Vilstrup, H. et al. 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, 715–735 (2014).

Article  PubMed  Google Scholar 

Riggio, O. et al. High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: a case-control study. Hepatology 42, 1158–1165 (2005).

Article  PubMed  Google Scholar 

Cordoba, J. et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J. Hepatol. 60, 275–281 (2014).

Article  PubMed  Google Scholar 

Sawhney, R. et al. Role of ammonia, inflammation, and cerebral oxygenation in brain dysfunction of acute-on-chronic liver failure patients: Brain Dysfunction and ACLF. Liver Transpl. 22, 732–742 (2016).

Article  PubMed  Google Scholar 

Wright, G., Sharifi, Y., Jover-Cobos, M. & Jalan, R. The brain in acute on chronic liver failure. Metab. Brain Dis. 29, 965–973 (2014).

CAS  PubMed Central  Article  PubMed  Google Scholar 

Jalan, R., Moreau, R. & Arroyo, V. Acute-on-chronic liver failure. Reply. N. Engl. J. Med. 383, 893–894 (2020).

PubMed  Google Scholar 

Lauridsen, M. M. et al. Validation of a simple quality-of-life score for identification of minimal and prediction of overt hepatic encephalopathy. Hepatol. Commun. 4, 1353–1361 (2020).

PubMed Central  Article  PubMed  Google Scholar 

Ladegaard Grønkjær, L., Hoppe Sehstedt, T., Norlyk, A. & Vilstrup, H. Overt hepatic encephalopathy experienced by individuals with cirrhosis: a qualitative interview study. Gastroenterol. Nurs. 41, 468–476 (2018).

PubMed  Google Scholar 

Fabrellas, N. et al. Psychological burden of hepatic encephalopathy on patients and caregivers. Clin. Transl. Gastroenterol. 11, e00159 (2020).

PubMed Central  Article  PubMed  Google Scholar 

Shrestha, D. et al. Factors affecting psychological burden on the informal caregiver of patients with cirrhosis: looking beyond the patient. J. Clin. Exp. Hepatol. 10, 9–16 (2020).

Article  PubMed  Google Scholar 

Rose, C. F. et al. Hepatic encephalopathy: novel insights into classification, pathophysiology and therapy. J. Hepatol. 73, 1526–1547 (2020).

Article  PubMed  Google Scholar 

Wendon, J. et al. EASL clinical practical guidelines on the management of acute (fulminant) liver failure. J. Hepatol. 66, 1047–1081 (2017).

Article  PubMed  Google Scholar 

Nicoletti, V. et al. Hepatic encephalopathy in patients with non-cirrhotic portal hypertension: description, prevalence and risk factors. Dig. Liver Dis. 48, 1072–1077 (2016).

Article  PubMed  Google Scholar 

Kraglund, F., Jepsen, P., Amanavicius, N. & Aagaard, N. K. Long-term effects and complications of the transjugular intrahepatic portosystemic shunt: a single-centre experience. Scand. J. Gastroenterol. 54, 899–904 (2019).

Article  PubMed  Google Scholar 

Sepanlou, S. G. et al. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 5, 245–266 (2020).

Article  Google Scholar 

Lauridsen, M. M., Jepsen, P. & Vilstrup, H. Critical flicker frequency and continuous reaction times for the diagnosis of minimal hepatic encephalopathy. A comparative study of 154 patients with liver disease. Metab. Brain Dis. 26, 135–139 (2011).

Article  PubMed  Google Scholar 

Rathi, S. et al. Prevalence of minimal hepatic encephalopathy in patients with liver cirrhosis: a cross-sectional, clinicoepidemiological, multicenter, nationwide study in India: the PREDICT study. J. Clin. Exp. Hepatol. 9, 476–483 (2019).

Article  PubMed  Google Scholar 

Tapper, E. B., Henderson, J. B., Parikh, N. D., Ioannou, G. N. & Lok, A. S. Incidence of and risk factors for hepatic encephalopathy in a population-based cohort of Americans with cirrhosis. Hepatol. Commun. 3, 1510–1519 (2019).

CAS  PubMed Central  Article  PubMed  Google Scholar 

Jepsen, P., Ott, P., Andersen, P. K., Sørensen, H. T. & Vilstrup, H. Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study. Hepatology 51, 1675–1682 (2009).

Article  Google Scholar 

Moreau, R. et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 144, 1426–1437 (2013).

Article  PubMed  Google Scholar 

Hirode, G., Vittinghoff, E. & Wong, R. J. Increasing burden of hepatic encephalopathy among hospitalized adults: an analysis of the 2010–2014 national inpatient sample. Dig. Dis. Sci. 64, 1448–1457 (2019).

CAS  Article  PubMed  Google Scholar 

Di Pascoli, M. et al. Hospitalizations due to cirrhosis: clinical aspects in a large cohort of italian patients and cost analysis report. Dig. Dis. 35, 433–438 (2017).

Article  PubMed  Google Scholar 

Riggio, O. et al. A Model for predicting development of overt hepatic encephalopathy in patients with cirrhosis. Clin. Gastroenterol. Hepatol. 13, 1346–1352 (2015).

Article  PubMed  Google Scholar 

Guevara, M. et al. Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: a prospective study with time-dependent analysis. Am. J. Gastroenterol. 104, 1382–1389 (2009).

Article  PubMed  Google Scholar 

Gil-Gómez, A. et al. Development and validation of a clinical-genetic risk score to predict hepatic encephalopathy in patients with liver cirrhosis. Am. J. Gastroenterol. 116, 1238–1247 (2021).

Article  PubMed  Google Scholar 

Yoo, H. Y., Edwin, D. & Thuluvath, P. J. Relationship of the model for end-stage liver disease (MELD) scale to hepatic encephalopathy, as defined by electroencephalography and neuropsychometric testing, and ascites. Am. J. Gastroenterol. 98, 1395–1399 (2003).

Article  PubMed  Google Scholar 

Praktiknjo, M. et al. Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis. J. Hepatol. 72, 1140–1150 (2020).

Article  PubMed  Google Scholar 

Yin, X. et al. A nomogram to predict the risk of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in cirrhotic patients. Sci. Rep. 10, 9381 (2020).

CAS  PubMed Central  Article  PubMed  Google Scholar 

Zhou, Y. et al. PTFE-covered TIPS is an effective treatment for secondary preventing variceal rebleeding in cirrhotic patients with high risks. Eur. J. Gastroenterol. Hepatol. 32, 1235–1243 (2020).

CAS  Google Scholar 

Qi, X., Tian, Y., Zhang, W., Yang, Z. & Guo, X. Covered versus bare stents for transjugular intrahepatic portosystemic shunt: an updated meta-analysis of randomized controlled trials. Ther. Adv. Gastroenterol. 10, 32–41 (2016).

Article  Google Scholar 

Nicoară-Farcău, O. et al. Preemptive TIPS Individual Data Metanalysis, International Variceal Bleeding Study and Baveno Cooperation Study groups. Effects of early placement of transjugular portosystemic shunts in patients with high-risk acute variceal bleeding: a meta-analysis of individual patient data. Gastroenterology 160, 193–205 (2021).

Article  CAS  PubMed  Google Scholar 

Jepsen, P., Watson, H., Andersen, P. K. & Vilstrup, H. Diabetes as a risk factor for hepatic encephalopathy in cirrhosis patients. J. Hepatol. 63, 1133–1138 (2015).

Article  PubMed  Google Scholar 

Ampuero, J. et al. Role of diabetes mellitus on hepatic encephalopathy. Metab. Brain Dis. 28, 277–279 (2012).

Article  CAS  PubMed  Google Scholar 

Vilar-Gomez, E. et al. Type 2 diabetes and metformin use associate with outcomes of patients with nonalcoholic steatohepatitis-related, child-pugh a cirrhosis. Clin. Gastroenterol. Hepatol. 19, 136–145.e6 (2021).

CAS  Article  PubMed  Google Scholar 

Elkrief, L. et al. Diabetes mellitus is an independent prognostic factor for major liver-related outcomes in patients with cirrhosis and chronic hepatitis C. Hepatology 60, 823–831 (2014).

CAS  Article  PubMed  Google Scholar 

Jepsen, P., Christensen, J., Weissenborn, K., Watson, H. & Vilstrup, H. Epilepsy as a risk factor for hepatic encephalopathy in patients with cirrhosis: a cohort study. BMC Gastroenterol. 16, 77–77 (2016).

PubMed Central  Article  CAS  PubMed  Google Scholar 

Nardelli, S. et al. Muscle alterations are associated with minimal and overt hepatic encephalopathy in patients with liver cirrhosis. Hepatology 70, 1704–1713 (2019).

Article  PubMed  Google Scholar 

Shawcross, D. L., Davies, N. A., Williams, R. & Jalan, R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J. Hepatol. 40, 247–254 (2004).

CAS  Article  PubMed  Google Scholar 

Merli, M. et al. Increased risk of cognitive impairment in cirrhotic patients with bacterial infections. J. Hepatol. 59, 243–250 (2013).

Article  PubMed  Google Scholar 

Yuan, L.-T. et al. Multiple bacterial infections increase the risk of hepatic encephalopathy in patients with cirrhosis. PLoS ONE 13, e0197127 (2018).

PubMed Central  Article  CAS  PubMed  Google Scholar 

Solé, C. et al. Alterations in gut microbiome in cirrhosis as assessed by quantitative metagenomics: relationship with acute-on-chronic liver failure and prognosis. Gastroenterology 160, 206–218.e13 (2021).

Article  CAS  PubMed  Google Scholar 

Bajaj, J. S. et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J. Hepatol. 60, 940–947 (2014).

CAS  Article  PubMed