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Zhan L, Yang Y, Nie B, Kou Y, Du S, Tian Y, Huang Y, Ye R, Huang Z, Luo B, Ge L, Ye S. A prolonged activated partial thromboplastin time indicates poor short-term prognosis in patients with hepatic encephalopathy: insights from the MIMIC database. Front Med (Lausanne) 2025; 12:1514327. [PMID: 40018344 PMCID: PMC11865095 DOI: 10.3389/fmed.2025.1514327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 01/23/2025] [Indexed: 03/01/2025] Open
Abstract
Objectives This study investigates serum markers for short-term prognosis in hepatic encephalopathy patients. Background Patients with hepatic encephalopathy face elevated mortality rates and bleak prognoses. However, effective prognostic models or indicators are lacking. This study aims to explore serum markers for predicting short-term prognosis in these patients. Methods We conducted a retrospective analysis of 552 patients with hepatic encephalopathy, categorizing 429 individuals meeting exclusion criteria into normal and high activated partial thromboplastin time (APTT) groups. We assessed 12-day and 25-day survival rates using Kaplan-Meier analysis and Cox regression models to examine associations between groups and outcomes. Results Upon comparing baseline characteristics, the high APTT group exhibited significant disparities in acute kidney injury, sepsis, coagulation disorders, and ascites (p < 0.05). In the multivariate COX regression model, the hazard ratios [HRs; 95% confidence interval (CI)] of 12- and 25-day mortality were 1.012 (1.001, 1.022, p = 0.033) and 1.010 (1.002, 1.018, p = 0.013), respectively. We discovered that APTT demonstrated an independent association with prognosis. Our findings revealed that the ability of APTT to predict short-term prognosis surpasses that of the traditional MELD model. Regarding 12- and 25-day survival, Kaplan-Meier survival curves from these groups demonstrated a lower survival probability for patients in the high APTT group than the normal group (log-rank p < 0.05). The results of subgroup analysis and interaction analysis indicate that APTT is not influenced by other confounding factors. Conclusion A prolonged APTT suggests a poorer short-term prognosis in patients with hepatic encephalopathy.
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Affiliation(s)
- Liping Zhan
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Yuping Yang
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Biao Nie
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
- Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Yanqi Kou
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Shenshen Du
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
- Department of Gastroenterology, Huanghe Sanmenxia Hospital, Sanmenxia, China
| | - Yuan Tian
- Department of Pathology, Guangdong Medical University, Zhanjiang, China
| | - Yujie Huang
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Ruyin Ye
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Zhe Huang
- Department of Colorectal Surgery, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Botao Luo
- Department of Pathology, Guangdong Medical University, Zhanjiang, China
| | - Lei Ge
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Shicai Ye
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
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Wang Y, Yang L, Shang Y, Huang Y, Ju C, Zheng H, Zhao W, Liu J. Identifying Minimal Hepatic Encephalopathy: A New Perspective from Magnetic Resonance Imaging. J Magn Reson Imaging 2025; 61:11-24. [PMID: 38149764 DOI: 10.1002/jmri.29179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 12/28/2023] Open
Abstract
Type C hepatic encephalopathy (HE) is a condition characterized by brain dysfunction caused by liver insufficiency and/or portal-systemic blood shunting, which manifests as a broad spectrum of neurological or psychiatric abnormalities, ranging from minimal HE (MHE), detectable only by neuropsychological or neurophysiological assessment, to coma. Though MHE is the subclinical phase of HE, it is highly prevalent in cirrhotic patients and strongly associated with poor quality of life, high risk of overt HE, and mortality. It is, therefore, critical to identify MHE at the earliest and timely intervene, thereby minimizing the subsequent complications and costs. However, proper and sensitive diagnosis of MHE is hampered by its unnoticeable symptoms and the absence of standard diagnostic criteria. A variety of neuropsychological or neurophysiological tests have been performed to diagnose MHE. However, these tests are nonspecific and susceptible to multiple factors (eg, aging, education), thereby limiting their application in clinical practice. Thus, developing an objective, effective, and noninvasive method is imperative to help detect MHE. Magnetic resonance imaging (MRI), a noninvasive technique which can produce many objective biomarkers by different imaging sequences (eg, Magnetic resonance spectroscopy, DWI, rs-MRI, and arterial spin labeling), has recently shown the ability to screen MHE from NHE (non-HE) patients accurately. As advanced MRI techniques continue to emerge, more minor changes in the brain could be captured, providing new means for early diagnosis and quantitative assessment of MHE. In addition, the advancement of artificial intelligence in medical imaging also presents the potential to mine more effective diagnostic biomarkers and further improves the predictive efficiency of MHE. Taken together, advanced MRI techniques may provide a new perspective for us to identify MHE in the future. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Yisong Wang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Longtao Yang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Youlan Shang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yijie Huang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Chao Ju
- Department of Radiology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Hairong Zheng
- Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Wei Zhao
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
- Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- Clinical Research Center for Medical Imaging in Hunan Province, Changsha, China
| | - Jun Liu
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
- Clinical Research Center for Medical Imaging in Hunan Province, Changsha, China
- Department of Radiology Quality Control Center in Hunan Province, Changsha, China
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Martins YC, Daniel-Ribeiro CT. A hypothesis to explain malaria-induced neurocognitive sequelae. Trends Parasitol 2024; 40:1077-1080. [PMID: 39500670 DOI: 10.1016/j.pt.2024.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 10/11/2024] [Accepted: 10/13/2024] [Indexed: 12/07/2024]
Abstract
The development of malaria-induced neurocognitive and behavioral sequelae is not entirely understood. We hypothesize that liver dysfunction caused by Plasmodium infection is responsible for malaria-induced neurocognitive and behavioral sequelae. Our metabolic hypothesis not only explains neurocognitive sequelae after cerebral malaria (CM) but also after other severe, non-severe, and asymptomatic malaria infections.
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Affiliation(s)
- Yuri Chaves Martins
- Department of Anesthesiology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
| | - Cláudio Tadeu Daniel-Ribeiro
- Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz and Centro de Pesquisa, Diagnóstico e Treinamento em Malária, Fiocruz, Rio de Janeiro, RJ, Brazil
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Lin S, Wang X, Xu Z, Li L, Kang R, Li S, Wu X, Zhu Y, Gao H. Construction of a prediction model for hepatic encephalopathy in acute-on-chronic liver failure patients. Ann Med 2024; 56:2410403. [PMID: 39387525 PMCID: PMC11469415 DOI: 10.1080/07853890.2024.2410403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 03/14/2024] [Accepted: 09/08/2024] [Indexed: 10/15/2024] Open
Abstract
OBJECTIVE Hepatic encephalopathy (HE) is a serious complication of acute-on-chronic liver failure (ACLF) that requires early detection and intervention to positively impact patient prognosis. This study aimed to develop a reliable model to predict HE in ACLF patients during hospitalization. METHODS Retrospectively recruiting 255 hepatitis B-related ACLF patients, including 67 who developed HE during hospitalization, the study analysed clinical data and biochemical indices collected during the first week of admission. The least absolute shrinkage and selection operator (LASSO) was used to identify characteristic predictors for hospitalization HE events, and a logistic regression model was subsequently developed. Receiver operating characteristic (ROC) curves, calibration curves, and bootstrap resampling were used to evaluate the model's discrimination, consistency, and accuracy, and a nomogram was created to visualize the model. An external validation cohort of 236 liver failure patients collected from the same medical centre between 2007 and 2010 was used to validate the model. RESULTS The study found that blood urea nitrogen (BUN), alpha-fetoprotein (AFP), international normalized ratio (INR), serum ammonia, and infection complications during hospitalization were risk factors for HE in ACLF patients. The new model predicted the development of HE in ACLF patients with an area under the receiver operating characteristic curve (AUROC) of 85.2%, which was superior to other models. The best threshold for the new model was 0.28, resulting in a specificity of 81.4% and a sensitivity of 80.6%. In the validation group, the new model showed similar results, with an AUROC of 79% and a specificity of 83.6% and a sensitivity of 56.6%. CONCLUSION This study developed and validated a new prediction model for HE in ACLF patients offering a useful tool for early identification of patients with a high risk of HE in clinical settings. However, to ascertain the model's general effectiveness, future prospective multicentre studies are warranted.
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Affiliation(s)
- Shenglong Lin
- Department of Severe Hepatopathy, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
- Department of Hepatology, Hepatology Research Institute, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
| | - Xiangmei Wang
- Department of Severe Hepatopathy, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
| | - Zixin Xu
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Lu Li
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Rui Kang
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Songtao Li
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Xiaoyong Wu
- Fujian Medical University, Fuzhou, Fujian Province, China
| | - Yueyong Zhu
- Department of Hepatology, Hepatology Research Institute, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Clinical Research Center for Liver and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Haibing Gao
- Department of Severe Hepatopathy, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
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Weiss N, Pflugrad H, Kandiah P. Altered Mental Status in the Solid-Organ Transplant Recipient. Semin Neurol 2024; 44:670-694. [PMID: 39181120 DOI: 10.1055/s-0044-1789004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/27/2024]
Abstract
Patients undergoing solid-organ transplantation (SOT) face a tumultuous journey. Prior to transplant, their medical course is characterized by organ dysfunction, diminished quality of life, and reliance on organ support, all of which are endured in hopes of reaching the haven of organ transplantation. Peritransplant altered mental status may indicate neurologic insults acquired during transplant and may have long-lasting consequences. Even years after transplant, these patients are at heightened risk for neurologic dysfunction from a myriad of metabolic, toxic, and infectious causes. This review provides a comprehensive examination of causes, diagnostic approaches, neuroimaging findings, and management strategies for altered mental status in SOT recipients. Given their complexity and the numerous etiologies for neurologic dysfunction, liver transplant patients are a chief focus in this review; however, we also review lesser-known contributors to neurological injury across various transplant types. From hepatic encephalopathy to cerebral edema, seizures, and infections, this review highlights the importance of recognizing and managing pre- and posttransplant neurological complications to optimize patient outcomes.
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Affiliation(s)
- Nicolas Weiss
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Neurological ICU, Paris, France
| | - Henning Pflugrad
- Department of Neurology, Agaplesion Ev. Klinikum Schaumburg, Obernkirchen, Germany
| | - Prem Kandiah
- Department of Neurology, Emory University Hospital, Atlanta, Georgia
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Johnson CD, Stevens CM, Bennett MR, Litch AB, Rodrigue EM, Quintanilla MD, Wallace E, Allahyari M. The Role of Vitamin D Deficiency in Hepatic Encephalopathy: A Review of Pathophysiology, Clinical Outcomes, and Therapeutic Potential. Nutrients 2024; 16:4007. [PMID: 39683402 DOI: 10.3390/nu16234007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/18/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
Hepatic encephalopathy (HE) is a neuropsychiatric condition frequently associated with cirrhosis and portosystemic shunting (PSS). It imposes a significant clinical and economic burden, with increasing attention toward identifying modifiable factors that could improve outcomes. Emerging evidence suggests that vitamin D deficiency (VDD), prevalent in patients with cirrhosis, may contribute to the development and severity of HE. This review explores the association between VDD and HE by analyzing the underlying pathophysiology, including oxidative stress, ammonia accumulation, and impaired hepatic function. Additionally, we summarize recent studies highlighting the correlation between low serum 25-hydroxy vitamin D (25-OHD) levels and worsening grades of HE. Despite strong observational data, interventional studies on vitamin D (VD) supplementation for HE remains limited. Current evidence suggests that VD's antioxidant properties may alleviate oxidative stress in HE, with potential benefits in mitigating disease severity. Future research should focus on longitudinal studies and randomized controlled trials to evaluate the clinical impact of VD supplementation on HE outcomes and explore VD's role in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedures. Understanding the therapeutic potential of VD could lead to improved management strategies for HE and cirrhotic patients at large.
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Affiliation(s)
- Coplen D Johnson
- School of Medicine, Louisiana State University Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
| | - Christopher M Stevens
- School of Medicine, Louisiana State University Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
| | - Matthew R Bennett
- School of Medicine, Louisiana State University Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
| | - Adam B Litch
- School of Medicine, Louisiana State University Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
| | - Eugenie M Rodrigue
- School of Medicine, Louisiana State University Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
| | - Maria D Quintanilla
- School of Medicine, Louisiana State University Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
| | - Eric Wallace
- Department of Radiology, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
| | - Massoud Allahyari
- Department of Radiology, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
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Redfield R, Latt N, Munoz SJ. Minimal Hepatic Encephalopathy. Clin Liver Dis 2024; 28:237-252. [PMID: 38548436 DOI: 10.1016/j.cld.2024.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
Minimal hepatic encephalopathy (MHE) is a pervasive frequent complication of cirrhosis of any etiology. The diagnosis of MHE is difficult as the standard neurologic examination is essentially within normal limits. None of the symptoms and signs of overt HE is present in a patient with MHE, such as confusion, disorientation, or asterixis. Progress has been made in diagnostic tools for detection of attention and cognitive deficits at the point of care of MHE. The development of MHE significantly impacts quality of life and activities of daily life in affected patients including driving motor vehicles and machine operation.
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Affiliation(s)
- Rachel Redfield
- Thomas Jefferson Hospital, Division of Gastroenterology, 132 S. 10th Street, Suite 480, Philadelphia, PA 19106, USA
| | - Nyan Latt
- Virtua Health System, Center for Liver Disease and Transplant Program, 63 Kresson Road, Suite 101, Cherry Hill, NJ 08034, USA
| | - Santiago J Munoz
- The Johns Hopkins University School of Medicine and Medical Institutions, Division of Gastroenterology and Hepatology, 600 N. Wolfe Street, Blalock Building, Suite 465, Baltimore, MD 21287, USA.
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He Q, Mao C, Chen Z, Zeng Y, Deng Y, Hu R. Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials. Arab J Gastroenterol 2024; 25:84-92. [PMID: 38403493 DOI: 10.1016/j.ajg.2024.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 11/12/2023] [Accepted: 01/06/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND AND STUDY AIMS Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE) and is highly prevalent. The efficacy of L-ornithine L-aspartate (LOLA) for the treatment of HE is well known but its role in MHE remains uncertain. The objectives of the current study were to evaluate the efficacy of LOLA for the treatment of MHE in patients with cirrhosis. METHODS The Cochrane Library, PubMed, EMBASE, Web of Science and Ovid databases were searched. Only randomized controlled trials (RCTs) that compared the efficacy of LOLA with placebo or no intervention for the treatment of MHE in patients with cirrhosis were included from inception to January 2023. The primary outcomes were reversal of MHE and development of overt hepatic encephalopathy (OHE). RESULTS Overall, six RCTs comprising 292 patients were included. Compared with placebo or no intervention, LOLA was more effective in reversing MHE (RR = 2.264, 95 % CI = 1.528, 3.352, P = 0.000, I2 = 0.0 %) and preventing progression of OHE (RR = 0.220, 95 % CI = 0.076, 0.637, P = 0.005, I2 = 0.0 %). Based on subgroup analyses, oral LOLA treatment appeared more likely to reverse MHE (RR = 2.648, 95 % CI = 1.593, 4.402, P = 0.000, I2 = 0.0 %), intravenous LOLA treatment yielded a similar probability of reversing MHE (RR = 1.669, 95 % CI = 0.904, 3.084, P = 0.102, I2 = 0.0 %). LOLA did not show a superior possibility in reducing mortality (RR = 0.422, 95 % CI = 0.064, 2.768, P = 0.368, I2 = 0.0 %) and ammonia levels (SMD = 0.044, 95 % CI = -0.290, 0.379, P = 0.795, I2 = 0.0 %) compared with placebo or no intervention. CONCLUSIONS LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.
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Affiliation(s)
- Qiufeng He
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Chuangjie Mao
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Zhili Chen
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Yilan Zeng
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Yang Deng
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Rong Hu
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China.
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Thabut D, Roux J, Sultanik P, Tamberou C, Prost PL, Hagège H. Population characteristics, healthcare pathways and outcomes of patients with cirrhosis hospitalized with overt hepatic encephalopathy in France: A study of the French Hospital-Discharge Database. Clin Res Hepatol Gastroenterol 2024; 48:102274. [PMID: 38154597 DOI: 10.1016/j.clinre.2023.102274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 12/13/2023] [Accepted: 12/15/2023] [Indexed: 12/30/2023]
Abstract
Hepatic encephalopathy (HE) is a severe complication of cirrhosis, independently associated with a poor survival. The objectives of this study were to describe the prevalence of overt hepatic encephalopathy (OHE) requiring hospitalization, and the healthcare pathways and outcomes of patients hospitalized for OHE in France. Data from the French Hospital-Discharge Database (Programme de Medicalisation des Systemes d'information, PMSI) within the 5-year period from 2014 to 2018 were analysed. Since the disease lacks a PMSI code in the ICD-10, an identification algorithm was developed. The analysis identified 57,191 patients with OHE including 48,566 patients (85 %) who had been hospitalized twice or more during the study period. Each year, an average of over 20,000 patients were hospitalized in France for OHE as the primary or secondary reason for hospitalization. Among these patients, between 11,500 and 13,500 had been hospitalized at least twice in that year with an average of 3.4 hospitalisations per year. 25 % of admissions occurred following consultation at the emergency unit. Among hospitalisations, 15 % involved admission to the critical care resuscitation unit or intensive care. For all patients identified as suffering from OHE and hospitalized, the 5-year mortality was 46.5 % (26,621 patients). This pioneering study revealed that, in France, despite a probable underestimation of OHE episodes due to the lack of specific PMSI coding, the prevalence of OHE was very high, with frequent recurrences and readmissions, and high mortality.
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Affiliation(s)
- Dominique Thabut
- APHP Sorbonne-Université, Hôpital Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75013 Paris, France; Brain Liver Pitié-Salpêtrière Study Group (BLIPS), France; INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Julia Roux
- Service d'hépato-gastroentérologie, CHI de Villeneuve Saint Georges, 40 allée de la Source 94195 Villeneuve-Saint-Georges Cedex, France
| | - Philippe Sultanik
- APHP Sorbonne-Université, Hôpital Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75013 Paris, France; Brain Liver Pitié-Salpêtrière Study Group (BLIPS), France; INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Cheikh Tamberou
- GERSDATA,137 Rue d'Aguesseau, 92100 Boulogne-Billancourt, France
| | | | - Hervé Hagège
- CHI Creteil, 40 Avenue de Verdun 94000 Créteil, France.
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Lu H, Zhang H, Wu Z, Li L. Microbiota-gut-liver-brain axis and hepatic encephalopathy. MICROBIOME RESEARCH REPORTS 2024; 3:17. [PMID: 38841407 PMCID: PMC11149093 DOI: 10.20517/mrr.2023.44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 01/16/2024] [Accepted: 01/19/2024] [Indexed: 06/07/2024]
Abstract
Hepatic encephalopathy (HE) is a clinical manifestation of neurological and psychiatric abnormalities that are caused by complications of liver dysfunction including hyperammonemia, hyperuricemia, and portal hypertension. Accumulating evidence suggests that HE could be reversed through therapeutic modifications of gut microbiota. Multiple preclinical and clinical studies have indicated that gut microbiome affects the physiological function of the liver, such as the regulation of metabolism, secretion, and immunity, through the gut-liver crosstalk. In addition, gut microbiota also influences the brain through the gut-brain crosstalk, altering its physiological functions including the regulation of the immune, neuroendocrine, and vagal pathways. Thus, key molecules that are involved in the microbiota-gut-liver-brain axis might be able to serve as clinical biomarkers for early diagnosis of HE, and could be effective therapeutic targets for clinical interventions. In this review, we summarize the pathophysiology of HE and further propose approaches modulating the microbiota-gut-liver-brain axis in order to provide a comprehensive understanding of the prevention and potential clinical treatment for HE with a microbiota-targeted therapy.
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Affiliation(s)
| | | | | | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China
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Hammd M, Elghezewi A, Abdulhadi A, Alabid A, Alabid A, Badi Y, Kamal I, Hesham Gamal M, Mohamed Fisal K, Mujtaba M, Sherif A, Frandah W. Efficacy and Safety of Variable Treatment Options in the Prevention of Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis. Cureus 2024; 16:e53341. [PMID: 38435950 PMCID: PMC10907550 DOI: 10.7759/cureus.53341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2024] [Indexed: 03/05/2024] Open
Abstract
There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine the most effective possible treatment among the single treatment options or the combined treatment options for decreasing the morbidity and mortality of HE. We evaluated the outcomes by various parameters such as the quality of life, reduction in ammonia, all causes of mortality, adverse events, reversal of minimal HE, and development of overt HE. We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023 for studies that assess various treatment options for HE. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The Cochrane Tool was used to assess the randomized controlled trials' quality (RCT), while the NIH tool was used to assess the quality of the included cohort studies. Utilizing the R software, the network meta-analysis was conducted. In addition to a significant variation in cases of (Lactulose and Rifaximin) compared with Rifaximin (RR= 0.39, 95% CI [0.17; 0.89]), the results demonstrated a significantly lower incidence of overt HE in (Lactulose and Rifaximin) compared with placebo (RR=0.19, 95% CI [0.09; 0.40]). Most arms demonstrated a statistically significant reduction in the incidence of overt HE compared to albumin and placebo. The results also demonstrated a significant reduction in ammonia between L-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07]). This network meta-analysis has significant data for managing subclinical HE in people without a history of overt HE. Our analysis showed that (Lactulose and Rifaximin), followed by (Rifaximin and L-carnitine), followed by (Lactulose and Rifaximin with zinc) were the best combinations regarding overt HE. LOLA reduced ammonia best, followed by Nitazoxanide and finally Lactulose. (Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly.
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Affiliation(s)
- Mohamed Hammd
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Abdelwahap Elghezewi
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Ahmed Abdulhadi
- Internal Medicine, Faculty of Medicine, Tripoli University, Tripoli, LBY
| | - Abdelwahhab Alabid
- Internal Medicine, Faculty of Medicine, Tripoli University, Tripoli, LBY
| | - Abdulfatah Alabid
- Internal Medicine, Faculty of Medicine, Tripoli University, Tripoli, LBY
| | - Yasra Badi
- Internal Medicine, All Saints University School of Medicine, Dominica, USA
| | - Ibrahem Kamal
- General Medicine, Al-Azhar University, Alexandria, EGY
| | - Mohamed Hesham Gamal
- Pharmacology and Therapeutics, Faculty of Pharmacy, Tanta University, Banha, EGY
| | - Khalid Mohamed Fisal
- Pharmacology and Therapeutics, Faculty of Pharmacy, Deraya University, Minia, EGY
| | - Mohamed Mujtaba
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Ahmed Sherif
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Wesam Frandah
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
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12
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Chigakova IA, Minenko IA, Strokova OA, Nazarova ER. [Effect of low-intensity laser-therapy in the correction of encephalopathy in obstructive jaundice]. VOPROSY KURORTOLOGII, FIZIOTERAPII, I LECHEBNOI FIZICHESKOI KULTURY 2024; 101:19-24. [PMID: 39718954 DOI: 10.17116/kurort202410106119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2024]
Abstract
Hepatic encephalopathy is an early and severe complication of obstructive jaundice and is characterized by occurrence of non-focal and focal neurological manifestations. Different methods of therapy are applied for disorder correction. Low-intensity laser blood irradiation has a pronounced antioxidant and vasoactive effect. OBJECTIVE To analyze the results of pharmaceutical treatment and low-intensity laser therapy use in encephalopathy correction in obstructive jaundice of non-neoplastic origin. MATERIAL AND METHODS The study was performed at the surgery department in the S.V. Katkov Republican Clinical Hospital (Saransk). The trial included 54 patients with moderate obstructive jaundice of non-neoplastic origin with latent encephalopathy, who were divided into 2 groups: the 1st group (control) consisted of 27 patients receiving standard pharmaceutical treatment; the 2nd group (study) - 27 patients receiving standard treatment and laser therapy (low-intensity laser irradiation in red emission at the cubital vein projection for 15 minutes). A comparative group (norm) included 20 healthy volunteers. All patients underwent biochemical studies (alanine aminotransferase and total bilirubin levels in the blood were assessed) after treatment. Registration of microcirculatory disorders and psychometric testing were conducted to reveal latent hepatic encephalopathy along with the evaluation of liver functional condition. RESULTS Correlation analysis showed the association of psychoneurological status improvement with liver functional condition (indicators of microcirculation and biochemical blood analysis were considered) in patients receiving a comprehensive therapy with laser irradiation. Correlation coefficient amounted to 0.87-0.96 (p<0.05). CONCLUSION The use of above vascular laser blood irradiation in a comprehensive treatment of moderate obstructive jaundice leads to improvement of liver functional condition (the first barrier organ on the toxin pathway) and to a significant reduction of latent encephalopathy's manifestations. The conducted treatment resulted in a reduction of initially elevated levels of alanine aminotransferase and total bilirubin. Laser therapy has an ability to restore microcirculation that leads to the improvement of psychoneurological status in patients with moderate obstructive jaundice.
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Affiliation(s)
- I A Chigakova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Polyclinic No. 3 of the Medical Sanitary Unit of the Ministry of Internal Affairs of the Russian Federation, Moscow, Russia
| | - I A Minenko
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - O A Strokova
- N.P. Ogarev National Research Mordovia State University, Saransk, Russia
| | - E R Nazarova
- Polyclinic No. 3 of the Medical Sanitary Unit of the Ministry of Internal Affairs of the Russian Federation, Moscow, Russia
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13
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Glal KAM, El-Haggar SM, Abdel-Salam SM, Mostafa TM. Allopurinol Prevents Cirrhosis-Related Complications: A Quadruple Blind Placebo-Controlled Trial. Am J Med 2024; 137:55-64. [PMID: 37832758 DOI: 10.1016/j.amjmed.2023.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 09/06/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023]
Abstract
BACKGROUND Complications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the study aimed to explore the use of allopurinol in preventing the recurrence of liver cirrhosis-related complications. METHODS One hundred patients with hepatic decompensation were randomized into 1:1 ratio to receive either allopurinol 300 mg or placebo tablets once daily for 6 months. The primary endpoint was the incidence of cirrhosis-related complications (overt ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy). RESULTS Six months following treatment, allopurinol reduced the relative risk (RR) of any first complication experienced after enrollment by 56% (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.27-0.62); P ˂ .001). Allopurinol decreased the RR of overt ascites by 67% (HR 0.33; 95% CI, 0.0098-0.94); P = .039] and reduced the RR of spontaneous bacterial peritonitis by about 75% (HR 0.25; 95% CI, 0.05-0.76; P = .01). Likewise, allopurinol was linked to an 80% reduction in the RR of developing hepatorenal syndrome (HR 0.2; 95% CI, 0.04-0.87; P = .033). CONCLUSION Allopurinol significantly decreased the recurrence of overall liver cirrhosis-related complications. Therefore, allopurinol may constitute a promising agent for patients with hepatic decompensation. These positive outcomes could be a result of its ability to reduce bacterial translocation and inflammation. CLINICALTRIALS GOV IDENTIFIER NCT005545670.
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Affiliation(s)
| | | | - Sherief M Abdel-Salam
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
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14
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Orzeł-Gajowik K, Milewski K, Zielińska M. miRNA-ome plasma analysis unveils changes in blood-brain barrier integrity associated with acute liver failure in rats. Fluids Barriers CNS 2023; 20:92. [PMID: 38066639 PMCID: PMC10709860 DOI: 10.1186/s12987-023-00484-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 10/30/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) symptoms associated with liver insufficiency are linked to the neurotoxic effects of ammonia and other toxic metabolites reaching the brain via the blood-brain barrier (BBB), further aggravated by the inflammatory response. Cumulative evidence documents that the non-coding single-stranded RNAs, micro RNAs (miRs) control the BBB functioning. However, miRs' involvement in BBB breakdown in HE is still underexplored. Here, we hypothesized that in rats with acute liver failure (ALF) or rats subjected to hyperammonemia, altered circulating miRs affect BBB composing proteins. METHODS Transmission electron microscopy was employed to delineate structural alterations of the BBB in rats with ALF (thioacetamide (TAA) intraperitoneal (ip.) administration) or hyperammonemia (ammonium acetate (OA) ip. administration). The BBB permeability was determined with Evans blue dye and sodium fluorescein assay. Plasma MiRs were profiled by Next Generation Sequencing (NGS), followed by in silico analysis. Selected miRs, verified by qRT-PCR, were examined in cultured rat brain endothelial cells. Targeted protein alterations were elucidated with immunofluorescence, western blotting, and, after selected miR mimics transfection, through an in vitro resistance measurement. RESULTS Changes in BBB structure and increased permeability were observed in the prefrontal cortex of TAA rats but not in the brains of OA rats. The NGS results revealed divergently changed miRNA-ome in the plasma of both rat models. The in silico analysis led to the selection of miR-122-5p and miR-183-5p with their target genes occludin and integrin β1, respectively, as potential contributors to BBB alterations. Both proteins were reduced in isolated brain vessels and cortical homogenates in TAA rats. We documented in cultured primary brain endothelial cells that ammonia alone and, in combination with TNFα increases the relative expression of NGS-selected miRs with a less pronounced effect of TNFα when added alone. The in vitro study also confirmed miR-122-5p-dependent decrease in occludin and miR-183-5p-related reduction in integrin β1 expression. CONCLUSION This work identified, to our knowledge for the first time, potential functional links between alterations in miRs residing in brain endothelium and BBB dysfunction in ALF.
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Affiliation(s)
- Karolina Orzeł-Gajowik
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland
| | - Krzysztof Milewski
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland
- Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura St. 3, 02-093, Warsaw, Poland
| | - Magdalena Zielińska
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland.
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15
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Yao C, Huang L, Wang M, Mao D, Wang M, Zheng J, Long F, Huang J, Liu X, Zhang R, Xie J, Cheng C, Yao F, Huang G. Establishment and validation of a nomogram model for riskprediction of hepatic encephalopathy: a retrospective analysis. Sci Rep 2023; 13:19544. [PMID: 37945916 PMCID: PMC10636098 DOI: 10.1038/s41598-023-47012-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 11/08/2023] [Indexed: 11/12/2023] Open
Abstract
To establish a high-quality, easy-to-use, and effective risk prediction model for hepatic encephalopathy, to help healthcare professionals with identifying people who are at high risk of getting hepatic encephalopathy, and to guide them to take early interventions to reduce the occurrence of hepatic encephalopathy. Patients (n = 1178) with decompensated cirrhosis who attended the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were selected for the establishment and validation of a nomogram model for risk prediction of hepatic encephalopathy. In this study, we screened the risk factors for the development of hepatic encephalopathy in patients with decompensated cirrhosis by univariate analysis, LASSO regression and multifactor analysis, then established a nomogram model for predicting the risk of getting hepatic encephalopathy for patients with decompensated cirrhosis, and finally performed differentiation analysis, calibration analysis, clinical decision curve analysis and validation of the established model. A total of 1178 patients with decompensated cirrhosis who were hospitalized and treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were included for modeling and validation. Based on the results of univariate analysis, LASSO regression analysis and multifactor analysis, a final nomogram model with age, diabetes, ascites, spontaneous peritonitis, alanine transaminase, and blood potassium as predictors of hepatic encephalopathy risk prediction was created. The results of model differentiation analysis showed that the AUC of the model of the training set was 0.738 (95% CI 0.63-0.746), while the AUC of the model of the validation set was 0.667 (95% CI 0.541-0.706), and the two AUCs indicated a good discrimination of this nomogram model. According to the Cut-Off value determined by the Jorden index, when the Cut-Off value of the training set was set at 0.150, the sensitivity of the model was 72.8%, the specificity was 64.8%, the positive predictive value was 30.4%, and the negative predictive value was 91.9%; when the Cut-Off value of the validation set was set at 0.141, the sensitivity of the model was 69.7%, the specificity was 57.3%, the positive predictive value was 34.5%, and the negative predictive value was 84.7%. The calibration curve and the actual events curve largely overlap at the diagonal, indicating that the prediction with this model has less error. The Hosmer-Lemeshow test for goodness of fit was also applied, and the results showed that for the training set, χ2 = 1.237587, P = 0.998, and for the validation set, χ2 = 31.90904, P = 0.0202, indicating that there was no significant difference between the predicted and actual observed values. The results of the clinical decision curve analysis showed that the model had a good clinical benefit, compared with the two extreme clinical scenarios (all patients treated or none treated), and the model also had a good clinical benefit in the validation set. This study showed that aged over 55 years, complications of diabetes, ascites, and spontaneous bacterial peritonitis, abnormal glutamate aminotransferase and abnormal blood potassium are independent risks indicators for the development of hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model based on the indicators mentioned above can effectively and conveniently predict the risk of developing hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model established on this study can help clinical healthcare professionals to timely and early identify patients with high risk of developing hepatic encephalopathy.
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Affiliation(s)
- Chun Yao
- Guangxi University of Chinese Medicine, Nanning, 530001, Guangxi, People's Republic of China
| | - Liangjiang Huang
- Guangxi University of Chinese Medicine, Nanning, 530001, Guangxi, People's Republic of China
| | - Meng Wang
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Dewen Mao
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Minggang Wang
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Jinghui Zheng
- Guangxi University of Chinese Medicine, Nanning, 530001, Guangxi, People's Republic of China
| | - Fuli Long
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Jingjing Huang
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Xirong Liu
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Rongzhen Zhang
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Jiacheng Xie
- Guangxi University of Chinese Medicine, Nanning, 530001, Guangxi, People's Republic of China
| | - Chen Cheng
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Fan Yao
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China
| | - Guochu Huang
- First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Nanning, 530001, Guangxi, People's Republic of China.
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Bakulin IG, Ivanova KN, Eremina EY, Marchenko NV. Comparative Analysis of the Efficacy of Different Regimens of 12 Months Rifaximin-Alfa Therapy in Patients with Liver Cirrhosis and Minimal Hepatic Encephalopathy. Diagnostics (Basel) 2023; 13:3239. [PMID: 37892060 PMCID: PMC10606376 DOI: 10.3390/diagnostics13203239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/16/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
It is a matter of current interest which rifaximin-α regimens in patients with liver cirrhosis and minimal hepatic encephalopathy are the most efficient. STUDY OBJECTIVE to evaluate the effect of various rifaximin-α regimens for 12 months on clinical and laboratory parameters and quality of life in patients with liver cirrhosis and minimal hepatic encephalopathy. METHODS It was a multicenter, prospective, open-label, observational study that included 288 patients with liver cirrhosis and minimal hepatic encephalopathy of both sexes over the age of 18 years, who were prescribed a 12-month course of treatment with rifaximin-α in accordance with the product label. Statistical analysis was performed in the population of patients who completed all visits according to the protocol (n = 258). Retrospectively, the patients were divided into two subgroups: subgroup 1 (continuous course)-patients who received the study drug for a year and the number of days of administration was 360 days (n = 41); subgroup 2 (cyclic course)-patients who received the study drug during the year for less than 360 days (n = 217). At each of the 4 visits, the quality of life was assessed using the CLDQ questionnaire, the time to perform the number connection test, the severity of symptoms associated with hepatic encephalopathy, and laboratory parameters. RESULTS During the 12-month observation period, an increase in the total score on the CLDQ quality of life questionnaire in patients with chronic liver diseases was revealed, which indicates an improvement in the quality of life of patients receiving rifaximin-α therapy. When patients were divided into subgroups depending on the duration of therapy, some benefits of continuous rifaximin-α therapy were noted in the more pronounced dynamics of decrease in the time to perform the number connection test, and in decreased severity of the following symptoms associated with hepatic encephalopathy: impaired concentration and memory, cognitive impairment, and decreased performance. Laboratory findings showed positive dynamics in both subgroups. CONCLUSION A continuous rifaximin-α regimen in patients with liver cirrhosis and minimal hepatic encephalopathy for 12 months was superior to cyclic use with a more pronounced effect on the quality of life of patients and on the symptoms associated with hepatic encephalopathy.
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Affiliation(s)
- Igor G. Bakulin
- Department of Propaedeutics of Internal Medicine, Gastroenterology and Dietetics Named after S.M. Ryss «Mechnikov North-Western State Medical University» of the Ministry of Health of Russia, 191015 St. Petersburg, Russia
| | - Kristina N. Ivanova
- Department of Propaedeutics of Internal Medicine, Gastroenterology and Dietetics Named after S.M. Ryss «Mechnikov North-Western State Medical University» of the Ministry of Health of Russia, 191015 St. Petersburg, Russia
| | - Elena Y. Eremina
- Department of Propaedeutics of Internal Diseases, Federal State Budgetary Educational Institution of Higher Education «National Research Mordovian State University Named after. N.P. Ogarev», 430005 Saransk, Russia
| | - Natalya V. Marchenko
- Clinical and Educational Center, Gastroenterology and Hepatology, St. Petersburg State University, 199034 St. Petersburg, Russia
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Testino G, Bottaro LC, Andorno E, Bandini F, Balbinot P, Beltramini S, Bottino S, Caltabellotta M, Caputo F, Caviglia E, Curone P, DI Biagio A, Gagliano C, Gandolfo N, Pestarino L, Rollero A, Romairone E, Sampietro L, Torre E, Zuccarelli S, Pellicano R. Hepatic encephalophathy: management and diagnostic therapeutic assistance path of Ligurian Local Health Company 3 (ASL3). Minerva Med 2023; 114:698-718. [PMID: 36952221 DOI: 10.23736/s0026-4806.22.08408-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2023]
Abstract
Hepatic encephalophathy (HE) is a neuropsychiatric syndrome with a prevalence in the cirrhotic population ranging from 20 to 80%. HE is a cause of inappropriate hospitalization, caregiver burdening and increased social costs. There is need to create dedicated care pathways to better manage patients and support family caregivers. The data used for the preparation of this diagnostic therapeutic assistance path (DTAP) are based on a detailed analysis of the scientific literature published before June 30, 2022 (PubMed, Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted in particular the guidelines/ position papers of International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN), Italian Association for the Study of the Liver (AISF), European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD), Italian Society on Alcohol (Società Italiana di Alcologia [SIA]) and other relevant papers. DTAP was created based on the most recent recommendations of the international scientific literature. The present DTAP highlight the need for a multidisciplinary activity integrated with territorial medicine in close connection with caregivers. This guarantees improved therapeutic adherence, hospital readmission reduction, improved quality of life for patients and caregivers and a significant reduction in costs.
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Affiliation(s)
- Gianni Testino
- Addiction and Hepatology Unit/Alcohological Regional Centre and Study Centre "Self Help, Community Program and Caregiver Training" ASL3, Genoa, Italy -
| | | | - Enzo Andorno
- Liver Transplantation Unit, San Martino Polyclinic Hospital, Genoa, Italy
| | | | - Patrizia Balbinot
- Addiction and Hepatology Unit/Alcohological Regional Centre and Study Centre "Self Help, Community Program and Caregiver Training" ASL3, Genoa, Italy
| | | | | | | | - Fabio Caputo
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Center for the Study and Treatment of Chronic Inflammatory Intestinal Diseases (IBD) and Gastroenterological Manifestations of Rare Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Department of Internal Medicine, Santissima Annunziata Hospital, University of Ferrara, Ferrara, Italy
| | | | | | - Antonio DI Biagio
- Department of Health Sciences, Infectious Diseases Clinic, IRCCS San Martino Polyclinic Hospital, University of Genoa, Genoa, Italy
| | | | | | | | | | | | | | - Enrico Torre
- Unit of Endocrinology, Metabolic Diseases and Diabetology, ASL3 Liguria, Genoa, Italy
| | | | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
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Marti-Aguado D, Gougol A, Gomez-Medina C, Jamali A, Abo-Zed A, Morales-Arraez D, Jimenez-Sosa A, Burns K, Bawa A, Hernández A, Pujol C, Alvarado-Tapias E, Szafranska J, Chiu WK, Villagrasa A, Ventura-Cots M, Gandicheruvu H, Lluch P, Chen HW, Rachakonda V, Duarte-Rojo A, Bataller R. Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study. EClinicalMedicine 2023; 61:102046. [PMID: 37415844 PMCID: PMC10319982 DOI: 10.1016/j.eclinm.2023.102046] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 05/29/2023] [Accepted: 05/31/2023] [Indexed: 07/08/2023] Open
Abstract
Background The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3-27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05-2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31-3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36-0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02-4.64) and phenobarbital (HR = 2.99, 95% CI 1.07-8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44-3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38-4.49), and ICU admission (OR = 1.96, 95% CI 1.19-3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40-3.82), 90-day (HR = 1.78, 95% CI 1.18-2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06-2.24). Interpretation AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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Affiliation(s)
- David Marti-Aguado
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain
| | - Amir Gougol
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- University of California, San Francisco (UCSF), San Francisco, CA, USA
| | - Concepcion Gomez-Medina
- Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain
| | - Arsia Jamali
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Abdelrhman Abo-Zed
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Dalia Morales-Arraez
- Department of Gastroenterology, Hospital Universitario de Canarias, Tenerife, Spain
| | - Alejandro Jimenez-Sosa
- Statistical Consultant Research Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | - Keith Burns
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Aditi Bawa
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Anjara Hernández
- Department of Gastroenterology, Hospital Universitario de Canarias, Tenerife, Spain
| | - Claudia Pujol
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Institut de Recerca Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - Edilmar Alvarado-Tapias
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Institut de Recerca Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Justyna Szafranska
- Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Wai Kan Chiu
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ares Villagrasa
- Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Meritxell Ventura-Cots
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Haritha Gandicheruvu
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Paloma Lluch
- Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain
| | | | | | - Andres Duarte-Rojo
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ramon Bataller
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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19
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Qin B, Liang S, Tang S, Liang H, Zhang Y, Liang Z. Altered Spontaneous Brain Activity in Cirrhotic Patients with Minimal Hepatic Encephalopathy: A Meta-Analysis of Resting-State Functional Imaging. Brain Sci 2023; 13:960. [PMID: 37371438 DOI: 10.3390/brainsci13060960] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
(1) Background: Minimal hepatic encephalopathy (MHE) is an important complication of decompensated cirrhosis. Previous studies have demonstrated spontaneous brain activity alterations in cirrhotic patients with MHE. However, the reported results are inconsistent, which has limited our understanding of the potential neural mechanisms. Thus, we conducted a quantitative meta-analysis of resting-state functional imaging studies to identify the regional activity alterations consistently involved in MHE. (2) Methods: We searched six databases to include resting-state functional imaging studies and compared spontaneous brain activity patterns between MHE patients and healthy controls (HCs), and between cirrhotic patients without minimal hepatic encephalopathy (NMHE) and HCs. Then, a separate whole-brain voxel-wise meta-analysis between MHE or NMHE patients and HCs was conducted using seed-based d mapping with permutation of subject images. We further conducted the conjunction analysis to assess the distinct regional activity alterations between MHE and NMHE patients as compared to HCs. (3) Results: Thirteen studies with twenty datasets were included in this meta-analysis. Compared with HCs, MHE patients showed decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. Compared with NMHE patients, MHE patients indicated decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. (4) Conclusions: MHE is associated with spontaneous brain activity alterations involving the left superior frontal gyrus and median cingulate/paracingulate gyri, which may implicate primarily in spatial working memory and emotional disorders. These findings may contribute to a better understanding of the potential neural mechanisms, and guide further research.
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Affiliation(s)
- Bin Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Shuolin Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Shiting Tang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Huo Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Yunli Zhang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Zhijian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
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20
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Nadinskaia MY, Kodzoeva KB, Gulyaeva KA, Khen MDE, Koroleva DI, Privalov MA, Tekaeva AK, Fedorov VR, Prokofev SG. Risk Factors of Portal Vein Thrombosis in Patients with Different Child-Pugh Classes Liver Cirrhosis. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:45-59. [DOI: 10.22416/1382-4376-2023-33-2-45-59] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Aim: to evaluate the frequency of portal vein thrombosis (PVT) and build predictive models of the development of PVT for patients with liver cirrhosis (LC) of A and B/C classes by Child-Pugh.Materials and methods. Research design is a case-control. The Case group included 130 patients with newly diagnosed PVT not caused by invasive hepatocellular carcinoma (HCC); 29 patients were assigned to class A, 101 patients were assigned to class B/C. From the database of cirrhotic patients without PVT 60 Controls for class A and 205 for B/C were selected using sratified randomization by sex, age and etiology of cirrhosis. The Mann-Whitney U-test and Pearson's chi-squared test were used to compare the groups. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated. Logistic regression models are constructed with the separation of the sample into training and test (0.7; 0.3). The operational characteristics of the models were calculated on the test sample; ROC analysis was carried out, the area under the ROC curve (AUC) was calculated.Results. The overall frequency of PVT was 4.1 % (95 % CI 2.7-5.8 %) in class A and 10.4 % (95 % CI 8.5-12.5 %) class B/C. Patients with class A and B/C PVT differed from the corresponding controls by more severe portal hypertension: the frequency of bleeding / number of interventions on varices compared with the control were 41/45 % vs. 7/8 % (p < 0.001) for class A and 25.7/30.7 % vs. 16.1/16.1 % (p < 0.05) for class B/C, ascites frequency was 24 % vs. 8 % (p < 0.05) for class A and 89.1 % vs. 68.3 % (p < 0.001) for class B/C. The cutoff by the portal vein diameter was the same for both classes — 13.4 mm; the spleen length was similar and amounted 17.5 mm for class A, 17.1 mm for class B/C. Patients with PVT differed from the corresponding controls by neutrophil-to-lymphocyte ratio: class A 2.33 (1.82; 3.61) vs. 1.76 (1.37; 2.20), p < 0.01, class B/C 2.49 (1.93; 3.34) vs. 2.15 (1.49; 3.26), p < 0.05. Patients of class B/C had a higher incidence of newly diagnosed malignant tumors - 23.8% (primarily HCC that does not invade the portal vein), compared with control and cases of class A - 6.3 % and 3 % (p < 0.05), respectively. The best model for class A included variceal bleeding, ascites, portal vein diameter, absolute number of neutrophils, for class B — ascites, spleen length, portal vein diameter, malignant tumors / local factors; sensitivity, specificity, accuracy and AUC were 79.3 %, 90 %, 86.5 %, 0.897 and 73.3 %, 68.3 %, 69.9 %, 0.789, respectively.Conclusion. Independently of the Child-Pugh class of LC, the main risk factor for PVT is severe portal hypertension.
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Affiliation(s)
- M. Yu. Nadinskaia
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Kh. B. Kodzoeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University); V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs
| | - K. A. Gulyaeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M.-D. E. Khen
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - D. I. Koroleva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M. A. Privalov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. Kh. Tekaeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - V. R. Fedorov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - S. G. Prokofev
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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21
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Kim MJ, Kim JH, Jung JH, Kim SE, Kim HS, Jang MK, Park SH, Lee MS, Suk KT, Kim DJ, Choi EK, Park JW. Serum S100B Levels in Patients with Liver Cirrhosis and Hepatic Encephalopathy. Diagnostics (Basel) 2023; 13:diagnostics13030333. [PMID: 36766438 PMCID: PMC9914222 DOI: 10.3390/diagnostics13030333] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/08/2023] [Accepted: 01/13/2023] [Indexed: 01/18/2023] Open
Abstract
Hepatic encephalopathy (HE) is one of the main complications of liver cirrhosis (LC) and is classified into minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy (overt HE). S100B is expressed mainly in astrocytes and other glial cells, and S100B has been reported to be associated with various neurological disorders. The present study aimed to investigate the diagnostic ability of serum S100B to discriminate the grade of HE and the parameters correlated with serum S100B levels. Additionally, we investigated whether serum S100B levels can be used to predict 1-year mortality in cirrhotic patients. In total, 95 cirrhotic patients were consecutively enrolled and divided into the following three groups: (i) without any types of HEs; (ii) with MHE; and (iii) with overt HE. The diagnosis of MHE was made by the Mini-Mental State Examination (MMSE) and Psychometric Hepatic Encephalopathy Score (PHES). Among the three groups, there were no significant differences in serum S100B levels regardless of HE severity. The clinical parameters correlated with serum S100B levels were age, serum bilirubin, and creatinine levels. The Model for End-Stage Liver Disease (MELD) score showed a significant positive correlation with serum S100B levels. The relationship between serum S100B levels and MELD score was maintained in 48 patients without any type of HE. Additionally, hyperammonemia, low cholesterol levels, and the combination of serum S100B levels ≥ 35 pg/mL with MELD score ≥ 13 were factors for predicting 1- year mortality. In conclusion, serum S100B level was not useful for differentiating the severity of HE. However, we found that serum S100B levels can be affected by age, serum bilirubin, and creatinine in cirrhotic patients and are associated with MELD scores. Additionally, serum S100B levels showed the possibility of predicting 1-year mortality in cirrhotic patients. These findings suggest that serum S100B levels may reflect liver dysfunction and prognosis in liver disease.
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Affiliation(s)
- Mo-Jong Kim
- Ilsong Institute of Life Science, Hallym University, Seoul 07247, Republic of Korea
- Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon-si 24252, Republic of Korea
| | - Jung-Hee Kim
- Department of Internal Medicine, Dongtan Sacred Heart Hospital of Hallym University Medical Center, 7, Keunjaebong-gil, Hwaseong-si 18450, Republic of Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Republic of Korea
| | - Jang-Han Jung
- Department of Internal Medicine, Dongtan Sacred Heart Hospital of Hallym University Medical Center, 7, Keunjaebong-gil, Hwaseong-si 18450, Republic of Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Republic of Korea
| | - Sung-Eun Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Republic of Korea
- Department of Internal Medicine, Hallym University Sacred Heart Hospital of Hallym University Medical Center, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si 14068, Republic of Korea
| | - Hyoung-Su Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Republic of Korea
- Department of Internal Medicine, Kangdong Sacred Heart Hospital of Hallym University Medical Center, 18, Cheonho-daero 173-gil, Gangdong-gu, Seoul 05355, Republic of Korea
| | - Myoung-Kuk Jang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Republic of Korea
- Department of Internal Medicine, Kangdong Sacred Heart Hospital of Hallym University Medical Center, 18, Cheonho-daero 173-gil, Gangdong-gu, Seoul 05355, Republic of Korea
| | - Sang-Hoon Park
- Department of Internal Medicine, Kangnam Sacred Heart Hospital of Hallym University Medical Center, 1, Singil-ro, Yeongdeungpo-gu, Seoul 07441, Republic of Korea
| | - Myung-Seok Lee
- Department of Internal Medicine, Kangnam Sacred Heart Hospital of Hallym University Medical Center, 1, Singil-ro, Yeongdeungpo-gu, Seoul 07441, Republic of Korea
| | - Ki Tae Suk
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Republic of Korea
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital of Hallym University Medical Center, 77, Sakju-ro, Chuncheon-si 24253, Republic of Korea
| | - Dong Joon Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Republic of Korea
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital of Hallym University Medical Center, 77, Sakju-ro, Chuncheon-si 24253, Republic of Korea
| | - Eun-Kyoung Choi
- Ilsong Institute of Life Science, Hallym University, Seoul 07247, Republic of Korea
- Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon-si 24252, Republic of Korea
| | - Ji-Won Park
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Republic of Korea
- Department of Internal Medicine, Hallym University Sacred Heart Hospital of Hallym University Medical Center, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si 14068, Republic of Korea
- Correspondence: ; Tel.: +82-31-380-3705
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22
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The Relationship and Changes of Liver Blood Supply, Portal Pressure Gradient, and Liver Volume following TIPS in Cirrhosis. Can J Gastroenterol Hepatol 2022; 2022:7476477. [PMID: 36531835 PMCID: PMC9754828 DOI: 10.1155/2022/7476477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 11/18/2022] [Indexed: 12/13/2022] Open
Abstract
AIM Transjugular intrahepatic portosystemic shunt (TIPS) alters the liver blood supply and reduces portal pressure. This study was to investigate the changes and associations of the hepatic blood flow, liver volume, and portal pressure gradient (PPG) after TIPS in liver cirrhosis. METHODS Twenty-one patients with liver cirrhosis who received TIPS were recruited. The contrast CT images were used to assess the iodine density (ID) of liver parenchymal and liver volume. The ID of the liver parenchyma was used to reflect hepatic blood flow. We used a paired t-test and regression analysis to investigate the effect of TIPS on hepatic blood flow, liver volume, and PPG in individuals with cirrhosis and the factors that affect changes in liver volume. RESULTS After TIPS, there was a significant improvement in the ID of liver parenchyma at arterial phase (AP) and PPG in individuals with cirrhosis (P < 0.05). Each 1 unit increase in the ID change of whole liver parenchyma at the venous phase (VP) was significantly associated with a 269.44 cm3 increase in the liver volume after TIPS (b = 269.44, P = 0.012). With an increasing ID change of whole liver parenchyma at VP, the change in liver volume followed an increasing trend (P for overall association = 0.005). CONCLUSIONS Our data indicate that there was a significant improvement in hepatic blood flow, especially at AP, after TIPS and the change in hepatic blood supply from the portal vein is positively associated with the change in liver volume after TIPS. Increasing the blood supply to the liver from the portal vein may improve the reduction of liver volume.
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23
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Hildenbrand FF, Murray FR, von Känel R, Deibel AR, Schreiner P, Ernst J, Zipser CM, Böettger S. Predisposing and precipitating risk factors for delirium in gastroenterology and hepatology: Subgroup analysis of 718 patients from a hospital-wide prospective cohort study. Front Med (Lausanne) 2022; 9:1004407. [PMID: 36530904 PMCID: PMC9747774 DOI: 10.3389/fmed.2022.1004407] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 11/15/2022] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND AND AIMS Delirium is the most common acute neuropsychiatric syndrome in hospitalized patients. Higher age and cognitive impairment are known predisposing risk factors in general hospital populations. However, the interrelation with precipitating gastrointestinal (GI) and hepato-pancreato-biliary (HPB) diseases remains to be determined. PATIENTS AND METHODS Prospective 1-year hospital-wide cohort study in 29'278 adults, subgroup analysis in 718 patients hospitalized with GI/HPB disease. Delirium based on routine admission screening and a DSM-5 based construct. Regression analyses used to evaluate clinical characteristics of delirious patients. RESULTS Delirium was detected in 24.8% (178/718). Age in delirious patients (median 62 years [IQR 21]) was not different to non-delirious (median 60 years [IQR 22]), p = 0.45). Dementia was the strongest predisposing factor for delirium (OR 66.16 [6.31-693.83], p < 0.001). Functional impairment, and at most, immobility increased odds for delirium (OR 7.78 [3.84-15.77], p < 0.001). Patients with delirium had higher in-hospital mortality rates (18%; OR 39.23 [11.85-129.93], p < 0.001). From GI and HPB conditions, cirrhosis predisposed to delirium (OR 2.11 [1.11-4.03], p = 0.023), while acute renal failure (OR 4.45 [1.61-12.26], p = 0.004) and liver disease (OR 2.22 [1.12-4.42], p = 0.023) were precipitators. Total costs were higher in patients with delirium (USD 30003 vs. 10977; p < 0.001). CONCLUSION Delirium in GI- and HPB-disease was not associated with higher age per se, but with cognitive and functional impairment. Delirium needs to be considered in younger adults with acute renal failure and/or liver disease. Clinicians should be aware about individual risk profiles, apply preventive and supportive strategies early, which may improve outcomes and lower costs.
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Affiliation(s)
- Florian F. Hildenbrand
- Department of Gastroenterology and Hepatology, University Hospital, University of Zurich, Zurich, Switzerland
- Department of Gastroenterology and Hepatology, Stadtspital Zurich, Zurich, Switzerland
| | - Fritz R. Murray
- Department of Gastroenterology and Hepatology, University Hospital, University of Zurich, Zurich, Switzerland
- Department of Gastroenterology and Hepatology, Stadtspital Zurich, Zurich, Switzerland
| | - Roland von Känel
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, Zurich, Switzerland
| | - Ansgar R. Deibel
- Department of Gastroenterology and Hepatology, University Hospital, University of Zurich, Zurich, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital, University of Zurich, Zurich, Switzerland
| | - Jutta Ernst
- Center of Clinical Nursing Science, University of Zurich, University Hospital of Zurich, Zurich, Switzerland
| | - Carl M. Zipser
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, Zurich, Switzerland
- Department of Neurology and Neurophysiology, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | - Soenke Böettger
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, Zurich, Switzerland
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24
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Liu YB, Chen MK. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J Gastroenterol 2022; 28:5910-5930. [PMID: 36405106 PMCID: PMC9669831 DOI: 10.3748/wjg.v28.i41.5910] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 09/30/2022] [Accepted: 10/20/2022] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis causes a heavy global burden. In this review, we summarized up-to-date epidemiological features of cirrhosis and its complications. Recent epidemiological studies reported an increase in the prevalence of cirrhosis in 2017 compared to in 1990 in both men and women, with 5.2 million cases of cirrhosis and chronic liver disease occurring in 2017. Cirrhosis caused 1.48 million deaths in 2019, an increase of 8.1% compared to 2017. Disability-adjusted life-years due to cirrhosis ranked 16th among all diseases and 7th in people aged 50-74 years in 2019. The global burden of hepatitis B virus and hepatitis C virus-associated cirrhosis is decreasing, while the burden of cirrhosis due to alcohol and nonalcoholic fatty liver disease (NAFLD) is increasing rapidly. We described the current epidemiology of the major complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, renal disorders, and infections. We also summarized the epidemiology of hepatocellular carcinoma in patients with cirrhosis. In the future, NAFLD-related cirrhosis will likely become more common due to the prevalence of metabolic diseases such as obesity and diabetes, and the prevalence of alcohol-induced cirrhosis is increasing. This altered epidemiology should be clinically noted, and relevant interventions should be undertaken.
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Affiliation(s)
- Yuan-Bin Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei Province, China
| | - Ming-Kai Chen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei Province, China
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25
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Percutaneous transhepatic obliteration of a large portosystemic shunt associated with hepatic encephalopathy using a technique of n-butyl-2-cyanoacrylate injection inside hydrogel-coated coils: A case report. Radiol Case Rep 2022; 17:4738-4741. [PMID: 36212760 PMCID: PMC9539619 DOI: 10.1016/j.radcr.2022.09.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 09/11/2022] [Indexed: 11/20/2022] Open
Abstract
Portosystemic shunts with cirrhosis may lead to hepatic encephalopathy (HE), which is often pharmacotherapy-resistant. We report a case of a 66-year-old female patient diagnosed with alcoholic cirrhosis and uncontrolled HE. She underwent percutaneous transhepatic obliteration (PTO) for treatment of a large portosystemic shunt from the left and right gastric veins to the azygos vein. We embolized the target veins using hydro-coated coils and filled them with n-butyl-2-cyanoacrylate (NBCA), leading to firmed obstruction of the large portosystemic shunt without NBCA migration, thus reducing the number of coils required. The HE symptoms improved after PTO and could thereafter be controlled with conservative therapy. Our results showed that PTO using an NBCA injection inside hydrogel-coated coils for a large portosystemic shunt associated with HE is effective and safe.
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26
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Mallet M, Desplats V, Bouzbib C, Sultanik P, Alioua I, Marika Rudler MS, Weiss N, Thabut D. Blood ammonia in patients with chronic liver diseases: A better defined role in clinical practice. Anal Biochem 2022; 657:114873. [PMID: 36108794 DOI: 10.1016/j.ab.2022.114873] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 07/26/2022] [Accepted: 08/18/2022] [Indexed: 11/28/2022]
Abstract
Ammonia is one of the main players in the pathogenesis of hepatic encephalopathy (HE) in patients with chronic liver diseases. The usefulness of measuring ammonemia has been debated since many years. New data reveal that besides helping in the differential diagnosis of HE, ammonemia could be a prognostic marker not only in patients with HE, but also in patients without any neurological symptoms, suggesting a potential toxic role of ammonia beyond the brain. Finally, targeting ammonemia while monitoring therapeutic response could be a way to improve outcomes in patients with HE.
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Affiliation(s)
- Maxime Mallet
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Victor Desplats
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Charlotte Bouzbib
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Philippe Sultanik
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Imen Alioua
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (MTS), MetaboHUB, F-91191, Gif sur Yvette, France
| | - M S Marika Rudler
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Nicolas Weiss
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation à orientation Neurologique, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France & Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE) Sorbonne Université, France
| | - Dominique Thabut
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
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Maslennikov R, Efremova I, Ivashkin V, Zharkova M, Poluektova E, Shirokova E, Ivashkin K. Effect of probiotics on hemodynamic changes and complications associated with cirrhosis: A pilot randomized controlled trial. World J Hepatol 2022; 14:1667-1677. [PMID: 36157871 PMCID: PMC9453455 DOI: 10.4254/wjh.v14.i8.1667] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/12/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance.
AIM To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial.
METHODS This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis; 24 patients received probiotics (Saccharomyces boulardii) for 3 mo, and 16 patients received a placebo over the same period. Liver function and the systemic hemodynamic status were evaluated pre- and post-intervention. Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators. Cardiac output and systemic vascular resistance were calculated.
RESULTS Following a 3-mo course of probiotics in comparison to the control group, we observed amelioration of hyperdynamic circulation [a decrease in cardiac output (P = 0.026) and an increase in systemic vascular resistance (P = 0.026)] and systemic inflammation [a decrease in serum C-reactive protein levels (P = 0.044)], with improved liver function [an increase in serum albumin (P = 0.001) and a decrease in the value of Child-Pugh score (P = 0.001)] as well as a reduction in the severity of ascites (P = 0.022), hepatic encephalopathy (P = 0.048), and cholestasis [a decrease in serum alkaline phosphatase (P = 0.016) and serum gamma-glutamyl transpeptidase (P = 0.039) activity] and an increase in platelet counts (P < 0.001) and serum sodium level (P = 0.048).
CONCLUSION Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Consultative and Diagnostic Center No. 2 of Moscow Health Department , Moscow 107764, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Konstantin Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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28
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Impact of Optimizing the Emergency Care Process on the Emergency Effect and Prognosis of Patients with Hepatic Encephalopathy. Emerg Med Int 2022; 2022:4446215. [PMID: 36059559 PMCID: PMC9433260 DOI: 10.1155/2022/4446215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 07/16/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatic encephalopathy (HE) is a serious complication caused by liver disease and is one of the leading causes of death in patients. Studies have shown that proper emergency care for patients after the occurrence of HE can improve their prognosis and quality of life. Therefore, this study focuses on the effect of optimizing the emergency care process on the effectiveness and prognosis of emergency care for patients with hepatic encephalopathy. In this study, we set 32 patients with HE admitted to receive routine emergency care between May 2020 and March 2021 as the control group and 34 patients with HE admitted to receive optimized emergency care processes between April 2021 and February 2022 as the observation group. The satisfaction of patients' families with this care was assessed using a self-administered nursing satisfaction questionnaire to record the outcome of emergency care, quality of care, and prognosis of patients in the two groups of palliative care. The data collected were analyzed using SPSS17.0 software, and the results showed that the time spent on diagnosis, resuscitation, DTP, and DTT was much lower in the observation group than in the control group, and the scores related to the quality of care, such as ambulance technique, humanistic care, resuscitation efficiency, and resuscitation effect, were all higher than those of the control group, and the satisfaction of the family members in the observation group was also significantly higher than that of the control group (P < 0.05). The success rate of first aid in the observation group was 100.00%, which was higher than 93.72% in the control group, but the difference between the two groups was not significant (P > 0.05). It can be seen that the application of an optimized emergency nursing process in HE patients is effective, which can effectively improve the success rate of HE resuscitation, shorten the resuscitation time and condition diagnosis, improve the resuscitation effect, improve the quality of nursing care, and improve the prognosis of patients to a certain extent.
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29
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Seshadri A, Appelbaum R, Carmichael SP, Cuschieri J, Hoth J, Kaups KL, Kodadek L, Kutcher ME, Pathak A, Rappold J, Rudnick SR, Michetti CP. Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document. Trauma Surg Acute Care Open 2022; 7:e000936. [PMID: 35991906 PMCID: PMC9345092 DOI: 10.1136/tsaco-2022-000936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/20/2022] [Indexed: 11/04/2022] Open
Abstract
Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.
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Affiliation(s)
- Anupamaa Seshadri
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Rachel Appelbaum
- Department of Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Samuel P Carmichael
- Department of Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Joseph Cuschieri
- Department of Surgery, San Francisco General Hospital and Trauma Center, San Francisco, California, USA
| | - Jason Hoth
- Department of Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
| | - Krista L Kaups
- Department of Surgery, UCSF Fresno, Fresno, California, USA
| | - Lisa Kodadek
- Surgery, Yale University School of Medicine, New Haven, Connecticut, USA,Department of Surgery, Yale New Haven Hospital, New Haven, Connecticut, USA
| | - Matthew E Kutcher
- Surgery, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Abhijit Pathak
- Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
| | - Joseph Rappold
- Department of Surgery, Maine Medical Center, Portland, Oregon, USA
| | - Sean R Rudnick
- Department of Gastroenterology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA
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30
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Ben Khaled N, Allgeier J, Lutz T, Weber S, Lange CM. Medikamentöse Therapie bei Patienten mit Leberzirrhose. DIE GASTROENTEROLOGIE 2022. [PMCID: PMC9247913 DOI: 10.1007/s11377-022-00635-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Die Leberzirrhose ist das Endstadium chronischer Lebererkrankungen und insbesondere im fortgeschrittenen Stadium mit einer hohen Morbidität und Mortalität verbunden. Patienten mit Leberfunktionseinschränkung sind permanent von einer Vielzahl schwerwiegender Komplikationen bedroht. Ein optimales pharmakologisches Management bei Patienten mit Leberinsuffizienz kann die Progression der Grunderkrankung verlangsamen, Hospitalisationen verhindern sowie Lebensqualität und Überleben verbessern. Dieser Artikel gibt einen Überblick über den aktuellen Stand und neue Entwicklungen der Pharmakotherapie bei Patienten mit Leberzirrhose.
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Affiliation(s)
- Najib Ben Khaled
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Marchioninistr. 15, 81377 München, Bayern Deutschland
| | - Julian Allgeier
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Marchioninistr. 15, 81377 München, Bayern Deutschland
| | - Teresa Lutz
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Marchioninistr. 15, 81377 München, Bayern Deutschland
| | - Sabine Weber
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Marchioninistr. 15, 81377 München, Bayern Deutschland
| | - Christian M. Lange
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Marchioninistr. 15, 81377 München, Bayern Deutschland
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31
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Lee HA, Chang Y, Sung PS, Yoon EL, Lee HW, Yoo JJ, Lee YS, An J, Song DS, Cho YY, Kim SU, Kim YJ. Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases. Clin Mol Hepatol 2022; 28:425-472. [PMID: 35850495 PMCID: PMC9293616 DOI: 10.3350/cmh.2022.0186] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 06/29/2022] [Indexed: 11/05/2022] Open
Abstract
The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non-antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4'-dimethoxy-5,6,5',6'-dimethylenedixoybiphenyl-2,2'-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non-antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.
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Affiliation(s)
- Han Ah Lee
- Departments of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Pil Soo Sung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.,The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Do Seon Song
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Youn Cho
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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32
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Lemoine CP, Superina R. Letter to the editor: Is transjugular intrahepatic portosystemic shunt the best treatment for adults without cirrhosis with extrahepatic portal vein obstruction and portal hypertension? Hepatology 2022; 75:1667-1668. [PMID: 35106796 DOI: 10.1002/hep.32386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 01/14/2022] [Indexed: 12/08/2022]
Affiliation(s)
- Caroline P Lemoine
- Division of Transplant and Advanced Hepatobiliary SurgeryAnn & Robert H. Lurie Children's Hospital of ChicagoNorthwestern University Feinberg School of MedicineChicagoIllinoisUSA
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33
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Kreisel W, Lazaro A, Trebicka J, Grosse Perdekamp M, Schmitt-Graeff A, Deibert P. Cyclic GMP in Liver Cirrhosis-Role in Pathophysiology of Portal Hypertension and Therapeutic Implications. Int J Mol Sci 2021; 22:10372. [PMID: 34638713 PMCID: PMC8508925 DOI: 10.3390/ijms221910372] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 09/20/2021] [Accepted: 09/21/2021] [Indexed: 01/10/2023] Open
Abstract
The NO-cGMP signal transduction pathway plays a crucial role in tone regulation in hepatic sinusoids and peripheral blood vessels. In a cirrhotic liver, the key enzymes endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and phosphodiesterase-5 (PDE-5) are overexpressed, leading to decreased cyclic guanosine-monophosphate (cGMP). This results in constriction of hepatic sinusoids, contributing about 30% of portal pressure. In contrast, in peripheral arteries, dilation prevails with excess cGMP due to low PDE-5. Both effects eventually lead to circulatory dysfunction in progressed liver cirrhosis. The conventional view of portal hypertension (PH) pathophysiology has been described using the "NO-paradox", referring to reduced NO availability inside the liver and elevated NO production in the peripheral systemic circulation. However, recent data suggest that an altered availability of cGMP could better elucidate the contrasting findings of intrahepatic vasoconstriction and peripheral systemic vasodilation than mere focus on NO availability. Preclinical and clinical data have demonstrated that targeting the NO-cGMP pathway in liver cirrhosis using PDE-5 inhibitors or sGC stimulators/activators decreases intrahepatic resistance through dilation of sinusoids, lowering portal pressure, and increasing portal venous blood flow. These results suggest further clinical applications in liver cirrhosis. Targeting the NO-cGMP system plays a role in possible reversal of liver fibrosis or cirrhosis. PDE-5 inhibitors may have therapeutic potential for hepatic encephalopathy. Serum/plasma levels of cGMP can be used as a non-invasive marker of clinically significant portal hypertension. This manuscript reviews new data about the role of the NO-cGMP signal transduction system in pathophysiology of cirrhotic portal hypertension and provides perspective for further studies.
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Affiliation(s)
- Wolfgang Kreisel
- Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany
| | - Adhara Lazaro
- Institute for Exercise and Occupational Medicine, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany; (A.L.); (P.D.)
| | - Jonel Trebicka
- Translational Hepatology, Department of Internal Medicine I, Goethe University Clinic Frankfurt, 60590 Frankfurt, Germany;
| | - Markus Grosse Perdekamp
- Institute of Forensic Medicine, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany;
| | | | - Peter Deibert
- Institute for Exercise and Occupational Medicine, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany; (A.L.); (P.D.)
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