Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B

Hai Li, Liu-Ying Chen, Nan-Nan Zhang, Shu-Ting Li, Bo Zeng, Marco Pavesi, Àlex Amorós, Rajeshwar P Mookerjee, Qian Xia, Feng Xue, Xiong Ma, Jing Hua, Li Sheng, De-Kai Qiu, Qing Xie, Graham R Foster, Geoffrey Dusheiko, Richard Moreau, Pere Gines, Vicente Arroyo, Rajiv Jalan, Hai Li, Liu-Ying Chen, Nan-Nan Zhang, Shu-Ting Li, Bo Zeng, Marco Pavesi, Àlex Amorós, Rajeshwar P Mookerjee, Qian Xia, Feng Xue, Xiong Ma, Jing Hua, Li Sheng, De-Kai Qiu, Qing Xie, Graham R Foster, Geoffrey Dusheiko, Richard Moreau, Pere Gines, Vicente Arroyo, Rajiv Jalan

Abstract

The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were 'hepatic' and 'coagulation'. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles.

Conflict of interest statement

There are potential competing financial interests as follows. Rajiv Jalan received research funding from Vital Therapies, has served on Scientific Advisory Board for Conatus Pharma, and received lecture fees from Gambro and has on-going research collaboration with Gambro, Grifols and is the Principal Investigator of an Industry sponsored study (Sequana Medical). He is also inventor for a drug, L-ornithine phenyl acetate which UCL has licensed to Ocera Therapeutics. Vicente Arroyo has research grants from Grifols.

Figures

Figure 1. Screening, enrollment, and flow of…
Figure 1. Screening, enrollment, and flow of patients according to the presence or absence of ACLF according to CLIF-C OF score.
Figure 2
Figure 2
(A) Relationship between the severity of ACLF and the WCC.(B) Mortality rate at 28 days and 90 days according to the grade of ACLF.
Figure 3. Relationship between the expected probability…
Figure 3. Relationship between the expected probability of death at 28-days, the presence or the absence of ACLF and the white cell count.
Figure 4
Figure 4
Panel (A): Accuracy of the CLIF-C ACLFs (red line) as compared to MELDs (green) and MELD-Nas (orange) in predicting 28-day and 90-day mortality of patients with ACLF associated to cirrhosis due to HBV infection. Comparison of the areas under the ROC curves (AUROCs) estimated for each score. The CLIF-C ACLFs showed a significantly higher predictive ability in comparison with the MELDs and MELD-Nas scores for both the 28-day and 90-day mortality. Panel (B): Accuracy of the CLIF-C ADs (red line) as compared to MELDs (green) and MELD-Nas (orange) in predicting 6-month and 1-year mortality of patients with AD (without ACLD) due to HBV associated cirrhosis. Comparison of the AUROCs estimated for each score. The CLIF-C ADs showed significantly higher predictive ability in comparison to the MELDs.

References

    1. Jalan R. et al.. Acute-on chronic liver failure. J Hepatol 57, 1336–1348, doi: 10.1016/j.jhep.2012.06.026 (2012).
    1. Olson J. C. et al.. Intensive care of the patient with cirrhosis. Hepatology 54, 1864–1872, doi: 10.1002/hep.24622 (2011).
    1. Jalan R. et al.. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 61, 1038–1047, doi: 10.1016/j.jhep.2014.06.012 (2014).
    1. 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, 1437.e1421-1429, doi: 10.1053/j.gastro.2013.02.042 (2013).
    1. Jalan R. et al.. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 62, 831–840, doi: 10.1016/j.jhep.2014.11.012 (2015).
    1. Bajaj J. S. et al.. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology 60, 250–256, doi: 10.1002/hep.27077 (2014).
    1. Sarin S. K. et al.. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 3, 269–282, doi: 10.1007/s12072-008-9106-x (2009).
    1. Bajaj J. S. Defining acute-on-chronic liver failure: will East and West ever meet? Gastroenterology 144, 1337–1339, doi: 10.1053/j.gastro.2013.04.024 (2013).
    1. Jalan R. et al.. Toward an improved definition of acute-on-chronic liver failure. Gastroenterology 147, 4–10, doi: 10.1053/j.gastro.2014.05.005 (2014).
    1. Li H. et al.. Submassive hepatic necrosis distinguishes HBV-associated acute-on chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol, doi: 10.1016/j.jhep.2015.01.029 (2015).
    1. Mookerjee R. P. et al.. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis. J Hepatol 55, 1103–1111, doi: 10.1016/j.jhep.2011.02.021 (2011).
    1. Katoonizadeh A. et al.. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 59, 1561–1569, doi: 10.1136/gut.2009.189639 (2010).
    1. Singal A. K. & Fontana R. J. Meta-analysis: oral anti-viral agents in adults with decompensated hepatitis B virus cirrhosis. Aliment Pharmacol Ther 35, 674–689, doi: 10.1111/j.1365-2036.2011.04990.x (2012).
    1. Wai C. T. et al.. Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States. J Viral Hepat 12, 192–198, doi: 10.1111/j.1365-2893.2005.00581.x (2005).
    1. Dao D. Y. et al.. Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure. Dig Dis Sci 57, 1349–1357, doi: 10.1007/s10620-011-2013-3 (2012).
    1. Perrillo R. P. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology 120, 1009–1022 (2001).
    1. Dao D. Y. et al.. Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels. Hepatology 55, 676–684, doi: 10.1002/hep.24732 (2012).
    1. Trawale J. M. et al.. The spectrum of renal lesions in patients with cirrhosis: a clinicopathological study. Liver Int 30, 725–732, doi: 10.1111/j.1478-3231.2009.02182.x (2010).
    1. Shah N. et al.. Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis. Liver Int 33, 398–409, doi: 10.1111/liv.12047 (2013).
    1. Jalan R. et al.. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol 60, 1310–1324, doi: 10.1016/j.jhep.2014.01.024 (2014).
    1. Kim W. R. et al.. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med 359, 1018–1026, doi: 10.1056/NEJMoa0801209 (2008).
    1. Medzhitov R., Schneider D. S. & Soares M. P. Disease tolerance as a defense strategy. Science 335, 936–941, doi: 10.1126/science.1214935 (2012).
    1. Kamath P. S. & Kim W. R. The model for end-stage liver disease (MELD). Hepatology 45, 797–805, doi: 10.1002/hep.21563 (2007).
    1. Shi Y. et al.. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 62, 232–242, doi: 10.1002/hep.27795 (2015).
    1. Theocharidou E. et al.. The Royal Free Hospital score: a calibrated prognostic model for patients with cirrhosis admitted to intensive care unit. Comparison with current models and CLIF-SOFA score. Am J Gastroenterol 109, 554–562, doi: 10.1038/ajg.2013.466 (2014).
    1. Silva P. E. et al.. 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, doi: 10.1111/liv.12597 (2014).
    1. Pan H. C. et al.. Scoring systems for 6-month mortality in critically ill cirrhotic patients: a prospective analysis of chronic liver failure - sequential organ failure assessment score (CLIF-SOFA). Aliment Pharmacol Ther 40, 1056–1065, doi: 10.1111/apt.12953 (2014).
    1. McPhail M. J. et al.. Increased Survival for Patients With Cirrhosis and Organ Failure in Liver Intensive Care and Validation of the Chronic Liver Failure-Sequential Organ Failure Scoring System. Clin Gastroenterol Hepatol, doi: 10.1016/j.cgh.2014.08.041 (2014).
    1. Lee M. et al.. CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis. Liver Int 35, 46–57, doi: 10.1111/liv.12683 (2015).
    1. Dhiman R. K., Agrawal S., Gupta T., Duseja A. & Chawla Y. Chronic Liver Failure-Sequential Organ Failure Assessment is better than the Asia-Pacific Association for the Study of Liver criteria for defining acute-on-chronic liver failure and predicting outcome. World J Gastroenterol 20, 14934–14941, doi: 10.3748/wjg.v20.i40.14934 (2014).
    1. Agrawal S., Duseja A., Gupta T., Dhiman R. K. & Chawla Y. Simple organ failure count versus CANONIC grading system for predicting mortality in acute-on-chronic liver failure. J Gastroenterol Hepatol 30, 575–581, doi: 10.1111/jgh.12778 (2015).
    1. Lok A. S. & McMahon B. J. Chronic hepatitis B. Hepatology 45, 507–539, doi: 10.1002/hep.21513 (2007).
    1. Hui C. K. et al.. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology 131, 59–68, doi: 10.1053/j.gastro.2006.04.015 (2006).
    1. Hoofnagle J. H. Reactivation of hepatitis B. Hepatology 49, S156–165, doi: 10.1002/hep.22945 (2009).
    1. Harrell F. E. Jr., Lee K. L. & Mark D. B. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15, 361–387, doi: 10.1002/(sici)1097-0258(19960229)15:4<361::aid-sim168>;2-4 (1996).

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe