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Re-re-treatment of hepatitis C virus: Eight patients who relapsed twice after direct-acting-antiviral drugs

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World Journal of Gastroenterology 2015年第43期21卷 12430-12438页

作者： Joshua Hartman Kian Bichoupan Neal Patel Sweta Chekuri Alyson Harty Douglas Dieterich Ponni Perumalswami andrea D branch Department of Medicine Icahn School of Medicine at the Mount Sinai Medical Center Division of Liver Disease Icahn School of Medicine at the Mount Sinai Medical Center

AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment ***: All HCV mono-infected patients who received treatment at our institution were *** was restricted to patients who previously failed treatment with boceprevir(BOC) or telaprevir(TVR) and started simeprevir(SMV) and sofosbuvir(SOF) ± ribavirin(RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus(HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December,31 st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics,HCV infection,and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/***: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon(PEG) and RBV who failed this triple therapy were subsequently retreated with an off-label all-oral regimen of SMV and SOF for 12 wk,with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response,but later relapsed. Eight(100%) patients were male. Mean age was 56(range,49-64). Eight(100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6(mean 3.8). Eight(100%) patients were male had liver cirrhosis as determi

关键词： Hepatitis C Protease inhibitor Relapse Simeprevir

Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus

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World Journal of Gastroenterology 2016年第9期22卷 2844-2854页

作者： Neal Patel Kian Bichoupan Lawrence Ku Rachana Yalamanchili Alyson Harty Donald Gardenier Michel Ng David Motamed Viktoriya Khaitova Nancy Bach Charissa Chang Priya Grewal Meena Bansal Ritu Agarwal Lawrence Liu Gene Im Jennifer Leong Leona Kim-Schluger Joseph Odin Jawad Ahmad Scott Friedman Douglas Dieterich Thomas Schiano Ponni Perumalswami andrea branch Division of Liver Diseases Icahn School of Medicine at Mount Sinai Recanati Miller Transplant Institute Icahn School of Medicine at Mount Sinai

AIM: To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV ***: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite ***: Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P 2, 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for ***: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

关键词： Hepatitis C virus Sofosbuvir Ribavirin Anemia Hepatic decompensation Serious adverse event Liver transplant

Factors associated with success of telaprevir-and boceprevir-based triple therapy for hepatitis C virus infection

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World Journal of Hepatology 2017年第11期9卷 551-561页

作者： Kian Bichoupan Neeta Tandon Valerie Martel-Laferriere Neal M Patel David Sachs Michel Ng Emily A Schonfeld Alexis Pappas James Crismale Alicia Stivala Viktoriya Khaitova Donald Gardenier Michael Linderman William Olson Ponni V Perumalswami Thomas D Schiano Joseph A Odin Lawrence U Liu Douglas T Dieterich andrea D branch Division of Liver Diseases Icahn School of Medicine at Mount Sinai Icahn Medical Instititute Janssen Pharmaceuticals Com-panies Division of Janssen Scientific Affairs Inc. Genetics and Genomics Icahn School of Medicine at Mount Sinai

To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed. METHODSOutcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir). RESULTSThe median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis (FIB-4 ≥ 3.25). Only 42% (94/223) of patients achieved SVR24 on an intention-to-treat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio (OR) = 5.92, 95% confidence interval (CI): 2.34-14.96], HCV sub-genotype 1b (OR = 2.81, 95%CI: 1.45-5.44), platelet count (OR = 1.10, per x 104 cells/μL, 95%CI: 1.05-1.16), and IL28B CC genotype (OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 103/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22). CONCLUSIONThe SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.

关键词： Sustained virologic response Hepatitis C virus Relapse Telaprevir Boceprevir Triple-therapy Classification and regression Adverse event Real-world

Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama andrea Kwakowsky Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： andrea Kwakowsky Thulani H.Palpagama Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： andrea Bartolomé-Nafría Javier García-Pardo Salvador Ventura Institut de Biotecnologia i de Biomedicina(IBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

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Neural Regeneration Research 2025年第1期20卷 130-138页

作者： Ilaria Martinelli Jessica Mandrioli andrea Ghezzi Elisabetta Zucchi Giulia Gianferrari Cecilia Simonini Francesco Cavallieri Franco Valzania Department of Neurosciences Azienda Ospedaliero Universitaria di ModenaModenaItaly Clinical and Experimental Medicine Ph.D.Program University of Modena and Reggio EmiliaModenaItaly Department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly Neurology Unit Neuromotor&Rehabilitation DepartmentAzienda USL-IRCCS di Reggio EmiliaReggio EmiliaItaly

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal *** the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of *** superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized *** numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this *** this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during *** multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

关键词： amyotrophic lateral sclerosis(ALS) autonomic extramotor genotype-phenotype multisystem involvement Parkinson’s disease sensory SOD1 superoxide dismutase 1 urinary vocal cord palsy

Lighting the shades of hidden pain:a role for spinal cord neurons and microglia in vestibulodynia

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Neural Regeneration Research 2025年第10期20卷 2898-2900页

作者： Rosmara Infantino Francesca Gargano Serena Boccella Carmela Belardo andrea Maria Morace Francesca Guida Sabatino Maione Livio Luongo Department of Experimental Medicine Division of PharmacologyUniversitàdegli Studi della Campania“L.Vanvitelli”Italy UniversitàCampus Bio-medico di Roma RomeItaly

Vulvodynia,a chronic pain disorder affecting the vulvar region,represents a significant challenge in both diagnosis and treatment within the field of women’s *** condition is characterized by chronic pain that significantly affects the quality of life of afflicted *** present perspective paper examines the role of spinal sensitization and microglial activation in vulvodynia.

关键词： pain diagnosis activation

Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results

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World Journal of Virology 2017年第4期6卷 59-72页

作者： Kian Bichoupan Neeta Tandon James F Crismale Joshua Hartman David Del Bello Neal Patel Sweta Chekuri Alyson Harty Michel Ng Keith M Sigel Meena B Bansal Priya Grewal Charissa Y Chang Jennifer Leong Gene Y Im Lawrence U Liu Joseph A Odin Nancy Bach Scott L Friedman Thomas D Schiano Ponni V Perumalswami Douglas T Dieterich andrea D branch Division of Liver Diseases Icahn School of Medicine at Mount Sinai Janssen Scientific Affairs LLC Division of General Internal Medicine Icahn School of Medicine at Mount Sinai

AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) *** The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic *** SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.

关键词： Cirrhosis Cost Sustained virological response Protease inhibitor Polymerase inhibitor