Nomogram Analysis for HBV Related Acute-on-chronic Liver Failure

Liver Failure Clinical Trial

Official title:

Establishment and Validation of Prognostic Nomograms for HBV-related Acute-on-Chronic Liver Failure in South of China

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03992898
• Other study ID #: Survival Study Cohort(SSC001)
• Status: Completed
• Start date: January 1, 2019
• Est. completion date: November 1, 2019

Study information

• Verified date: January 2020
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver diseases, which progresses rapidly, with a mortality rate of more than 50%.MELD score is used to evaluate the patients' condition. However, MELD score only concerned about the variables of total bilirubin, international normalize ratio (INR) and creatinine which is not enough to access ACLF patients' condition accurately.

Scholars of US and China suggested to divided ACLF patients into 3 subgroups base on the different "chronic liver disease" . Type A ACLF patients have chronic liver disease without cirrhosis. Type B ACLF patients with compensated cirrhosis, while type C ACLF patients with decompensated cirrhosis. Currently, no studies have assessed the prognosis of different types of ACLF patients, especially for HBV-related ACLF patients.

Investigators conducted a retrospective study which enrolls HBV-related ACLF patients between January 2010 and March 2018 in the Third Affiliated Hospital of Sun Yat-sen University. Clinical data, survival time and information regarding liver transplantation after enrolment were collected. A nomogram was formulated based on the results of multivariable Cox regression analysis. The performance of the nomogram was evaluated by the concordance index (C-index) and assessed by comparing nomogram-predicted vs observed Kaplan-Meier estimates of survival probability, and bootstraps with 1000 resamples were applied to these activities. Comparisons between the nomogram, MELD Score，MELD-Na Score and CTP Score in the entire population were performed and were tested by the C-index. A larger C-index indicated more accurate prognostic stratification.

Description:

Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver diseases, which progresses rapidly, with a mortality rate of more than 50%. Liver transplantation is the only therapy that has been proven beneficial, but the number of liver donor is limited. MELD score is used to evaluate the patients' condition before transplantation to decide who is in greatest need. However, MELD score only concerned about the variables of total bilirubin, international normalize ratio (INR) and creatinine. Other important valuables such as age, hepatic encephalopathy, and indexes of infection (e.g. white blood cell counts) were excluded. Many studies showed that application of MELD score only is not enough to access the liver failure patients' condition accurately.

Both APASL and Chinese Society of Infectious Disease considered the "chronic liver disease" included chronic liver disease with/without cirrhosis. Scholars of US and China suggested to divided ACLF patients into 3 subgroups base on the different "chronic liver disease" . Type A ACLF patients have chronic liver disease without cirrhosis. Type B ACLF patients with compensated cirrhosis, while type C ACLF patients with decompensated cirrhosis. Currently, no studies have assessed the prognosis of different types of ACLF patients, especially for HBV-related ACLF patients.

Investigators conducted a retrospective study which enrolls HBV-related ACLF patients between January 2010 and March 2018 in the Third Affiliated Hospital of Sun Yat-sen University. Clinical data of demographic data, admission causes, cirrhosis complications, and precipitating events associated with acute decompensation or severe liver injury, laboratory measurements (e.g., serum albumin, sodium, alanine aminotransferase, aspartate aminotransferase, total bilirubin, INR and creatinine levels), mean arterial pressure, HBV infection biomarkers, HBV-DNA levels, antiviral treatment for HBV (nucleoside analogues, including lamivudine, adefovir, entecavir, telbivudine and tenofovir, within 6 months prior to and during hospitalisation), and prognosis would be collected. Survival time and information regarding liver transplantation after enrolment were also collected. A nomogram was formulated based on the results of multivariable Cox regression analysis. The performance of the nomogram was evaluated by the concordance index (C-index) and assessed by comparing nomogram-predicted vs observed Kaplan-Meier estimates of survival probability, and bootstraps with 1000 resamples were applied to these activities. Comparisons between the nomogram, MELD Score, MELD-Na Score and CTP Score in the entire population were performed and were tested by the C-index. A larger C-index indicated more accurate prognostic stratification.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2739
• Est. completion date: November 1, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years; Serum total bilirubin = 10 mg/dl; International normalized ratio=1.5 or prothrombin activity <40%; Complicated within 4 weeks by ascites and/or encephalopathy; Positive serum hepatitis B surface antigen for more than 6 months.

Exclusion Criteria:

• Drug induce liver diseases; Autoimmune liver diseases; Alcohol or drug abusers (average alcohol consumption >40g/d for men, >20g/d for women); Liver diseases caused by metabolic factors; Superinfection with hepatitis A, C, D, E viruses; Infected by HIV virus; Pregnancy or lactation; Liver failure caused by recurrence of hepatitis b after transplantation.

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• End Stage Liver Disease
• Hepatic Insufficiency
• Liver Failure

Intervention

Other:
• No special intervention was suitable for this observational study
Investegators divided patients into 3 corhort according to the liver condition at enrollment (i.e. chronic liver disease, compemsated cirrhosis, decompensated cirrhosis). All patients received standard medical treatment, including nutritional supplementation; administration of human serum albumin, fresh frozen plasma, antivirus treatment and appropriate treatment for complications. No special intervention was suitable for this observational study.

Locations

Country	Name	City	State
China	The Third Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (9)

Duseja A, Choudhary NS, Gupta S, Dhiman RK, Chawla Y. APACHE II score is superior to SOFA, CTP and MELD in predicting the short-term mortality in patients with acute-on-chronic liver failure (ACLF). J Dig Dis. 2013 Sep;14(9):484-90. doi: 10.1111/1751-2980.12074. — View Citation

Jalan R, Pavesi M, Saliba F, Amorós A, Fernandez J, Holland-Fischer P, Sawhney R, Mookerjee R, Caraceni P, Moreau R, Ginès P, Durand F, Angeli P, Alessandria C, Laleman W, Trebicka J, Samuel D, Zeuzem S, Gustot T, Gerbes AL, Wendon J, Bernardi M, Arroyo V; CANONIC Study Investigators; EASL-CLIF Consortium. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol. 2015 Apr;62(4):831-40. doi: 10.1016/j.jhep.2014.11.012. Epub 2014 Nov 22. Erratum in: J Hepatol. 2015 Jul;63(1):291. — View Citation

Jalan R, Yurdaydin C, Bajaj JS, Acharya SK, Arroyo V, Lin HC, Gines P, Kim WR, Kamath PS; World Gastroenterology Organization Working Party. Toward an improved definition of acute-on-chronic liver failure. Gastroenterology. 2014 Jul;147(1):4-10. doi: 10.1053/j.gastro.2014.05.005. Epub 2014 May 20. — View Citation

Lin B, Pan CQ, Xie D, Xie J, Xie S, Zhang X, Wu B, Lin C, Gao Z. Entecavir improves the outcome of acute-on-chronic liver failure due to the acute exacerbation of chronic hepatitis B. Hepatol Int. 2013 Jun;7(2):460-7. doi: 10.1007/s12072-012-9415-y. Epub 2013 Feb 11. — View Citation

Luo Y, Xu Y, Li M, Xie Y, Gong G. A new multiparameter integrated MELD model for prognosis of HBV-related acute-on-chronic liver failure. Medicine (Baltimore). 2016 Aug;95(34):e4696. doi: 10.1097/MD.0000000000004696. — View Citation

Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, Gustot T, Saliba F, Domenicali M, Gerbes A, Wendon J, Alessandria C, Laleman W, Zeuzem S, Trebicka J, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL–CLIF Consortium. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013 Jun;144(7):1426-37, 1437.e1-9. doi: 10.1053/j.gastro.2013.02.042. Epub 2013 Mar 6. — View Citation

Peng Y, Qi X, Tang S, Deng H, Li J, Ning Z, Dai J, Hou F, Zhao J, Wang R, Guo X. Child-Pugh, MELD, and ALBI scores for predicting the in-hospital mortality in cirrhotic patients with acute-on-chronic liver failure. Expert Rev Gastroenterol Hepatol. 2016 Aug;10(8):971-80. doi: 10.1080/17474124.2016.1177788. Epub 2016 Apr 25. — View Citation

Shi KQ, Cai YJ, Lin Z, Dong JZ, Wu JM, Wang XD, Song M, Wang YQ, Chen YP. Development and validation of a prognostic nomogram for acute-on-chronic hepatitis B liver failure. J Gastroenterol Hepatol. 2017 Feb;32(2):497-505. doi: 10.1111/jgh.13502. — View Citation

Silva PE, Fayad L, Lazzarotto C, Ronsoni MF, Bazzo ML, Colombo BS, Dantas-Correa EB, Narciso-Schiavon JL, Schiavon LL. Single-centre validation of the EASL-CLIF consortium definition of acute-on-chronic liver failure and CLIF-SOFA for prediction of mortality in cirrhosis. Liver Int. 2015 May;35(5):1516-23. doi: 10.1111/liv.12597. Epub 2014 Jun 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival status	Patients will be follow-up for 90 days until death or received liver transplantation. And survival days of each patients will be recorded.	90 days