Elsevier

Digestive and Liver Disease

Volume 44, Issue 2, February 2012, Pages 166-171
Digestive and Liver Disease

Liver, Pancreas and Biliary Tract
Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure

https://doi.org/10.1016/j.dld.2011.08.029Get rights and content

Abstract

Background

Acute-on-chronic liver failure (ACLF) is characterised by acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in patients with previously diagnosed or undiagnosed chronic liver disease. We studied the clinical, biochemical and etiological profiles of ACLF patients investigating variables which could predict mortality.

Methods

Consecutive ACLF patients were enrolled and given standard intensive care management. They were monitored for predictors of 90-day mortality.

Results

91 patients were included; besides jaundice (median bilirubin 23.1 mg/dL) and coagulopathy, acute onset ascites with or without encephalopathy was the presenting symptom in 92%. In all patients a first diagnosis of chronic liver disease was made, mainly due to hepatitis B (37%) or alcohol (34%). Reactivation of chronic hepatitis B and alcoholic hepatitis were the common acute insults. The 90-day mortality was 63%. On multivariate analysis, hepatic encephalopathy, low serum sodium, and high INR were found to be independent baseline predictors of mortality. Amongst all severity scores studied, MELD, SOFA and APACHE-II scores had AUROCs of >0.8 which was significantly higher than that of Child–Turcotte–Pugh.

Conclusions

ACLF has very high mortality. Hepatic encephalopathy, low serum sodium and high INR predict poor outcome. Mortality can also be predicted by baseline MELD, SOFA or APACHE-II scores.

Introduction

Severe hepatic dysfunction or liver failure could present in the setting of a previously healthy liver (acute liver failure), or as an acute deterioration of known or unknown underlying chronic liver disease (acute-on-chronic liver failure; ACLF), or as further deterioration of decompensated end-stage liver disease. A common but poorly understood clinical scenario is presentation as acute liver failure in a patient with chronic liver disease which was asymptomatic till now [1]. Acute liver failure per se is far less common than acute deterioration of a patient with previously undiagnosed chronic liver disease. O’Grady et al. had previously shown that patients with hyperacute liver failure have a better survival than those with a protracted subacute hepatic failure [2]. In fact, most of the patients belonging to the later group probably already have some underlying hepatic dysfunction [3]. It is extremely important to suspect and diagnose underlying chronic liver disease at the earliest so as to prevent progression from liver dysfunction to multiorgan failure. Furthermore, since the duration of hepatic insult is rather short, hepatocellular injury is likely to be less and timely interventions could help overcome the acute crisis [3]. Recently, ACLF has been defined as “an acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease” [3].

The liver failure in ACLF could be of varying severity and depending on the duration and extent of hepatic injury, the clinical manifestations, disease course and occurrence of multi-organ failure (M-OF) develops. ACLF can have a rapidly progressive course and an urgent need for assessment and referral for liver transplantation. The importance of diagnosing impending or early organ failure cannot be over emphasized in this particular group of patients, as timely intervention can prevent or reverse the process and improve survival.

Several series of patients with acute deterioration of chronic liver disease have been recently reported [4], [5], [6], [7]. However, most of them have included patients only after one or more organ failure such as hepatorenal syndrome or hepatic encephalopathy has already set in besides severe liver failure [4], [5]. Patients belonging to such categories probably already have a far advanced liver disease and systemic dysfunction. The natural history and clinical profile of patients with ACLF of varying degrees of severity has not been well described in the literature. Moreover, many known prognostic models being used for cirrhosis of liver have been applied for the evaluation of ACLF. However, ideal prognostic model and predictors of mortality in ACLF have not been determined.

We prospectively studied the clinical profile, natural history and outcome of patients with ACLF. We also attempted to determine predictors of mortality and assessed various severity scores for mortality in these patients.

Section snippets

Patients

This prospective study was carried out in the Department of Gastroenterology, GB Pant Hospital, New Delhi, India, between December 2007 and January 2009. Consecutive patients of ACLF were enrolled. The inclusion criterion was ACLF as per the APASL guidelines [3] (patients with acute hepatic insult manifesting as jaundice with bilirubin ≥5 mg/dL, coagulopathy with international normalized ratio [INR] ≥1.5 and complicated by ascites and/or encephalopathy within 4 weeks of jaundice). These patients

Patients

From December 2007 to January 2009, 113 patients presenting as ACLF were screened. Of these, 91 patients were enrolled in the study and rest 22 were excluded due to the following reasons: evidence of decompensated cirrhosis prior to the onset of acute hepatic insult (n = 12), presence of hepatocellular carcinoma (n = 4), portal vein thrombosis (n = 2) and no evidence of chronic liver disease (n = 4).

Clinical presentation (Table 1)

The median age of the patients was 36 (range 15 to 80) years with a predominance of males (n = 65 [74%]).

Discussion

This is the first prospective large carefully conducted study which describes the clinical profile, natural history and predictors of mortality in patients of ACLF. The data clearly show that ACLF is a serious condition with a high mortality rate. Approximately two-thirds of patients may die in the absence of liver transplantation. Most patients already have multi-organ failure at presentation which has a spiralling downhill course leading to mortality. Presence of hepatic encephalopathy, low

Conflict of interest

None declared.

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