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Wright EC, Kapuria D, Ben-Yakov G, Sharma D, Basu D, Cho MH, Abijo T, Wilkins KJ. Time to Publication for Randomized Clinical Trials Presented as Abstracts at Three Gastroenterology and Hepatology Conferences in 2017. GASTRO HEP ADVANCES 2023; 2:370-379. [PMID: 36938381 PMCID: PMC10022591 DOI: 10.1016/j.gastha.2022.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022]
Abstract
Background & Aims Results of randomized clinical trials are often first presented as conference abstracts, but these abstracts may be difficult to find, and trial results included in the abstract may not be followed by subsequent journal publications. In a review of abstracts submitted to eight major medical and surgical conferences in 2017, we identified 237 abstracts reporting primary results of randomized clinical trials accepted for presentation at three major gastroenterology and hepatology conferences. The aims of this new analysis were to determine the publication rate for these abstracts and the proportion of publications that included trial registration numbers in the publication abstract. Methods Clinical trial registries, PubMed, Europe PMC, and Google Scholar were searched through November 1, 2021, for publications reporting trial results for the selected abstracts. Publications were reviewed to determine if they included a trial registration number and if the registration number was in the abstract. Results Publications were found for 157 abstracts (66%) within four years of the conference. Publications were found more frequently for the 194 abstracts reporting results of registered trials (144, 74%) than for the 43 abstracts reporting unregistered trials (13, 30%), but only 67% of these 144 publications included the registration number in the publication abstract. Ten unpublished trials had summary results posted on ClinicalTrials.gov. Conclusions Clinical trial results could be more accessible if all trials were registered, authors included registration numbers in both conference and journal abstracts, and journal editors required the inclusion of registration numbers in publication abstracts for registered clinical trials.
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Affiliation(s)
- Elizabeth C. Wright
- Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Devika Kapuria
- Department of Gastroenterology, Washington University in St. Louis, St. Louis, Missouri
| | - Gil Ben-Yakov
- The Center for liver diseases Sheba, Tel-Hashomer medical center, Ramat Gan, Israel
| | - Disha Sharma
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Dev Basu
- Medstar Good Samaritan Hospital, Baltimore, Maryland
| | - Min Ho Cho
- Department of Medicine, Baystate Medical Center, Springfield, Massachusetts
| | - Tomilowo Abijo
- Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Kenneth J. Wilkins
- Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
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Ryu AJ, Rahimi RS, Leise MD. The Current Hepatic Encephalopathy Pipeline. J Clin Exp Hepatol 2020; 10:377-385. [PMID: 32655239 PMCID: PMC7335727 DOI: 10.1016/j.jceh.2020.01.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 01/06/2020] [Indexed: 02/08/2023] Open
Abstract
Hepatic encephalopathy (HE) is a complication of acute or chronic liver failure; its mechanism is complex, involving multiple organ systems, and is still being elucidated. The standard of care, lactulose, has remained generally unchanged for decades. However, in recent years, better understanding of the pathophysiology has yielded new therapeutic targets for this reversible condition. These novel treatments act both on traditional pathways established in the ammonia hypothesis and through more recently discovered mechanisms. Here, we review contemporary investigational therapies for HE. We used narrative reviews and searched ClinicalTrials.gov database for the condition "hepatic encephalopathy" through August 29, 2019. Our review yielded six key areas of therapeutic focus: (1) antibiotics against urease-producing gut bacteria, (2) intravenous ammonia scavengers, (3) modified synthetic probiotics, (4) fecal microbiota transplant, (5) brain steroid-modulating agents, and 6) nonlactulose laxatives. Active trials are ongoing in each of these therapeutic areas.
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Key Words
- CHESS, clinical hepatic encephalopathy staging scale
- FMT, fecal microbiota transplant
- HE, hepatic encephalopathy
- HESA, hepatic encephalopathy scoring algorithm
- MAD, multiple-ascending dose
- MES, modified encephalopathy scale
- ORT, object recognition test
- PEG, polyethylene glycol-3350
- SAD, single-ascending dose
- SEV, saccadic eye velocity
- ammonia
- antibiotics
- fecal microbiota transplant
- hepatic encephalopathy
- lactulose
- therapy
- trials
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Affiliation(s)
- Alexander J. Ryu
- Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, United States
| | - Robert S. Rahimi
- Division of Hepatology, Baylor Scott & White Health, Dallas, TX, United States
| | - Michael D. Leise
- Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN, United States
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Abstract
Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV's epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.
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Liu Z, Sun J, Hou J. Lower Risk of Hepatocellular Carcinoma With Tenofovir vs Entecavir in Patients With Chronic Hepatitis B. JAMA Oncol 2020; 5:915. [PMID: 31021388 DOI: 10.1001/jamaoncol.2019.0644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Zhihong Liu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Jian Sun
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Jinlin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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Shin S, Lee SH, Lee M, Kim JH, Lee W, Lee HW, Park MS, Park S, Kim TS, Choi DH. Aspirin and the risk of hepatocellular carcinoma development in patients with alcoholic cirrhosis. Medicine (Baltimore) 2020; 99:e19008. [PMID: 32118712 PMCID: PMC7478404 DOI: 10.1097/md.0000000000019008] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Aspirin therapy has shown protective effects against hepatocellular carcinoma (HCC) in preclinical studies. However, it is unclear whether aspirin therapy lowers the risk of HCC in patients with alcoholic cirrhosis.A retrospective analysis of data from 949 consecutive patients with alcoholic cirrhosis who abstained from alcoholic drinking was performed. The primary and secondary outcomes were development of HCC and gastrointestinal bleeding events, respectively. Risk was compared between patients with aspirin treatment and patients who were not treated (non-aspirin group) using a time-varying Cox proportional hazards model for total population and propensity score-matching analysis.The aspirin group included 224 patients and the non-aspirin group had 725 patients. During the study period of median duration of 3.1 years, 133 patients (13.6%) developed HCC. In time-varying Cox proportional analyses, the aspirin group showed a significantly lower risk of HCC (adjusted hazard ratio [aHR]: 0.13; 95% confidence interval [CI]: 0.08-0.21; P < .001). In propensity score-matched pairs, aspirin therapy significantly reduced the risk of HCC (aHR: 0.14; 95% CI: 0.09-0.22; P < .001). In bleeding risk, treatment with aspirin alone was not significantly associated with a higher bleeding risk (aHR: 0.81; 95% CI: 0.45-1.44; P = .46).Aspirin therapy was associated with the lower risk of HCC in patients with alcoholic cirrhosis.
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Affiliation(s)
- Sangdeok Shin
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Sang Hoon Lee
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Minjong Lee
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
- Department of Internal Medicine, Ewha Womans University College of Medicine, Ewha Womans University Seoul Hospital, Gonghang-daero, Gangseo-gu, Seoul, Republic of Korea
| | - Ji Hyun Kim
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Wongu Lee
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Hyun Woo Lee
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Min Soo Park
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Seungwoo Park
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Tae Suk Kim
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Dae Hee Choi
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
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Jiang L, Sheng Y, Feng X, Wu J. The effects and safety of vasopressin receptor agonists in patients with septic shock: a meta-analysis and trial sequential analysis. Crit Care 2019; 23:91. [PMID: 30871607 PMCID: PMC6419432 DOI: 10.1186/s13054-019-2362-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 02/17/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The aim of this study was to evaluate the effects and safety of vasopressin receptor agonists in patients with septic shock. METHODS PubMed, EMBASE, and Cochrane library were searched for randomized controlled trials evaluating the effects of vasopressin receptor agonists in septic shock patients. Two reviewers performed literature selection, data extraction, and quality evaluation independently. The primary outcome was mortality. And secondary outcomes included intensive care unit (ICU) length of stay, duration of mechanical ventilation, and incidence of adverse events. In addition, a trial sequential analysis (TSA) was performed. RESULTS Twenty studies were eligible for meta-analysis. The results showed vasopressin receptor agonists use was associated with reduced mortality (relative risk (RR) 0.92; 95% confidence interval (CI) 0.84 to 0.99; I2 = 0%). Nevertheless, they had no significant effects on ICU length of stay (mean deviation (MD) - 0.08, 95% CI, - 0.68 to 0.52, I2 = 0%) and duration of mechanical ventilation (MD - 0.58, 95% CI - 1.47 to 0.31, I2 = 57%). Additionally, there was no significant difference in total adverse events between two groups (RR 1.28, 95% CI 0.87 to 1.90, I2 = 57%), but vasopressin receptor agonists administration could significantly increase the risk of digital ischemia (RR 4.85, 95% CI 2.81 to 8.39, I2 = 26%). Finally, there was no statistical difference of cardiovascular events (RR 0.91, 95% CI 0.53 to 1.57, I2 = 1%), arrhythmia (0.77, 95% CI 0.48 to 1.23, I2 = 23%), mesenteric ischemia (0.83, 95% CI 0.44 to 1.55, I2 = 0%), diarrhea (2.47, 95% CI 0.77 to 7.96, I2 = 49%), cerebrovascular events (1.36, 95% CI 0.18 to 10.54, I2 = 0%), and hyponatremia (1.47, 95% CI 0.84 to 2.55, I2 = 0%) between two groups. Egger's test showed there was no significant publication bias among studies (P = 0.36). CONCLUSIONS The use of vasopressin might result in reduced mortality in patients with septic shock. An increased risk of digital ischemia must be taken into account.
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Affiliation(s)
- Libing Jiang
- Department of Emergency Medicine, Second Affiliated Hospital, School of Medicine & Institute of Emergency Medicine, Zhejiang University, No 88, Jiefang Rd, Hangzhou, China
| | - Yi Sheng
- Yuhang Branch of The Second Affiliated Hospital of Zhenjiang University, No.369 Yingbin Road, Yuhang District, Hangzhou, 311100 Zhenjiang Province China
| | - Xia Feng
- Department of Respiratory, The Third People’s Hospital of Hangzhou, West Lake Avenue 38, Hangzhou, China
| | - Jing Wu
- Department of Emergency Medicine, Second Affiliated Hospital, School of Medicine & Institute of Emergency Medicine, Zhejiang University, No 88, Jiefang Rd, Hangzhou, China
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Finkelmeier F, Czauderna C, Perkhofer L, Ettrich TJ, Trojan J, Weinmann A, Marquardt JU, Vermehren J, Waidmann O. Feasibility and safety of nivolumab in advanced hepatocellular carcinoma: real-life experience from three German centers. J Cancer Res Clin Oncol 2019; 145:253-259. [PMID: 30374657 DOI: 10.1007/s00432-018-2780-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 10/24/2018] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Nivolumab is the first checkpoint-inhibitor approved for the treatment of advanced HCC patients. Real-life experience data of nivolumab treatment in HCC patients, especially those with advanced liver disease, is scarce. MATERIALS AND METHODS All patients with confirmed advanced HCC and nivolumab treatment from three large German centers were retrospectively analyzed. Clinical parameters and outcome were assessed. RESULTS A total of 34 patients were included. At the time of treatment initiation 5 patients (14.7%) were classified as stage BCLC B and 29 (85.3%) BCLC C, respectively. 25 (73.5) patients had received prior sorafenib treatment. All patients presented with cirrhosis, namely Child-Pugh stages A (56%) or B (41%), respectively. At time of patient's assessment, 20 out of 34 (58.8%) patients had died. Grade 3 toxicities occurred in two patients (5.9%). Best overall responses were partial response in four patients (11.8%) and stable disease in eight patients (23.5%). The median overall survival of the whole cohort was 7.5 weeks (range 0-46). Child-Pugh B stage disease at treatment start was significantly associated with poor outcome. DISCUSSION Nivolumab treatment seems safe and clinical efficacious. Patients with advanced liver disease require further prospective evaluation due to probable limited efficacy of nivolumab.
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Affiliation(s)
- Fabian Finkelmeier
- Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
| | - Carolin Czauderna
- Department of Gastroenterology and Hepatology, University Hospital Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Lukas Perkhofer
- Medical Clinic I, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany
| | - Thomas J Ettrich
- Medical Clinic I, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany
| | - Jörg Trojan
- Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany
| | - Arndt Weinmann
- Department of Gastroenterology and Hepatology, University Hospital Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Jens U Marquardt
- Department of Gastroenterology and Hepatology, University Hospital Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Johannes Vermehren
- Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany
| | - Oliver Waidmann
- Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany
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Cleveland E, Bandy A, VanWagner LB. Diagnostic challenges of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Clin Liver Dis (Hoboken) 2018; 11:98-104. [PMID: 30147867 PMCID: PMC6103635 DOI: 10.1002/cld.716] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Accepted: 03/12/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
- Erin Cleveland
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern UniversityFeinberg School of MedicineChicagoIL
| | - Andrew Bandy
- Department of Pathology, Northwestern UniversityFeinberg School of MedicineChicagoIL
| | - Lisa B. VanWagner
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern UniversityFeinberg School of MedicineChicagoIL
- Department of Preventive Medicine, Northwestern UniversityFeinberg School of MedicineChicagoIL
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Butt AS, Sharif F, Abid S. Impact of direct acting antivirals on occurrence and recurrence of hepatocellular carcinoma: Biologically plausible or an epiphenomenon? World J Hepatol 2018; 10:267-276. [PMID: 29527262 PMCID: PMC5838445 DOI: 10.4254/wjh.v10.i2.267] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 02/06/2018] [Accepted: 02/09/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection (HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals (DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical data that investigate the impact of DAAs on occurrence and recurrence of HCC.
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Affiliation(s)
- Amna Subhan Butt
- Section of Gastroenterology, Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Fatima Sharif
- Section of Gastroenterology, Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Shahab Abid
- Section of Gastroenterology, Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
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