Minimal Hepatic Encephalopathy Is Associated With Falls

OBJECTIVES:Minimal hepatic encephalopathy (MHE) reduces quality of life and impacts daily functioning. It is known to impair fitness to drive, but deficits in attention and reaction may also be associated with falls. Falls may have important consequences in patients with cirrhosis due to coagulopathy, osteoporosis, and operative risk. However, the relationship between MHE and falls has not yet been evaluated. The objective of this study is to retrospectively investigate whether MHE is associated with falls in patients with cirrhosis.METHODS:We included 130 cirrhotic outpatients and 43 controls. MHE was diagnosed according to the results of the psychometric hepatic encephalopathy score (PHES). We recorded the reported incidence and number of falls in the 12 months before the study, the severity of injuries, and the need for healthcare services.RESULTS:Forty-five (34.6%) patients with cirrhosis exhibited MHE. The proportion of patients with MHE that reported falls (40%) was higher than those without MHE (12.9%, P<0.001), which was similar to controls (11.6%). In patients with MHE, there was a higher need for primary healthcare services (8.8 vs. 0%, P=0.004) and hospitalization (6.6 vs. 2.3%, P=0.34) due to falls than in patients without MHE. Patients on psychoactive drugs (n=21) showed a stronger association between MHE and falls: 6/8 (75%) patients with MHE presented falls vs. 2/13 (15.3%) patients without MHE (P=0.01). In patients not receiving psychoactive drugs (n=109), the incidence of falls was 12/37 (32.4%) in patients with MHE vs. 9/72 (12.5%) in those without MHE (P=0.01). Multivariate analysis showed that MHE (odds ratio (OR): 2.91, 95% confidence interval (CI): 1.13–7.48, P=0.02), previous encephalopathy (OR: 2.87, 95% CI: 1.10–7.50, P=0.03), and antidepressant therapy (OR: 3.91, 95% CI: 0.96–15.9, P=0.05) were independent factors associated to previous falls.CONCLUSIONS:Falls are more frequent in cirrhotic patients with MHE, particularly in those on treatment with psychoactive drugs, and are a significant cause for healthcare and hospitalization requirements.

[1]  J. Richards,et al.  Effect of selective serotonin reuptake inhibitors on the risk of fracture. , 2007, Archives of internal medicine.

[2]  L. Tchambaz,et al.  Pharmacokinetic Changes of Psychotropic Drugs in Patients with Liver Disease , 2009, Drug safety.

[3]  Claudia Cesaro,et al.  Rifaximin in the treatment of hepatic encephalopathy , 2011, Hepatic medicine : evidence and research.

[4]  M. Tinetti,et al.  The patient who falls: "It's always a trade-off". , 2010, JAMA.

[5]  P. Vestergaard Fracture risks of antidepressants , 2009, Expert review of neurotherapeutics.

[6]  J. Aparicio,et al.  Minimal hepatic encephalopathy and extrapyramidal signs in patients with cirrhosis. , 2003 .

[7]  B. Sharma,et al.  Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo. , 2009, Gastroenterology.

[8]  P. Lips,et al.  Fall risk: the clinical relevance of falls and how to integrate fall risk with fracture risk. , 2009, Best practice & research. Clinical rheumatology.

[9]  S. Gates,et al.  Multifactorial assessment and targeted intervention for preventing falls and injuries among older people in community and emergency care settings: systematic review and meta-analysis , 2007, BMJ : British Medical Journal.

[10]  Ritesh Agarwal,et al.  Lactulose improves cognitive functions and health‐related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy , 2007, Hepatology.

[11]  R. Hoffmann,et al.  Minimal hepatic encephalopathy is associated with motor vehicle crashes: The reality beyond the driving test , 2009, Hepatology.

[12]  J. Rodés,et al.  Severity of cholestasis and advanced histological stage but not menopausal status are the major risk factors for osteoporosis in primary biliary cirrhosis. , 2005, Journal of hepatology.

[13]  William M. Lee,et al.  Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. , 2010, Gastroenterology.

[14]  W. Frishman,et al.  Pathophysiology, Diagnosis, and Treatment of Orthostatic Hypotension and Vasovagal Syncope , 2008, Cardiology in review.

[15]  J. Aparicio,et al.  Minimal hepatic encephalopathy and extrapyramidal signs in patients with cirrhosis , 2003, American Journal of Gastroenterology.

[16]  Thomas A Hammeke,et al.  Inhibitory control test for the diagnosis of minimal hepatic encephalopathy. , 2008, Gastroenterology.

[17]  Lillemor Lundin-Olsson,et al.  Prognostic validity of the Timed Up-and-Go test, a modified Get-Up-and-Go test, staff's global judgement and fall history in evaluating fall risk in residential care facilities. , 2008, Age and ageing.

[18]  Paul J. Gaglio,et al.  MINIMAL HEPATIC ENCEPHALOPATHY IMPAIRS FITNESS TO DRIVE , 2004 .

[19]  R. Hoffmann,et al.  Minimal Hepatic Encephalopathy: A Vehicle for Accidents and Traffic Violations , 2007, The American Journal of Gastroenterology.

[20]  Lars Timmermann,et al.  Critical flicker frequency for quantification of low‐grade hepatic encephalopathy , 2002, Hepatology.

[21]  K Weissenborn,et al.  Neuropsychological characterization of hepatic encephalopathy. , 2001, Journal of hepatology.

[22]  W A Ray,et al.  Antidepressants and the risk of falls among nursing home residents. , 1998, The New England journal of medicine.

[23]  R. Butterworth,et al.  Increased brain serotonin turnover correlates with the degree of shunting and hyperammonemia in rats following variable portal vein stenosis. , 2004, Journal of hepatology.

[24]  S. Posen,et al.  Osteoporosis and skeletal fractures in chronic liver disease. , 1990, Gut.

[25]  J. Bajaj Minimal hepatic encephalopathy matters in daily life. , 2008, World journal of gastroenterology.

[26]  J. Collier Bone disorders in chronic liver disease , 2007, Hepatology.

[27]  R. Esteban,et al.  Quality of life in cirrhosis is related to potentially treatable factors , 2010, European journal of gastroenterology & hepatology.

[28]  M. Romero-Gómez,et al.  Prognostic value of altered oral glutamine challenge in patients with minimal hepatic encephalopathy , 2004, Hepatology.

[29]  Antonino Vallesi,et al.  Impairment of Response Inhibition Precedes Motor Alteration in the Early Stage of Liver Cirrhosis: A Behavioral and Electrophysiological Study , 2005, Metabolic Brain Disease.

[30]  N. Kerse,et al.  Falls, Depression and Antidepressants in Later Life: A Large Primary Care Appraisal , 2008, PloS one.

[31]  Niklas Zethraeus,et al.  Long-term cost and effect on quality of life of osteoporosis-related fractures in Sweden , 2008, Acta orthopaedica.

[32]  Cameron Swift,et al.  Prevention of falls in the elderly trial (PROFET): a randomised controlled trial , 1999, The Lancet.

[33]  H. Te,et al.  Operative risk of total hip and knee arthroplasty in cirrhotic patients. , 2005, The Journal of arthroplasty.

[34]  S. Riordan,et al.  Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis , 2004, Hepatology.

[35]  Victoria J. Fraser,et al.  Patterns and Predictors of Inpatient Falls and Fall-Related Injuries in a Large Academic Hospital , 2005, Infection Control &#x0026; Hospital Epidemiology.

[36]  Manuel Romero-Gómez,et al.  Value of the critical flicker frequency in patients with minimal hepatic encephalopathy , 2007, Hepatology.

[37]  R. Cumming,et al.  Interventions for preventing falls in elderly people. , 2003, The Cochrane database of systematic reviews.

[38]  P. Angeli,et al.  Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients. , 2001, Journal of hepatology.

[39]  J. Meulstee,et al.  The diagnosis of subclinical hepatic encephalopathy in patients with cirrhosis using neuropsychological tests and automated electroencephalogram analysis , 1996, Hepatology.

[40]  A. Fernández,et al.  Tablas de normalidad de la población española para los tests psicométricos utilizados en el diagnóstico de la encefalopatía hepática mínima , 2006 .

[41]  Thomas A Hammeke,et al.  Navigation skill impairment: Another dimension of the driving difficulties in minimal hepatic encephalopathy , 2007, Hepatology.

[42]  Hari Sharma,et al.  Direct and Indirect Costs of Non-Vertebral Fracture Patients with Osteoporosis in the US , 2012, PharmacoEconomics.

[43]  R. Lucke,et al.  Driving under the influence of minimal hepatic encephalopathy , 2004, Hepatology.

[44]  H Schomerus,et al.  Latent portasystemic encephalopathy , 1981, Digestive Diseases and Sciences.

[45]  W. Hop,et al.  Screening of subclinical hepatic encephalopathy. , 2000, Journal of hepatology.

[46]  J. Córdoba,et al.  Minimal hepatic encephalopathy: diagnosis, clinical significance and recommendations. , 2005, Journal of hepatology.