Original Article
Impact of Hepatic and Extrahepatic Insults on the Outcome of Acute-on-Chronic Liver Failure

https://doi.org/10.1016/j.jceh.2016.10.006Get rights and content

Background

To study the differences in outcome and predictors of mortality in acute-on-chronic liver failure (ACLF) precipitated by hepatic or extrahepatic insults.

Methods

Consecutive patients of cirrhosis with acute decompensation were prospectively included and followed up for 90 days from admission. ACLF was defined based on chronic liver failure (CLIF) acute-on-chronic liver failure in cirrhosis (CANONIC study) criteria. Acute worsening due to acute viral hepatitis A and E, hepatitis B flare, alcoholic hepatitis, autoimmune hepatitis flare, or drug-induced liver injury were categorized as hepatic ACLF and that due to bacterial infection, upper gastrointestinal bleed or surgery as extrahepatic ACLF. Patients with both hepatic and extrahepatic insults were included in combined insult group.

Results

Of 179 patients of acute decompensation, 122 had ACLF (hepatic insults 47 and extrahepatic insults 51). Alcohol (64.8%) was the most common etiology of cirrhosis while infection (36%) was the most common acute insult followed by alcoholic hepatitis (24.6%). Higher proportion of extrahepatic ACLF patients had history of prior decompensation than hepatic ACLF patients (62.7% vs. 27.7%, P < 0.001). There was no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days (53.2% vs. 56.9%, P = 0.715 and 85% vs. 74.5%, P = 0.193, respectively). Area under receiver-operating curve (AUROC) for 28-day mortality in extrahepatic ACLF group was 0.788, 0.724, 0.718, 0.634, and 0.726 and in hepatic-ACLF group was 0.786, 0.625, 0.802, 0.761, and 0.648 for chronic liver failure-sequential organ failure assessment (CLIF-SOFA), model for end stage liver disease (MELD), integrated MELD score (iMELD), acute physiology and chronic health evaluation score (APACHE-II), and Child–Turcotte–Pugh score scores, respectively.

Conclusion

There is no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days. iMELD and CLIF-SOFA have highest AUROC to predict 28-day mortality in hepatic and extrahepatic ACLF groups, respectively.

Section snippets

Methods

This was a prospective, observational cohort study, which screened inpatients of cirrhosis admitted in the Department of Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India from July 2013 to June 2015. The PGIMER, Chandigarh ethics committee approved the study (INT/IEC/2015/493, dated 11/09/2015). All study participants, or their legal guardian, provided informed written consent prior to study enrollment and the study protocol confirmed to the

Acute Decompensation

The diagnosis of cirrhosis was based on clinical, biochemical, and ultrasonography or liver histological data.8, 13 Acute decompensation of cirrhosis was defined as per the criteria of the CANONIC study as development of upper gastrointestinal bleeding, overt ascites over 2 weeks, new onset hepatic encephalopathy (HE), and/or bacterial infection.2 Acute bacterial infection was diagnosed by presence of spontaneous bacterial peritonitis (SBP) (ascitic fluid polymorphonuclear leukocytes >250 

Management of Patients

All patients were clinically evaluated including history, physical examination, and routine biochemical and imaging parameters. Work-up for the cause of cirrhosis and acute insult(s) was done for each case. The diagnosis of acute viral hepatitis was based on a positive serology for hepatitis E virus (IgM anti-HEV) or hepatitis A virus (IgM anti-HAV) by ELISA. HBV flare, autoimmune hepatitis (AIH), and Wilson disease were diagnosed based on American Association for the Study of Liver Diseases

Patients

Out of 480 patients with cirrhosis, 179 were found to have acute decompensation. ACLF was diagnosed in 122 patients on admission (Figure 1). Among 122 patients of ACLF, acute insult was hepatic in 47 (38.5%), extrahepatic in 51 (41.8%), combined hepatic and extrahepatic in 15 (12.3%), and was unknown in 9 (7.4%) patients (Figure 1). Alcohol was the most common etiology of cirrhosis in 79 (64.8%) patients followed by cryptogenic, hepatitis C, hepatitis B, AIH, Wilson disease, and primary biliary

Discussion

This study demonstrated that patients with ACLF have higher mortality than patients with acute decompensation not amounting to ACLF; however, there is no difference in 28- and 90-day mortalities based on whether the acute insult was hepatic or extrahepatic. The best prognostic score for hepatic group is iMELD and for extrahepatic group is CLIF-SOFA. Similar to our previous data,7, 8 in the present study, alcohol was the predominant cause of chronic liver disease, alcoholic hepatitis was the

Conclusion

This study demonstrates that while there are differences in severity of underlying liver disease and occurrence of liver failure after the acute insult, there is no difference in extrahepatic organ failure or mortality between ACLF caused by hepatic or extrahepatic insults.

Authors’ Contribution

RKD conceived the idea for the study, wrote the protocol, performed analyses, interpreted data, and prepared the manuscript. TG wrote the protocol, performed analyses, interpreted data, and prepared the manuscript. SR assisted in data collection and patient care management. SA assisted in data analyses, interpreting data, and in preparing the manuscript. ST, AD, and YKC were involved in patient care management and assisted in the interpretation of the data and in preparing the manuscript.

Conflicts of Interest

The authors have none to declare.

Acknowledgements

Tarana Gupta received the best poster award from Indian Society of Gastroenterology for presentation of her research at the 56th Annual Meeting of the Indian Society of Gastroenterology, Indore, India, in November 2015.

References (23)

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  • Cited by (15)

    • The role of the CLIF-C OF and the 2016 MELD in prognosis of cirrhosis with and without acute-on-chronic liver failure

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      First, this study confirms that ACLF is an individual entity characterized by high mortality (> 15%) with values reaching 43.6% and 64.1%, respectively for 28 and 90-day, with significant differences from the group without ACLF. This higher mortality, when compared with the CANONIC study (29.6% and 51.1%), can be justified by our very high rate of acute infection in the ACLF group (74.4%) that is known to be a crucial prognosis factor for poor outcome.17-20 Additionally, this study included a considerable percentage of patients with alcohol consumption even when other CLD causes, like chronic HBV or HCV infection, were present.

    • Current Diagnosis and Classification of Hepatic Encephalopathy

      2018, Journal of Clinical and Experimental Hepatology
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      The main reason behind this proposal is the more severe prognostic value of HE in the context of ACLF,21 even if there is no proof of peculiar pathophysiological mechanisms.22 The finding that the increased brain water content is parallel with the degree of HE23 is in line with the view of increased astrocyte hydration in HE.24 It should be emphasized that the concept of brain hyperhydration (‘edema’) should not be confused with the one of intracranial hypertension.

    • Liver Transplantation for Acute on Chronic Liver Failure

      2017, Journal of Clinical and Experimental Hepatology
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      Some of the Indian studies evaluating mortality of patients with ACLF are shown in Table 2.8,14–21 These studies show a mortality rate ranging from 41.4% (median of 8 days) to 74.5% at 90 days.18,19 It has also been shown that mortality at 28 days and 90 days remains almost similar in presence of hepatic or non-hepatic acute event.19

    • Acute-on-Chronic Liver Failure: Etiology of Chronic and Acute Precipitating Factors and Their Effect on Mortality

      2019, Journal of Clinical and Experimental Hepatology
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      All causes for AD were searched in a particular patient. Although, in this study, we recruited ACLF patients defined by APASL criteria, we took both hepatic and extrahepatic causes as precipitating factors as studies from western literature, and few Indian studies had taken both causes as precipitating factors.6,11 Data of the following variables were collected at the baseline: age, sex, clinical presentation, complete blood counts, liver function tests, kidney function tests, cause of hepatic decompensation, etiology of underlying chronic liver disease (CLD), and outcomes.

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