Acute-on-chronic liver failure: an update

Abstract

Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%-50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care.

Keywords: LIVER CIRRHOSIS; LIVER FAILURE.

Conflict of interest statement

Competing interests: PG declares that he has received research funding from Ferring Pharmaceuticals, Grifols S.A. and Sequana Medical. He has participated on Advisory Boards for Ferring Pharmaceuticals, Promethera and Novartis.

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Figures

Figure 1

Inflammation caused by microbes. Top: Microbes (bacteria, viruses, fungi) induce inflammation via two classes of molecules: pathogen-associated molecular patterns (PAMPs) and virulence factors. Sensors of the innate immune system recognise the invading microbe via recognition of PAMPs, which are conserved molecular patterns (structural feature recognition). Sensors are known as pattern-recognition receptors. The second class of microbial inducers of inflammation includes a large number of virulence factors. Most of these factors are generally not recognised by dedicated receptors but can be sensed via the effects of their activity (functional feature recognition). For example, there are bacterial virulence factors which cause modifications and inactivation of host Rho GTPases and these alterations are sensed by the Pyrin inflammasome. Infection may be associated with tissue damage caused by the bacteria or by the immune response to bacteria. Tissue damage can induce inflammation which is committed to tissue repair (see text and reference32). Bottom: Proposed interventions. MELD, Model For End-Stage Liver Disease score.

Figure 2

Relationship between organ failure and mortality in acute-on-chronic liver failure (ACLF). Twenty-eight-day mortality rates of patients with decompensated cirrhosis with (red bars) and without (green bars) ACLF according to the diagnostic criteria proposed in the CANONIC study. Patients are divided into the following categories: patients with no organ failure (OF); patients with a single non-kidney organ failure without kidney dysfunction (KD; a serum creatinine level of 1.5–1.9 mg/dL) or brain dysfunction (BD; grade 1–2 hepatic encephalopathy); patients with a single kidney failure; patients with a single non-kidney organ failure with KD and/or BD; patients with two organ failures and patients with three or more organ failures. Adapted with permission from Arroyo et al.

Figure 3

Comparison of the area under the receiver operating curves (AUROCs) to predict 28-day (panel A) and 90-day (panel B) mortality of the chronic liver failure Consortium (CLIF-C) acute-on-chronic liver failure (ACLF) score compared with Model For End-Stage Liver Disease (MELD), Model For End-Stage Liver Disease sodium score (MELD-Na) and Child-Pugh-Turcotte scores (CPs). Adapted with permission from Jalan et al.

Figure 4

Proposed algorithm for the management of patients with acute-on-chronic liver failure (ACLF) or decompensated cirrhosis. A proposed management strategy for patients with ACLF based on mortality rate data from the CANONIC study. The first step is the assessment of ACLF grade at days 3–7 after initiation of medical management, including organ support. Liver transplantation should be assessed in all patients with ACLF because of high 90-day mortality rates (>20%). Liver transplantation should be performed as early as possible in patients with ACLF grade 2 and grade 3 as they are at considerable risk of short-term (28-day) mortality. In the case of contraindication of liver transplantation, the presence of four or more organ failures (OFs) or a Chronic Liver Failure Consortium (CLIF-C) ACLF score of >64 at days 3–7 after diagnosis could indicate the futility of care. ICU, intensive care unit. Adapted from Gustot et al and obtained from Arroyo et al with permission.