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

Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05140837
• Other study ID #: CHESS2106
• Status: Recruiting
• Start date: December 9, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2023
• Source: Hepatopancreatobiliary Surgery Institute of Gansu Province
• Contact: Xiaolong Qi
• Phone: 8618588602600
• Email: qixiaolong[@]vip.163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10000
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Cirrhosis
• Fibrosis
• Hepatic Encephalopathy

Intervention

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.

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.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia
China	Beijing Ditan Hospital, Capital Medical University	Beijing	Beijing
China	Bethune First Hospital of Jilin University	Changchun	Jilin
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	Chongqing Public Health Medical Treatment Center	Chongqing	Chongqing
China	MengChao Hepatobiliary Hospital of Fujian Medical University	Fuzhou	Fujian
China	Ganzhou City Fifth People's Hospital	Ganzhou	Jiangxi
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	The Second Affiliated Hospital of Hainan Medical College	Haikou	Hainan
China	Hangzhou Xixi Hospital	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Second People's Hospital of Yunnan Province	Kunming	Yunnan
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	The Third People's Hospital of Tibet Autonomous Region	Lhasa	Tibetan
China	Jiangsu People's Hospital	Nanjing	Jiangsu
China	Guangxi Zhuang Autonomous Region People's Hospital	Nanning	Guangxi
China	The 10th People's Hospital affiliated to Tongji University	Shanghai	Shanghai
China	The First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	Shenzhen Third People's Hospital	Shenzhen	Guangdong
China	The Third Affiliated Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Third People's Hospital of Taiyuan	Taiyuan	Shanxi
China	Tianjin Third Central Hospital	Tianjin	Tianjin
China	Xinjiang Autonomous Region People's Hospital	Ürümqi	Xinjiang
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Xi'an Hi-tech Hospital	Xi'an	Shaanxi
China	Xichang People's Hospital	Xichang	Sichuan
China	The Fourth People's Hospital of Qinghai Province	Xining	Qinghai
China	Ningxia Medical University General Hospital	Yinchuan	Ningxia
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (32)

Lead Sponsor

Collaborator

Hepatopancreatobiliary Surgery Institute of Gansu Province

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

Country where clinical trial is conducted

China, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Clinical decompensation and death	Clinically evident decompensating events (specifically ascites, variceal hemorrhage).	2 year
Primary	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