Early Diagnosis and Timely Treatment of Cirrhotic Patients With Minimal Hepatic Encephalopathy (CHESS-NCRCID 2106)

Hepatic encephalopathy (HE) is a common complication of cirrhosis, which seriously damages the life quality of patients. As the disease progresses, 50-80% of patients with cirrhosis develop HE. Minimal hepatic encephalopathy (MHE) is a manifestation of HE, in which the patient usually has no obvious clinical symptoms and can only be detected by neuropsychological testing. Early identification and timely treatment are the keys to improve the prognosis of HE, and the diagnosis of MHE are the priority in the process of the disease intervention. Guidelines in many countries suggest that MHE does not recommend routine treatment. However, patients with cirrhosis usually have complex clinical complications, so whether timely treatment should be taken remains to be explored. The purpose of this study is to investigate the incidence of MHE in cirrhotic patients, and to establish a real-world cohort for further study on drug therapy and efficacy evaluation.

Study Overview

• Status: Recruiting
• Conditions: Hepatic Encephalopathy; Cirrhosis
• Intervention / Treatment: Diagnostic test: Psychometric hepatic encephalopathy score & Stroop test; Drug: Drug therapy

Detailed Description

According to the 2017 Global Burden of Disease study, there are 10.6 million patients with decompensated cirrhosis and 112 million patients with compensated cirrhosis worldwide. From 1990 to 2016, the number of patients with cirrhosis and chronic liver disease in China has increased from nearly 7 million (6833 300) to nearly 12 million (11 869 600), and the prevalence of all age groups increased by 44%. Hepatic encephalopathy (HE) is a common complication of cirrhosis, which seriously damages the life quality of patients. As the disease progresses, 50-80% of patients with cirrhosis develop HE. Minimal hepatic encephalopathy (MHE) is a manifestation of HE, in which the patient usually has no obvious clinical symptoms and can only be detected by neuropsychological testing. Early identification and timely treatment are the keys to improve the prognosis of HE, and the diagnosis of MHE are the priority in the process of the disease intervention. Guidelines in many countries suggest that MHE does not recommend routine treatment. However, patients with cirrhosis usually have complex clinical complications, so whether timely treatment should be taken remains to be explored. The purpose of this study is to investigate the incidence of MHE in cirrhotic patients, and to establish a real-world cohort for further study on drug therapy and efficacy evaluation.

• Study Type: Observational
• Enrollment (Anticipated): 10000

Contacts and Locations

• Study Contact: Name: Xiaolong Qi; Phone Number: 8618588602600; Email: qixiaolong@vip.163.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Not yet recruiting
      • The First Affiliated Hospital of Anhui Medical University
      • Contact: Yufeng Gao, MD
  • Beijing
    • Beijing, Beijing, China
      • Not yet recruiting
      • Beijing Ditan Hospital, Capital Medical University
      • Contact: Wen Xie, MD
  • Chongqing
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • Chongqing Public Health Medical Treatment Center
      • Contact: Xiangbo Chi, MD
  • Fujian
    • Fuzhou, Fujian, China
      • Not yet recruiting
      • Mengchao Hepatobiliary Hospital of Fujian Medical University
      • Contact: Yongyi Zeng, MD
  • Gansu
    • Lanzhou, Gansu, China
      • Recruiting
      • The First Hospital of Lanzhou University
      • Contact: Liting Zhang, MD
  • Guangdong
    • Shenzhen, Guangdong, China
      • Not yet recruiting
      • Shenzhen Third People's Hospital
      • Contact: Qing He, MD
  • Guangxi
    • Nanning, Guangxi, China
      • Not yet recruiting
      • Guangxi Zhuang Autonomous Region People's Hospital
      • Contact: Guo Zhang, MD
  • Guizhou
    • Guiyang, Guizhou, China
      • Not yet recruiting
      • Guizhou Provincial People's Hospital
      • Contact: Xinhua Luo, MD
  • Hainan
    • Haikou, Hainan, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Hainan Medical College
      • Contact: Weizhong Yang, MD
  • Hebei
    • Shijiazhuang, Hebei, China
      • Not yet recruiting
      • The Third Affiliated Hospital of Hebei Medical University
      • Contact: Caiyan Zhao, MD
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Harbin Medical University
      • Contact: Shuchen Li, MD
  • Henan
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Provincial People's Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Xin Zheng, MD
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Xiangya Hospital of Central South University
      • Contact: Yan Huang, MD
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Baotou Medical College
      • Contact: Tong Dang, MD
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Jiangsu People's Hospital
  • Jiangxi
    • Ganzhou, Jiangxi, China
      • Not yet recruiting
      • Ganzhou City Fifth People's Hospital
      • Contact: Guanlin Zhou, MD
  • Jilin
    • Changchun, Jilin, China
      • Not yet recruiting
      • Bethune First Hospital Of Jilin University
      • Contact: Zhongfeng Wang, MD
  • Liaoning
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • The First Affiliated Hospital of China Medical University
      • Contact: Yiling Li, MD
  • Ningxia
    • Yinchuan, Ningxia, China
      • Not yet recruiting
      • Ningxia Medical University General Hospital
      • Contact: Shaoqi Yang, MD
  • Qinghai
    • Xining, Qinghai, China
      • Not yet recruiting
      • The Fourth People's Hospital of Qinghai Province
      • Contact: Hongmei Zu, MD
  • Shaanxi
    • Xi'an, Shaanxi, China
      • Not yet recruiting
      • Xi'an Hi-tech Hospital
      • Contact: Ying Song, MD
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Yanjing Gao, MD
  • Shanghai
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • The 10th People's Hospital affiliated to Tongji University
      • Contact: Huixiong Xu, MD
  • Shanxi
    • Taiyuan, Shanxi, China
      • Not yet recruiting
      • The Third People's Hospital of Taiyuan
      • Contact: Ying Guo, MD
  • Sichuan
    • Xichang, Sichuan, China
      • Not yet recruiting
      • Xichang People's Hospital
      • Contact: Huasong Huang, MD
  • Tianjin
    • Tianjin, Tianjin, China
      • Not yet recruiting
      • Tianjin Third Central Hospital
      • Contact: Huiling Xiang, MD
  • Tibetan
    • Lhasa, Tibetan, China
      • Not yet recruiting
      • The Third People's Hospital of Tibet Autonomous Region
      • Contact: Xiaosong Yan, MD
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • Not yet recruiting
      • Xinjiang Autonomous Region People's Hospital
      • Contact: Yongping Zhang, MD
  • Yunnan
    • Kunming, Yunnan, China
      • Not yet recruiting
      • Second People's Hospital of Yunnan Province
      • Contact: Jia Wei, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Hangzhou Xixi Hospital
      • Contact: Shourong Liu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients with cirrhosis

Description

Inclusion Criteria:

1. age 18-65 years;
2. confirmed cirrhosis based on clinical or pathological criteria;
3. no history of grade 1-4 hepatic encephalopathy;
4. with written informed consent.

Exclusion Criteria:

1. with other neurological or mental diseases (such as Alzheimer's disease, Parkinson's disease, etc.);
2. with alcohol or drug addiction and unstable vital signs;
3. with liver cancer or other malignant tumors;
4. fail to comply with psychological tests;
5. incomplete data collection.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
cross-sectional study	Diagnostic test: Psychometric hepatic encephalopathy score & Stroop test; MHE was assessed according to neuropsychological methods. Psychometric hepatic encephalopathy score include number connection test (NCT), digit-symbol test (DST), line-tracing test (LTT) and serial dotting test (SDT). Stroop test can assess psychomotor speed and cognitive flexibility by recording the interference response time between recognizing color fields and writing color names.
real-world cohort study	Drug: Drug therapy; Real-world cohort study. The outcomes were examined and registered, so as to evaluate the relationship between therapeutic effects and health outcomes. Psychometric hepatic encephalopathy score and quality of life scale were measured at 3, 6, 12, 18 and 24 months of follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychometric hepatic encephalopathy score (PHES)	The PHES is a battery of neuropsychological tests used in the diagnosis of minimal hepatic encephalopathy (MHE). The sum of scores for PHES ranges between +5 and -15. Patients with cirrhosis having a PHES score of <-4 SD are considered to have MHE.	1 year
Clinical decompensation and death	Clinically evident decompensating events (specifically ascites, variceal hemorrhage).	2 year
EuroQol Five Dimensions Questionnaire (EQ5D)	EQ5D is used to evaluate the quality of life. EQ-5D consists of two main parts: Descriptive System and Visual Analogue Scale. Five dimensions are used to describe the health state: Mobility, self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression. A scale ranges from 0 to 100, with 0 representing "your worst imagined health" and 100 "your best imagined health." Self-rated information from respondents can be used as a quantitative indicator of health outcomes.	2 year

Collaborators and Investigators

• Sponsor: Hepatopancreatobiliary Surgery Institute of Gansu Province
• Collaborators: The First Affiliated Hospital of Anhui Medical University; Xiangya Hospital of Central South University; LanZhou University; Beijing Ditan Hospital; Qilu Hospital of Shandong University; The First Hospital of Jilin University; Henan Provincial People's Hospital; Wuhan Union Hospital, China; First Hospital of China Medical University; Tianjin Third Central Hospital; The Second Affiliated Hospital of Harbin Medical University; Guizhou people's Hospital; Second People's Hospital of Yunnan Province; Meng Chao Hepatobiliary Hospital of Fujian Medical University; Shenzhen Third People's Hospital; The Second Affiliated Hospital of Baotou Medical College; The Third People's Hospital of Taiyuan; The Fourth People's Hospital of Qinghai Province; The Third Affiliated Hospital of Hebei Medical University; Guangxi Zhuang Autonomous Region People's Hospital; Ningxia Medical University General Hospital; The Second Affiliated Hospital of Hainan Medical University; The Third People's Hospital of Tibet Autonomous Region; Hangzhou Xixi hospital; Jiangsu People's Hospital; Chongqing Public Health Medical Treatment Center; Ganzhou Fifth People's Hospital; Xi'an High-tech Hospital; The 10th People's Hospital affiliated to Tongji University; Xichang People's Hospital; Xinjiang Autonomous Region People's Hospital

Publications and helpful links

General Publications

• GBD 2017 Cirrhosis Collaborators. 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. 2020 Mar;5(3):245-266. doi: 10.1016/S2468-1253(19)30349-8. Epub 2020 Jan 22.
• Li M, Wang ZQ, Zhang L, Zheng H, Liu DW, Zhou MG. Burden of Cirrhosis and Other Chronic Liver Diseases Caused by Specific Etiologies in China, 1990-2016: Findings from the Global Burden of Disease Study 2016. Biomed Environ Sci. 2020 Jan 20;33(1):1-10. doi: 10.3967/bes2020.001.
• Xiao J, Wang F, Wong NK, He J, Zhang R, Sun R, Xu Y, Liu Y, Li W, Koike K, He W, You H, Miao Y, Liu X, Meng M, Gao B, Wang H, Li C. Global liver disease burdens and research trends: Analysis from a Chinese perspective. J Hepatol. 2019 Jul;71(1):212-221. doi: 10.1016/j.jhep.2019.03.004. Epub 2019 Mar 12.
• Zimmermann M, Reichert AS. Rapid metabolic and bioenergetic adaptations of astrocytes under hyperammonemia - a novel perspective on hepatic encephalopathy. Biol Chem. 2021 Jul 30;402(9):1103-1113. doi: 10.1515/hsz-2021-0172. Print 2021 Aug 26.
• Bale A, Pai CG, Shetty S, Balaraju G, Shetty A. Prevalence of and Factors Associated With Minimal Hepatic Encephalopathy in Patients With Cirrhosis of Liver. J Clin Exp Hepatol. 2018 Jun;8(2):156-161. doi: 10.1016/j.jceh.2017.06.005. Epub 2017 Jun 20.
• Sharma K, Pant S, Misra S, Dwivedi M, Misra A, Narang S, Tewari R, Bhadoria AS. Effect of rifaximin, probiotics, and l-ornithine l-aspartate on minimal hepatic encephalopathy: a randomized controlled trial. Saudi J Gastroenterol. 2014 Jul-Aug;20(4):225-32. doi: 10.4103/1319-3767.136975.
• Cabrera-Pastor A, Llansola M, Montoliu C, Malaguarnera M, Balzano T, Taoro-Gonzalez L, Garcia-Garcia R, Mangas-Losada A, Izquierdo-Altarejos P, Arenas YM, Leone P, Felipo V. Peripheral inflammation induces neuroinflammation that alters neurotransmission and cognitive and motor function in hepatic encephalopathy: Underlying mechanisms and therapeutic implications. Acta Physiol (Oxf). 2019 Jun;226(2):e13270. doi: 10.1111/apha.13270. Epub 2019 Mar 22.
• Wang JY, Zhang NP, Chi BR, Mi YQ, Meng LN, Liu YD, Wang JB, Jiang HX, Yang JH, Xu Y, Li X, Xu JM, Zhang G, Zhou XM, Zhuge YZ, Tian DA, Ye J, Liu YL. Prevalence of minimal hepatic encephalopathy and quality of life evaluations in hospitalized cirrhotic patients in China. World J Gastroenterol. 2013 Aug 14;19(30):4984-91. doi: 10.3748/wjg.v19.i30.4984.
• Xu XY, Ding HG, Li WG, Jia JD, Wei L, Duan ZP, Liu YL, Ling-Hu EQ, Zhuang H, Hepatology CSO, Association CM. Chinese guidelines on management of hepatic encephalopathy in cirrhosis. World J Gastroenterol. 2019 Sep 28;25(36):5403-5422. doi: 10.3748/wjg.v25.i36.5403.
• Flud CR, Duarte-Rojo A. Prognostic Implications of Minimal/Covert Hepatic Encephalopathy: Large-scale Validation Cohort Studies. J Clin Exp Hepatol. 2019 Jan-Feb;9(1):112-116. doi: 10.1016/j.jceh.2018.04.009. Epub 2018 May 4.
• Bajaj JS, Lauridsen M, Tapper EB, Duarte-Rojo A, Rahimi RS, Tandon P, Shawcross DL, Thabut D, Dhiman RK, Romero-Gomez M, Sharma BC, Montagnese S. Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus. Am J Gastroenterol. 2020 Jul;115(7):989-1002. doi: 10.14309/ajg.0000000000000603.
• Reuter B, Walter K, Bissonnette J, Leise MD, Lai J, Tandon P, Kamath PS, Biggins SW, Rose CF, Wade JB, Bajaj JS. Assessment of the spectrum of hepatic encephalopathy: A multicenter study. Liver Transpl. 2018 May;24(5):587-594. doi: 10.1002/lt.25032.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: November 21, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Cirrhosis; Minimal hepatic encephalopathy; Psychometric hepatic encephalopathy score
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Fibrosis; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: CHESS2106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No