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Mohr I, Brand M, Weber C, Langel A, Langel J, Michl P, Leidner VY, Olkus A, Köhrer S, Merle U. Mental and Physical Health in Wilson Disease Patients With SARS-CoV-2 Infection and Relevance of Long-COVID. JIMD Rep 2025; 66:e70021. [PMID: 40337099 PMCID: PMC12055521 DOI: 10.1002/jmd2.70021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 04/16/2025] [Accepted: 04/22/2025] [Indexed: 05/09/2025] Open
Abstract
SARS-CoV-2 infection and Long COVID (LC) might lead to a significant deterioration of physical and mental health. Wilson disease (WD) patients have a chronic liver and/or neuropsychiatric disease, making it particularly interesting to investigate LC in WD. 51 WD patients were retrospectively examined, evaluating physical and mental health by a survey and neuropsychological tests (SF-12, PSQI, ISI, Epworth, Chalder-fatigue scale, PHQ-9, GAD-7, PSS, FLei) before and ~11 months after SARS-CoV-2 infection. LC was defined as the development of new, at least moderately severe symptoms (shortness of breath, chest pain, fatigue, brain fog, exercise capacity, concentration disturbances) and/or worsening of pre-existing symptoms. 70.6% had predominant hepatic and 29.4% had neuropsychiatric symptoms at WD diagnosis. Median age was 39 years; 56.1% were female. Patients were in stable maintenance phase with a median treatment duration of 23 years. When compared to before COVID-19, WD patients had significantly worse physical life quality, sleeping quality, and fatigue. After COVID-19, a high percentage of WD patients reported concentration disorders (60%), fatigue (55%), reduced exercise capacity (50%), shortness of breath (40%), chest pain (20%) and feeling of brain fog (15%). 39.2% (n = 20) of the WD patients were classified as LC. This LC-WD subgroup showed significantly impaired quality of life, a high stress level, and sleeping disturbances, fatigue, depression, anxiety, and cognitive impairment. A large proportion of WD patients experience LC symptoms, reduced life quality, and sleeping disorders after SARS-CoV-2 infection. WD patients post-infection should be well monitored and supported if they develop persisting symptoms or neuro-psychological problems.
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Affiliation(s)
- Isabelle Mohr
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Maximilian Brand
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Christophe Weber
- Internal Medicine III Department of Internal Medicine and CardiologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Andrea Langel
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Jessica Langel
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Patrick Michl
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Viola Yuriko Leidner
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Alexander Olkus
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Sebastian Köhrer
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
| | - Uta Merle
- Internal Medicine IV, Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
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Hashida R, Kawaguchi T, Nakano D, Tsutsumi T, Kawaguchi M, Takahashi H, Tajima H, Matsuse H, Golabi P, Gerber LH, Younossi ZM, Hiraoka K. Fast score is associated with patient-reported outcomes in patients with metabolic dysfunction-associated steatotic liver disease. Eur J Gastroenterol Hepatol 2025; 37:190-197. [PMID: 39621860 DOI: 10.1097/meg.0000000000002895] [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] [Indexed: 12/22/2024]
Abstract
BACKGROUNDS People with metabolic dysfunction-associated steatotic liver disease (MASLD) frequently report fatigue. This symptom is associated with hepatic inflammation and fibrosis. FibroScan-aspartate aminotransferase (FAST) score is a noninvasive measurement tool that can be used to assess the severity of MASLD. We aimed to investigate the independent factors associated with patient-reported outcomes (PROs) including fatigue, and their FAST scores. METHODS We enrolled 116 patients with MASLD. PROs were assessed by the Chronic Liver Disease Questionnaire for nonalcoholic fatty liver disease (CLDQ-NAFLD), which consists of six domains including fatigue. Each domain score that was less than 6 was classified into the impairment group. A cutoff value of 0.67 in the FAST score was used to categorize a high or low FAST score. Independent factors associated with impaired PROs and fatigue were analyzed using logistic regression analysis and a graphical model. RESULTS For factor total, in the logistic regression analysis, the high FAST score was only identified as a negative independent factor for impaired total CLDQ-NAFLD (odds ratio: 5.9, 95% confidence interval: 1.11-31.20, P = 0.034). The graphical model revealed that FAST score, BMI, and age directly interact with impaired total CLDQ-NAFLD. For fatigue, there was no statistically significant factor in the logistic regression analysis. The graphical model revealed that the FAST score, BMI, estimated glomerular filtration rate, and age directly interact with fatigue. CONCLUSION We found that the FAST score directly interacted with total CLDQ-NAFLD and the domain of fatigue. The FAST score may be a useful tool to assess impaired CLDQ-NAFLD.
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Affiliation(s)
- Ryuki Hashida
- Department of Orthopedics, Kurume University School of Medicine, Kurume
- Division of Rehabilitation, Kurume University Hospital, Fukuoka, Japan
- The Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume
| | - Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume
| | - Machiko Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume
| | | | - Hiroshi Tajima
- Department of Orthopedics, Kurume University School of Medicine, Kurume
- Division of Rehabilitation, Kurume University Hospital, Fukuoka, Japan
| | - Hiroo Matsuse
- Department of Orthopedics, Kurume University School of Medicine, Kurume
- Division of Rehabilitation, Kurume University Hospital, Fukuoka, Japan
| | - Pegah Golabi
- The Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
| | - Lynn H Gerber
- The Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
| | - Zobair M Younossi
- The Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- The Global NASH Council, Washington, DC, USA
| | - Koji Hiraoka
- Department of Orthopedics, Kurume University School of Medicine, Kurume
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Jiao W, Lin J, Deng Y, Ji Y, Liang C, Wei S, Jing X, Yan F. The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms. J Neuroinflammation 2025; 22:10. [PMID: 39828676 PMCID: PMC11743025 DOI: 10.1186/s12974-024-03312-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 11/26/2024] [Indexed: 01/22/2025] Open
Abstract
Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to depressive disorders. This review elucidates the complex interplay between peripheral and central immune components underlying depressive disorder pathology. Peripherally, systemic inflammation, gut immune dysregulation, and immune dysfunction in organs including gut, liver, spleen and adipose tissue influence brain function through neural and molecular pathways. Within the central nervous system, aberrant microglial and astrocytes activation, cytokine imbalances, and compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, and promoting neuronal injury. The crosstalk between peripheral and central immunity creates a vicious cycle exacerbating depressive neuropathology. Unraveling these multifaceted immune-mediated mechanisms provides insights into major depressive disorder's pathogenic basis and potential biomarkers and targets. Modulating both peripheral and central immune responses represent a promising multidimensional therapeutic strategy.
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Affiliation(s)
- Wenli Jiao
- School of Nursing, Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, Guangdong, China
| | - Jiayi Lin
- School of Nursing, Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, Guangdong, China
| | - Yanfang Deng
- Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Yelin Ji
- School of Nursing, Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, Guangdong, China
| | - Chuoyi Liang
- School of Nursing, Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, Guangdong, China
| | - Sijia Wei
- School of Nursing, Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, Guangdong, China
| | - Xi Jing
- School of Nursing, Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, Guangdong, China.
- Guangdong-Hong Kong-Macau Great Bay Area Geoscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
| | - Fengxia Yan
- School of Nursing, Jinan University, No.601, West Huangpu Avenue, Guangzhou, 510632, Guangdong, China.
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Zhou L, Yan M, Luo Q, Qiu W, Guo YR, Guo XQ, Yu HB, Huo JR, Feng YL, Wang DP, Sun T, Wang KF, Shi JY, Shang X, Wu MN, Wang L, Cao JM. Elevated Bile Acids Induce Circadian Rhythm Sleep Disorders in Chronic Liver Diseases. Cell Mol Gastroenterol Hepatol 2024; 19:101439. [PMID: 39667579 PMCID: PMC11786901 DOI: 10.1016/j.jcmgh.2024.101439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 12/03/2024] [Accepted: 12/04/2024] [Indexed: 12/14/2024]
Abstract
BACKGROUND & AIMS Sleep disorders (SDs) are common in chronic liver diseases (CLDs). Some SDs arise from impaired internal clock and are, hence, circadian rhythm SDs (CRSDs). Bile acids (BAs), whose levels are increased in many CLDs, reciprocally interact with circadian rhythm. This study explores the mechanisms underlying CRSDs in CLDs and novel therapies. METHODS We monitored the sleep of patients with CLD using actigraphic watch and established male mouse cholemia models by feeding with BA or bile duct ligation. Sleep-wake cycle and circadian rhythm were analyzed by electroencephalogram-electromyography and locomotor wheel-running experiments. RESULTS Patients with CLD showed CRSD-like phenotypes including increased night activity and early awakening, which were strongly correlated with increased BA levels (ie, cholemia). CRSDs, including shortened circadian period, were recapitulated in 2 cholemic mouse models. Mechanistically, elevated BAs in the suprachiasmatic nucleus (SCN) activated BA receptor Takeda G protein-coupled receptor 5 (Tgr5), which, in turn, increased the level and phosphorylation of Period2 (Per2), a master rhythm regulator, through extracellular signal-regulated kinase (Erk) and casein kinase 1ε (CK1ε). Per2 phosphorylation inhibited its nuclear import, which would release its transcriptional inhibition and expedite the circadian cycle. Cholemia also blunted the light entrainment response and light-induced phase change of SCN mediated by the neurons expressing gastrin releasing peptide through Tgr5-Per2 axis. BA sequestrant or CK1 inhibitor reversed the CRSDs in cholemic mice by restoring Per2 distribution. CONCLUSIONS Cholemia is a major risk factor for CRSDs in CLDs and, hence, a promising target in future clinical study.
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Affiliation(s)
- Lan Zhou
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Min Yan
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Qin Luo
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Wen Qiu
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Yu-Ru Guo
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Xiao-Qing Guo
- Department of Hepatology, Taiyuan Third People's Hospital, Taiyuan, China
| | - Hong-Bin Yu
- Department of General Surgery, Cancer Hospital of Shanxi Medical University, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Jing-Ru Huo
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Yan-Lin Feng
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - De-Ping Wang
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Teng Sun
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Kai-Fang Wang
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Cardiology, The First Hospital and First College of Clinical Medicine, Shanxi Medical University, Taiyuan, China
| | - Jian-Yun Shi
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Xuan Shang
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Mei-Na Wu
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Lin Wang
- Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, Taiyuan, China; Department of Physiology, Shanxi Medical University, Taiyuan, China.
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Younossi ZM, Kremer AE, Swain MG, Jones D, Bowlus C, Trauner M, Henry L, Gerber L. Assessment of fatigue and its impact in chronic liver disease. J Hepatol 2024; 81:726-742. [PMID: 38670320 DOI: 10.1016/j.jhep.2024.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/19/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024]
Abstract
Patient-reported outcomes (PROs), such as health-related quality of life (HRQL), are important outcome measures for patients with chronic liver diseases (CLDs). Presence of cirrhosis and advanced liver disease have been associated with worsened HRQL and fatigue. On the other hand, some patients with earlier stages of CLD also experience fatigue, causing PRO impairment. Treatment for some CLDs may improve HRQL and, sometimes, levels of fatigue. We aimed to provide an in-depth expert review of concepts related to fatigue and HRQL in patients with primary biliary cholangitis, hepatitis C virus and MASLD (metabolic dysfunction-associated steatotic liver disease). A panel of experts in fatigue and CLD reviewed and discussed the literature and collaborated to provide this expert review of fatigue in CLD. Herein, we review and report on the complexity of fatigue, highlighting that it is comprised of peripheral (neuromuscular failure, often in conjunction with submaximal cardiorespiratory function) and central (central nervous system dysfunction) causes. Fatigue and HRQL are measured using validated self-report instruments. Additionally, fatigue can be measured through objective tests (e.g. grip strength). Fatigue has deleterious effects on HRQL and one's ability to be physically active and socially engaged but does not always correlate with CLD severity. Treatments for hepatitis C virus and MASLD can improve levels of fatigue and HRQL, but current treatments for primary biliary cholangitis do not seem to affect levels of fatigue. We conclude that obtaining PRO data, including on HRQL and fatigue, is essential for determining the comprehensive burden of CLD and its potential treatments.
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Affiliation(s)
- Zobair M Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA; The Global Liver Council, Washington DC, USA.
| | - Andreas E Kremer
- Department of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Mark G Swain
- Professor of Medicine, Cal Wenzel Family Foundation Chair in Hepatology, University of Calgary Liver Unit, Calgary, Canada
| | - David Jones
- Professor of Liver Immunology, Newcastle University, Newcastle upon Tyne, UK
| | - Christopher Bowlus
- Lena Valente Professor and Chief, Division of Gastroenterology and Hepatology, University of California Davis, United States
| | - Michael Trauner
- Div. of Gastroenterology & Hepatology, Dept. of Internal Medicine III, MedUni Wien, Medical University of Vienna, Austria
| | - Linda Henry
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA; The Global Liver Council, Washington DC, USA; Center for Outcomes Research in Liver Diseases, Washington DC, USA
| | - Lynn Gerber
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, VA, USA; The Global Liver Council, Washington DC, USA
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6
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Busebee B, Watt KD, Dupuy-McCauley K, DuBrock H. Sleep disturbances in chronic liver disease. Liver Transpl 2024; 30:1058-1071. [PMID: 38535627 DOI: 10.1097/lvt.0000000000000369] [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: 11/13/2023] [Accepted: 03/15/2024] [Indexed: 05/03/2024]
Abstract
Sleep disturbances are common in chronic liver disease and significantly impact patient outcomes and quality of life. The severity and nature of sleep disturbances vary by liver disease etiology and severity. While there is ongoing research into the association between liver disease and sleep-wake dysfunction, the underlying pathophysiology varies and, in many cases, is poorly understood. Liver disease is associated with alterations in thermoregulation, inflammation, and physical activity, and is associated with disease-specific complications, such as HE, that may directly affect sleep. In this article, we review the relevant pathophysiologic processes, disease-specific sleep-wake disturbances, and clinical management of CLD-associated sleep-wake disturbances.
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Affiliation(s)
- Bradley Busebee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Kara Dupuy-McCauley
- Division of Pulmonology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Hilary DuBrock
- Division of Pulmonology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
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7
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Dong S, Zhou S, Liu J, Chen N, Li J, Han Z, Liu R, Xuan C, Wang W, Guo L, Zhou L. Associations between sleep disorders and clinical outcomes of patients with primary biliary cholangitis. Adv Med Sci 2024; 69:385-390. [PMID: 39209159 DOI: 10.1016/j.advms.2024.08.002] [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: 12/10/2023] [Revised: 03/16/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
PURPOSE Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by a range of symptoms, including sleep disturbances. The present study aimed to investigate the prevalence of sleep disorders and the associations between sleep disorders and clinical outcomes in PBC. PATIENTS AND METHODS We enrolled 177 patients with PBC and 165 healthy controls (age- and sex-matched). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Demographic and clinical data were collected from comprehensive clinical records to investigate whether sleep disorder was correlated with disease severity, therapeutic response and liver cirrhosis. RESULTS The prevalence of sleep disorders in patients with PBC (50.8 %) was significantly higher than healthy controls (18.2 %). Patients with sleep disorders presented with higher levels of laboratory parameters including globulin (GLO), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL) and immunoglobulin M (IgM), as well as higher ratio of poor therapeutic response and liver cirrhosis (p < 0.05). There was a positive correlation between global PSQI score and AST, ALP, GGT, TBIL, DBIL and IgM in patients with PBC. Patients with poor therapeutic response and liver cirrhosis in PBC had a higher proportion of sleep disorders and more chaotic sleep patterns, whereas a stronger correlation between sleep quality and laboratory parameters was found in patients with liver cirrhosis. CONCLUSIONS Sleep disorders were prevalent and manifested as adverse effects in PBC. Assessment of sleep quality and intervention were essential to the overall clinical management of patients with PBC.
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Affiliation(s)
- Shijing Dong
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Simin Zhou
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Jiangpeng Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Nian Chen
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Jiwen Li
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Zongze Han
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Ruiyun Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Chenyang Xuan
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Weirong Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Liping Guo
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.
| | - Lu Zhou
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.
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Hassan A, Hurtado Diaz De Leon I, Tapper EB. Symptom burden in chronic liver disease. Gastroenterol Rep (Oxf) 2024; 12:goae078. [PMID: 39131950 PMCID: PMC11315653 DOI: 10.1093/gastro/goae078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 07/03/2024] [Indexed: 08/13/2024] Open
Abstract
Chronic liver disease (CLD) is a significant contributor to global mortality. For people who are living with CLD, however, there is a substantial and often overlooked burden of physical and psychological symptoms that significantly affect health-related quality of life. CLD frequently presents with a multitude of interrelated and intricate symptoms, including fatigue, pruritus, muscle cramps, sexual dysfunction, and falls. Increasingly, there is interest in studying and developing interventional strategies to provide a more global approach to managing these complex patients. Moreover, in addition to established guidelines for the management of conventional complications, such as ascites and hepatic encephalopathy, there have been efforts in developing evidence-based guidance for the treatment of the more subjective yet still problematic elements. This review will address the management of these less "classical" but nonetheless important symptoms.
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Affiliation(s)
- Ammar Hassan
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health West, University of Michigan Medicine, Grand Rapids, MI, USA
| | - Ivonne Hurtado Diaz De Leon
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
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9
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Zou J, Li J, Wang X, Tang D, Chen R. Neuroimmune modulation in liver pathophysiology. J Neuroinflammation 2024; 21:188. [PMID: 39090741 PMCID: PMC11295927 DOI: 10.1186/s12974-024-03181-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 07/19/2024] [Indexed: 08/04/2024] Open
Abstract
The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area.
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Affiliation(s)
- Ju Zou
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Jie Li
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xiaoxu Wang
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Ruochan Chen
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Du X, Hu J, Xue J, Zhuang Y, Tang X, Xu Z. Rate and Associated Factors of Fatigue in Chinese Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Survey. Int J Gen Med 2024; 17:2945-2953. [PMID: 38984071 PMCID: PMC11231026 DOI: 10.2147/ijgm.s466980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 06/25/2024] [Indexed: 07/11/2024] Open
Abstract
Purpose Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients' quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients. Patients and Methods A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ2 tests and logistic regression models. Results We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue. Conclusion This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.
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Affiliation(s)
- Xian Du
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
| | - Jun Hu
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
| | - Jianhua Xue
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
| | - Yuan Zhuang
- The Affiliated Hospital of Nantong University, Nantong, People's Republic of China
| | - Xuefeng Tang
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
| | - Zhiyue Xu
- Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People's Republic of China
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11
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Hsieh HC, Chang WP, Huang PJ, Wang CH, Lin YH. Effectiveness of Exercise Interventions on Body Composition, Exercise Capacity, Fatigue, and Quality of Life in Patients with Liver Cirrhosis: A Meta-Analysis of Randomized Controlled Trials. Dig Dis Sci 2024; 69:2655-2666. [PMID: 38656415 DOI: 10.1007/s10620-024-08447-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 04/09/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND Diminished muscle protein synthesis in cirrhosis leads to reduced strength and mass, impacting daily activities and overall quality of life. AIMS This study aimed to examine the effectiveness of exercise intervention in body composition, exercise capacity, fatigue, and quality of life in patients with liver cirrhosis. METHODS A systematic search of medical databases, including PubMed, Embase, Cochrane, and CINAHL, was executed from their inception to November 2022. The inclusion criteria were randomized controlled trials comparing exercise interventions with a control group that did not receive exercise interventions. RESULTS From the initially identified 2,565 articles, eight studies with a total of 220 patients were eligible for inclusion in this meta-analysis. According to the meta-analysis, exercise significantly improved the six-minute walk distance (6MWD) by 68.93 m (95% CI 14.29-123.57) compared to the control group. Furthermore, the subgroup analysis revealed that combing exercise with amino acid supplementation had a greater positive effect on the 6MWD (MD = 144.72, 95% CI 87.44-202.01). Exercise also significantly increased thigh circumference (MD = 1.26, 95% CI 0.12-2.39) and the thigh ultrasound average compression index (MD = 0.07, 95% CI 0.00-0.14). Moreover, exercise significantly decreased fatigue levels by 0.7 points in patients with liver cirrhosis (95% CI 0.38-1.03). However, no significant effects were observed on body mass index (BMI), fat mass, fat-free mass, and quality of life. CONCLUSIONS Exercise can improve exercise capacity, thigh muscle thickness, and fatigue in patients with cirrhosis, but it does not have a significant impact on fat mass, BMI, or quality of life.
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Affiliation(s)
- Huei-Chi Hsieh
- Department of Nursing, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan
| | - Wen-Pei Chang
- Department of Nursing, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Po-Jui Huang
- Division of Gastroenterology, Wan Fang Hospital, Taipei Medical University, Taipei, 110301, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wuxing St., Xinyi Dist., Taipei, 11031, Taiwan
| | - Chia-Hui Wang
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Yu-Huei Lin
- Post-Baccalaureate Program in Nursing, College of Nursing, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031, Taiwan.
- Research Center in Nursing Clinical Practice, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
- Department of Nursing, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
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12
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Takano K, Kaneda M, Aoki Y, Fujita N, Chiba S, Michihara S, Han LK, Takahashi R. The protective effects of Ninjin'yoeito against liver steatosis/fibrosis in a non-alcoholic steatohepatitis model mouse. J Nat Med 2024; 78:514-524. [PMID: 38498120 PMCID: PMC11101552 DOI: 10.1007/s11418-024-01786-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 02/01/2024] [Indexed: 03/20/2024]
Abstract
Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic form of non-alcoholic fatty liver disease. Liver fibrosis leads to liver cancer and cirrhosis, and drug therapy for NASH remains lacking. Ninjin'yoeito (NYT) has shown antifibrotic effects in a model of liver fibrosis without steatosis but has not been studied for NASH. Therefore, we evaluated the efficacy of NYT in mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a NASH model. Compared with the normal diet group, mice fed CDAHFD showed decreased body weight and increased white adipose tissue, liver weight, and triglyceride content in the liver. Furthermore, a substantial increase in the hepatic concentration of hydroxyproline, expression of α-smooth muscle actin (α-SMA), and transforming growth factor-β was observed in CDAHFD-fed mice. Masson's trichrome and Picro-Sirius red staining revealed a remarkable increase in collagen fiber compared with the normal diet group. Compared with mice that received CDAHFD alone, those supplemented with NYT exhibited reduced hepatic triglyceride and hydroxyproline levels and α-SMA expression. Additionally, compared with the group fed CDAHFD alone, the stained liver tissues of NYT-treated mice exhibited a reduction in Masson's trichrome- and Picro-Sirius red-positive areas. Locomotor activity was significantly reduced in the CDAHFD-fed group compared with the normal diet group. In the NYT-treated group, the CDAHFD-induced decrease in locomotor activity was significantly suppressed. The findings indicate that NYT inhibited fatty and fibrotic changes in the livers of NASH mice and alleviated the decrease in locomotor activity. Therefore, NYT may serve as a novel therapeutic approach for NASH.
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Affiliation(s)
- Kyohei Takano
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan.
| | - Marisa Kaneda
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Yayoi Aoki
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Nina Fujita
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Shigeki Chiba
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Seiwa Michihara
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Li-Kun Han
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
| | - Ryuji Takahashi
- Kampo Research Laboratory, Pharmaceutical Company, Kracie, Ltd., 3-1 Kanebo-Machi, Takaoka, Toyama, Japan
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Drazilova S, Koky T, Macej M, Janicko M, Simkova D, Tsedendamba A, Komarova S, Jarcuska P. Pruritus, Fatigue, Osteoporosis and Dyslipoproteinemia in Pbc Patients: A Clinician’s Perspective. GASTROENTEROLOGY INSIGHTS 2024; 15:419-432. [DOI: 10.3390/gastroent15020030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2025] Open
Abstract
In this review article, we summarize the most common clinical manifestations of Primary biliary cholangitis (PBC): pruritus, fatigue, osteoporosis, and dyslipoproteinemia and discuss their impact of the patients’ quality of life. More than half of PBC patients suffer from pruritus or fatigue at the time of diagnosis. We discuss the pathophysiological aspects of the PBC clinical manifestations and treatment options. The pathophysiology of pruritus and fatigue is not adequately elucidated, but IL-31 is associated with the severity of pruritus and could be used to objectify the subjective reporting by questionnaires. Although PBC patients suffer from atherogenic dyslipidemia, they do not seem to have a higher cardiovascular risk; however, this observation needs to be clarified by further clinical studies. The second-line of PBC treatment affects pruritus severity: Obeticholic acid (OCA) worsens pruritus while fibrates improve it. Itching can be alleviated by both non-pharmacological and pharmacological approach, however the are multiple barriers to pharmacological treatment. There is no adequate treatment for fatigue today. Treatment of osteoporosis and dyslipidemia is similar for non-PBC patients; stage of liver disease should be considered in treatment. Further research to clarify the pathophysiology and to eventually discover an effective treatment to improve survival and quality of life (especially pruritus and fatigue) in PBC patients is needed.
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Affiliation(s)
- Sylvia Drazilova
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Tomas Koky
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Marian Macej
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Martin Janicko
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Dagmar Simkova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine IKEM, Videnska 1921, 140 21 Prague, Czech Republic
| | - Ariunzaya Tsedendamba
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Slavomira Komarova
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
| | - Peter Jarcuska
- 2nd Department of Internal Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Safarik University, Trieda SNP 1, 040 11 Kosice, Slovakia
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14
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Chen CY, Huang BS, Hong JH, Chang JTC, Chen MC, Tang WR, Shun SC, Chen ML. Persistent Fatigue in Patients With Hepatocellular Carcinoma Receiving Radiotherapy. J Nurs Res 2024; 32:e319. [PMID: 38506576 DOI: 10.1097/jnr.0000000000000606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Radiation therapy has attracted much attention in the treatment of patients with hepatocellular carcinoma (HCC). However, the association between radiotherapy-related fatigue and HCC has been examined in only a few studies. PURPOSE This study was designed to explore the change over time in fatigue in patients with HCC treated with radiotherapy and related factors. METHODS One hundred patients were enrolled in this prospective longitudinal study using convenience sampling at a medical center in northern Taiwan. The Functional Assessment of Chronic Illness Therapy-Fatigue scale, the Brief Pain Inventory-Short Form, and the psychological subscale of Memorial Symptom Assessment Scale-Short Form were used to assess the symptoms at five time points: before radiotherapy (T0), during treatment (T1), and at 1 month (T2), 3 months (T3), and 6 months (T4) after radiotherapy. The generalized estimating equations method was used to determine the changes in fatigue and the influencing factors. RESULTS Fatigue levels at T1, T2, T3, and T4 were significantly higher than that at T0. Higher fatigue was significantly associated with lower income and poorer functional status. Having worse pain levels and psychological symptoms were both associated with higher fatigue. CONCLUSIONS/IMPLICATIONS FOR PRACTICE The results indicate fatigue does not recover to the baseline (pretherapy) level by 6 months after radiotherapy. Thus, fatigue in patients with HCC receiving radiotherapy should be regularly and effectively assessed, and patients experiencing pain and psychological symptoms should be given greater attention from clinicians.
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Affiliation(s)
- Chiao-Yi Chen
- MS, RN, School of Nursing, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Bing-Shen Huang
- MD, Associate Professor, Department of Radiation Oncology, Chang Gung Memorial Hospital; and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ji-Hong Hong
- MD, PhD, Professor, Department of Radiation Oncology, Chang Gung Memorial Hospital; and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Joseph Tung-Chieh Chang
- MD, MHA, Professor, Department of Radiation Oncology, Chang Gung Memorial Hospital; and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Min-Chi Chen
- PhD, Professor, Department of Public Health and Biostatistics Consulting Center, College of Medicine, Chang Gung University, Taoyuan; and Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Woung-Ru Tang
- PhD, RN, Professor, School of Nursing, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shiow-Ching Shun
- PhD, RN, Professor, School of Nursing, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Mei-Ling Chen
- PhD, RN, Professor, School of Nursing, College of Medicine, Chang Gung University, Taoyuan; Division of Medical Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan; and Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan
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15
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Ekerfors U, Simrén M, Marschall HU, Demir D, Josefsson A. The influence of muscle performance and fatigue on prognosis in patients with compensated liver disease. BMC Gastroenterol 2023; 23:302. [PMID: 37674115 PMCID: PMC10483859 DOI: 10.1186/s12876-023-02885-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 07/12/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Poor muscle function is associated with a negative prognosis in advanced liver disease but the impact in compensated chronic liver disease is unknown. Similar prognostic uncertainty applies to fatigue. We aimed to assess the prognostic value of muscle performance and fatigue in a cohort of patients with compensated chronic liver disease. METHODS We followed 241 patients with compensated chronic liver disease included in a study between 2010 and 2014. Subjects were 52 ± 15 years (mean ± SD; 134 females). All subjects performed four muscle function tests: "Timed Up and Go" test, walking speed, handgrip strength, and standing heel-rises. Fatigue was evaluated by fatigue impact scale. Follow up data was acquired through hospital records and registries. RESULTS During follow up of 6.75 ± 1.4 years, 13 patients died (5.5%) and 11 (4.5%) patients underwent liver transplantation. A timed up and go over 10 s was not significantly associated with a lower survival (Kaplan-Meier, log rank test p = 0.132), or with transplant free survival (p = 0.543), Fig. 3. It was also not specifically associated with liver related causes of death (p = 0.597). The other physical functioning tests and fatigue were not significantly associated with mortality or transplant-free survival (p > 0.05 for all) except for maximal walking speed (2.2 vs. 1.9 m/s, p = 0.007). CONCLUSIONS Our study suggests that muscle function and fatigue are not key prognostic factors in compensated chronic liver disease. However, further confirmation in future studies is needed.
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Affiliation(s)
- Ulrika Ekerfors
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
- Institute of Internal Medicine Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Göteborg, 41345, Sweden.
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Hanns-Ulrich Marschall
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Daghan Demir
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Axel Josefsson
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
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16
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Nguyen HH, Swain MG. Avenues within the gut-liver-brain axis linking chronic liver disease and symptoms. Front Neurosci 2023; 17:1171253. [PMID: 37521690 PMCID: PMC10372440 DOI: 10.3389/fnins.2023.1171253] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 06/09/2023] [Indexed: 08/01/2023] Open
Abstract
Symptoms of fatigue, social withdrawal and mood disturbances are commonly encountered in patients with chronic liver disease and have a detrimental effect on patient quality of life. Treatment options for these symptoms are limited and a current area of unmet medical need. In this review, we will evaluate the potential mechanistic avenues within the gut-liver-brain axis that may be altered in the setting of chronic liver disease that drive the development of these symptoms. Both clinical and pre-clinical studies will be highlighted as we discuss how perturbations in host immune response, microbiome, neural responses, and metabolites composition can affect the central nervous system.
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Affiliation(s)
- Henry H. Nguyen
- University of Calgary Liver Unit, Departments of Medicine and Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Mark G. Swain
- University of Calgary Liver Unit, Department of Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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17
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Trivella J, John BV, Levy C. Primary biliary cholangitis: Epidemiology, prognosis, and treatment. Hepatol Commun 2023; 7:02009842-202306010-00027. [PMID: 37267215 DOI: 10.1097/hc9.0000000000000179] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 04/10/2023] [Indexed: 06/04/2023] Open
Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease characterized by a destructive, small duct, and lymphocytic cholangitis, and marked by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC vary widely in different regions and time periods, and although disproportionally more common among White non-Hispanic females, contemporary data show a higher prevalence in males and racial minorities than previously described. Outcomes largely depend on early recognition of the disease and prompt institution of treatment, which, in turn, are directly influenced by provider bias and socioeconomic factors. Ursodeoxycholic acid remains the initial treatment of choice for PBC, with obeticholic acid and fibrates (off-label therapy) reserved as add-on therapy for the management of inadequate responders or those with ursodeoxycholic acid intolerance. Novel and repurposed drugs are currently at different stages of clinical development not only for the treatment of PBC but also for its symptomatic management. Here, we summarize the most up-to-date data regarding the epidemiology, prognosis, and treatment of PBC, providing clinically useful information for its holistic management.
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Affiliation(s)
- Juan Trivella
- Department of Medicine, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Binu V John
- Department of Medicine, Division of Gastroenterology and Hepatology, Miami VA Medical System, Miami, Florida, USA
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Cynthia Levy
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
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Vold JH, Chalabianloo F, Løberg EM, Aas CF, Lim AG, Vickerman P, Johansson KA, Fadnes LT. The efficacy of integrated hepatitis C virus treatment in relieving fatigue in people who inject drugs: a randomized controlled trial. Subst Abuse Treat Prev Policy 2023; 18:25. [PMID: 37095561 PMCID: PMC10123982 DOI: 10.1186/s13011-023-00534-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 04/18/2023] [Indexed: 04/26/2023] Open
Abstract
BACKGROUND Most people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment. METHODS This multi-center, randomized controlled trial evaluated fatigue as a secondary outcome of integrated HCV treatment (the INTRO-HCV trial). From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in specialized infectious disease outpatient clinics at referral hospitals. Fatigue was assessed prior to treatment and 12 weeks after treatment using the nine-item Fatigue Severity Scale (FSS-9). We applied a linear mixed model to evaluate the impact of integrated HCV treatment on changes in FSS-9 (ΔFSS-9) sum scores. RESULTS At baseline, the mean FSS-9 sum score was 46 (standard deviation (SD): 15) for participants on integrated HCV treatment and 41 (SD: 16) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean FSS-9 sum score for participants receiving integrated HCV treatment was 42 (SD: 15) and 40 (SD: 14) for those receiving standard HCV treatment. Integrated HCV treatment did not reduce the FSS-9 scores compared to standard HCV treatment (ΔFSS-9: -3.0, 95% confidence interval (CI): -6.4;0.4). CONCLUSIONS Fatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue. TRIAL REGISTRATION ClinicalTrials.gov.no NCT03155906, 16/05/2017.
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Affiliation(s)
- Jørn Henrik Vold
- Department of Addiction Medicine, Haukeland University Hospital, Jonas Lies Vei 65, N-5021, Bergen, Norway.
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
| | - Fatemeh Chalabianloo
- Department of Addiction Medicine, Haukeland University Hospital, Jonas Lies Vei 65, N-5021, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Else-Marie Løberg
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Psychology, University of Bergen, Bergen, Norway
| | - Christer F Aas
- Department of Addiction Medicine, Haukeland University Hospital, Jonas Lies Vei 65, N-5021, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
| | - Aaron G Lim
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Peter Vickerman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Kjell Arne Johansson
- Department of Addiction Medicine, Haukeland University Hospital, Jonas Lies Vei 65, N-5021, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Lars Thore Fadnes
- Department of Addiction Medicine, Haukeland University Hospital, Jonas Lies Vei 65, N-5021, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
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Liu J, Gong X, Lv H, Liu S, Jiang Y, Zhu G, Ma X, Wang J, Ye X, Gao Y, Li J, Chen G, Shi J. Is fatigue related to the severity of liver inflammation in patients with chronic liver disease? A cross-sectional study. BMJ Open 2023; 13:e069028. [PMID: 37080620 PMCID: PMC10124276 DOI: 10.1136/bmjopen-2022-069028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/22/2023] Open
Abstract
OBJECTIVES Fatigue is common in patients with chronic liver disease; however, its pathogenesis is unclear. This study aimed to provide insights into the pathogenesis of chronic liver disease-related fatigue by assessing the relationship between fatigue and the degree of inflammation in chronic liver disease. DESIGN We performed a cross-sectional study of 1374 patients with pathologically proven chronic liver disease diagnosed at the Affiliated Hospital of Hangzhou Normal University in Hangzhou, China. SETTING Primary single-centre study. PARTICIPANTS One thousand three hundred and seventy-four patients with liver biopsy-proven chronic liver disease. INTERVENTIONS The patients were divided into fatigue and non-fatigue groups according to the Chronic Liver Disease Questionnaire. Propensity score matching was used to match the baseline features of the patients in the two groups. PRIMARY AND SECONDARY OUTCOME MEASURES Liver steatosis, ballooning, inflammation and fibrosis were measured according to the pathological results of liver biopsy. Fatigue was measured using the Chronic Liver Disease Questionnaire. RESULTS Of the 1374 patients, 262 (19.67%) experienced fatigue. There were 242 and 484 patients with and without fatigue, respectively, who were successfully matched for sex, age and classification of chronic liver disease by propensity score matching. After matching, the fatigue group showed higher liver enzyme levels, inflammation grades and fibrosis stages than the non-fatigue group (p<0.05). Multivariate analysis showed that age (OR: 2.026; p=0.003), autoimmune liver disease (OR: 2.749; p=0.002) and active inflammation (OR: 1.587; p=0.003) were independent risk factors for fatigue after adjusting for confounders. The OR of the risk for fatigue increased in a stepwise manner with increasing inflammation grade in young-aged and middle-aged patients (p<0.05). This tendency was not observed in elderly patients (p>0.05). CONCLUSION Patients with chronic liver disease were burdened by fatigue, which increased progressively with rising liver inflammation severity in young-aged and middle-aged rather than elderly patients.
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Affiliation(s)
- Jing Liu
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Xiying Gong
- Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Haifeng Lv
- Department of Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Shiyi Liu
- Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Yanming Jiang
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Geli Zhu
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Xiaojie Ma
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Jie Wang
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Xiaoping Ye
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Yidan Gao
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Jie Li
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Gongying Chen
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Junping Shi
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Department of Translational Medicine Platform, Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, China
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20
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Younossi ZM, Stepanova M, Myers RP, Younossi I, Henry L. The Potential Role of Fatigue in Identifying Patients With NASH and Advanced Fibrosis Who Experience Disease Progression. Clin Gastroenterol Hepatol 2023; 21:970-977.e1. [PMID: 35533993 DOI: 10.1016/j.cgh.2022.04.023] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 04/06/2022] [Accepted: 04/12/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Fatigue is common in patients with advanced liver disease. We investigated fatigue and clinical outcomes among patients with advanced nonalcoholic steatohepatitis (NASH). METHODS In this study, patients with biopsy confirmed NASH and bridging fibrosis (F3) or compensated cirrhosis (F4) were followed for up to 2 years. The Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis (CLDQ-NASH) fatigue domain at baseline (range, 1-7; lower score indicating worse fatigue) quantified fatigue. The Cox proportional hazards model was used to study time to liver-related clinical events (progression to histologic cirrhosis or hepatic decompensation in F3, hepatic decompensation in F4). RESULTS Of the 1679 NASH patients with fibrosis, 802 had F3 and 877 had F4 (58 ± 9 years of age, 40% male, 74% type 2 diabetes). During median follow-up of 16 months (interquartile range, 14-18), 15% (n = 123) of NASH F3 patients experienced liver-related events and 3.5% (n = 31) of NASH F4 patients experienced hepatic decompensation. Mean baseline CLDQ-NASH fatigue score in F3 patients was 4.77 ± 1.36; NASH F3 patients who experienced liver-related events had lower baseline scores: 4.47 ± 1.36 vs 4.83 ± 1.35 (P = .0091). The mean fatigue score in F4 was 4.56 ± 1.44; these scores were lower in patients who decompensated in follow-up: 3.74 ± 1.31 vs 4.59 ± 1.43 (P = .0011). The association of lower fatigue scores and risk of liver-related or decompensation events was significant after adjustment for confounders (adjusted hazard ratio per 1 point in fatigue score in F3, 0.85; 95% confidence interval, 0.74-0.97; P = .02; adjusted hazard ratio in F4, 0.62; 95% confidence interval, 0.48-0.81; P = .0004). CONCLUSION Worse fatigue at baseline is associated with a higher risk of adverse clinical events in patients with NASH-related advanced fibrosis and cirrhosis.
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Affiliation(s)
- Zobair M Younossi
- Medicine Service Line, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.
| | - Maria Stepanova
- Medicine Service Line, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Center for Outcomes Research in Liver Diseases, Washington DC
| | | | - Issah Younossi
- Center for Outcomes Research in Liver Diseases, Washington DC
| | - Linda Henry
- Medicine Service Line, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Center for Outcomes Research in Liver Diseases, Washington DC
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21
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Jones D, Carbone M, Invernizzi P, Little N, Nevens F, Swain MG, Wiesel P, Levy C. Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial. Hepatol Commun 2023; 7:e0057. [PMID: 36809195 PMCID: PMC9949832 DOI: 10.1097/hc9.0000000000000057] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 12/04/2022] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND There is a real unmet need for primary biliary cholangitis (PBC) treatments that can improve quality of life impacting symptoms. In this post hoc analysis, we evaluated potential effects of the NADP oxidase 1/4 inhibitor, setanaxib, on patient-reported quality of life from a phase 2 trial in PBC. PATIENTS AND METHODS The underpinning double-blind, randomized, placebo-controlled trial (NCT03226067) recruited 111 patients with PBC and inadequate response/intolerance to ursodeoxycholic acid. Patients self-administered oral placebo (n=37), setanaxib 400 mg once daily (OD; n=38), or setanaxib 400 mg twice daily (BID; n=36), in addition to ursodeoxycholic acid for 24 weeks. Quality of life outcomes were assessed using the validated PBC-40 questionnaire. Patients were stratified post hoc by baseline fatigue severity. RESULTS At week 24, patients treated with setanaxib 400 mg BID reported greater mean (SE) absolute reductions from baseline in PBC-40 fatigue domain score [-3.6 (1.3)] versus those receiving setanaxib 400 mg OD [-0.8 (1.0)]) or placebo [0.6 (0.9)]. Similar observations were made across all PBC-40 domains except itch. In the setanaxib 400 mg BID arm, patients with moderate-to-severe fatigue at baseline had a greater reduction in mean fatigue score at week 24 [-5.8 (2.1)] versus those with mild fatigue [-0.6 (0.9)]; results were similar across all domains. Reduced fatigue was correlated with emotional, social, symptom, and cognitive improvements. CONCLUSIONS These results support further investigation of setanaxib as a treatment for patients with PBC, particularly for those with clinically significant fatigue.
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Affiliation(s)
- David Jones
- Newcastle University Medical School, Newcastle Upon Tyne, UK
| | - Marco Carbone
- Division of Gastroenterology, Department of Medicine and Surgery, Centre for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology, Department of Medicine and Surgery, Centre for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | | | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospital KU Leuven, Health Care Provider of the ERN RARE-LIVER, Leuven, Belgium
| | - Mark G. Swain
- University of Calgary Liver Unit, Calgary, Alberta, Canada
| | | | - Cynthia Levy
- Schiff Center for Liver Diseases, University of Miami, Florida, USA
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22
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Patel P, Ali H, Inayat F, Pamarthy R, Giammarino A, Ilyas F, Smith-Martinez LA, Satapathy SK. Racial and gender-based disparities and trends in common psychiatric conditions in liver cirrhosis hospitalizations: A ten-year United States study. World J Hepatol 2023; 15:289-302. [PMID: 36926245 PMCID: PMC10011900 DOI: 10.4254/wjh.v15.i2.289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/01/2023] [Accepted: 01/31/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Chronic liver disease is associated with various neuropsychiatric conditions. There are currently no large studies assessing and comparing the prevalence of psychiatric illnesses based on patient profiles and the etiology of cirrhosis. AIM To examine the trends of hospitalizations among psychiatric conditions in cirrhosis. METHODS We used the National Inpatient Sample database 2016-2019 for the primary diagnosis of liver cirrhosis. The outcomes included the prevalence, trends, and associations of psychiatric diagnoses in these hospitalizations. Chi-square for categorical variables and the Wilcoxon rank test for continuous variables were utilized. RESULTS The prevalence of generalized anxiety disorder (GAD) in liver cirrhosis hospitalizations increased from 0.17% in 2009 to 0.92% in 2019 (P < 0.001). The prevalence of depression increased from 7% in 2009 to 12% in 2019 (P < 0.001). Attention deficit hyperactivity disorder (ADHD) prevalence increased from 0.06% to 0.24%. The prevalence of schizophrenia increased from 0.59% to 0.87% (P < 0.001). Schizoaffective disorder prevalence increased from 0.10% to 0.35% (P < 0.001). Post-traumatic stress disorder (PTSD) prevalence displayed increasing trends from 0.36% in 2009 to 0.93% in 2019 (P < 0.001). The prevalence of suicidal ideation increased from 0.23% to 0.56% in 2019. Cirrhosis related to alcoholic liver disease [adjusted odds ratios (aOR) 1.18, 95%CI 1.08-1.29, P < 0.001] and non-alcoholic fatty liver disease (NAFLD) (aOR 1.14, 95%CI 1.01-1.28, P = 0.025) was associated with depression more than other causes. Alcohol- and NAFLD-associated cirrhosis had a stronger link to psychiatric disorders. Females had a higher association with GAD (aOR 2.56, 95%CI 2.14-3.06, P < 0.001), depression (aOR 1.78, 95%CI 1.71-1.84, P < 0.001), bipolar disorder (aOR 1.64, 95%CI 1.52-1.77, P < 0.001] and chronic fatigue (aOR 2.31, 95%CI 1.31-4.07, P < 0.001) when compared to males. Blacks, Hispanics, and Asian/Native Americans had a significantly lower association with GAD, depression, bipolar disorder, PTSD, and ADHD when compared to the white race. CONCLUSION The prevalence of psychiatric comorbidities in liver cirrhosis hospitalizations has increased over the last decade. Females had a higher association with psychiatric disorders compared to males. Blacks, Hispanics, and Asian/Native Americans had lower associations with psychiatric comorbidities compared to the white race.
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Affiliation(s)
- Pratik Patel
- Department of Gastroenterology, Mather Hospital and Hofstra University Zucker School of Medicine, Port Jefferson, NY 11777, United States
| | - Hassam Ali
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States.
| | - Faisal Inayat
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore 54550, Punjab, Pakistan
| | - Rahul Pamarthy
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Alexa Giammarino
- Department of Internal Medicine, North Shore University Hospital and Hofstra University Zucker School of Medicine, Port Jefferson, NY 11777, United States
| | - Fariha Ilyas
- Department of Internal Medicine, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Lucia Angela Smith-Martinez
- Department of Psychiatry, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Sanjaya K Satapathy
- Department of Hepatology, North Shore University Hospital and Hofstra University Zucker School of Medicine, Manhasset, NY 11030, United States
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23
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Săndulescu O, Streinu-Cercel A, Miron VD, Covăcescu SM, Streinu-Cercel A, Craiu M. Liver Transaminases in Pediatric Adenovirus Infection-A Five-Year Study in Two Major Reference Centers from Romania. Microorganisms 2023; 11:microorganisms11020302. [PMID: 36838267 PMCID: PMC9961354 DOI: 10.3390/microorganisms11020302] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/16/2023] [Accepted: 01/18/2023] [Indexed: 01/25/2023] Open
Abstract
Human adenovirus causes infections with a very heterogeneous clinical picture, and children are often the most frequently affected group. Interest in adenovirus has increased with the 2022 outbreak of severe acute hepatitis of unknown etiology as human adenovirus was considered as one of the possible etiological agents. We conducted a retrospective study over a 5-year period in two major tertiary hospitals in the Romanian capital with the aim to characterize the clinical picture and the dynamics of liver function tests in children with confirmed adenovirus infection. The study included 1416 children with a median age of 1.1 years (IQR: 0.3, 2.3 years). Digestive symptoms were predominant in 95.2% of children, mainly diarrhea (90.5%) and vomiting (50.5%), and 38.0% had respiratory symptoms. Increased transaminases were identified in 21.5% of patients. Age over 1 year, lethargy, vomiting and dehydration significantly increased the odds of liver cytolysis independent of other risk factors such as chronic conditions or co-infections. Aspartate aminotransferase (AST) was more commonly increased compared to alanine aminotransferase (ALT). Only six children had transaminase increases above 500 U/L, three of which had co-infections with rotavirus, Epstein-Barr virus (EBV), or respiratory syncytial virus (RSV). Liver function tests should be part of routine monitoring for pediatric patients with adenovirus infection. The current study fills a gap in current knowledge related to the frequency and the extent of liver involvement in human adenovirus infection among pediatric patients.
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Affiliation(s)
- Oana Săndulescu
- Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Anca Streinu-Cercel
- Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Victor Daniel Miron
- Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute of Mother and Child Health “Alessandrescu-Rusescu”, 020395 Bucharest, Romania
- Correspondence:
| | - Silvia Mirela Covăcescu
- Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute of Mother and Child Health “Alessandrescu-Rusescu”, 020395 Bucharest, Romania
| | - Adrian Streinu-Cercel
- Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Mihai Craiu
- Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute of Mother and Child Health “Alessandrescu-Rusescu”, 020395 Bucharest, Romania
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24
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Holman A, Parikh N, Clauw DJ, Williams DA, Tapper EB. Contemporary management of pain in cirrhosis: Toward precision therapy for pain. Hepatology 2023; 77:290-304. [PMID: 35665522 PMCID: PMC9970025 DOI: 10.1002/hep.32598] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 02/03/2023]
Abstract
Chronic pain is highly prevalent in patients with cirrhosis and is associated with poor health-related quality of life and poor functional status. However, there is limited guidance on appropriate pain management in this population, and pharmacologic treatment can be harmful, leading to adverse outcomes, such as gastrointestinal bleeding, renal injury, falls, and hepatic encephalopathy. Chronic pain can be categorized mechanistically into three pain types: nociceptive, neuropathic, and nociplastic, each responsive to different therapies. By discussing the identification, etiology, and treatment of these three mechanistic pain descriptors with a focus on specific challenges in patients with cirrhosis, we provide a framework for better tailoring treatments, including nonpharmacologic therapies, to patients' needs.
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Affiliation(s)
- Alexis Holman
- Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Neehar Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Dan J. Clauw
- Chronic Pain and Fatigue Research Center, Anesthesiology Department, University of Michigan, Ann Arbor, Michigan, USA
| | - David A. Williams
- Chronic Pain and Fatigue Research Center, Anesthesiology Department, University of Michigan, Ann Arbor, Michigan, USA
| | - Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
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25
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Shea S, Lionis C, Atkinson L, Kite C, Lagojda L, Chaggar SS, Kyrou I, Randeva HS. Support Needs and Coping Strategies in Non-Alcoholic Fatty Liver Disease (NAFLD): A Multidisciplinary Approach to Potential Unmet Challenges beyond Pharmacological Treatment. LIVERS 2022; 3:1-20. [DOI: 10.3390/livers3010001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most frequently occurring chronic liver disease, affecting approximately 25–30% of the adult general population worldwide. NAFLD reflects excess hepatic accumulation of fat in the absence of increased alcohol intake, and, due to its close association with obesity, is frequently referred to as the ‘hepatic manifestation’ of metabolic syndrome. Indeed, a high percentage of individuals with NAFLD present with a combination of the cardio-metabolic comorbidities that are associated with the metabolic syndrome. In addition to its well-established link with the metabolic syndrome and increased risk for cardiovascular disease, NAFLD has also been associated with certain mental health issues (e.g., depression and stress). Although this link is now being increasingly recognized, there are still unmet needs regarding the holistic management of patients with NAFLD, which could further contribute to feelings of social isolation and loneliness. The latter conditions are also increasingly reported to pose a substantial risk to overall health and quality of life. To date, there is limited research that has explored these issues among patients with NAFLD, despite existing data which indicate that perceived loneliness and isolation may pose an additional health risk. Notably, many features associated with NAFLD have been related to these concepts, such as perceived stigma, fatigue, stress, and confusion regarding this diagnosis. As such, this review aimed to assess such potential problems faced by patients with NAFLD, and to explore the possibility of unmet support needs which could lead to perceived social isolation. Moreover, the importance of a compassionate approach towards such patients is discussed, together with potential coping strategies. Future research directions and the need for a multidisciplinary approach are also highlighted.
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Affiliation(s)
- Sue Shea
- Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
| | - Christos Lionis
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece
| | - Lou Atkinson
- Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Chris Kite
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- School of Public Health Studies, Faculty of Education, Health and Wellbeing, University of Wolverhampton, Wolverhampton WV1 1LY, UK
- Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry CV1 5FB, UK
| | - Lukasz Lagojda
- Clinical Evidence Based Information Service (CEBIS), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
| | | | - Ioannis Kyrou
- Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry CV1 5FB, UK
- Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK
- Laboratory of Dietetics & Quality of Life, Department of Food Science & Human Nutrition, School of Food & Nutritional Sciences, Agricultural University of Athens, 11855 Athens, Greece
| | - Harpal S. Randeva
- Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
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26
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Yassine M, Hassan SA, Sommer S, Yücel LA, Bellert H, Hallenberger J, Sohn D, Korf HW, von Gall C, Ali AAH. Radiotherapy of the Hepatocellular Carcinoma in Mice Has a Time-Of-Day-Dependent Impact on the Mouse Hippocampus. Cells 2022; 12:cells12010061. [PMID: 36611854 PMCID: PMC9818790 DOI: 10.3390/cells12010061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/18/2022] [Accepted: 12/19/2022] [Indexed: 12/28/2022] Open
Abstract
Chronic liver diseases including hepatocellular carcinoma (HCC) create a state of chronic inflammation that affects the brain via the liver-brain axis leading to an alteration of neurotransmission and cognition. However, little is known about the effects of HCC on the hippocampus, the key brain region for learning and memory. Moreover, radiotherapy used to treat HCC has severe side effects that impair patients' life quality. Thus, designing optimal strategies, such as chronotherapy, to enhance the efficacy and reduce the side effects of HCC treatment is critically important. We addressed the effects of HCC and the timed administration of radiotherapy in mice on the expression of pro-inflammatory cytokines, clock genes, markers for glial activation, oxidative stress, neuronal activity and proliferation in the hippocampal neurogenic niche. Our data showed that HCC induced the upregulation of genes encoding for pro-inflammatory cytokines, altered clock gene expressions and reduced proliferation in the hippocampus. Radiotherapy, in particular when applied during the light/inactive phase enhanced all these effects in addition to glial activation, increased oxidative stress, decreased neuronal activity and increased levels of phospho(p)-ERK. Our results suggested an interaction of the circadian molecular clockwork and the brain's innate immune system as key players in liver-brain crosstalk in HCC and that radiotherapy when applied during the light/inactive phase induced the most profound alterations in the hippocampus.
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Affiliation(s)
- Mona Yassine
- Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
| | - Soha A. Hassan
- Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
- Zoology Department, Faculty of Science, Suez University, Cairo-Suez Road, Suez 43533, Egypt
| | - Simon Sommer
- Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
| | - Lea Aylin Yücel
- Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
| | - Hanna Bellert
- Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
| | - Johanna Hallenberger
- Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
| | - Dennis Sohn
- Laboratory of Molecular Radiooncology, Clinic and Policlinic for Radiation Therapy and Radiooncology, Medical Faculty, Heinrich-Heine-University, Universität Strasse 1, 40225 Düsseldorf, Germany
| | - Horst-Werner Korf
- Institute of Anatomy I, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
| | - Charlotte von Gall
- Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
- Correspondence: ; Tel.: +49-21-1811-5046
| | - Amira A. H. Ali
- Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany
- Department of Human Anatomy and Embryology, Medical Faculty, Mansoura University, El-Gomhoria St. 1, Mansoura 35516, Egypt
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27
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Hattori K, Sobue T, Zha L, Kitamura T, Shimomura Y, Iwasaki M, Inoue M, Yamaji T, Tsugane S, Sawada N. Association between working hours and cancer risk in Japan: The Japan public health center-based prospective study. J Occup Health 2022; 64:e12375. [PMID: 36502469 PMCID: PMC9741916 DOI: 10.1002/1348-9585.12375] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 10/19/2022] [Accepted: 11/15/2022] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES In this study, we evaluated the association between working hours and cancer risk in the Japanese population, which has not been evaluated. METHODS Using a cohort database from a Japan Public Health Center-based Prospective Study, we evaluated 26 738 participants (16 351 men and 10 387 women), who responded to a questionnaire about working hours and followed these participants from 1993-1994 to 2013. Participants were divided into four groups according to working hours (≤6, 7-8, 9-10, ≥11 h/day). The hazard ratio (HR) and 95% confidence interval (CI) of each cancer incidence were calculated using a multivariable-adjusted Cox proportional hazard model. RESULTS During 488 383 person-years of follow-up, 481 patients with newly diagnosed cancers were identified. There was no clear association between long working hours and overall cancer, lung cancer, and stomach cancer risks. Long working hours tended to increase prostate cancer risk in men and breast cancer risk in women, although the difference was not statistically significant. Increased liver cancer risk with short working hours (HR [95% CI]; 3.15 [1.44-6.88] in the ≤6 h/day group vs. 7-8 h/day) was observed. Colorectal cancer also tended to increase risk in short working hours, however, there were not statistically significance. CONCLUSIONS In this population, long working hours were not associated with cancer risk with statistically significance. The association between short working hours and liver cancer risk was observed, probably due to the reverse causation of liver cancer.
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Affiliation(s)
- Kana Hattori
- Department of Social and Environmental MedicineGraduate School of Medicine, Osaka University, SuitaOsakaJapan
| | - Tomotaka Sobue
- Department of Social and Environmental MedicineGraduate School of Medicine, Osaka University, SuitaOsakaJapan
| | - Ling Zha
- Department of Social and Environmental MedicineGraduate School of Medicine, Osaka University, SuitaOsakaJapan
| | - Tetsuhisa Kitamura
- Department of Social and Environmental MedicineGraduate School of Medicine, Osaka University, SuitaOsakaJapan
| | - Yoshimitsu Shimomura
- Department of Social and Environmental MedicineGraduate School of Medicine, Osaka University, SuitaOsakaJapan
| | - Motoki Iwasaki
- Division of EpidemiologyNational Cancer Center Institute for Cancer Control, National Cancer CenterChuo‐kuJapan
| | - Manami Inoue
- Division of PreventionNational Cancer Center Institute for Cancer Control, National Cancer CenterChuo‐kuJapan
| | - Taiki Yamaji
- Division of EpidemiologyNational Cancer Center Institute for Cancer Control, National Cancer CenterChuo‐kuJapan
| | - Shoichiro Tsugane
- Division of Cohort ResearchNational Cancer Center Institute for Cancer Control, National Cancer CenterChuo‐kuJapan
| | - Norie Sawada
- Division of Cohort ResearchNational Cancer Center Institute for Cancer Control, National Cancer CenterChuo‐kuJapan
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28
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Wetten A, Ogle L, Mells G, Hegade VS, Jopson L, Corrigan M, Palmer J, Johansson M, Bäckström T, Doverskog M, Jones DEJ, Dyson JK. Neurosteroid Activation of GABA-A Receptors: A Potential Treatment Target for Symptoms in Primary Biliary Cholangitis? Can J Gastroenterol Hepatol 2022; 2022:3618090. [PMID: 36523650 PMCID: PMC9747297 DOI: 10.1155/2022/3618090] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS A third of patients with primary biliary cholangitis (PBC) experience poorly understood cognitive symptoms, with a significant impact on quality of life (QOL), and no effective medical treatment. Allopregnanolone, a neurosteroid, is a positive allosteric modulator of gamma-aminobutyricacid-A (GABA-A) receptors, associated with disordered mood, cognition, and memory. This study explored associations between allopregnanolone and a disease-specific QOL scoring system (PBC-40) in PBC patients. METHOD Serum allopregnanolone levels were measured in 120 phenotyped PBC patients and 40 age and gender-matched healthy controls. PBC subjects completed the PBC-40 at recruitment. Serum allopregnanolone levels were compared across PBC-40 domains for those with none/mild symptoms versus severe symptoms. RESULTS There were no overall differences in allopregnanolone levels between healthy controls (median = 0.03 ng/ml (IQR = 0.025)) and PBC patients (0.031 (0.42), p = 0.42). Within the PBC cohort, higher allopregnanolone levels were observed in younger patients (r (120) = -0.53, p < 0.001) but not healthy controls (r (39) = -0.21, p = 0.21). Allopregnanolone levels were elevated in the PBC-40 domains, cognition (u = 1034, p = 0.02), emotional (u = 1374, p = 0.004), and itch (u = 795, p = 0.03). Severe cognitive symptoms associated with a younger age: severe (50 (12)) vs. none (60 (13); u = 423 p = 0.001). CONCLUSION Elevated serum allopregnanolone is associated with severe cognitive, emotional, and itch symptoms in PBC, in keeping with its known action on GABA-A receptors. Existing novel compounds targeting allopregnanolone could offer new therapies in severely symptomatic PBC, satisfying a significant unmet need.
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Affiliation(s)
- Aaron Wetten
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK
- Freeman Hospital, Newcastle-upon-Tyne, UK
| | - Laura Ogle
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK
- Freeman Hospital, Newcastle-upon-Tyne, UK
| | - George Mells
- Department of Human Genetics, University of Cambridge, Cambridge, UK
| | | | - Laura Jopson
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK
- Freeman Hospital, Newcastle-upon-Tyne, UK
| | | | - Jeremy Palmer
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK
| | | | - Torbjörn Bäckström
- Umecrine Cognition AB, Solna, Sweden
- Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umea, Sweden
| | | | - David E. J. Jones
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK
- Freeman Hospital, Newcastle-upon-Tyne, UK
| | - Jessica K. Dyson
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK
- Freeman Hospital, Newcastle-upon-Tyne, UK
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Choi JI, Lee YL, Lee SY. Efficacy and safety of fermented Prunus mume vinegar on fatigue improvement in adults with unexplained fatigue: A randomized controlled trial. Front Nutr 2022; 9:990418. [PMID: 36438753 PMCID: PMC9682036 DOI: 10.3389/fnut.2022.990418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 10/19/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND The accumulation of fatigue leads to reduced physical, emotional, psychological, and social functions. OBJECTIVES Fermented Prunus mume vinegar (PV) improves fatigue in animals; however, studies in humans have not been conducted. We aimed to examine the effects and safety of consuming fermented PV for 8 weeks on fatigue indices in adults with unexplained fatigue while considering the placebo effect. METHODS A randomized, double-blind, placebo-controlled trial was conducted in adults of >19 years, who were diagnosed with unexplained fatigue for at least 1 month. Eighty participants were randomly assigned to receive daily 70 mL of fermented PV (2.56 mg/g, chlorogenic acid, and 15.3 mg/g, citric acid) or a placebo for 8 weeks. At baseline and 4 and 8 weeks after treatment, the participants were visited for blood tests (liver enzyme, glucose, creatinine, lactate, malondialdehyde [MDA], and creatine kinase [CK]) and questionnaires (Fatigue Severity Scale [FSS], fatigue visual analog scale [VAS], Beck Depression Inventory [BDI], the Korean version of the Brief Encounter Psychosocial Instrument [BEPSI-K], EQ-5D-3L, and EQ-VAS]). RESULTS Fermented PV supplementation for 8 weeks did not remarkably improve the fatigue indices when compared to placebo. Additionally, differences in fatigue VAS, BDI, BEPSI-K, EQ-5D-3L, EQ-VAS, lactate, CK, and MDA concentrations between the groups were not observed. However, FSS had positively correlated with fatigue VAS, BDI, and BEPSI-K, whereas it was negatively correlated with EQ-5D-3L and EQ-VAS at the baseline and 8 weeks. None of the participants reported adverse events. CONCLUSION The efficacy of fermented PV did not exceed the efficacy of placebo in adults with unexplained fatigue. CLINICAL TRIAL REGISTRATION [ClinicalTrials.gov], identifier [NCT04319692].
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Affiliation(s)
- Jung In Choi
- Family Medicine Clinic and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Ye Li Lee
- Integrated Research Institute for Natural Ingredients and Functional Foods, Yangsan, South Korea
| | - Sang Yeoup Lee
- Family Medicine Clinic and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, South Korea
- Integrated Research Institute for Natural Ingredients and Functional Foods, Yangsan, South Korea
- Department of Medical Education, Pusan National University School of Medicine, Yangsan, South Korea
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Vitality, mental health and role-physical mediate the influence of coping on depressive symptoms and self-efficacy in patients with non-alcoholic fatty liver disease: A cross-sectional study. J Psychosom Res 2022; 162:111045. [PMID: 36174369 DOI: 10.1016/j.jpsychores.2022.111045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 09/14/2022] [Accepted: 09/17/2022] [Indexed: 11/21/2022]
Abstract
OBJECTIVE Our aim was to determine whether the association between active coping and depressive symptoms in patients with non-alcoholic fatty liver disease (NAFLD) was mediated by vitality, and whether diabetes and obesity could impact on this relationship. We also wanted to find out whether mental health and role-physical modulated the relationship between passive/avoidance coping and self-efficacy, and the role of liver fibrosis. METHODS Depressive symptoms (BDI-II), self-efficacy (GSE), coping (COPE-28) and quality of life (SF-12) were evaluated in 509 biopsy-proven NAFLD patients in this cross-sectional study. Mediation and moderated mediation models were conducted using the SPSS PROCESS v3.5 macro. RESULTS Vitality mediated the relationship between active coping and depressive symptoms (-2.254, CI = -2.792 to -1.765), with diabetes (-0.043, p = 0.017) and body mass index (BMI) (-0.005, p = 0.009) moderating the association. In addition, mental health (-6.435, CI = -8.399 to -4.542) and role-physical (-1.137, CI = -2.141 to -0.315) mediated the relationship between passive/avoidance coping and self-efficacy, with fibrosis stage (0.367, p < 0.001) moderating this association. Specifically, the presence of diabetes and significant fibrosis, and a higher BMI, were associated with greater negative impact on participant depressive symptoms or self-efficacy. CONCLUSION A maladaptive coping style was associated with poorer vitality, mental health and role-physical in NAFLD patients, which along with the presence of metabolic comorbidity (diabetes and obesity) and significant fibrosis predicted more depressive symptoms or poorer self-efficacy in these patients. These results suggested incorporating emotional and cognitive evaluation and treatment in patients with NAFLD.
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Rogal SS, Hansen L, Patel A, Ufere NN, Verma M, Woodrell CD, Kanwal F. AASLD Practice Guidance: Palliative care and symptom-based management in decompensated cirrhosis. Hepatology 2022; 76:819-853. [PMID: 35103995 PMCID: PMC9942270 DOI: 10.1002/hep.32378] [Citation(s) in RCA: 91] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 01/14/2022] [Indexed: 12/15/2022]
Affiliation(s)
- Shari S. Rogal
- Departments of Medicine and Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare Center, Pittsburgh, Pennsylvania, USA
| | - Lissi Hansen
- School of Nursing, Oregon Health and Science University, Portland, Oregon, USA
| | - Arpan Patel
- Division of Digestive Diseases, David Geffen School of Medicine at University of California, Los Angeles, California, USA
- Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at University of California, Los Angeles, California, USA
| | - Nneka N. Ufere
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Manisha Verma
- Department of Medicine, Einstein Healthcare Network, Philadelphia, Pennsylvania, USA
| | - Christopher D. Woodrell
- Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA
| | - Fasiha Kanwal
- Sections of Gastroenterology and Hepatology and Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
- VA HSR&D Center for Innovations in Quality, Effectiveness, and Safety (IQuESt) and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
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32
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Lu L, Chinese Society of Hepatology and Chinese Medical Association. Guidelines for the Management of Cholestatic Liver Diseases (2021). J Clin Transl Hepatol 2022; 10:757-769. [PMID: 36062287 PMCID: PMC9396310 DOI: 10.14218/jcth.2022.00147] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/17/2022] [Accepted: 04/18/2022] [Indexed: 12/04/2022] Open
Abstract
In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology issued a consensus statement on the diagnosis and management of cholestatic liver diseases. More clinical data on this topic have appeared during recent years. The Autoimmune Liver Disease Group of the Chinese Society of Hepatology organized an expert group to review recent evidence and provide an update to these previous guidelines. Herein, we provide 22 recommendations as a working reference for the management of cholestatic liver diseases by clinical practitioners.
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Affiliation(s)
- Lungen Lu
- Correspondence to: Lungen Lu, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China. ORCID: https://orcid.org/0000-0002-1533-4068. Tel: +86-13381616206, E-mail:
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Świątczak M, Młodziński K, Sikorska K, Raczak A, Lipiński P, Daniłowicz-Szymanowicz L. Chronic Fatigue Syndrome in Patients with Deteriorated Iron Metabolism. Diagnostics (Basel) 2022; 12:diagnostics12092057. [PMID: 36140459 PMCID: PMC9498000 DOI: 10.3390/diagnostics12092057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/11/2022] [Accepted: 08/23/2022] [Indexed: 11/16/2022] Open
Abstract
Fatigue is a common, non-specific symptom that often impairs patients’ quality of life. Even though fatigue may be the first symptom of many serious diseases, it is often underestimated due to its non-specific nature. Iron metabolism disorders are a prominent example of conditions where fatigue is a leading symptom. Whether it is an iron deficiency or overload, tiredness is one of the most common features. Despite significant progress in diagnosing and treating iron pathologies, the approach to chronic fatigue syndrome in such patients is not precisely determined. Our study aims to present the current state of knowledge on fatigue in patients with deteriorated iron metabolism.
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Affiliation(s)
- Michał Świątczak
- II Department of Cardiology and Electrotherapy, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Krzysztof Młodziński
- II Department of Cardiology and Electrotherapy, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Katarzyna Sikorska
- Department of Tropical Medicine and Epidemiology, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Alicja Raczak
- Clinical Psychology Department, Faculty of Health Sciences, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Paweł Lipiński
- Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Wólka Kosowska, 05-552 Jastrzębiec, Poland
| | - Ludmiła Daniłowicz-Szymanowicz
- II Department of Cardiology and Electrotherapy, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
- Correspondence:
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Gable KL, Peric S, Lutz MW, Bozovic I, Petrovic M, Stojanov A, Basta I, Allen JA. A longitudinal evaluation of fatigue in chronic inflammatory demyelinating polyneuropathy. Brain Behav 2022; 12:e2712. [PMID: 35862228 PMCID: PMC9392529 DOI: 10.1002/brb3.2712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/24/2022] [Accepted: 07/03/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Fatigue is a common but poorly understood complaint in patients with immune-mediated polyneuropathies. We sought to evaluate changes in fatigue over 1 year in a cohort of chronic inflammatory demyelinating polyneuropathy (CIDP) patients and to correlate changes in fatigue with changes in disability and quality of life. Investigation into other factors that may contribute to fatigue with a particular interest in the role other chronic disease states may play was also performed. METHODS Fifty patients with CIDP who satisfied the 2010 EFNS/PNS diagnostic criteria were followed over the period of 1 year at three tertiary care centers in Serbia. Assessments of disability, quality of life, and patient perception of change and fatigue were collected at two time points 12 months apart. Comorbidities, treatment regimens, and sedating medication use was collected. RESULTS Disability, quality of life, and patient perception of change showed statistically significant correlations with change in fatigue (p < .01). Increased levels of fatigue were noted in patients who used sedating medications (p = .05) and who had a comorbid chronic medical condition (p = .01). INTERPRETATION Worsening fatigue correlates over time with increased disability and worse quality of life. Fatigue is not specific to CIDP, but is common in many chronic medical conditions and with the use of sedating medications. Our findings support the importance of identifying and supportively managing fatigue in patients with CIDP, but cautions against considering fatigue as a CIDP diagnostic symptom or using fatigue to justify immunotherapy utilization.
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Affiliation(s)
- Karissa L Gable
- Duke Neurological Disorders Clinic, Duke University Medical Center, Durham, North Carolina, USA
| | - Stojan Peric
- Faculty of Medicine and University Clinical Center of Serbia, Neurology Clinic, University of Belgrade, Belgrade, Serbia
| | - Michael W Lutz
- Duke Neurological Disorders Clinic, Duke University Medical Center, Durham, North Carolina, USA
| | - Ivo Bozovic
- Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia
| | - Milutin Petrovic
- Neurology Clinic, University Clinical Center of Kragujevac, Kragujevac, Serbia
| | | | - Ivana Basta
- Faculty of Medicine and University Clinical Center of Serbia, Neurology Clinic, University of Belgrade, Belgrade, Serbia
| | - Jeffrey A Allen
- Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA
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Abstract
Hypothalamus-pituitary-adrenal axis assessment in patients with cirrhosis is challenging. The phenotype of fatigue, hypotension, electrolyte disarray, and abdominal pain characterizing primary adrenal insufficiency (AI) overlaps significantly with decompensated liver disease. Reliance on total cortisol assays in hypoproteinemic states is problematic, yet abnormal stimulated levels in cirrhosis are associated with poor clinical outcomes. Alternative measures including free plasma or salivary cortisol levels have theoretical merit but are limited by unclear prognostic significance and undefined cirrhosis-specific reference ranges. Further complicating matters is that AI in cirrhosis represents a spectrum of impairment. Although absolute cortisol deficiency can occur, this represents a minority of cases. Instead, there is an emerging concept that cirrhosis, with or without critical illness, may induce a “relative” cortisol deficiency during times of stress. In addition, the limitations posed by decreased synthesis of binding globulins in cirrhosis necessitate re-evaluation of traditional AI diagnostic thresholds.
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Affiliation(s)
- Brian J Wentworth
- Division of Gastroenterology & Hepatology, School of Medicine, University of Virginia , Charlottesville, VA
| | - Helmy M Siragy
- Division of Endocrinology & Metabolism, School of Medicine, University of Virginia , Charlottesville, VA
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36
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Kaplan A, Rosenblatt R. Symptom Management in Patients with Cirrhosis: a Practical Guide. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2022; 20:144-159. [PMID: 35313484 PMCID: PMC8928010 DOI: 10.1007/s11938-022-00377-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 02/14/2022] [Indexed: 12/03/2022]
Abstract
Purpose of the review
Though it is well known that cirrhosis is associated with significant morbidity and mortality, management of symptoms in cirrhosis can be difficult. This review serves to offer practical guidance in the management of liver-specific symptoms of cirrhosis as well as other symptoms with special hepatic considerations. Recent findings We discuss liver-specific symptoms and management, including ascites and refractory ascites, hepatic encephalopathy, pruritus, and muscle cramping. We also discuss the challenges of treating more generalized symptoms in cirrhosis, including pain, depression/anxiety, appetite, and fatigue. Medication management is, especially complex in this population given the altered metabolism of drugs, and we consider some strategies to approach this. Summary With the right tools, provided throughout this review, hepatologists should be well equipped to manage the nuanced liver-specific and generalized symptoms in patients with cirrhosis.
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Affiliation(s)
- Alyson Kaplan
- Department of Gastroenterology and Hepatology, New York Presbyterian, Weill Cornell Medicine, New York, NY USA
| | - Russell Rosenblatt
- Department of Gastroenterology and Hepatology, New York Presbyterian, Weill Cornell Medicine, New York, NY USA
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El-Khoueiry AB, Meyer T, Cheng AL, Rimassa L, Sen S, Milwee S, Kelley RK, Abou-Alfa GK. Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child-Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial. BMC Cancer 2022; 22:377. [PMID: 35397508 PMCID: PMC8994237 DOI: 10.1186/s12885-022-09453-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 03/16/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) and Child-Pugh B liver cirrhosis have poor prognosis and are underrepresented in clinical trials. The CELESTIAL trial, in which cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with HCC and Child-Pugh A liver cirrhosis at baseline, was evaluated for outcomes in patients who had Child-Pugh B cirrhosis at Week 8. METHODS This was a retrospective analysis of adult patients with previously treated advanced HCC. Child-Pugh B status was assessed by the investigator. Patients were randomised 2:1 to cabozantinib (60 mg once daily) or placebo. RESULTS Fifty-one patients receiving cabozantinib and 22 receiving placebo had Child-Pugh B cirrhosis at Week 8. Safety and tolerability of cabozantinib for the Child-Pugh B subgroup were consistent with the overall population. For cabozantinib- versus placebo-treated patients, median OS from randomisation was 8.5 versus 3.8 months (HR 0.32, 95% CI 0.18-0.58), median PFS was 3.7 versus 1.9 months (HR 0.44, 95% CI 0.25-0.76), and best response was stable disease in 57% versus 23% of patients. CONCLUSIONS These encouraging results with cabozantinib support the initiation of prospective studies in patients with advanced HCC and Child-Pugh B liver function. CLINICAL TRIAL REGISTRATION NCT01908426.
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Affiliation(s)
| | - Tim Meyer
- Royal Free Hospital, University College London, London, UK
| | | | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | | | | | - Robin Kate Kelley
- UCSF Helen Diller Family Comprehensive Cancer Center, CA, San Francisco, USA
| | - Ghassan K Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
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A Study of Logistic Regression for Fatigue Classification Based on Data of Tongue and Pulse. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2454678. [PMID: 35287309 PMCID: PMC8917949 DOI: 10.1155/2022/2454678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 01/05/2022] [Indexed: 12/02/2022]
Abstract
Methods The Tongue and Face Diagnosis Analysis-1 instrument and Pulse Diagnosis Analysis-1 instrument were used to collect the tongue image and sphygmogram of the subhealth fatigue population (n = 252) and disease fatigue population (n = 1160), and we mainly analyzed the tongue and pulse characteristics and constructed the classification model by using the logistic regression method. Results The results showed that subhealth fatigue people and disease fatigue people had different characteristics of tongue and pulse, and the logistic regression model based on tongue and pulse data had a good classification effect. The accuracies of models of healthy controls and subhealth fatigue, subhealth fatigue and disease fatigue, and healthy controls and disease fatigue were 68.29%, 81.18%, and 84.73%, and the AUC was 0.698, 0.882, and 0.924, respectively. Conclusion This study provided a new noninvasive method for the fatigue diagnosis from the perspective of objective tongue and pulse data, and the modern tongue diagnosis and pulse diagnosis have good application prospects.
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Abstract
Fatigue is a common symptom in patients with liver disease and has a significant impact on the health-related quality of life (HR-QoL). Its pathogenesis is poorly understood and is considered multifactorial. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the production, storage, and release of substrate for energy generation. Also, the liver "cross-talks" with the key organs that are responsible for this symptom complex-gut, skeletal muscle, and brain. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) components. The treatment strategies for the management of fatigue are behavioral changes and pharmacotherapy, along with dietetic intervention and exercise. However, there is no consensus on management strategies for fatigue in patients with liver disease. This article gives an overview of fatigue as a concept, its pathophysiology, measures to evaluate fatigue in patients with liver disease, the impact of fatigue on chronic liver disease, assessment of fatigue in an appropriate clinical setting, and various interventions to manage fatigue.
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Key Words
- 6MWD, 6 min walk distance
- ACG, anterior cingulate gyrus
- ADL, activities of daily living
- BBB, blood-brain barrier
- BNST, bed nucleus of stria terminalis
- CEC, cerebral endothelial cell
- CFS, chronic fatigue syndrome
- CPET, cardio-pulmonary exercise testing
- CRH, corticotropin release hormone
- DA, dopamine
- FAS, fatigue assessment scale
- FIS, fatigue impact scale
- FSS, fatigue severity scale
- HGS, hand-grip strength
- HPA, hypothalamus-pituitary-adrenal
- HR-QoL, health-related quality of life
- IADL, instrumental activities of daily living
- ME, meningo-encephalomyelitis
- ME, meningoencephalitis
- NAFLD, nonalcoholic fatty liver disease
- NM, neuromuscular
- NO, nitric oxide
- PGE2, prostaglandins
- PRO, patient-reported outcomes
- PROMIS-F, patient-reported outcome measure information system for fatigue
- PSC, primary sclerosing cholangitis
- SAMe, S-adenosyl-methionine
- SN, substantia nigra
- SPPB, short-physical performance battery
- VAS-F, visual analog scalefatigue
- VTA, ventral tegmental area
- central fatigue
- chronic liver disease
- health-related quality of life [HR-QoL]
- iNOS, inducible nitric oxide synthase
- patient-related outcomes [PRO]
- peripheral fatigue
- vmPFC, ventromedial prefrontal cortex
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Affiliation(s)
| | - Dharmesh Kapoor
- Address for correspondence: Dr. Dharmesh Kapoor, Department of Hepatology, Yashoda Hospitals, Alexander X road, Secunderabad, Telangana, 500026, India.
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Kremer AE, Mayo MJ, Hirschfield G, Levy C, Bowlus CL, Jones DE, Steinberg A, McWherter CA, Choi YJ. Seladelpar improved measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with primary biliary cholangitis. Liver Int 2022; 42:112-123. [PMID: 34403559 DOI: 10.1111/liv.15039] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 08/11/2021] [Accepted: 08/15/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Primary biliary cholangitis (PBC) can result in life-altering cholestatic pruritus and fatigue, but treatment options are limited. Seladelpar, a peroxisome proliferator-activated receptor-delta (PPARδ) agonist, has demonstrated potent anti-cholestatic effects in clinical studies. This open-label, uncontrolled phase 2 study in PBC patients evaluated the effects of 1-year of seladelpar treatment on measures of pruritus and quality of life. METHODS Self-reported experiences of 101 PBC patients were collected at baseline and after 1 year of seladelpar treatment using the pruritus visual analog scale (VAS), 5D-itch scale, and PBC-40 questionnaires along with bile acid profiles. RESULTS In patients with moderate-to-severe pruritus, substantial improvement in pruritus was seen in 58% and 93% of patients in 5/10 mg and 10 mg treatment groups, respectively. After 1 year, patients reporting improvement substantially outnumbered those who worsened in the total 5-D itch (including individual domains) and PBC-40 (itch and fatigue domains) questionnaires. Improvement in sleep disturbance at 1-year was reported in 81% (5/10 mg) and 78% (10 mg) of the patients with baseline itch-related sleep disturbance by 5-D itch score with similar results using the PBC-40 sleep questionnaire. Seladelpar-treated patients had significant reductions of 46% (5/10 mg) and 31% (10 mg) in the serum bile acid precursor C4 and reductions of up to 38% in serum bile acids. CONCLUSIONS Seladelpar treatment for 1 year led to consistent improvement in both symptom burden and biochemical response, suggesting its potential as a single agent to address two key unmet needs in PBC patients.
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Affiliation(s)
- Andreas E Kremer
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.,Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX, USA
| | - Gideon Hirschfield
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine. Miami, Florida, USA
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA
| | - David E Jones
- Clinical and Translation Research Institute, Newcastle University, Newcastle upon Tyne, UK
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Sleep and liver disease: a bidirectional relationship. Lancet Gastroenterol Hepatol 2021; 6:850-863. [PMID: 34273289 DOI: 10.1016/s2468-1253(21)00169-2] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/06/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023]
Abstract
Sleep is a complex, highly regulated process essential for human health and wellbeing. Increasingly, sleep-wake disturbance has been implicated in the pathogenesis of chronic liver disease, particularly the development and progression of non-alcoholic fatty liver disease and alcohol-related liver disease. Patients with cirrhosis also have a high burden of sleep abnormalities with substantial implications for their quality of life and physical health. This Review summarises the epidemiology and pathophysiology of sleep-wake disturbance in liver disease and discusses the multiple converging pathways leading to abnormal sleeping patterns in patients with cirrhosis. This includes contributions from altered melatonin metabolism, neuromuscular complications, and aberrant thermoregulation. In turn, a vicious cycle is established whereby disrupted sleep can further contribute to liver disease progression. We also begin to unravel the complex, interlinking relationship between sleep-wake disturbance and hepatic encephalopathy, discussing both overlapping and distinct mechanisms and clinical features. Finally, we summarise the current and future therapeutic approaches aiming to improve sleep quality in patients with cirrhosis.
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Pavlov AI, Ivolgin AF, Katenko SV, Eremin MN, Molodova AI, Levchenko OB, Karakozov AG. Diagnostics and treatment of non-alcoholic fatty liver disease with concomitant asthenic syndrome. TERAPEVT ARKH 2021; 93:890-896. [DOI: 10.26442/00403660.2021.08.200974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 09/01/2021] [Indexed: 11/22/2022]
Abstract
Aim. Analysis of the effectiveness of therapy for non-alcoholic fatty liver disease (NAFLD) with severe asthenic syndrome.
Materials and methods. In the period from 2017 to 2019, on the basis of the gastroenterology center of the Vishnevsky 3-rd Central Military Clinical Hospital, 247 patients with NAFLD, including those at the stage of steatohepatitis, and severe asthenic syndrome were examined and treated. The main group included 124 patients, the control group 123 patients. All patients underwent complex laboratory and instrumental diagnostics and neuropsychological research using the subjective asthenia assessment scale (MFI-20). In both groups, domestic drugs were included in the therapy regimen: from the 1st to the 10th day, Heptrong solution 3 ml intramuscularly in the morning; from the 1st to the 60th day UDCA 250 mg orally, 3 capsules at bedtime, Omega-3 forte 1000 mg, 2 capsules in the morning with meals. In group I patients received additionally from the 1st to the 10th day intravenous drip Cytoflavin 10 ml + 0.9% NaCl solution 200 ml; pentoxifylline solution 5 ml + 0.9% NaCl solution 200 ml. Then, from the 11th to the 60th day, Cytoflavin inside, 2 tablets 2 times a day. Pentoxifylline inside 400 mg 1 tablet 3 times a day. All patients underwent neuropsychological examination using the subjective asthenia rating scale (MFI-20).
Results. The effectiveness of treatment in patients of both groups was assessed by clinical, laboratory data and neuropsychological studies. In the main group, a significant reduction in asthenic syndrome was achieved against the background of diagnosed NAFLD compared with the control group.
Conclusion. The early inclusion of patients with NAFLD and severe asthenic syndrome in the treatment regimen, in addition to the basic therapy of Cytoflavin, achieved a significantly high therapeutic effect in the form of normalization of the main clinical, laboratory and instrumental parameters, as well as a significant reduction in the manifestations of asthenia.
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Wunsch E, Stadnik A, Kruk B, Szczepankiewicz B, Kotarska K, Krawczyk M, Górnicka B, Wójcicki M, Milkiewicz P. Chronic Fatigue Persists in a Significant Proportion of Female Patients After Transplantation for Primary Sclerosing Cholangitis. Liver Transpl 2021; 27:1032-1040. [PMID: 33641247 DOI: 10.1002/lt.26033] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 01/27/2021] [Accepted: 02/08/2021] [Indexed: 12/15/2022]
Abstract
Chronic fatigue and an impairment of general health-related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC-40 and Short Form 36 (SF-36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well-being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one-third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF-36 and PBC-40 domains. Recurrent PSC and unemployment negatively affected the well-being of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.
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Affiliation(s)
- Ewa Wunsch
- Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Anna Stadnik
- Department of Radiology, Medical University of Warsaw, Warsaw, Poland
| | - Beata Kruk
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | | | - Katarzyna Kotarska
- Faculty of Physical Culture and Health, University of Szczecin, Szczecin, Poland
| | - Marcin Krawczyk
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.,Department of Medicine II, Saarland University Medical, Homburg, Germany.,European Reference Network, Saarland University Medical Center, Homburg, Germany
| | - Barbara Górnicka
- Department of Pathology, Medical University of Warsaw, Warsaw, Poland
| | - Maciej Wójcicki
- European Reference Network, Saarland University Medical Center, Homburg, Germany.,Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Milkiewicz
- Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland.,Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.,European Reference Network, Medical University of Warsaw Hospital, Warsaw, Poland
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Valery PC, Bernardes CM, Mckillen B, Amarasena S, Stuart KA, Hartel G, Clark PJ, Skoien R, Rahman T, Horsfall L, Hayward K, Gupta R, Lee A, Pillay L, Powell EE. The Patient's Perspective in Cirrhosis: Unmet Supportive Care Needs Differ by Disease Severity, Etiology, and Age. Hepatol Commun 2021; 5:891-905. [PMID: 34027276 PMCID: PMC8122374 DOI: 10.1002/hep4.1681] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/09/2020] [Accepted: 12/26/2020] [Indexed: 12/13/2022] Open
Abstract
Patients with cirrhosis have significant physical, psychological, and practical needs. We documented patients' perceived need for support with these issues and the differences with increasing liver disease severity, etiology, and age. Using the supportive needs assessment tool for cirrhosis (SNAC), we examined the rate of moderate-to-high unmet needs (Poisson regression; incidence rate ratio [IRR]) and the correlation between needs and sociodemographic/clinical characteristics (multivariable linear regression) in 458 Australians adults with cirrhosis. Primary liver disease etiology was alcohol in 37.6% of patients, chronic viral hepatitis C in 25.5%, and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in 23.8%. A total of 64.6% of patients had Child-Pugh class A cirrhosis. Most patients (81.2%) had at least one moderate-to-high unmet need item; more than 25% reported a moderate-to-high need for help with "lack of energy," "sleep poorly," "feel unwell," "worry about … illness getting worse (liver cancer)," "have anxiety/stress," and "difficulty with daily tasks." Adjusting for key sociodemographic/clinical factors, patients with Child-Pugh C had a greater rate of "practical and physical needs" (vs. Child-Pugh A; IRR = 2.94, 95% confidence interval [CI] 2.57-3.37), patients with NAFLD/NASH had a greater rate of needs with "lifestyle changes" (vs. alcohol; IRR = 1.81, 95% CI 1.18-2.77) and "practical and physical needs" (IRR = 1.43, 95% CI 1.23-1.65), and patients aged ≥65 years had fewer needs overall (vs. 18-64 years; IRR = 0.70, 95% CI 0.64-0.76). Higher overall SNAC scores were associated with Child-Pugh B and C (both P < 0.001), NAFLD/NASH (P = 0.028), patients with "no partner, do not live alone" (P = 0.004), unemployment (P = 0.039), ascites (P = 0.022), and dyslipidemia (P = 0.024) compared with their counterparts. Conclusion: Very high levels of needs were reported by patients with cirrhosis. This information is important to tailor patient-centered care and facilitate timely interventions or referral to support services.
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Affiliation(s)
| | | | - Benjamin Mckillen
- Department of Gastroenterology and HepatologyPrincess Alexandra HospitalBrisbaneQLDAustralia.,Centre for Liver Disease ResearchTranslational Research InstituteFaculty of MedicineUniversity of QueenslandBrisbaneQLDAustralia
| | - Samath Amarasena
- Department of Gastroenterology and HepatologyRoyal Brisbane and Women's HospitalBrisbaneQLDAustralia
| | - Katherine A Stuart
- Department of Gastroenterology and HepatologyPrincess Alexandra HospitalBrisbaneQLDAustralia
| | - Gunter Hartel
- QIMR Berghofer Medical Research InstituteHerstonQLDAustralia
| | - Paul J Clark
- Department of Gastroenterology and HepatologyPrincess Alexandra HospitalBrisbaneQLDAustralia.,Department of Gastroenterology and HepatologyMater HospitalsBrisbaneQLDAustralia
| | - Richard Skoien
- Department of Gastroenterology and HepatologyRoyal Brisbane and Women's HospitalBrisbaneQLDAustralia
| | - Tony Rahman
- Gastroenterology & Hepatology DepartmentPrince Charles HospitalChermsideQLDAustralia
| | - Leigh Horsfall
- Department of Gastroenterology and HepatologyPrincess Alexandra HospitalBrisbaneQLDAustralia.,Centre for Liver Disease ResearchTranslational Research InstituteFaculty of MedicineUniversity of QueenslandBrisbaneQLDAustralia
| | - Kelly Hayward
- Department of Gastroenterology and HepatologyPrincess Alexandra HospitalBrisbaneQLDAustralia.,Centre for Liver Disease ResearchTranslational Research InstituteFaculty of MedicineUniversity of QueenslandBrisbaneQLDAustralia
| | - Rohit Gupta
- Gastroenterology & Hepatology DepartmentPrince Charles HospitalChermsideQLDAustralia
| | - Andrew Lee
- Department of Gastroenterology and HepatologyMater HospitalsBrisbaneQLDAustralia
| | - Leshni Pillay
- Department of Gastroenterology and HepatologyLogan HospitalMeadowbrookQLDAustralia
| | - Elizabeth E Powell
- Department of Gastroenterology and HepatologyPrincess Alexandra HospitalBrisbaneQLDAustralia.,Centre for Liver Disease ResearchTranslational Research InstituteFaculty of MedicineUniversity of QueenslandBrisbaneQLDAustralia
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45
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Gupta R, Gupta R, Kumar N, Rawat VS, Ulfberg J, Allen RP. Restless legs syndrome among subjects having chronic liver disease: A systematic review and meta-analysis. Sleep Med Rev 2021; 58:101463. [PMID: 33836477 DOI: 10.1016/j.smrv.2021.101463] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 03/03/2021] [Accepted: 03/03/2021] [Indexed: 12/14/2022]
Abstract
Sleep disturbances are commonly reported in patients with chronic liver disease (CLD). Changes in quality of sleep in patients with CLD could be related to multiple factors viz., elevated levels of tryptophan, histamine, and increased turnover of dopamine in caudate-putamen and cingulate cortex. Also, iron metabolism disturbances are reported in patients with CLD. These changes may result in restless legs syndrome (RLS) that worsens sleep-quality. There have been reports suggesting an increased prevalence of RLS among patients with CLD. Literature was searched in PubMed, EMBASE, and Google Scholar. A total of twenty-two relevant articles were found. Out of these, nine studies have assessed the prevalence of RLS among patients with chronic liver disease or cirrhosis in the clinical population. Population prevalence reported from various studies was used to calculate odds ratio. Having included studies using various methods for diagnosis (clinical as well as questionnaires) pooled odds-ratio for the RLS was 8.62. It remains unaffected by study-method, gender, age, and geographical-area. However, studies using clinical diagnosis for RLS had lower odds compared to questionnaire based diagnosis. Studies varied with regards to diagnostic methods, age, gender, etiology, and severity of liver dysfunction. The severity and etiology of CLD and biochemical correlate of CLD were not found to be associated with RLS. Possible pathophysiological mechanisms are discussed for the occurrence of RLS in this population. In conclusion, the prevalence of RLS is higher among patients with CLD, however, the correlates are unknown.
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Affiliation(s)
- Ravi Gupta
- Department of Pyshciatry, Division of Sleep Medicine, All India Institute of Medical Sciences, Rishikesh, 249203, India
| | - Rohit Gupta
- Department of Gastroenterology, All India Institute of Medical Sciences, Rishikesh, 249203, India.
| | - Niraj Kumar
- Department of Neurology and Division of Sleep Medicine, All India Institute of Medical Sciences, Rishikesh, 249203, India
| | - Vikram Singh Rawat
- Department of Pyshciatry, Division of Sleep Medicine, All India Institute of Medical Sciences, Rishikesh, 249203, India
| | - Jan Ulfberg
- Sleep Clinic, Capio Medical Center, Hamnplan, Örebro, Sweden
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Yamamura S, Nakano D, Hashida R, Tsutsumi T, Kawaguchi T, Okada M, Isoda H, Takahashi H, Matsuse H, Eguchi Y, Sumida Y, Nakajima A, Gerber L, Younossi ZM, Torimura T. Patient-reported outcomes in patients with non-alcoholic fatty liver disease: A narrative review of Chronic Liver Disease Questionnaire-non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2021; 36:629-636. [PMID: 32627871 DOI: 10.1111/jgh.15172] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/17/2020] [Accepted: 07/01/2020] [Indexed: 12/14/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the leading causes of hepatocellular carcinoma and liver transplantation. Moreover, patients with NAFLD frequently complain of non-specific symptoms including fatigue, abdominal discomfort, as well as anxiety, and NAFLD is reported to affect patient-reported outcomes (PROs). Thus, for clarifying the total burden of NAFLD, it is crucial to assess all associated outcomes, including not only clinical and economic outcomes but also PROs. PROs are thought to reflect what is happening in one's daily life and is an important way patients and health-care professionals communicate. There are various instruments for the assessment of PROs. Recently, a NAFLD/non-alcoholic steatohepatitis (NASH)-specific instrument called "Chronic Liver Disease Questionnaire (CLDQ)-NAFLD/NASH" has been developed. CLDQ-NAFLD/NASH comprises six domains: (i) abdominal symptoms, (ii) activity/energy, (iii) emotional health, (iv) fatigue, (v) systemic symptoms, and (vi) worry. CLDQ-NAFLD/NASH has demonstrated excellent internal consistency, face validity, content validity, and test-retest reliability. It has been sufficiently validated in two international phase 3 clinical trials. In this review, we summarize features of various instruments for assessing PROs by focusing on CLDQ-NAFLD/NASH. We also examine the validity of CLDQ-NAFLD/NASH in Japanese patients and alterations in CLDQ-NAFLD/NASH score in Japanese patients with significant hepatic fibrosis. Moreover, we discuss the utility of CLDQ-NAFLD/NASH in phase 3 clinical trials and in a real-world clinical setting.
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Affiliation(s)
- Sakura Yamamura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Ryuki Hashida
- Department of Orthopedics, Kurume University School of Medicine, Kurume, Japan.,Division of Rehabilitation, Kurume University Hospital, Kurume, Japan
| | - Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Michiaki Okada
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Nabeshima, Japan
| | - Hiroshi Isoda
- Liver Center, Saga University Hospital, Nabeshima, Japan
| | - Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Nabeshima, Japan
| | - Hiroo Matsuse
- Department of Orthopedics, Kurume University School of Medicine, Kurume, Japan.,Division of Rehabilitation, Kurume University Hospital, Kurume, Japan
| | - Yuichiro Eguchi
- Liver Center, Saga University Hospital, Nabeshima, Japan.,Locomedical General Institution, Medical cooperation Locomedical, Ogi, Japan
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Lynn Gerber
- Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Zobair M Younossi
- Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Phaw NA, Leighton J, Dyson JK, Jones DE. Managing cognitive symptoms and fatigue in cholestatic liver disease. Expert Rev Gastroenterol Hepatol 2021; 15:235-241. [PMID: 33131347 DOI: 10.1080/17474124.2021.1844565] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Patients with cholestatic diseases may develop fatigue and cognitive symptoms. The impact of symptom burden may be significant in some patients. To date, there are no effective pharmacological therapies to improve cognitive symptoms or fatigue in cholestasis and we are wholly reliant on supportive approaches. Area covered: This review provides an overview of cognitive symptoms and fatigue in the cholestatic liver disease primary biliary cholangitis (PBC), including pathophysiology and our approach to the management of these symptoms. Expert opinion: The impact of fatigue and cognitive symptoms on the perceived quality of life can be profound for patients with PBC. The pathophysiology of these symptoms is complex and poorly understood, making the development of therapeutic trials of symptom-directed therapies challenging. The current recommended management for fatigue and cognitive symptoms is mainly supportive.
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Affiliation(s)
- Naw April Phaw
- Faculty of Medical Sciences, Institute of Translational and Clinical Research, Newcastle University , UK.,Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Trust , Newcastle upon Tyne, England
| | - Jessica Leighton
- Faculty of Medical Sciences, Institute of Translational and Clinical Research, Newcastle University , UK
| | - Jessica Katharine Dyson
- Faculty of Medical Sciences, Institute of Translational and Clinical Research, Newcastle University , UK.,Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Trust , Newcastle upon Tyne, England
| | - David Ej Jones
- Faculty of Medical Sciences, Institute of Translational and Clinical Research, Newcastle University , UK.,Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Trust , Newcastle upon Tyne, England.,National Institute of Health Research Newcastle Biochemical Research Centre, Newcastle University School of Clinical Medical Sciences , Newcastle upon Tyne, UK
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Gut Microbiome and Nonalcoholic Fatty Liver Disease (NAFLD): Implications for Nursing Care of Individuals Living With Chronic Metabolic Diseases. Gastroenterol Nurs 2021; 44:E18-E22. [PMID: 33538526 DOI: 10.1097/sga.0000000000000545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/01/2020] [Indexed: 11/25/2022] Open
Abstract
At present, the incidence of nonalcoholic fatty liver disease (NAFLD) in adults is increasing year by year and at a younger age. Evidence-based healthcare has confirmed that NAFLD is closely related to obesity, cardiovascular disease, type 2 diabetes, metabolic syndrome, and other chronic metabolic diseases. Despite the growing prevalence of NAFLD, little is known about symptoms for patients at risk of NAFLD progression, thus preventing healthcare providers from intervening at an early stage. In addition, these symptoms usually cause problems for patients to cope with other chronic metabolic diseases. Symptoms may have a biological basis; especially as the changes of gut microbes may affect the symptoms of metabolic diseases. This article aims to describe the new role of gut microbes in the development of NAFLD, focusing on the potential relationship between gut microbes and symptoms of NAFLD, as well as the mechanism of action of the "gut-liver-brain" axis. This information can be useful in developing precise nursing interventions for NAFLD patients, restoring the "health" of gut microbes, and alleviating the symptom burden of chronic metabolic disease in NAFLD.
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Plotogea OM, Ilie M, Bungau S, Chiotoroiu AL, Stanescu AMA, Diaconu CC. Comprehensive Overview of Sleep Disorders in Patients with Chronic Liver Disease. Brain Sci 2021; 11:142. [PMID: 33499194 PMCID: PMC7911845 DOI: 10.3390/brainsci11020142] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/16/2021] [Accepted: 01/19/2021] [Indexed: 12/12/2022] Open
Abstract
The impact of sleep disorders (SDs) on patients with chronic liver diseases (CLD) is tremendous. SDs are frequently encountered among these patients and interfere with their quality of life. This review aims to present the data available so far about the prevalence, phenotypes, and proposed pathophysiological mechanisms of SDs in CLD. Moreover, we proposed to search the literature regarding the most reliable methods to assess SDs and the possible therapeutic options in patients with CLD. The main results of this review show that when it comes to prevalence, the percentages reported vary widely between studies performed among populations from the USA or Europe and those coming from Asian countries. Furthermore, it has been proven that SDs may also be present in the absence of neurocognitive disorders attributable to hepatic encephalopathy (HE), which contradicts traditional suppositions where SDs were considered part of the clinical scenario of HE. Currently, there are no specific recommendations or protocols to assess SDs in CLD patients and data about the therapeutic management are limited. Taking into consideration their impact, a protocol for diagnosing and managing SDs should be developed and included in the daily practice of hepatologists.
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Affiliation(s)
- Oana-Mihaela Plotogea
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Madalina Ilie
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | | | | | - Camelia Cristina Diaconu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
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50
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Abe K, Fujita M, Hayashi M, Takahashi A, Ohira H. The Efficacy of Levocarnitine Treatment in Relieving Fatigue in Patients with Cirrhosis but without Overt Hepatic Encephalopathy. Intern Med 2021; 60:3533-3542. [PMID: 34776465 PMCID: PMC8666222 DOI: 10.2169/internalmedicine.7175-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Objective In the present study, we prospectively examined the efficacy of levocarnitine in relieving symptoms of fatigue in patients with cirrhosis but without overt hepatic encephalopathy. Methods Twenty-one cirrhotic patients who were able to undergo fatigue symptom evaluations at our institution were enrolled. A total of 12 cirrhotic patients underwent levocarnitine treatment (1,200-1,800 mg/day), while 9 did not undergo levocarnitine treatment. As primary endpoints, we investigated whether or not levocarnitine treatment exerted any beneficial effects by assessing the symptoms of fatigue [8-item Short-Form Health Survey (SF-8) and Fisk Fatigue Severity Score (FFSS)] at baseline and three months after treatment. Furthermore, as exploratory secondary endpoints, we investigated whether or not levocarnitine treatment exerted ameliorative effects on oxidative stress by assessing the serum thioredoxin (TRX) and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Results The median age of the patients was 73 years old. Three men and 18 women were categorized by their Child-Pugh class (A and B in 14 and 7 patients, respectively). There were no significant differences in the clinical laboratory values between the two groups. The FFSS and SF-8 scores were significantly improved in the patients with cirrhosis who underwent levocarnitine treatment (p<0.01) but not in those who did not undergo levocarnitine treatment. Furthermore, three months after levocarnitine treatment, the serum carnitine concentrations were significantly increased, and the serum thioredoxin levels were decreased in the patients with cirrhosis who underwent levocarnitine treatment (p<0.05). Conclusion These results suggest that levocarnitine treatment may relieve symptoms of fatigue in cirrhotic patients by reducing oxidative stress.
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Affiliation(s)
- Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Masashi Fujita
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Manabu Hayashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Atsushi Takahashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
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