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Chen DF, Farrque M, Karakis I, Gupta N, Rodriguez Ruiz A, Kandiah P. Continuous Electroencephalography in Acute Liver Failure: Findings and Prognostic Value. Neurocrit Care 2025:10.1007/s12028-025-02216-1. [PMID: 39920548 DOI: 10.1007/s12028-025-02216-1] [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: 06/19/2024] [Accepted: 01/13/2025] [Indexed: 02/09/2025]
Abstract
BACKGROUND Neurologic complications contribute significantly to morbidity and mortality in acute liver failure (ALF). However, clinical assessment of neurologic function in this population is often challenging. Continuous electroencephalography (cEEG) is a low-risk, noninvasive diagnostic tool that can monitor real-time cerebral function. We aimed to investigate cEEG findings and prognostic significance of specific EEG features in a cohort of strictly defined patients with ALF. METHODS This was a retrospective, single-center study of adult patients with ALF who underwent cEEG monitoring for at least 6 h between 2013 and 2022. Clinical, laboratory, imaging, and treatment characteristics were evaluated. cEEG variables included background continuity, background frequency, the presence of sporadic epileptiform discharges, rhythmic or periodic patterns, and electrographic or electroclinical seizures. The primary outcome was mortality or transition to end-of-life care during the index admission. RESULTS A total of 32 patients with ALF were included. 56.3% of patients had rhythmic or periodic patterns, of which the majority were generalized periodic discharges (37.5%). 12.5% of patients had sporadic epileptiform discharges, and 6.3% of patients demonstrated electrographic or clinical seizures. Eighteen (56.3%) patients died or were transitioned to end-of-life care during the index admission. Worsening background continuity or frequency over the course of the cEEG recording was significantly associated with poor outcome (p = 0.001, p = 0.007, respectively), with a 100% mortality rate in patients demonstrating these EEG trends. A worst recorded continuity of suppression, attenuation, and burst-suppression was also associated with poor outcome (p = 0.012). The presence of rhythmic or periodic patterns, sporadic epileptiform discharges, or seizures was not predictive of outcome. CONCLUSIONS Worsening cEEG background continuity or frequency is associated with poor outcome in adults with ALF. cEEG may contribute useful prognostic information in these patients, in conjunction with other laboratory and clinical markers of disease severity.
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Affiliation(s)
- Denise F Chen
- Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
| | - Mirza Farrque
- Department of Neurocritical Care, Emory University School of Medicine, Atlanta, GA, USA
| | - Ioannis Karakis
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA
- Department of Neurology, University of Crete School of Medicine, Heraklion, Greece
| | - Navnika Gupta
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA
| | | | - Prem Kandiah
- Department of Neurocritical Care, Emory University School of Medicine, Atlanta, GA, USA
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Oyelade T, Moore KP, Mani AR. Physiological network approach to prognosis in cirrhosis: A shifting paradigm. Physiol Rep 2024; 12:e16133. [PMID: 38961593 PMCID: PMC11222171 DOI: 10.14814/phy2.16133] [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: 04/30/2024] [Revised: 06/12/2024] [Accepted: 06/24/2024] [Indexed: 07/05/2024] Open
Abstract
Decompensated liver disease is complicated by multi-organ failure and poor prognosis. The prognosis of patients with liver failure often dictates clinical management. Current prognostic models have focused on biomarkers considered as individual isolated units. Network physiology assesses the interactions among multiple physiological systems in health and disease irrespective of anatomical connectivity and defines the influence or dependence of one organ system on another. Indeed, recent applications of network mapping methods to patient data have shown improved prediction of response to therapy or prognosis in cirrhosis. Initially, different physical markers have been used to assess physiological coupling in cirrhosis including heart rate variability, heart rate turbulence, and skin temperature variability measures. Further, the parenclitic network analysis was recently applied showing that organ systems connectivity is impaired in patients with decompensated cirrhosis and can predict mortality in cirrhosis independent of current prognostic models while also providing valuable insights into the associated pathological pathways. Moreover, network mapping also predicts response to intravenous albumin in patients hospitalized with decompensated cirrhosis. Thus, this review highlights the importance of evaluating decompensated cirrhosis through the network physiologic prism. It emphasizes the limitations of current prognostic models and the values of network physiologic techniques in cirrhosis.
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Affiliation(s)
- Tope Oyelade
- Institute for Liver and Digestive Health, Division of MedicineUCLLondonUK
- Network Physiology Laboratory, Division of MedicineUCLLondonUK
| | - Kevin P. Moore
- Institute for Liver and Digestive Health, Division of MedicineUCLLondonUK
| | - Ali R. Mani
- Institute for Liver and Digestive Health, Division of MedicineUCLLondonUK
- Network Physiology Laboratory, Division of MedicineUCLLondonUK
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Abid NUH, Lum Cheng In T, Bottaro M, Shen X, Hernaez Sanz I, Yoshida S, Formentin C, Montagnese S, Mani AR. Application of short-term analysis of skin temperature variability in prediction of survival in patients with cirrhosis. FRONTIERS IN NETWORK PHYSIOLOGY 2024; 3:1291491. [PMID: 38250541 PMCID: PMC10796461 DOI: 10.3389/fnetp.2023.1291491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 12/12/2023] [Indexed: 01/23/2024]
Abstract
Background: Liver cirrhosis is a complex disorder, involving several different organ systems and physiological network disruption. Various physiological markers have been developed for survival modelling in patients with cirrhosis. Reduction in heart rate variability and skin temperature variability have been shown to predict mortality in cirrhosis, with the potential to aid clinical prognostication. We have recently reported that short-term skin temperature variability analysis can predict survival independently of the severity of liver failure in cirrhosis. However, in previous reports, 24-h skin temperature recordings were used, which are often not feasible in the context of routine clinical practice. The purpose of this study was to determine the shortest length of time from 24-h proximal temperature recordings that can accurately and independently predict 12-month survival post-recording in patients with cirrhosis. Methods: Forty individuals diagnosed with cirrhosis participated in this study and wireless temperature sensors (iButtons) were used to record patients' proximal skin temperature. From 24-h temperature recordings, different length of recordings (30 min, 1, 2, 3 and 6 h) were extracted sequentially for temperature variability analysis using the Extended Poincaré plot to quantify both short-term (SD1) and long-term (SD2) variability. These patients were then subsequently followed for a period of 12 months, during which data was gathered concerning any cases of mortality. Results: Cirrhosis was associated with significantly decreased proximal skin temperature fluctuations among individuals who did not survive, across all durations of daytime temperature recordings lasting 1 hour or more. Survival analysis showcased 1-h daytime proximal skin temperature time-series to be significant predictors of survival in cirrhosis, whereby SD2, was found to be independent to the Model for End-Stage Liver Disease (MELD) score and thus, the extent of disease severity. As expected, longer durations of time-series were also predictors of mortality for the majority of the temperature variability indices. Conclusion: Crucially, this study suggests that 1-h proximal skin temperature recordings are sufficient in length to accurately predict 12-month survival in patients with cirrhosis, independent from current prognostic indicators used in the clinic such as MELD.
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Affiliation(s)
- Noor-Ul-Hoda Abid
- Network Physiology Laboratory, Division of Medicine, UCL, London, United Kingdom
- UCL Medical School, UCL, London, United Kingdom
| | - Travis Lum Cheng In
- Network Physiology Laboratory, Division of Medicine, UCL, London, United Kingdom
| | - Matteo Bottaro
- Department of Medicine, University of Padova, Padova, Italy
| | - Xinran Shen
- Network Physiology Laboratory, Division of Medicine, UCL, London, United Kingdom
| | - Iker Hernaez Sanz
- Network Physiology Laboratory, Division of Medicine, UCL, London, United Kingdom
| | - Satoshi Yoshida
- Network Physiology Laboratory, Division of Medicine, UCL, London, United Kingdom
| | | | - Sara Montagnese
- Department of Medicine, University of Padova, Padova, Italy
- Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
| | - Ali R. Mani
- Network Physiology Laboratory, Division of Medicine, UCL, London, United Kingdom
- Institute for Liver and Digestive Health (ILDH), Division of Medicine, UCL, London, United Kingdom
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Torre A, Cisneros-Garza LE, Castillo-Barradas M, Navarro-Alvarez N, Sandoval-Salas R, González-Huezo MS, Pérez-Hernández JL, Méndez-Guerrero O, Ruiz-Manríquez JA, Trejo-Estrada R, Chavez-Tapia NC, Solís-Gasca LC, Moctezuma-Velázquez C, Aguirre-Valádez J, Flores-Calderón J, Higuera-de-la-Tijera F, García-Juárez I, Canedo-Castillo NA, Malé-Velázquez R, Montalvo-Gordon I, Vilatobá M, Márquez-Guillén E, Córdova-Gallardo J, Flores-García NC, Miranda-Zazueta G, Martínez-Saldívar BI, Páez-Zayas VM, Muñoz-Espinosa LE, Solís-Galindo FA. Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology. Ann Hepatol 2023; 28:101140. [PMID: 37482299 DOI: 10.1016/j.aohep.2023.101140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/26/2023] [Accepted: 05/31/2023] [Indexed: 07/25/2023]
Abstract
Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.
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Affiliation(s)
- Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
| | - Laura Esthela Cisneros-Garza
- Gastroenterology and Hepatology Department, Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - Nalu Navarro-Alvarez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Osvely Méndez-Guerrero
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Luis Carlos Solís-Gasca
- Gastroenterology Department, Hospital General de Zona #12 Benito Juárez del Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico
| | - Carlos Moctezuma-Velázquez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Medicine - Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | | | - Judith Flores-Calderón
- Pediatrics Department, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | | | - Ignacio García-Juárez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Iaarah Montalvo-Gordon
- Clinic of Gastrointestinal and Hepatic Specialties, Hospital Faro del Mayab, Mérida, Yucatán, Mexico
| | - Mario Vilatobá
- Transplant Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Ernesto Márquez-Guillén
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Hospital Ángeles del Pedregal, Mexico City, Mexico
| | - Jacqueline Córdova-Gallardo
- Hepatology Department - General Surgery Service, Hospital General Dr. Manuel Gea González, Mexico City, Mexico
| | - Nayeli Cointa Flores-García
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Godolfino Miranda-Zazueta
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Linda Elsa Muñoz-Espinosa
- Universidad Autónoma de Nuevo León. Liver Unit, Department of Internal Medicine, University Hospital 'Dr. José E. González', Monterrey, Nuevo León, Mexico
| | - Francisco Alfonso Solís-Galindo
- Gastroenterology Department, Unidad Médica de Alta Especialidad # 71 Instituto Mexicano del Seguro Social, Torreón, Coahuila, Mexico
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Rubinos C, Bruzzone MJ, Viswanathan V, Figueredo L, Maciel CB, LaRoche S. Electroencephalography as a Biomarker of Prognosis in Acute Brain Injury. Semin Neurol 2023; 43:675-688. [PMID: 37832589 DOI: 10.1055/s-0043-1775816] [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: 10/15/2023]
Abstract
Electroencephalography (EEG) is a noninvasive tool that allows the monitoring of cerebral brain function in critically ill patients, aiding with diagnosis, management, and prognostication. Specific EEG features have shown utility in the prediction of outcomes in critically ill patients with status epilepticus, acute brain injury (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage, and traumatic brain injury), anoxic brain injury, and toxic-metabolic encephalopathy. Studies have also found an association between particular EEG patterns and long-term functional and cognitive outcomes as well as prediction of recovery of consciousness following acute brain injury. This review summarizes these findings and demonstrates the value of utilizing EEG findings in the determination of prognosis.
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Affiliation(s)
- Clio Rubinos
- Department of Neurology, University of North Carolina, Chapel Hill, North Carolina
| | | | - Vyas Viswanathan
- Department of Neurology, University of North Carolina, Chapel Hill, North Carolina
| | - Lorena Figueredo
- Department of Neurology, University of Florida, Gainesville, Florida
| | - Carolina B Maciel
- Department of Neurology, University of Florida, Gainesville, Florida
| | - Suzette LaRoche
- Department of Neurology, University of North Carolina, Chapel Hill, North Carolina
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Riggio O, Celsa C, Calvaruso V, Merli M, Caraceni P, Montagnese S, Mora V, Milana M, Saracco GM, Raimondo G, Benedetti A, Burra P, Sacco R, Persico M, Schepis F, Villa E, Colecchia A, Fagiuoli S, Pirisi M, Barone M, Azzaroli F, Soardo G, Russello M, Morisco F, Labanca S, Fracanzani AL, Pietrangelo A, Di Maria G, Nardelli S, Ridola L, Gasbarrini A, Cammà C. Hepatic encephalopathy increases the risk for mortality and hospital readmission in decompensated cirrhotic patients: a prospective multicenter study. Front Med (Lausanne) 2023; 10:1184860. [PMID: 37305121 PMCID: PMC10248517 DOI: 10.3389/fmed.2023.1184860] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Accepted: 04/28/2023] [Indexed: 06/13/2023] Open
Abstract
INTRODUCTION Hepatic encephalopathy (HE) affects the survival and quality of life of patients with cirrhosis. However, longitudinal data on the clinical course after hospitalization for HE are lacking. The aim was to estimate mortality and risk for hospital readmission of cirrhotic patients hospitalized for HE. METHODS We prospectively enrolled 112 consecutive cirrhotic patients hospitalized for HE (HE group) at 25 Italian referral centers. A cohort of 256 patients hospitalized for decompensated cirrhosis without HE served as controls (no HE group). After hospitalization for HE, patients were followed-up for 12 months until death or liver transplant (LT). RESULTS During follow-up, 34 patients (30.4%) died and 15 patients (13.4%) underwent LT in the HE group, while 60 patients (23.4%) died and 50 patients (19.5%) underwent LT in the no HE group. In the whole cohort, age (HR 1.03, 95% CI 1.01-1.06), HE (HR 1.67, 95% CI 1.08-2.56), ascites (HR 2.56, 95% CI 1.55-4.23), and sodium levels (HR 0.94, 95% CI 0.90-0.99) were significant risk factors for mortality. In the HE group, ascites (HR 5.07, 95% CI 1.39-18.49) and BMI (HR 0.86, 95% CI 0.75-0.98) were risk factors for mortality, and HE recurrence was the first cause of hospital readmission. CONCLUSION In patients hospitalized for decompensated cirrhosis, HE is an independent risk factor for mortality and the most common cause of hospital readmission compared with other decompensation events. Patients hospitalized for HE should be evaluated as candidates for LT.
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Affiliation(s)
- Oliviero Riggio
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
- Department of Gastroenterology, “Santa Maria Goretti” Hospital, “Sapienza” Polo Pontino, Latina, Italy
| | - Ciro Celsa
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Paolo Caraceni
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, Center for Biomedical Applied Research, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | | | - Vincenzina Mora
- Medicina Interna e Gastroenterologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Martina Milana
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome, Italy
| | - Giorgio Maria Saracco
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Antonio Benedetti
- Department of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy
| | - Patrizia Burra
- Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Rodolfo Sacco
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, Salerno, Italy
| | - Filippo Schepis
- Gastroenterology Unit, Department of Medical Specialities, University Hospital of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Erica Villa
- Gastroenterology Unit, Department of Medical Specialities, University Hospital of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Medical Specialities, University Hospital of Modena, University of Modena and Reggio Emilia, Modena, Italy
- Unit of Gastroenterology, Borgo Trento University Hospital, Verona, Italy
| | - Stefano Fagiuoli
- Gastroentyerology, University of Milan Bicocca, Milan, Italy
- Gastroenterology, Hepatology and Transplantation Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Internal Medicine Unit, Azienda Ospedaliera Universitaria (AOU) Maggiore della Carità Hospital, Novara, Italy
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, Bari, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Department of Surgical and Medical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giorgio Soardo
- Clinic of Internal Medicine-Liver Unit, Department of Medical Area (DAME), University of Udine, Udine, Italy
- Italian Liver Foundation, Area Science Park, Trieste, Italy
| | - Maurizio Russello
- Liver Unit, Azienda di Rilievo Nazionale ed Alta Specializzazione (ARNAS) Garibaldi-Nesima, Catania, Italy
| | - Filomena Morisco
- Gastroenterology and Hepatology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy
| | - Sara Labanca
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Anna Ludovica Fracanzani
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonello Pietrangelo
- Department of Internal and Emergency Medicine, University Hospital of Modena, Modena, Italy
| | - Gabriele Di Maria
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Calogero Cammà
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
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King JJ, Halliday N, Mantovani A, Gerussi A, Wey EQ, Tan J, Ryan J, Patch D, Tsochatzis E, Westbrook RH. Bacterascites confers poor patient prognosis beyond MELD prediction. Liver Transpl 2023; 29:356-364. [PMID: 36691984 DOI: 10.1097/lvt.0000000000000068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 11/18/2022] [Indexed: 01/25/2023]
Abstract
Spontaneous bacterial peritonitis (SBP) is a well-recognized clinical entity with a poor prognosis. In comparison, the prevalence, microbiological flora, and prognostic significance of bacterascites (BA) (the presence of organism on culture but ascitic PMN <250 cells/mm³) is largely unknown. We, therefore, assessed the prognosis and predictors of outcome in patients with BA in comparison with those with SBP. Ascitic fluid cultures from consecutive patients with cirrhosis from 2008 to 2018 were reviewed retrospectively, and patients with SBP and BA were identified. Baseline demographic, laboratory, and microbiological data were collated and analyzed as prognostic indicators, and clinical outcomes were recorded. Patients were censored at the time of LT, death, or last follow-up. For this study 176 and 213 cases of SBP and BA, respectively, were identified and included. Patients with SBP had significantly higher Model for End-Stage Liver Disease (MELD) ( p =<0.01), peripheral blood WCC ( p < 0.01), and higher rates of Enterobacteriaceae ( p < 0.01) and multi-drug resistant pathogens ( p < 0.01). Survival at 1 and 3 months was lower in patients with SBP ( p < 0.01) when compared with BA but at 6 months and beyond, no significant difference remained. After the exclusion of deaths within 30 days of presentation, survival between SBP and BA was equivocal at all time points. Mortality was substantially higher across all MELD groupings for both SBP and BA when compared with the predicted mortality calculated by the MELD score alone. BA has a negative impact on patient survival above that predicted by the MELD score. It has similar impact to SBP on patient survival beyond 1 month suggesting it should be seen as a poor prognostic marker and prompt consideration of LT where appropriate. Further studies evaluating the role of secondary prophylaxis in this group are required.
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Affiliation(s)
- Ji Jade King
- The Royal Free Hospital, Sheila Sherlock Liver Centre, Pond Street, London, UK
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Vidal-Cevallos P, Chávez-Tapia NC, Uribe M. Current approaches to hepatic encephalopathy. Ann Hepatol 2022; 27:100757. [PMID: 36115576 DOI: 10.1016/j.aohep.2022.100757] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 09/07/2022] [Indexed: 02/04/2023]
Abstract
Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunts. Between 30%-40% of patients with cirrhosis will present overt HE during their lifetime. While the pathophysiology of HE is not entirely understood, three critical factors have been identified: hyperammonaemia, systemic inflammation and oxidative stress by glutaminase gene alterations. Minimal HE is defined by the presence of signs of cognitive abnormalities in a patient without asterixis or disorientation; it can only be diagnosed with neuropsychological or psychometric tests. The diagnosis of overt HE is based on clinical examination with clinical scales. Currently, only overt HE should be routinely treated. The aims of treatment in an acute episode should be to improve the mental status, identify and treat the precipitating factor, reduce duration and limit consequences. Treatment strategies are targeted at reducing ammonia production and/or increasing its elimination. Even though minimal HE has negative effects on the patient's quality of life and effects on prognosis, indications for treatment are still controversial. There are still many unanswered questions regarding the pathophysiology and management of HE. We should also endeavor to develop more accurate and objective diagnostic methods for overt HE that would permit early detection and help improve outcomes on quality of life and economic burden.
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Affiliation(s)
- Paulina Vidal-Cevallos
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico
| | - Norberto C Chávez-Tapia
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico
| | - Misael Uribe
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico.
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9
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Buchhalter J, Neuray C, Cheng JY, D’Cruz O, Datta AN, Dlugos D, French J, Haubenberger D, Hulihan J, Klein P, Komorowski RW, Kramer L, Lothe A, Nabbout R, Perucca E, der Ark PV. EEG Parameters as Endpoints in Epilepsy Clinical Trials- An Expert Panel Opinion Paper. Epilepsy Res 2022; 187:107028. [DOI: 10.1016/j.eplepsyres.2022.107028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 08/29/2022] [Accepted: 09/26/2022] [Indexed: 11/30/2022]
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10
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Montagnese S, Rautou PE, Romero-Gómez M, Larsen FS, Shawcross DL, Thabut D, Vilstrup H, Weissenborn K. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol 2022; 77:807-824. [PMID: 35724930 DOI: 10.1016/j.jhep.2022.06.001] [Citation(s) in RCA: 178] [Impact Index Per Article: 59.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 06/01/2022] [Indexed: 12/12/2022]
Abstract
The EASL Clinical Practice Guidelines (CPGs) on the management of hepatic encephalopathy (HE) present evidence-based answers to a set of relevant questions (where possible, formulated in PICO [patient/population, intervention, comparison and outcomes] format) on the definition, diagnosis, differential diagnosis and treatment of HE. The document does not cover the pathophysiology of HE and does not cover all available treatment options. The methods through which it was developed and any information relevant to its interpretation are also provided.
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11
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Abid N, Mani AR. The mechanistic and prognostic implications of heart rate variability analysis in patients with cirrhosis. Physiol Rep 2022; 10:e15261. [PMID: 35439350 PMCID: PMC9017982 DOI: 10.14814/phy2.15261] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/19/2022] [Accepted: 03/23/2022] [Indexed: 06/14/2023] Open
Abstract
Chronic liver damage leads to scarring of the liver tissue and ultimately a systemic illness known as cirrhosis. Patients with cirrhosis exhibit multi-organ dysfunction and high mortality. Reduced heart rate variability (HRV) is a hallmark of cirrhosis, reflecting a state of defective cardiovascular control and physiological network disruption. Several lines of evidence have revealed that decreased HRV holds prognostic information and can predict survival of patients independent of the severity of liver disease. Thus, the aim of this review is to shed light on the mechanistic and prognostic implications of HRV analysis in patients with cirrhosis. Notably, several studies have extensively highlighted the critical role systemic inflammation elicits in conferring the reduction in patients' HRV. It appears that IL-6 is likely to play a central mechanistic role, whereby its levels also correlate with manifestations, such as autonomic neuropathy and hence the partial uncoupling of the cardiac pacemaker from autonomic control. Reduced HRV has also been reported to be highly correlated with the severity of hepatic encephalopathy, potentially through systemic inflammation affecting specific brain regions, involved in both cognitive function and autonomic regulation. In general, the prognostic ability of HRV analysis holds immense potential in improving survival rates for patients with cirrhosis, as it may indeed be added to current prognostic indicators, to ultimately increase the accuracy of selecting the recipient most in need of liver transplantation. However, a network physiology approach in the future is critical to delineate the exact mechanistic basis by which decreased HRV confers poor prognosis.
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Affiliation(s)
- Noor‐Ul‐Hoda Abid
- Network Physiology LabDivision of MedicineUCLLondonUK
- Lancaster Medical SchoolLancaster UniversityLancasterUK
| | - Ali R. Mani
- Network Physiology LabDivision of MedicineUCLLondonUK
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12
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Zhang H, Oyelade T, Moore KP, Montagnese S, Mani AR. Prognosis and Survival Modelling in Cirrhosis Using Parenclitic Networks. FRONTIERS IN NETWORK PHYSIOLOGY 2022; 2:833119. [PMID: 36926100 PMCID: PMC10013061 DOI: 10.3389/fnetp.2022.833119] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 02/07/2022] [Indexed: 12/12/2022]
Abstract
Background: Liver cirrhosis involves multiple organ systems and has a high mortality. A network approach to complex diseases often reveals the collective system behaviours and intrinsic interactions between organ systems. However, mapping the functional connectivity for each individual patient has been challenging due to the lack of suitable analytical methods for assessment of physiological networks. In the present study we applied a parenclitic approach to assess the physiological network of each individual patient from routine clinical/laboratory data available. We aimed to assess the value of the parenclitic networks to predict survival in patients with cirrhosis. Methods: Parenclitic approach creates a network from the perspective of an individual subject in a population. In this study such an approach was used to measure the deviation of each individual patient from the existing network of physiological interactions in a reference population of patients with cirrhosis. 106 patients with cirrhosis were retrospectively enrolled and followed up for 12 months. Network construction and analysis were performed using data from seven clinical/laboratory variables (serum albumin, bilirubin, creatinine, ammonia, sodium, prothrombin time and hepatic encephalopathy) for calculation of parenclitic deviations. Cox regression was used for survival analysis. Result: Initial network analysis indicated that correlation between five clinical/laboratory variables can distinguish between survivors and non-survivors in this cohort. Parenclitic deviations along albumin-bilirubin (Hazard ratio = 1.063, p < 0.05) and albumin-prothrombin time (Hazard ratio = 1.138, p < 0.05) predicted 12-month survival independent of model for end-stage liver disease (MELD). Combination of MELD with the parenclitic measures could predict survival better than MELD alone. Conclusion: The parenclitic network approach can predict survival of patients with cirrhosis and provides pathophysiologic insight on network disruption in chronic liver disease.
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Affiliation(s)
- Han Zhang
- Network Physiology Laboratory, Division of Medicine, University College London, London, United Kingdom
| | - Tope Oyelade
- Network Physiology Laboratory, Division of Medicine, University College London, London, United Kingdom.,Institute for Liver and Digestive Health, Division of Medicine, University College London, London, United Kingdom
| | - Kevin P Moore
- Institute for Liver and Digestive Health, Division of Medicine, University College London, London, United Kingdom
| | | | - Ali R Mani
- Network Physiology Laboratory, Division of Medicine, University College London, London, United Kingdom.,Institute for Liver and Digestive Health, Division of Medicine, University College London, London, United Kingdom
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13
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Schmid W, Fan Y, Chi T, Golanov E, Regnier-Golanov AS, Austerman RJ, Podell K, Cherukuri P, Bentley T, Steele CT, Schodrof S, Aazhang B, Britz GW. Review of wearable technologies and machine learning methodologies for systematic detection of mild traumatic brain injuries. J Neural Eng 2021; 18. [PMID: 34330120 DOI: 10.1088/1741-2552/ac1982] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/30/2021] [Indexed: 12/16/2022]
Abstract
Mild traumatic brain injuries (mTBIs) are the most common type of brain injury. Timely diagnosis of mTBI is crucial in making 'go/no-go' decision in order to prevent repeated injury, avoid strenuous activities which may prolong recovery, and assure capabilities of high-level performance of the subject. If undiagnosed, mTBI may lead to various short- and long-term abnormalities, which include, but are not limited to impaired cognitive function, fatigue, depression, irritability, and headaches. Existing screening and diagnostic tools to detect acute andearly-stagemTBIs have insufficient sensitivity and specificity. This results in uncertainty in clinical decision-making regarding diagnosis and returning to activity or requiring further medical treatment. Therefore, it is important to identify relevant physiological biomarkers that can be integrated into a mutually complementary set and provide a combination of data modalities for improved on-site diagnostic sensitivity of mTBI. In recent years, the processing power, signal fidelity, and the number of recording channels and modalities of wearable healthcare devices have improved tremendously and generated an enormous amount of data. During the same period, there have been incredible advances in machine learning tools and data processing methodologies. These achievements are enabling clinicians and engineers to develop and implement multiparametric high-precision diagnostic tools for mTBI. In this review, we first assess clinical challenges in the diagnosis of acute mTBI, and then consider recording modalities and hardware implementation of various sensing technologies used to assess physiological biomarkers that may be related to mTBI. Finally, we discuss the state of the art in machine learning-based detection of mTBI and consider how a more diverse list of quantitative physiological biomarker features may improve current data-driven approaches in providing mTBI patients timely diagnosis and treatment.
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Affiliation(s)
- William Schmid
- Department of Electrical and Computer Engineering and Neuroengineering Initiative (NEI), Rice University, Houston, TX 77005, United States of America
| | - Yingying Fan
- Department of Electrical and Computer Engineering and Neuroengineering Initiative (NEI), Rice University, Houston, TX 77005, United States of America
| | - Taiyun Chi
- Department of Electrical and Computer Engineering and Neuroengineering Initiative (NEI), Rice University, Houston, TX 77005, United States of America
| | - Eugene Golanov
- Department of Neurosurgery, Houston Methodist Hospital, Houston, TX 77030, United States of America
| | | | - Ryan J Austerman
- Department of Neurosurgery, Houston Methodist Hospital, Houston, TX 77030, United States of America
| | - Kenneth Podell
- Department of Neurology, Houston Methodist Hospital, Houston, TX 77030, United States of America
| | - Paul Cherukuri
- Institute of Biosciences and Bioengineering (IBB), Rice University, Houston, TX 77005, United States of America
| | - Timothy Bentley
- Office of Naval Research, Arlington, VA 22203, United States of America
| | - Christopher T Steele
- Military Operational Medicine Research Program, US Army Medical Research and Development Command, Fort Detrick, MD 21702, United States of America
| | - Sarah Schodrof
- Department of Athletics-Sports Medicine, Rice University, Houston, TX 77005, United States of America
| | - Behnaam Aazhang
- Department of Electrical and Computer Engineering and Neuroengineering Initiative (NEI), Rice University, Houston, TX 77005, United States of America
| | - Gavin W Britz
- Department of Neurosurgery, Houston Methodist Hospital, Houston, TX 77030, United States of America
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14
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Long L, Li H, Deng G, Wang X, Lu S, Li B, Meng Z, Gao Y, Qian Z, Liu F, Lu X, Ren H, Shang J, Li H, Wang S, Zheng Y, Yan H, Yin S, Tan W, Zhang Q, Zheng X, Chen J, Luo S, Zhao J, Yuan W, Li T, Zheng R, Liu J, Liu X, Gu W, Li S, Mei X, Chen R, Huang Y. Impact of Hepatic Encephalopathy on Clinical Characteristics and Adverse Outcomes in Prospective and Multicenter Cohorts of Patients With Acute-on-Chronic Liver Diseases. Front Med (Lausanne) 2021; 8:709884. [PMID: 34409052 PMCID: PMC8365160 DOI: 10.3389/fmed.2021.709884] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/07/2021] [Indexed: 12/18/2022] Open
Abstract
Importance: Hepatic encephalopathy is a severe complication, and its contribution to clinical adverse outcomes in patients with acute-on-chronic liver diseases from the East is unclear. Objective: We aimed to investigate the impact of hepatic encephalopathy on clinical characteristics and adverse outcomes in prospective and multicenter cohorts of patients with acute-on-chronic liver diseases. Design: We conducted a cohort study of two multicenter prospective cohorts. Setting: China. Participants: Acute-on-chronic liver disease patients with various etiologies. Exposure: The diagnosis and severity of hepatic encephalopathy were assessed using the West Haven scale. Main Outcome Measure: The correlation between clinical adverse outcomes and varying hepatic encephalopathy grades was analyzed in the target patients. Results: A total of 3,949 patients were included, and 340 of them had hepatic encephalopathy. The incidence of hepatic encephalopathy was higher in patients with alcohol consumption (9.90%) than in those with hepatitis B virus infection (6.17%). The incidence of 28- and 90-day adverse outcomes increased progressively from hepatic encephalopathy grades 1-4. Logistic regression analysis revealed that hepatic encephalopathy grades 3 and 4 were independent risk factors for the 28- and 90-day adverse outcome in the fully adjusted model IV. Stratified analyses showed similar results in the different subgroups. Compared to grades 1-2 and patients without hepatic encephalopathy, those with grade 3 hepatic encephalopathy had a significant increase in clinical adverse outcomes, independent of other organ failures. Conclusions and Relevance: Hepatic encephalopathy grades 3-4 were independent risk factors for 28- and 90-day adverse outcomes. Hepatic encephalopathy grade 3 could be used as an indicator of brain failure in patients with acute-on-chronic liver disease.
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Affiliation(s)
- Liyuan Long
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Hai Li
- Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
- Key Laboratory of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
| | - Guohong Deng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xianbo Wang
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Sihong Lu
- Department of Infectious Diseases, Institute of Infection and Immunology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Beiling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhongji Meng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yanhang Gao
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Zhiping Qian
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Feng Liu
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Hepatology, Tianjin Institute of Hepatology, Nankai University Second People's Hospital, Tianjin, China
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Xiaobo Lu
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Haotang Ren
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Hai Li
- Department of Infectious Diseases, Affiliated Hospital of Logistics University of People's Armed Police Force, Tianjin, China
| | - Shaoyang Wang
- Department of Infectious Diseases, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China
| | - Yubao Zheng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huadong Yan
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Hepatology, Ningbo No. 2 Hospital, Ningbo, China
| | - Shan Yin
- Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
- Key Laboratory of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
| | - Wenting Tan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qun Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xin Zheng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, Institute of Infection and Immunology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Jinjun Chen
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Sen Luo
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Jinming Zhao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Wei Yuan
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Tao Li
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Rongjiong Zheng
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Junping Liu
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Xiaoxiao Liu
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Wenyi Gu
- Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
- Key Laboratory of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
| | - Sumeng Li
- Department of Infectious Diseases, Institute of Infection and Immunology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Xue Mei
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Ruochan Chen
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Yan Huang
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
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15
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Bottaro M, Abid NUH, El-Azizi I, Hallett J, Koranteng A, Formentin C, Montagnese S, Mani AR. Skin temperature variability is an independent predictor of survival in patients with cirrhosis. Physiol Rep 2021; 8:e14452. [PMID: 32562383 PMCID: PMC7305245 DOI: 10.14814/phy2.14452] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 04/22/2020] [Accepted: 04/27/2020] [Indexed: 12/18/2022] Open
Abstract
Background Cirrhosis is a disease with multisystem involvement. It has been documented that patients with cirrhosis exhibit abnormal patterns of fluctuation in their body temperature. However, the clinical significance of this phenomenon is not well understood. The aim of this study was to determine if temperature variability analysis can predict survival in patients with cirrhosis. Methods Thirty eight inpatients with cirrhosis were enrolled in the study. Wireless temperature sensors were used to record patients’ proximal skin temperature for 24 hr. The pattern of proximal temperature fluctuation was assessed using the extended Poincaré plot to measure short‐term and long‐term proximal temperature variability (PTV). Patients were followed up for 12 months, and information was collected on the occurrence of death/liver transplantation. Results During the follow‐up period, 15 patients (39%) died or underwent transplantation for hepatic decompensation. Basal proximal skin temperature absolute values were comparable in survivors and nonsurvivors. However, nonsurvivors showed a significant reduction in both short‐term and long‐term HRV indices. Cox regression analysis showed that both short‐term and long‐term PTV indices could predict survival in these patients. However, only measures of short‐term PTV were shown to be independent of the severity of hepatic failure in predicting survival. Finally, the prognostic value of short‐term PTV was also independent of heart rate variability, that is, a measure of autonomic dysfunction. Conclusion Changes in the pattern of patients’ temperature fluctuations, rather than their absolute values, hold key prognostic information, suggesting that impaired thermoregulation may play an important role in the pathophysiology of cirrhosis.
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Affiliation(s)
- Matteo Bottaro
- Department of Medicine, University of Padova, Padova, Italy
| | | | - Ilias El-Azizi
- Network Physiology Lab, Division of Medicine, UCL, London, UK
| | - Joseph Hallett
- Network Physiology Lab, Division of Medicine, UCL, London, UK
| | - Anita Koranteng
- Network Physiology Lab, Division of Medicine, UCL, London, UK
| | | | | | - Ali R Mani
- Network Physiology Lab, Division of Medicine, UCL, London, UK
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16
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Formentin C, Zarantonello L, Mangini C, Frigo AC, Montagnese S, Merkel C. Clinical, neuropsychological and neurophysiological indices and predictors of hepatic encephalopathy (HE). Liver Int 2021; 41:1070-1082. [PMID: 33411388 DOI: 10.1111/liv.14785] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/30/2020] [Accepted: 01/01/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The occurrence of overt hepatic encephalopathy (HE) marks a significant progression in the natural history of liver disease. The aims of the present study were to: 1) describe a large cohort of patients with cirrhosis in terms of neuropsychological or neurophysiological HE indices, and 2) test if the severity of liver disease and/or any such indices [Psychometric Hepatic Encephalopathy Score (PHES), Scan test, electroencephalography (EEG)] predicted mortality/HE risk in a subgroup of such cohort. METHOD Four hundred and sixty-one patients with cirrhosis (59 ± 10 years; 345 males) were included; information on previous overt HE episodes was available in 407. Follow-up information on mortality/HE-related hospitalization in 134/127 respectively. Information on previous overt HE episodes and both mortality and HE-related hospitalization over the follow-up in 124. RESULTS Patients with a history of overt HE (60%) had poorer liver function, worse neuropsychiatric indices, higher ammonia levels and higher prevalence of portal-systemic shunt. The risk of HE-related hospitalization over the follow-up was higher in patients with higher MELD score and worse Scan performance. Mortality was higher in those with higher MELD. Among patients without a history of overt HE, those with worse PHES had higher HE risk. Among patients with a history, those with higher MELD, better PHES and worse Scan performance had higher HE risk. CONCLUSIONS In patients without previous overt HE episodes, neuropsychological and neurophysiological tests predict HE, while in those with previous overt HE episodes, HE development largely depends on the severity of liver dysfunction.
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Affiliation(s)
- Chiara Formentin
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Lisa Zarantonello
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Chiara Mangini
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Anna C Frigo
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Sara Montagnese
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Carlo Merkel
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
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17
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Burke NT, Maurice JB, Nasralla D, Potts J, Westbrook R. Recent advances in liver transplantation. Frontline Gastroenterol 2021; 13:57-63. [PMID: 34970429 PMCID: PMC8666869 DOI: 10.1136/flgastro-2020-101425] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 10/19/2020] [Accepted: 11/08/2020] [Indexed: 02/04/2023] Open
Abstract
Liver transplant is a life-saving treatment with 1-year and 5-year survival rates of 90% and 70%, respectively. However, organ demand continues to exceed supply, such that many patients will die waiting for an available organ. This article reviews for the general gastroenterologist the latest developments in the field to reduce waiting list mortality and maximise utilisation of available organs. The main areas covered include legislative changes in organ donation and the new 'opt-out' systems being rolled out in the UK, normothermic machine perfusion to optimise marginal grafts, a new national allocation system to maximise benefit from each organ and developments in patient 'prehabilitation' before listing. Current areas of research interest, such as immunosuppression withdrawal, are also summarised.
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Affiliation(s)
- N Thomas Burke
- Hepatology and Liver Transplantation, Royal Free London NHS Foundation Trust, London, London, UK
| | - James B Maurice
- Hepatology and Liver Transplantation, Royal Free London NHS Foundation Trust, London, London, UK
| | - David Nasralla
- Hepatobiliary Surgery, Royal Free London NHS Foundation Trust, London, London, UK
| | - Jonathan Potts
- Hepatology and Liver Transplantation, Royal Free London NHS Foundation Trust, London, London, UK
| | - Rachel Westbrook
- Hepatology and Liver Transplantation, Royal Free London NHS Foundation Trust, London, London, UK
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18
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Huang CH, Tseng HJ, Amodio P, Chen YL, Wang SF, Chang SH, Hsieh SY, Lin CY. Hepatic Encephalopathy and Spontaneous Bacterial Peritonitis Improve Cirrhosis Outcome Prediction: A Modified Seven-Stage Model as a Clinical Alternative to MELD. J Pers Med 2020; 10:186. [PMID: 33105871 PMCID: PMC7711993 DOI: 10.3390/jpm10040186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/11/2020] [Accepted: 10/15/2020] [Indexed: 12/15/2022] Open
Abstract
Classification of cirrhosis based on clinical stages is rapid and based on five stages at present. Two other relevant events, hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP), can be considered in a clinical perspective but no study has implemented a seven-stage classification and confirmed its value before. In addition, long-term validation of the Model for End-Stage Liver Disease (MELD) in large cohorts of patients with cirrhosis and comparison with clinical findings are insufficient. Therefore, we performed a study to address these items. From the Chang-Gung Research Database (CGRD), 20,782 patients with cirrhosis were enrolled for an historical survival study. The MELD score, the five-stage clinical score (i.e., occurrence of esophageal varices (EV), EV bleeding, ascites, sepsis) and a novel seven-stage clinical score (i.e., occurrence of EV, EV bleeding, ascites, sepsis, HE, SBP) were compared with their Cox models by receiver operating characteristic (ROC) analysis. The addition of HE and SBP to the seven-stage model had a 5% better prediction result than the five-stage model did in the survival ROC analysis. The result showed that the seven clinical stages are associated with an increased risk for mortality. However, the predicted performances of the seven-stage model and MELD system are likely equivalent. In conclusion, the study (i) proved that clinical staging of cirrhosis based on seven items/stages had higher prognostic value than the five-stage model and (ii) confirmed the validity of the MELD criteria vs. clinical assessment.
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Affiliation(s)
- Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan; (C.-H.H.); (S.-F.W.); (C.-Y.L.)
- College of Medicine, Chang-Gung University, Taoyuan City 33305, Taiwan;
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan City 33305, Taiwan
| | - Hsiao-Jung Tseng
- Biostatistics Unit, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan;
| | - Piero Amodio
- Department of Medicine, University of Padova, 35122 Padova, Italy;
| | - Yu-Ling Chen
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan;
| | - Sheng-Fu Wang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan; (C.-H.H.); (S.-F.W.); (C.-Y.L.)
| | - Shang-Hung Chang
- College of Medicine, Chang-Gung University, Taoyuan City 33305, Taiwan;
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan;
- Department of Cardiology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan
| | - Sen-Yung Hsieh
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan; (C.-H.H.); (S.-F.W.); (C.-Y.L.)
- College of Medicine, Chang-Gung University, Taoyuan City 33305, Taiwan;
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan; (C.-H.H.); (S.-F.W.); (C.-Y.L.)
- College of Medicine, Chang-Gung University, Taoyuan City 33305, Taiwan;
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19
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Tan YY, Montagnese S, Mani AR. Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure. Front Physiol 2020; 11:983. [PMID: 32848892 PMCID: PMC7422730 DOI: 10.3389/fphys.2020.00983] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 07/20/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND A healthy individual has a high degree of functional connectivity between organ systems, which can be represented graphically in a network map. Disruption of this system connectivity is associated with mortality in life-threatening acute illnesses, demonstrated by a network approach. However, this approach has not been applied to chronic multisystem diseases and may be more reliable than conventional individual organ prognostic scoring methods. Cirrhosis is a chronic disease of the liver with multisystem involvement. Development of an efficient model for prediction of mortality in cirrhosis requires a profound understanding of the pathophysiologic processes that lead to poor prognosis. In the present study, we use a network approach to evaluate the differences in organ system connectivity between survivors and non-survivors in a group of well-characterized patients with cirrhosis. METHODS 201 patients with cirrhosis originally referred to the Clinic five at the University Hospital of Padova, with 13 clinical variables available representing hepatic, metabolic, haematopoietic, immune, neural and renal organ systems were retrospectively enrolled and followed up for 3, 6, and 12 months. Software was designed to compute the correlation network maps of organ system interaction in survivors and non-survivors using analysis indices: A. Bonferroni corrected Pearson's correlation coefficient and B. Mutual Information. Network structure was quantitatively evaluated using the measures of edges, average degree of connectivity and closeness, and qualitatively using clinical significance. Pair-matching was also implemented as a further step after initial general analysis to control for sample size and Model for End-Stage Liver Disease (MELD-Na) score between the groups. RESULTS There was a higher number of significant correlations in survivors, as indicated by both the analysis indices of Bonferroni corrected Pearson's correlation coefficient and the Mutual Information analysis. The number of edges, average degree of connectivity and closeness were significantly higher in survivors compared to non-survivors group. Pair-matching for MELD-Na was also associated with increased connectivity in survivors compared to non-survivors over 3 and 6 months follow up. CONCLUSION This study demonstrates the application of a network approach in evaluating functional connectivity of organ systems in liver cirrhosis, demonstrating a significant degree of network disruption in organ systems in non-survivors. Network analysis of organ systems may provide insight in developing novel prognostic models for organ allocation in patients with cirrhosis.
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Affiliation(s)
- Yen Yi Tan
- Network Physiology Laboratory, UCL Division of Medicine, University College London, London, United Kingdom
| | | | - Ali R. Mani
- Network Physiology Laboratory, UCL Division of Medicine, University College London, London, United Kingdom
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20
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Karanfilian BV, Cheung M, Dellatore P, Park T, Rustgi VK. Laboratory Abnormalities of Hepatic Encephalopathy. Clin Liver Dis 2020; 24:197-208. [PMID: 32245527 DOI: 10.1016/j.cld.2020.01.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Currently, there is no gold standard serologic or imaging modality to detect hepatic encephalopathy (HE). It is a clinical diagnosis gathered from the history and physical. Imaging is nonspecific; however, PET and MRI have shown areas of utility, but are not widely available, cost-efficient, or necessary for diagnosis. Electroencephalogram has shown promise as it can be used in conjunction with the Portal Systemic Hepatic Encephalopathy Score test to diagnose minimal HE. Further research on these techniques would need to be performed to identify strict criteria and cutoffs for diagnosing HE as well as associated sensitivities and specificities.
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Affiliation(s)
- Briette Verken Karanfilian
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA; Department of Medicine, 125 Paterson Street, New Brunswick, NJ 08901, USA
| | - Maggie Cheung
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA; Department of Medicine, 125 Paterson Street, New Brunswick, NJ 08901, USA
| | - Peter Dellatore
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA; Department of Medicine, 125 Paterson Street, New Brunswick, NJ 08901, USA
| | - Taeyang Park
- Department of Internal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA; Department of Medicine, 125 Paterson Street, New Brunswick, NJ 08901, USA
| | - Vinod K Rustgi
- Department Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, 125 Paterson Street, Suite 5100B, New Brunswick, NJ 08901, USA.
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21
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Newey CR, George P, Sarwal A, So N, Hantus S. Electro-Radiological Observations of Grade III/IV Hepatic Encephalopathy Patients with Seizures. Neurocrit Care 2019; 28:97-103. [PMID: 28791561 DOI: 10.1007/s12028-017-0435-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Neurological complications in liver failure are common. Often under-recognized neurological complications are seizures and status epilepticus. These may go unrecognized without continuous electroencephalography (CEEG). We highlight the observed electro-radiological changes in patients with grade III/IV hepatic encephalopathy (HE) found to have seizures and/or status epilepticus on CEEG and the associated neuroimaging. METHODS This study was a retrospective review of patients with West Haven grade III/IV HE and seizures/status epilepticus on CEEG. RESULTS Eleven patients were included. Alcohol was the most common cause of HE (54.5%). All patients were either stuporous/comatose. The most common CEEG pattern was diffuse slowing (100%) followed by generalized periodic discharges (GPDs; 36.4%) and lateralized periodic discharges (LPDs, 36.4%). The subtype of GPDs with triphasic morphology was only seen in 27.3%. All seizures and/or status epilepticus were without clinical signs. Magnetic resonance imaging (MRI) was available in six patients. Cortical hyperintensities on diffusion weighted imaging sequence were seen in all six patients. One patient had CEEG seizure concomitantly with the MRI. Seven patients died prior to discharge. CONCLUSION Seizures or status epilepticus in the setting of HE were without clinical findings and could go unrecognized without CEEG. The finding of cortical hyperintensity on MRI should lead to further evaluation for unrecognized seizure or status epilepticus.
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Affiliation(s)
- Christopher R Newey
- Department of Neurology, University of Missouri, 1 Hospital Drive, Columbia, MO, 65211, USA. .,Neurological Institute, Cerebrovascular Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA.
| | - Pravin George
- Neurological Institute, Cerebrovascular Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA
| | - Aarti Sarwal
- Neurology and Critical Care (Anesthesia), Wake Forest University School of Medicine, Reynolds M, Medical Center Blvd, Winston Salem, NC, 27157, USA
| | - Norman So
- Neurological Institute, Epilepsy Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA
| | - Stephen Hantus
- Neurological Institute, Cerebrovascular Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA.,Neurological Institute, Epilepsy Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA
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22
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Bhogal AS, De Rui M, Pavanello D, El-Azizi I, Rowshan S, Amodio P, Montagnese S, Mani AR. Which heart rate variability index is an independent predictor of mortality in cirrhosis? Dig Liver Dis 2019; 51:695-702. [PMID: 30293892 DOI: 10.1016/j.dld.2018.09.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 08/29/2018] [Accepted: 09/11/2018] [Indexed: 02/09/2023]
Abstract
BACKGROUND Liver cirrhosis is associated with reduced heart rate variability (HRV), which indicates impaired integrity of cardiovascular control in this patient population. There are several different indices for HRV quantification. The present study was designed to: 1) determine which of the HRV indices is best at predicting mortality in patients with cirrhosis; 2) verify if such ability to predict mortality is independent of the severity of hepatic failure. METHODS Ten minutes electrocardiogram was recorded in 74 patients with cirrhosis. Heart rate fluctuations were quantified using statistical, geometrical and non-linear analysis. The patients were followed-up for 18months and information was collected on the occurrence of death/liver transplantation. RESULTS During the follow-up period, 24 patients (32%) died or were transplanted for hepatic decompensation. Cox's regression analysis showed that SDNN (total HRV), cSDNN (corrected SDNN), SD1 (short-term HRV), SD2 (long-terms HRV) and spectral indices could predict survival in these patients. However, only SD2 and cSDNN were shown to be independent of MELD in predicting survival. The prognostic value of HRV indices was independent of age, gender, use of beta blockers, and the aetiology of liver disease. CONCLUSION Two HRV indices were identified that could predict mortality in patients with cirrhosis, independently of MELD. These indices are potentially useful tools for survival prediction.
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Affiliation(s)
- Amar S Bhogal
- Division of Medicine, University College London, London, UK
| | - Michele De Rui
- Department of Medicine, University of Padova, Padova, Italy
| | | | - Ilias El-Azizi
- Division of Medicine, University College London, London, UK
| | - Sadia Rowshan
- Division of Medicine, University College London, London, UK
| | - Piero Amodio
- Department of Medicine, University of Padova, Padova, Italy
| | - Sara Montagnese
- Department of Medicine, University of Padova, Padova, Italy.
| | - Ali R Mani
- Division of Medicine, University College London, London, UK.
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23
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Satti R, Abid NUH, Bottaro M, De Rui M, Garrido M, Raoufy MR, Montagnese S, Mani AR. The Application of the Extended Poincaré Plot in the Analysis of Physiological Variabilities. Front Physiol 2019; 10:116. [PMID: 30837892 PMCID: PMC6390508 DOI: 10.3389/fphys.2019.00116] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 01/30/2019] [Indexed: 01/12/2023] Open
Abstract
The Poincaré plot is a geometrical technique used to visualize and quantify the correlation between two consecutive data points in a time-series. Since the dynamics of fluctuations in physiological rhythms exhibit long-term correlation and memory, this study aimed to extend the Poincaré plot by calculating the correlation between sequential data points in a time-series, rather than between two consecutive points. By incorporating this so-called lag, we hope to integrate a temporal aspect into quantifying the correlation, to depict whether a physiological system holds prolonged association between events separated by time. In doing so, it attempts to instantaneously characterize the intrinsic behavior of a complex system. We tested this hypothesis on three different physiological time-series: heart rate variability in patients with liver cirrhosis, respiratory rhythm in asthma and body temperature fluctuation in patients with cirrhosis, to evaluate the potential application of the extended Poincaré method in clinical practice. When studying the cardiac inter-beat intervals, the extended Poincaré plot revealed a stronger autocorrelation for patients with decompensated liver cirrhosis compared to less severe cases using Pearson's correlation coefficient. In addition, long-term variability (known as SD2 in the extended Poincaré plot) appeared as an independent prognostic variable. This holds significance by acting as a non-invasive tool to evaluate patients with chronic liver disease and potentially facilitate transplant selection as an adjuvant to traditional criteria. For asthmatics, employing the extended Poincaré plot allowed for a non-invasive tool to differentially diagnose various classifications of respiratory disease. In the respiratory inter-breath interval analysis, the receiver operating characteristic (ROC) curve provided evidence that the extension of the Poincaré plot holds a greater advantage in the classification of asthmatic patients, over the traditional Poincaré plot. Lastly, the analysis of body temperature from patients using the extended Poincaré plot helped identify inpatients from outpatients with cirrhosis. Through these analyses, the extended Poincaré plot provided unique and additional information which could potentially make a difference in clinical practice. Conclusively, the potential use of our work lies in its possible application of predicting mortality for the organ allocation procedure in patients with cirrhosis and non-invasively distinguish between atopic and non-atopic asthma.
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Affiliation(s)
- Reem Satti
- UCL Division of Medicine, University College London, London, United Kingdom
| | - Noor-Ul-Hoda Abid
- UCL Division of Medicine, University College London, London, United Kingdom
| | - Matteo Bottaro
- Department of Medicine, University of Padova, Padova, Italy
| | - Michele De Rui
- Department of Medicine, University of Padova, Padova, Italy
| | - Maria Garrido
- Department of Medicine, University of Padova, Padova, Italy
| | | | | | - Ali R. Mani
- UCL Division of Medicine, University College London, London, United Kingdom
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24
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Montagnese S, Russo FP, Amodio P, Burra P, Gasbarrini A, Loguercio C, Marchesini G, Merli M, Ponziani FR, Riggio O, Scarpignato C. Hepatic encephalopathy 2018: A clinical practice guideline by the Italian Association for the Study of the Liver (AISF). Dig Liver Dis 2019; 51:190-205. [PMID: 30606696 DOI: 10.1016/j.dld.2018.11.035] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 11/27/2018] [Accepted: 11/28/2018] [Indexed: 12/11/2022]
Abstract
Hepatic encephalopathy (HE) is a common, worrisome and sometimes difficult to manage complication of end-stage liver disease. HE is often recurrent, requiring multiple hospital admissions. It can have serious implications in terms of a patient's ability to perform complex tasks (for example driving), their earning capacity, their social and family roles. This guideline reviews current knowledge on HE definition, pathophysiology, diagnosis and treatment, both by general principles and by way of a summary of available drugs and treatment strategies. The quality of the published, pertinent evidence is graded, and practical recommendations are made. Where possible, these are placed within the Italian health service context, with reference to local diagnosis and management experience.
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Affiliation(s)
| | | | - Piero Amodio
- Department of Medicine, University of Padova, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Carmela Loguercio
- Department of Clinical and Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Giulio Marchesini
- Unit of Metabolic Diseases & Clinical Dietetics, Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Manuela Merli
- Division of Gastroenterology, Department of Clinical Medicine, La Sapienza University of Rome, Italy
| | - Francesca Romana Ponziani
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Oliviero Riggio
- Division of Gastroenterology, Department of Clinical Medicine, La Sapienza University of Rome, Italy
| | - Carmelo Scarpignato
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Italy
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25
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Amodio P. Hepatic encephalopathy: Diagnosis and management. Liver Int 2018; 38:966-975. [PMID: 29624860 DOI: 10.1111/liv.13752] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 03/28/2018] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE) is a peculiar kind of brain dysfunction caused by liver insufficiency and/or portal-systemic shunting. It is related to gut-derived substances. It is a relevant cause of morbidity and hospitalisation for patients with cirrhosis. The prognosis of HE is important in terms of survival and re-hospitalisation. It is related to impaired quality of life, falls and poor driving; presents a relevant burden for caregivers and health services; and may negatively impact on patient's job and income. Proper diagnosis and classification are expected to improve HE management. Once diagnosed, the management and therapeutic options for HE are generally clear. The improvement of knowledge in recent years has also clarified which are the further aims of research in this field of medicine. Prophylaxis of overt HE should always be performed, and this is generally secondary prophylaxis. Primary prophylaxis should be done immediately after upper gastrointestinal bleeding. Great advances in the detection and treatment of mild forms of HE are expected to lead to further improvement in patient management.
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Affiliation(s)
- Piero Amodio
- Department of Medicine -DIMED- and CIRMANMEC, University of Padova, Padova, Italy
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26
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De Rui M, Montagnese S, Amodio P. Recent developments in the diagnosis and treatment of covert/minimal hepatic encephalopathy. Expert Rev Gastroenterol Hepatol 2016; 10:443-50. [PMID: 26758861 DOI: 10.1586/17474124.2016.1141675] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The terms minimal hepatic encephalopathy and covert hepatic encephalopathy are defined. Clinical assessment is unreliable and both require the use of diagnostic tools. Of these, psychometric tests are the most widely used. They require proper standardization and may be biased by patient cooperation or lack thereof. The measure of the critical flicker frequency and of the electroencephalogram, possibly quantified, are also useful. The alteration of any of them is not strictly parallel in size and may vary from patient to patient. When possible, the use of multiple measures might increase diagnostic reliability. These functional measures should be interpreted within the clinical/biochemical profile of the patient to exclude other disorders. A flow chart for treatment is proposed on the basis of current knowledge.
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Affiliation(s)
- M De Rui
- a Department of Medicine , University of Padua , Padua , Italy
| | - S Montagnese
- a Department of Medicine , University of Padua , Padua , Italy
| | - P Amodio
- a Department of Medicine , University of Padua , Padua , Italy
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27
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Bajaj JS, Kamath PS. The brain gets its say: Hepatic encephalopathy and its evolving role in transplant priority. Liver Transpl 2016; 22:1319-20. [PMID: 27509240 DOI: 10.1002/lt.24521] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Accepted: 07/25/2016] [Indexed: 01/13/2023]
Affiliation(s)
- Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic School of Medicine, Rochester, MN
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28
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Lucidi C, Ginanni Corradini S, Abraldes JG, Merli M, Tandon P, Ferri F, Parlati L, Lattanzi B, Poli E, Di Gregorio V, Farcomeni A, Riggio O. Hepatic encephalopathy expands the predictivity of model for end-stage liver disease in liver transplant setting: Evidence by means of 2 independent cohorts. Liver Transpl 2016; 22:1333-42. [PMID: 27434824 DOI: 10.1002/lt.24517] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 06/13/2016] [Accepted: 06/28/2016] [Indexed: 02/07/2023]
Abstract
Despite its documented prognostic relevance, hepatic encephalopathy (HE) is not considered in liver transplantation (LT) due to its possible poor objectivity. To override this problem, we aimed to analyze if an objective diagnosis of HE may confer additional mortality risk beyond MELD. Study and validation cohorts of patients with cirrhosis were considered in Italy and Canada, respectively. Patients were considered to be HE+ if an episode of overt HE was documented in a hospitalization. Of the 486 patients enrolled in Italy, 184 (38%) were HE+. During the 6-month follow-up, 77 patients died and 50 underwent transplantation. The 6-month mortality of HE+ versus HE- patients was significantly higher (P < 0.001). Model for End-Stage Liver Disease (MELD; subdistribution hazard ratio [sHR], 1.2; 95% confidence interval [CI], 1.1-1.2; P < 0.001), HE+ (sHR, 3.6; 95% CI, 1.8-7.1; P < 0.001), and sodium (sHR, 0.9; 95% CI, 0.8-0.9; P < 0.001) were independent predictors of 6-month mortality. In HE+ patients, short-term mortality increased across the entire MELD spectrum (range, 6-40). The results were unchanged by including or excluding patients with hepatocellular carcinoma or stratifying patients according to HE characteristics. The higher 6-month mortality of HE+ versus HE- patients was confirmed also in the Canadian cohort (P < 0.001; n = 300, 33% HE+; 33 died, 104 transplanted). A similar and statistically significant C-index increase derived by the incorporation of HE in MELD was observed both in the Italian (from 0.67 to 0.75) and Canadian (from 0.69 to 0.74) cohorts. A score based on MELD plus 7 points (95% CI, 4-10) for HE+ patients optimally predicted 6-month mortality in the 2 cohorts. According to the net reclassification index, by not considering HE, 29% of overall patients were misclassified by MELD score. In conclusion, the incorporation of HE in MELD score might improve the listing and allocation policy in LT. Liver Transplantation 22 1333-1342 2016 AASLD.
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Affiliation(s)
- Cristina Lucidi
- Division of Gastroenterology, Department of Clinical Medicine, University of Rome, Rome, Italy
| | | | - Juan G Abraldes
- Cirrhosis Care Clinic, Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Manuela Merli
- Division of Gastroenterology, Department of Clinical Medicine, University of Rome, Rome, Italy
| | - Puneeta Tandon
- Cirrhosis Care Clinic, Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Flaminia Ferri
- Division of Gastroenterology, Department of Clinical Medicine, University of Rome, Rome, Italy
| | - Lucia Parlati
- Division of Gastroenterology, Department of Clinical Medicine, University of Rome, Rome, Italy
| | - Barbara Lattanzi
- Division of Gastroenterology, Department of Clinical Medicine, University of Rome, Rome, Italy
| | - Edoardo Poli
- Division of Gastroenterology, Department of Clinical Medicine, University of Rome, Rome, Italy
| | - Vincenza Di Gregorio
- Division of Gastroenterology, Department of Clinical Medicine, University of Rome, Rome, Italy
| | - Alessio Farcomeni
- Public Health and Infectious Diseases, "Sapienza", University of Rome, Rome, Italy
| | - Oliviero Riggio
- Division of Gastroenterology, Department of Clinical Medicine, University of Rome, Rome, Italy.
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29
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Schiff S, Casa M, Di Caro V, Aprile D, Spinelli G, De Rui M, Angeli P, Amodio P, Montagnese S. A low-cost, user-friendly electroencephalographic recording system for the assessment of hepatic encephalopathy. Hepatology 2016; 63:1651-9. [PMID: 26833704 DOI: 10.1002/hep.28477] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 01/24/2016] [Indexed: 12/22/2022]
Abstract
UNLABELLED Electroencephalography (EEG) is useful to objectively diagnose/grade hepatic encephalopathy (HE) across its spectrum of severity. However, it requires expensive equipment, and hepatogastroenterologists are generally unfamiliar with its acquisition/interpretation. Recent technological advances have led to the development of low-cost, user-friendly EEG systems, allowing EEG acquisition also in settings with limited neurophysiological experience. The aim of this study was to assess the relationship between EEG parameters obtained from a standard-EEG system and from a commercial, low-cost wireless headset (light-EEG) in patients with cirrhosis and varying degrees of HE. Seventy-two patients (58 males, 61 ± 9 years) underwent clinical evaluation, the Psychometric Hepatic Encephalopathy Score (PHES), and EEG recording with both systems. Automated EEG parameters were calculated on two derivations. Strong correlations were observed between automated parameters obtained from the two EEG systems. Bland and Altman analysis indicated that the two systems provided comparable automated parameters, and agreement between classifications (normal versus abnormal EEG) based on standard-EEG and light-EEG was good (0.6 < κ < 0.8). Automated parameters such as the mean dominant frequency obtained from the light-EEG correlated significantly with the Model for End-Stage Liver Disease score (r = -0.39, P < 0.05), fasting venous ammonia levels (r = -0.41, P < 0.01), and PHES (r = -0.49, P < 0.001). Finally, significant differences in light-EEG parameters were observed in patients with varying degrees of HE. CONCLUSION Reliable EEG parameters for HE diagnosing/grading can be obtained from a cheap, commercial, wireless headset; this may lead to more widespread use of this patient-independent tool both in routine liver practice and in the research setting. (
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Affiliation(s)
- Sami Schiff
- Department of Medicine, University of Padua, Padua, Italy
| | - Mariella Casa
- Department of Medicine, University of Padua, Padua, Italy
| | | | - Daniele Aprile
- Department of Medicine, University of Padua, Padua, Italy
| | | | - Michele De Rui
- Department of Medicine, University of Padua, Padua, Italy
| | - Paolo Angeli
- Department of Medicine, University of Padua, Padua, Italy
| | - Piero Amodio
- Department of Medicine, University of Padua, Padua, Italy
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30
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Romeiro FG, Augusti L. Nutritional assessment in cirrhotic patients with hepatic encephalopathy. World J Hepatol 2015; 7:2940-2954. [PMID: 26730273 PMCID: PMC4691697 DOI: 10.4254/wjh.v7.i30.2940] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/23/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatic encephalopathy (HE) is one of the worst complications of liver disease and can be greatly influenced by nutritional status. Ammonia metabolism, inflammation and muscle wasting are relevant processes in HE pathophysiology. Malnutrition worsens the prognosis in HE, requiring early assessment of nutritional status of these patients. Body composition changes induced by liver disease and limitations superimposed by HE hamper the proper accomplishment of exams in this population, but evidence is growing that assessment of muscle mass and muscle function is mandatory due to the role of skeletal muscles in ammonia metabolism. In this review, we present the pathophysiological aspects involved in HE to support further discussion about advantages and drawbacks of some methods for evaluating the nutritional status of cirrhotic patients with HE, focusing on body composition.
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31
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Ampuero J, Simón M, Montoliú C, Jover R, Serra MÁ, Córdoba J, Romero-Gómez M. Minimal hepatic encephalopathy and critical flicker frequency are associated with survival of patients with cirrhosis. Gastroenterology 2015; 149:1483-9. [PMID: 26299413 DOI: 10.1053/j.gastro.2015.07.067] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 06/29/2015] [Accepted: 07/17/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Minimal hepatic encephalopathy (MHE) is associated with falls, traffic accidents, and overt HE. However, the association with survival is controversial. We assessed the effects of MHE on the long-term survival of patients with cirrhosis. METHODS We performed a prospective study of 117 consecutive patients with cirrhosis seen at a tertiary hospital in Seville, Spain (estimation cohort), followed by a validation study of 114 consecutive patients with cirrhosis seen at 4 hospitals in Spain from January 2004 through December 2007. Patients were examined every 6 months at outpatient clinics through December 2013 (follow-up periods of 5 ± 2.8 y and 4.4 ± 3.9 y for each group, respectively). Cirrhosis was identified by liver biopsy, ultrasound, endoscopic analysis, and biochemical parameters. Liver dysfunction was determined based on model for end-stage liver disease (MELD) and Child-Pugh scores. All patients were administered the critical flicker frequency (CFF) test and psychometric hepatic encephalopathy scores were used to detect MHE. Survival curves were compared using the log-rank test and multivariable analysis was performed using Cox proportional hazards models. RESULTS The distributions of Child-Pugh scores were as follows: 66% class A, 31% class B, and 3% class C in the estimation cohort, and 50% class A, 32% class B, and 18% class C in the validation cohort. In the estimation cohort, 24 of 35 patients (68.6%) with a CFF score less than 39 Hz survived for 5 years, whereas 50 of 61 patients (82%) with a CFF score of 39 Hz or higher survived during the follow-up period (log-rank score, 5.07; P = .024). Psychometric hepatic encephalopathy scores did not correlate with survival. In multivariable analysis, older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12; P = .009), CFF score less than 39 Hz (HR, 4.36; 95% CI, 1.67-11.37; P = .003), and MELD score (HR, 1.40; 95% CI, 1.21-1.63; P = .0001) were associated independently with survival during the follow-up period. In the validation cohort, CFF score less than 39 Hz and MELD score also were associated with patient survival during the follow-up period. MHE had no effect on the survival of patients with MELD scores less than 10 (among patients with CFF scores ≥39 Hz, 94.5% survived for 5 years vs 91.9% of patients with CFF scores <39 Hz; log-rank score, 0.64; P = .423). Fewer patients with MELD scores of 10-15 and MHE survived for 5 years (44.4%; 12 of 27) than those with MELD scores greater than 15 without MHE (61.5%; 8 of 13) (P < .05). Only 2 of 12 patients (16.7%) with MELD scores of 15 or higher and MHE survived for 5 years (log-rank score, 90.56; P = .0001). CONCLUSIONS MHE is associated with a reduced 5-year survival rate of patients with cirrhosis. Evaluation of MHE could help predict survival times and outcomes of patients with specific MELD scores. The CFF could help physicians determine prognoses of patients with cirrhosis.
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Affiliation(s)
- Javier Ampuero
- Unit for the Clinical Management of Digestive Diseases and Centro de Investigación Biomédica de Enfermedades Hepáticas y Digestivas, Valme University Hospital, Sevilla, Spain
| | - Macarena Simón
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebrón, Barcelona, Spain
| | | | - Rodrigo Jover
- Gastroenterology Department, Hospital General Universitario, Alicante, Spain
| | | | - Juan Córdoba
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebrón, Barcelona, Spain
| | - Manuel Romero-Gómez
- Unit for the Clinical Management of Digestive Diseases and Centro de Investigación Biomédica de Enfermedades Hepáticas y Digestivas, Valme University Hospital, Sevilla, Spain.
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Patidar KR, Thacker LR, Wade JB, Sterling RK, Sanyal AJ, Siddiqui MS, Matherly SC, Stravitz RT, Puri P, Luketic VA, Fuchs M, White MB, Noble NA, Unser AB, Gilles H, Heuman DM, Bajaj JS. Covert hepatic encephalopathy is independently associated with poor survival and increased risk of hospitalization. Am J Gastroenterol 2014; 109:1757-63. [PMID: 25178701 PMCID: PMC4321782 DOI: 10.1038/ajg.2014.264] [Citation(s) in RCA: 144] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Accepted: 07/02/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Despite the high prevalence of covert hepatic encephalopathy (CHE) in cirrhotics without previous overt HE (OHE), its independent impact on predicting clinically relevant outcomes is unclear. The aim of this study was to define the impact of CHE on time to OHE, hospitalization, and death/transplant in prospectively followed up patients without previous OHE. METHODS Outpatient cirrhotics without OHE were enrolled and were administered a standard paper-pencil cognitive battery for CHE diagnosis. They were systematically followed up and time to first OHE development, hospitalization (liver-related/unrelated), and transplant/death were compared between CHE and no-CHE patients at baseline using Cox regression. RESULTS A total of 170 cirrhotic patients (55 years, 58% men, 14 years of education, Model for End-Stage Liver Disease (MELD 9), 53% hepatitis C virus (HCV), 20% nonalcoholic etiology) were included, of whom 56% had CHE. The entire population was followed up for 13.0 ± 14.6 months, during which time 30% developed their first OHE episode, 42% were hospitalized, and 19% had a composite death/transplant outcome. Age, gender, etiology, the MELD score, and CHE status were included in Cox regression models for time to first OHE episode, hospitalization, death, and composite death/transplant outcomes. On Cox regression, despite controlling for MELD, those with CHE had a higher risk of developing OHE (hazard ratio: 2.1, 95% confidence interval 1.01-4.5), hospitalization (hazard ratio: 2.5, 95% confidence interval 1.4-4.5), and death/transplant (hazard ratio: 3.4, 95% confidence interval 1.2-9.7) in the follow-up period. CONCLUSIONS Covert HE is associated with worsened survival and increased risk of hospitalization and OHE development, despite controlling for the MELD score. Strategies to detect and treat CHE may improve these risks.
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Affiliation(s)
- Kavish R. Patidar
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Leroy R. Thacker
- Department of Biostatistics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - James B. Wade
- Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Richard K. Sterling
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Arun J. Sanyal
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Mohammad S. Siddiqui
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Scott C. Matherly
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - R. Todd Stravitz
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Puneet Puri
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Velimir A. Luketic
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Michael Fuchs
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Melanie B. White
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Nicole A. Noble
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Ariel B. Unser
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - HoChong Gilles
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Douglas M. Heuman
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
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Stewart J, Särkelä M, Koivusalo AM, Wennervirta J, Salmi T, Isoniemi H, Stenman UH, Viertiö-Oja H, Lapinlampi P, Lindgren L, Salminen US, Vakkuri A. Frontal electroencephalogram variables are associated with the outcome and stage of hepatic encephalopathy in acute liver failure. Liver Transpl 2014; 20:1256-65. [PMID: 24975240 DOI: 10.1002/lt.23944] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 06/23/2014] [Accepted: 06/24/2014] [Indexed: 01/12/2023]
Abstract
Acute liver failure (ALF) and hepatic encephalopathy (HE) can lead to an elevated intracranial pressure (ICP) and death within days. The impaired liver function increases the risks of invasive ICP monitoring, whereas noninvasive methods remain inadequate. The purpose of our study was to explore reliable noninvasive methods of neuromonitoring for patients with ALF in the intensive care unit (ICU) setting; more specifically, we wanted to track changes in HE and predict the outcomes of ALF patients treated with albumin dialysis. The study included 20 patients with severe ALF at admission who had been referred to the ICU of the liver transplantation (LT) center for albumin dialysis treatment and evaluation for transplantation. Data were collected from all study patients in the form of continuous frontal electroencephalography (EEG) recordings and transcranial Doppler (TCD) measurements of cerebral blood flow. Among the studied EEG variables, the 50% spectral edge frequency decreased and the delta power increased as the HE stage increased. Both variables were predictive of the stage of HE [prediction probability (PK) of 50% spectral edge frequency = 0.23, standard error (SE) = 0.03; PK of delta power = 0.76, SE = 0.03]. The total wavelet subband entropy, a novel variable that we used for tracking abnormal EEG activity, predicted the outcome of ALF patients treated with albumin dialysis (PK = 0.88, SE = 0.09). With a threshold value of 1.6, the TCD pulsatility index had an odds ratio of 1.1 (95% confidence interval = 0.1-9.3) for a poor outcome (LT or death). In conclusion, EEG variables are useful for the monitoring of HE and can be used to predict outcomes of ALF. TCD measurements do not predict patient outcomes.
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Affiliation(s)
- Juhani Stewart
- Department of Medicine, University of Helsinki, Helsinki, Finland; Department of Anesthesiology and Intensive Care, Helsinki University Central Hospital, Helsinki, Finland; Department of Anesthesiology and Intensive Care, Helsinki University Peijas Hospital, Helsinki, Finland
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