Clinical Profile of Patients with Acute-on-Chronic Liver Failure

Research Article

J Gastroenterol Liver Dis. 2016; 1(1): 1007.

Clinical Profile of Patients with Acute-on-Chronic Liver Failure

Gupta M, Dadhich S*, Bhargawa N, Ranjan P and Vatsya S

Department of Gastroenterology, Dr S. N. Medical College, India

*Corresponding author: Sunil Kumar Dadhich, Department of Gastroenterology, Dr S.N. Medical College, Jodhpur, Rajasthan, India

Received: August 28, 2016; Accepted: December 26, 2016; Published: December 27, 2016

Abstract

Background: Acute-on-Chronic Liver Failure (ACLF) is defined as sudden deterioration of liver functions due to acute insult in patients with known or unknown chronic liver disease. Its main feature is the reversibility, and high short term mortality due to Multi-Organ Failure (MOF).

Aims/Objectives: To study the clinical, laboratory, etiological profile and outcome of patients with ACLF.

Methods: This prospective observational study was conducted on 120 consecutive ACLF patients (WGO working party definition) admitted in department of gastroenterology, M.G Hospital, Dr S.N. Medical College from March 2016 to august 2016. Their clinical, laboratory, etiological profile and outcome were studied.

Results: Mean age ± standard deviation was 37.61 ± 8.54 years and 80% of patients were male. The most common aetiology of underlying chronic liver disease was alcohol (79.16%). Most common acute insult was alcoholic hepatitis (49.16%). Type C ACLF constitutes 70% of patients. Remaining 30 % of patients were of Type A/B ACLF. Twenty eight days mortality was 43.33% (52/120). Most patients who died had =1 organ failure, MELD score of 31 ± 5.75 and CLIF-SOFA score of 11.96 ± 2.82. Eighty nine patients (74.16%) had one or more organ failure. Of these, 51 (57.30%) died. Whereas, of the remaining thirty one patients without organ failure, only one died. The presence of 1, 2, =3 organ failure was seen in 18.33%, 23.33% and 32.5% of patients respectively. Mortality increases with the number of organ failure. The most common Organ Failure (OF) was liver failure in 34.66% of patients followed by coagulation failure in 18.6%. The other OF such as kidney, cerebral, circulatory and respiratory were seen in 16.8, 15.11, 8.88 and 5.7% respectively. Out of 52 patients who died, 39/52(75%) were not decompensate (WGO A/B) prior to illness. Mortality was more in alcoholic CLD 37/52(71.15%) in comparison to CLD patients of non alcoholic aetiology 15/52(28.84%). Independent predictors of mortality are low haemoglobin, high bilirubin, high MELD score and aetiologies of acute hepatic insult.

Conclusion: Most common cause of acute insult in ACLF was continued alcohol consumption leading to alcoholic hepatitis, which is preventable. Prognosis was worst in patients who were decompensated prior to illness (WGO-C), had multiple organ failure, and high MELD and SOFA score. Mortality increases with the number of organ failure.

Keywords: Chronic liver disease; Acute insult; Organ failure

Abbreviations

AASLD: American Association for the Study of Liver Diseases; ACLF: Acute On Chronic Liver Failure; ALT: Alanine Aminotransferase; ANA: Anti Nuclear Antibody; Anti HBc: Antibody Against Hepatitis B Core Antigen; Anti LKM1: Anti Liver Kidney Microsomal Antibody; APASL: Asia Pacific Association for the Study of Liver Disease; ASMA: Anti Smooth Muscle Antibody; AST: Aspartate Aminotransferase; ATT: Anti Tubercular Treatment; CANONIC: CLIF Acute on Chronic Liver Failure in Cirrhosis; CLIFSOFA: Chronic Liver Failure -Sequential Organ Failure Assessment; CLD: Chronic Liver Disease; DILI: Drug Induced Liver Injury; ELISA: Enzyme Linked Immune Sorbent Assay; GI: Gastro Intestinal; HAV: Hepatitis A Virus; HBV: Hepatitis B Virus; HBsAg: Hepatitis B Surface Antigen; HRS: Hepatorenal Syndrome; INASL: Indian National Association for the Study of Liver; INR: International Normalized Ratio; MELD: Model for End Stage Liver Disease; MOF: Multi Organ Failure; NASH: Non Alcoholic Steato Hepatitis; SBP: Spontaneous Bacterial Peritonitis

Introduction

The world gastroenterology organization consensus defines ACLF as “a syndrome in patients with CLD with or without previously diagnosed cirrhosis which is characterized by acute hepatic decompensation resulting in liver failure (jaundice and prolongation of INR)” and one or more extra hepatic organ failure that is associated with increased mortality within a period of 28 days and up to 3 months from onset [1].

ACLF occurs in about 30% of patients with an acute decompensation of cirrhosis and it has a significantly higher short term mortality of 30-50% than expected with decompensated liver disease [1,2].

It is usually associated with a precipitating event which can be reversed if diagnosed early. The causes of acute insult in ACLF are variable; they can be both hepatotropic and non-hepatotropic, infectious or non-infectious. Causes of acute insult are variable and depend on geographical area. The present study is conducted to evaluate the clinical, laboratory, etiological profile and outcome of patients with ACLF.

Materials and Methods

This study was conducted in Department of Gastroenterology, Dr S.N. Medical College, Jodhpur, Rajasthan. This is a prospective observational study conducted from March 2016 to august 2016. Written informed consent was taken from all patients before enrolment, except from patients with altered sensorium in whom consent was taken from a relative. The study was approved by the college ethical committee.

120 consecutive patients with ACLF as defined by WGO working party [1] were included. They were categorised into three different subtypes: Type A ACLF- non cirrhotic CLD with an acute flare; often indistinguishable from acute or sub acute liver failure. Type B ACLFwell compensated cirrhosis with an acute insult. Type C ACLFcirrhosis with previous hepatic decompensation.

Work-up for aetiology of acute hepatic injury and underlying CLD

Presence of cirrhosis, chronic hepatitis, metabolic liver disease or cholestatic liver disease was defined as chronic liver disease. Diagnosis of cirrhosis was made using combination of following criteria:

1. Previous liver biopsy findings if available

2. Clinical evaluation

3. Radiological (heterogenous echotexture of liver with irregular outline, altered liver size or porto-systemic collaterals).

4. Laboratory (low serum albumin, AST/ALT ratio >1).

5. Endoscopy (oesophageal varices > 5mm in size).

All patients were thoroughly evaluated to find out the aetiology of chronic liver disease and acute insults. All patients were investigated with HBsAg, anti-HBc IgM and anti-HCV by ELISA. Tests for hemochromatosis, wilsons disease and autoimmune liver disease (ANA, ASMA, anti-LKM1, ceruloplasmin, 24 Hr urinary copper and ferritin) were done.

Diagnosis of alcoholic hepatitis was made in a patient with a history of alcohol abuse within a span of 28 days of symptoms, typical symptoms and physical findings, abnormal compatible liver enzyme levels. Maddrey’s Discriminant Function was calculated to assess for severity of alcoholic hepatitis as follows:

[4.6 × (patient’s prothrombin time - control prothrombin time, in seconds)] + Serum bilirubin level, in milligrams per decilitre

Diagnosis of acute viral hepatitis was based on the clinical presentation, LFT and a positive viral serology (IgM Anti HEV, IgM Anti HAV by ELISA). Diagnosis of autoimmune hepatitis was based on the simplified criteria for AIH and that of hepatitis B flare based on AASLD.

MELD score was calculated to assess the severity. MELD score was calculated as follows: logarithmic equation (0.957 × log [creatinine mg/dl] + 0.378 × log [bilirubin mg/dl] + 1.120 × log [international normalized ratio] + 0.643).

The organ failure were defined as per the CLIF-sequential OF assessment score [1] (Table 1).