatic portosystemic shunt

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World Journal of Gastroenterology 2016年第25期22卷 5780-5789页

作者： Edward Wolfgang Lee Andrew Kuei Sammy Saab Ronald W busuttil Francisco Durazo steven-huy han Mohamed M El-Kabany Justin P Mc Williams Stephen T Kee Department of Radiology Division of Interventional Radiology Ronald Reagan Medical Center at UCLA David Geffen School of Medicine at UCLA Department of Medicine Division of Hepatology Pfleger Liver Institute University of California at Los Angeles Dumont-UCLA Transplant Center Pfleger Liver Institute Division of Liver and Pancreas Transplantation Department of Surgery David Geffen School of Medicine at University of California Los Angeles

AIM: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt (TIPS) in 15 ***: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and ***: Overall, 12.3% of patients died during hospitalization with downward trend in-hospital mortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients (OR = 1.809 vs Caucasian patients, P ber of diagnoses and number of procedures showed positive correlations with in-hospital death (OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure (OR = 8.246), acute kidney failure (OR = 4.359), hepatic encephalopathy (OR = 2.217) and esophageal variceal bleeding (OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites (OR = 0.136, P bidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders (OR = 2.823), coagulopathy (OR = 2.016), and lymphoma (OR = 1.842).CONCLUSION: The overall mortality of the TIPS procedure is stea

关键词： Transjugular intrahepatic portosystemic shunt Mortality Inpatient United States National Inpatient Sample database Health Cost and Utilization Project

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Clinical Food Addiction Is Not Associated with Development of Metabolic Complications in Liver Transplant Recipients

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Journal of Clinical and Translational Hepatology 2017年第4期5卷 335-342页

作者： Sammy Saab Cameron Sikavi Melissa Jimenez Matthew Viramontes Ruby Allen Youssef Challita Michelle Mai Negin Esmailzadeh Jonathan Grotts Gina Choi Francisco Durazo Mohamed El-Kabany steven-huy han Elisa Moreno Departments of Medicine the University of California at Los AngelesLos AngelesCAUSA Departments of Surgery the University of California at Los AngelesLos AngelesCAUSA Departments of Psychiatry the University of California at Los AngelesLos AngelesCAUSA

background and Aims:Given the increased risk of posttransplant metabolic syndrome(PTMS;defined by hypertension,diabetes mellitus and hyperlipidemia),we aimed to identify the potential role of food addiction in the development of metabolic complications in the post-liver transplant ***:Inclusion criteria included adult liver transplant recipients followed at our institution between June 2016 and November *** were administered a demographic survey as well as the Yale Food Assessment Scale 2.0,a 35-item questionnaire used to assess frequency of food addiction in accordance with the DSM-V guidelines of substance use *** and clinical data were ***:Our study included 236 liver transplant recipients(139 males,97 females).The median(interquartile range[IQR])bMI of participants was 26.8 kg/m2(24.2,30.4),and median(IQR)time since transplantation was 50.9 months(19.6,119.8).The prevalence rates of hypertension,hypercholesterolemia and diabetes mellitus were 54.7%,25.0%and 27.1%,*** participants(5.1%)were found to have a diagnosis of food addiction.A diagnosis of food misuse was made in 94(39.8%)of the transplant ***:Our findings are consistent with prior data that indicate high prevalence of metabolic complications among liver transplant *** addiction was not predictive of metabolic complications within this ***,we found that this population was at high risk of demonstrating symptoms of food misuse,and they were not likely to appreciate the risks of pathologic patterns of *** the increasing risk of cardiovascular morbidity and mortality in this population,efforts should be made to identify risk factors for the development of PTMS.

关键词： Food addiction Liver transplant Metabolic complications

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Effect of compressibility on bubbly cavitating flows

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Journal of Hydrodynamics 2020年第1期32卷 1-5页

作者： Harish Ganesh Anubhav bhatt Juliana Wu steven Ceccio Department of Naval Architecture and Marine Engineering University of MichiganAnn ArborMichiganUSA

Cavitating bubbly flows can form in separated flows and shear layers leading to local regions high vapor void fraction,and these flows often exhibit periodic shedding of vaporous ***,the presence of a liquid re-entrant flow,driven by the kinematics of liquid flow stagnation,has been identified as an important mechanism leading to cavity ***,high local vapor void fractions can also result in a reduced mixture speed of sound and a possible supersonic *** recent findings on different geometries indicate that propagating bubbly shocks in these flows are a primary mechanism of flow *** this study,we discuss the effect of compressibility on four geometries,mainly in the generation of propagating bubbly shocks that can influence the cavitation shedding *** order to elucidate the differences and similarities of the observed cavitation dynamics,and the influence of compressibility,we report observations from a backward facing step,backward facing wedge,NACA0015 hydrofoil,and a bluff body with a wedge cross section.

关键词： Cavitation bubbly shocks compressible vapor-liquid flows

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bubbly shock propagation as a mechanism of shedding in separated cavitating flows

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Journal of Hydrodynamics 2017年第6期29卷 907-916页

作者： Harish Ganesh Simo A.Makiharju steven L.Ceccio University of Michigan Ann ArborUSA University of California BerkeleyUSA

Stable attached partial cavitation in separated flows can transition to cloud shedding, and the mechanism of transition has been attributed to the presence of a re-entrant liquid jet. Our findings have revealed the presence of propagating bubbly shock waves as an alternative dominant mechanism of shedding when the compressibility of the bubbly mixture is appreciable. In the present paper, we discuss dynamics associated with these bubbly shock waves, interaction of shock waves with obstacles in their path, and means to manipulate their properties to control the shedding process by non-condensable gas injection.

关键词： Partial cavitation bubbly shock waves cloud cavitation X-ray densitometry

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Profiling of immune features to predict immunotherapy efficacy

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The Innovation 2022年第1期3卷 71-82页

作者： Youqiong Ye Yongchang Zhang Nong Yang Qian Gao Xinyu Ding Xinwei Kuang Rujuan bao Zhao Zhang Chaoyang Sun bingying Zhou Li Wang Qingsong Hu Chunru Lin Jianjun Gao Yanyan Lou steven HLin Lixia Diao Hong Liu Xiang Chen Gordon b.Mills Leng han Shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China Department of biochemistry and Molecular biology The University of Texas Health Science Center at Houston McGovern Medical SchoolHoustonTX 77030USA Department of Medical Oncology Lung Cancer and Gastrointestinal UnitHunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunan 410008China Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Molecular and Cellular Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Genitourinary Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Division of Hematology and Oncology Mayo ClinicJacksonvilleFL 32224USA Department of Radiation Oncology Division of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of bioinformatics and Computational biology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Knight Cancer Institute Oregon Health and Science UniversityPortlandOR 97239USA Center for Epigenetics and Disease Prevention Institute of Biosciences and TechnologyTexas A&M UniversityHoustonTX 77030USA Department of Translational Medical Sciences College of MedicineTexas A&M UniversityHoustonTX 77030 USA

Immune checkpoint blockade(ICb)therapies exhibit substantial clinical benefit in different cancers,but relatively low response rates in the majority of patients highlight the need to understand mutual relationships among immune ***,we reveal overall positive correlations among immune checkpoints and immune cell ***,patients benefiting from ICb exhibited increases for both immune stimulatory and inhibitory features after initiation of therapy,suggesting that the activation of the immune microenvironment might serve as the biomarker to predict immune *** proof-of-concept,we demonstrated that the immune activation score(ISD)based on dynamic alteration of interleukins in patient plasma as early as two cycles(4-6 weeks)after starting immunotherapy can accurately predict immunotherapy *** results reveal a systematic landscape of associations among immune features and provide a noninvasive,cost-effective,and time-efficient approach based on dynamic profiling of pre-and on-treatment plasma to predict immunotherapy efficacy.

关键词： immunotherapy features mutual

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