MHE occurs in over a quarter of patients diagnosed with cirrhosis of the liver and is characterized by deficits in attention, working memory, visual spatial abilities, and psychomotor speed, which are accompanied by disruptions in sleep patterns (Bajaj, Wade, & Sanyal, 2009; McCrea, Cordoba, Vessey, Blei, & Randolph, 1996; Montagnese et al., 2014). Symptoms of MHE are insidious with neurophysiological and neuropsychological abnormalities occurring with no apparent changes in mental status. MHE is also associated with altered brain connectivity and cortical electrical activity (Kullmann et al., 2001; Montoliu et al., 2014). Diagnosis of MHE is based on abnormal findings in well-established neuropsychological tests that are interpreted in the context of a thorough clinical workup. In terms of treatment, monitoring of symptoms is recommended, as MHE symptoms may diminish quality of life, impair driving, and increase risk of overt hepatic encephalopathy (Prasad et al., 2007; Vilstrup et al., 2014; Zipprich et al., 2012).
OHE occurs in over 10% of patients diagnosed with cirrhosis of the liver and approximately 25% of patients with decompensated cirrhosis (Vilstrup et al., 2014; Weissenborn, 1998; Zipprich et al., 2012). Symptoms of OHE vary in presentation, severity, and pervasiveness. While expert consensus uses disorientation or asterixis as the onset of OHE (Bajaj et al., 2011), personality changes (Wiltfang, Nolte, Weissenborn, Kornhuber, & Ruther, 1998), somnolence (Montagnese et al., 2014), and impaired motor functioning (Kim, Brown, Terrault, & El-Serag, 2002) also appear early on. If left untreated, OHE results in progressive disorientation, erratic behavior, stupor, and, finally, coma (Weissenborn, Bokemeyer, Krause, Ennen, & Ahl, 2005). Diagnosis is generally based on clinical examination (Vilstrup et al., 2014) and symptom severity is determined using available scales (e.g., the West Haven Criteria; the Glasgow Coma Scale). Treatment for OHE is largely standardized to include supportive care (e.g., nutritional assistance, monitor hydration) and acute therapy (e.g., identify and target precipitating causes and lower blood ammonia concentration). Though not necessary to establish a diagnosis, a comprehensive neuropsychological evaluation may help to characterize cognitive deficits as well as inform recommendations.
ABSTRACT: Umapathy, S., Dhiman, R. K., Grover, S., Duseja, A., & Chawla, Y. K. (2014). Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. The American Journal of Gastroenterology, 109(7), 1011-1019. doi: http://dx.doi.org/10.1053/j.gastro.2010.02.015
OBJECTIVES: Hepatic encephalopathy (HE) represents a spectrum of neurocognitive impairment seen in cirrhotic patients and is considered to be fully reversible with treatment; however, recent evidence suggests otherwise. This longitudinal study was carried out to evaluate the persistence of cognitive impairment in cirrhotics with prior overt HE (OHE) episode despite treatment.
METHODS: Of the 213 patients screened, 107 patients who met the eligibility criteria were enrolled and 102 patients completed the study (52 patients without prior OHE episode and 50 patients with prior OHE). All patients underwent psychometric hepatic encephalopathy score (PHES) evaluation at three separate visits (day 1, day 3, and between 30 and 60 days). A one-point improvement in PHES between the first and second evaluation was considered as a measure of learning.
RESULTS: Patients with a previous OHE episode showed learning impairment in PHES on repetition on day 3 (P = 0.084), whereas patients without a previous OHE episode demonstrated learning effect (P < 0.0001) irrespective of whether they had minimal HE (MHE) or not. Univariate analysis demonstrated that Child – Turcotte – Pugh score, lactulose and/ or rifaximin therapy, the presence of MHE, and previous OHE episodes were associated with learning impairment. Multivariate analysis demonstrated that only the presence of a previous episode of OHE (adjusted odds ratio 38.398; 95% confidence interval 9.192 – 160.4; P < 0.0001) significantly affected learning.
CONCLUSIONS: This study conclusively demonstrated learning impairment in cirrhotic patients with a previous episode of OHE despite normal mental status. Improvement in PHES on repetition may be a measure of learning.
RESOURCES: Asterixis or flapping tremor- Involuntary jerking of the hand- - https://youtu.be/5g8O7stkNII
West Haven Criteria- A semi-quantitative scale used to grade the severity of OHE symptoms. http://www.nature.com/ajg/journal/v104/n6/fig_tab/ajg2009160t1.html
Podcast/Webinar: CORE EM, official podcast of Bellevue and NYU Emergency Medicine residency program, Episode 24.0 – Hepatic Encephalopathy http://coreem.net/podcast/episode-24-0-hepatic-encephalopathy/
FURTHER READING AND REFERENCES: Bajaj, J. S., Thacker, L. R., Heuman, D. M., Fuchs, M., Sterling, R. K., Sanyal, A. J., ... & Luketic, V. (2013). The Stroop smartphone application is a short and valid method to screen for minimal hepatic encephalopathy. Hepatology, 58(3), 1122-1132. doi: http://dx.doi.org/10.1002/hep.26309
Bajaj, J. S., Wade, J. B., & Sanyal, A. J. (2009). Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology, 50(6), 2014-2021. doi: http://dx.doi.org/10.1002/hep.23216
Bajaj, J.S., Cordoba, J., Mullen, K.D., Amodio, P., Shawcross, D.L., Butterworth, R.F., & Morgan, M.Y. (2011). Review article: The design of clinical trials in hepatic encephalopathy–an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Alimentary pharmacology & therapeutics, 33(7), 739-747. doi: http://dx.doi.org/10.1111/j.1365-2036.2011.04590.x
Kim, W. R., Brown, R. S., Terrault, N. A., & El-Serag, H. (2002). Burden of liver disease in the United States: Summary of a workshop. Hepatology, 36(1), 227-242. doi: http://dx.doi.org/10.1053/jhep.2002.34734
Kullmann, Frank, Hollerbach, Stephan, Lock, Guntram, Holstege, Axel, Dierks, Thomas, & Schölmerich, Jürgen. (2001). Brain electrical activity mapping of EEG for the diagnosis of (sub) clinical hepatic encephalopathy in chronic liver disease. European journal of gastroenterology & hepatology, 13(5), 513-522. http://www.ncbi.nlm.nih.gov/pubmed/11396530
McCrea, Michael, Cordoba, Juan, Vessey, Ginger, Blei, Andres T, & Randolph, Christopher. (1996). Neuropsychological characterization and detection of subclinical hepatic encephalopathy. Arch Neurol, 53(8), 758-763. doi: http://dx.doi.org/10.1001/archneur.1996.00550080076015
Montagnese, S., De Pitta, C., De Rui, M., Corrias, M., Turco, M., Merkel, C., . . . Gatta, A. (2014). Sleep-wake abnormalities in patients with cirrhosis. Hepatology, 59(2), 705-712. doi: http://dx.doi.org/10.1002/hep.26555
Montoliu, Carmina, Urios, Amparo, Forn, Cristina, García-Panach, Javier, Avila, Cesar, Gimenez-Garzó, Carla, . . . Gonzalez, Olga. (2014). Reduced white matter microstructural integrity correlates with cognitive deficits in minimal hepatic encephalopathy. Gut, 63(6), 1028-1030. doi: http://dx.doi.org/10.1136/gutjnl-2013-306175
Prasad, Srinivasa, Dhiman, Radha K, Duseja, Ajay, Chawla, Yogesh K, Sharma, Arpita, & Agarwal, Ritesh. (2007). Lactulose improves cognitive functions and health‐related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology, 45(3), 549-559. doi: http://dx.doi.org/10.1002/hep.21533
Vilstrup, Hendrik, Amodio, Piero, Bajaj, Jasmohan, Cordoba, Juan, Ferenci, Peter, Mullen, Kevin D, . . . Wong, Philip. (2014). Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology, 60(2), 715-735. doi: http://dx.doi.org/10.1016/j.jhep.2014.05.042
Weissenborn, K., Bokemeyer, M., Krause, J., Ennen, J., & Ahl, B. (2005). Neurological and neuropsychiatric syndromes associated with liver disease. AIDS, 19 Suppl 3, S93-98. http://www.ncbi.nlm.nih.gov/pubmed/16251835
Weissenborn, Karin. (1998). Diagnosis of encephalopathy. Digestion, 59(Suppl. 2), 22-24. doi: http://dx.doi.org/10.1159/000051415
Wiltfang, J., Nolte, W., Weissenborn, K., Kornhuber, J., & Ruther, E. (1998). Psychiatric aspects of portal-systemic encephalopathy. Metab Brain Dis, 13(4), 379-389. http://www.ncbi.nlm.nih.gov/pubmed/10206828
Zipprich, A., Garcia-Tsao, G., Rogowski, S., Fleig, W. E., Seufferlein, T., & Dollinger, M. M. (2012). Prognostic indicators of survival in patients with compensated and decompensated cirrhosis. Liver Int, 32(9), 1407-1414. doi: http://dx.doi.org/10.1111/j.1478-3231.2012.02830.x