ABSTRACT

Summary

Acute-on-chronic liver failure (ACLF), which was described relatively recently (2013), is a severe form of acutely decompensated cirrhosis characterised by the existence of organ system failure(s) and a high risk of short-term mortality. ACLF is caused by an excessive systemic inflammatory response triggered by precipitants that are clinically apparent (e.g., proven microbial infection with sepsis, severe alcohol-related hepatitis) or not. Since the description of ACLF, some important studies have suggested that patients with ACLF may benefit from liver transplantation and because of this, should be urgently stabilised for transplantation by receiving appropriate treatment of identified precipitants, and full general management, including support of organ systems in the intensive care unit (ICU). The objective of the present Clinical Practice Guidelines is to provide recommendations to help clinicians recognise ACLF, make triage decisions (ICU vs. no ICU), identify and manage acute precipitants, identify organ systems that require support or replacement, define potential criteria for futility of intensive care, and identify potential indications for liver transplantation. Based on an in-depth review of the relevant literature, we provide recommendations to navigate clinical dilemmas followed by supporting text. The recommendations are graded according to the Oxford Centre for Evidence-Based Medicine system and categorised as ‘weak’ or ‘strong’. We aim to provide the best available evidence to aid the clinical decision-making process in the management of patients with ACLF.

Keywords

Organ failure, inflammation, precipitating event, infection, alcohol-related hepatitis, critical care, organ support, sarcopenia, frailty, liver,, transplantation, prognosis, futility, mortality

Main recommendations

MR1

ESGE recommends the following standards for Barrett esophagus (BE) surveillance:

• a minimum of 1-minute inspection time per cm of BE length during a surveillance endoscopy
• photodocumentation of landmarks, the BE segment including one picture per cm of BE length, and the esophagogastric junction in retroflexed position, and any visible lesions
• use of the Prague and (for visible lesions) Paris classification
• collection of biopsies from all visible abnormalities (if present), followed by random four-quadrant biopsies for every 2-cm BE length.

Strong recommendation, weak quality of evidence.

MR2

ESGE suggests varying surveillance intervals for dif ferent BE lengths. For BE with a maximum extent of ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE with a maximum extent of ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent of ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies.For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance are advised.
Weak recommendation, low quality of evidence.

MR3

ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient’s life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered.
Weak recommendation, very low quality of evidence.

MR4

ESGE recommends offering endoscopic eradication therapy using ablation to patients with BE and low grade dysplasia (LGD) on at least two separate endoscopies, both confirmed by a second experienced pathologist.
Strong recommendation, high level of evidence

MR5

ESGE recommends endoscopic ablation treatment for BE with confirmed high grade dysplasia (HGD) without visible lesions, to prevent progression to invasive cancer.
Strong recommendation, high level of evidence.

MR6

ESGE recommends offering complete eradication of all remaining Barrett epithelium by ablation after endoscopic resection of visible abnormalities containing any degree of dysplasia or esophageal adenocarcinoma (EAC).
Strong recommendation, moderate quality of evidence.

MR7

ESGE recommends endoscopic resection as curative treatment for T1a Barrett’s cancer with well/moderate differentiation and no signs of lymphovascular invasion.
Strong recommendation, high level of evidence.

MR8

ESGE suggests that low risk submucosal (T1b) EAC (i. e. submucosal invasion depth ≤ 500 μm AND no [lympho] vascular invasion AND no poor tumor differentiation) can be treated by endoscopic resection, provided that adequate follow-up with gastroscopy, endoscopic ultrasound (EUS), and computed tomography (CT)/positrion emission tomography-computed tomography (PET-CT) is performed in expert centers.
Weak recommendation, low quality of evidence.

MR9

ESGE suggests that submucosal (T1b) esophageal adenocarcinoma with deep submucosal invasion (tumor invasion > 500 μm into the submucosa), and/or (lympho)vascular invasion, and/or a poor tumor differentiation should be considered high risk. Complete staging and consideration of additional treatments (chemotherapy and/or radiotherapy and/or surgery) or strict endoscopic follow-up should be undertaken on an individual basis in a multidisciplinary discussion.
Strong recommendation, low quality of evidence

MR10a

ESGE recommends that the first endoscopic follow-up after successful endoscopic eradication therapy (EET) of BE is performed in an expert center.
Strong recommendation, very low quality of evidence.

MR10b

ESGE recommends careful inspection of the neosquamocolumnar junction and neo-squamous epithelium with high definition white-light endoscopy and virtual chromoendoscopy during post-EET surveillance, to detect recurrent dysplasia.
Strong recommendation, very low level of evidence.

MR10c

ESGE recommends against routine four-quadrant biopsies of neo-squamous epithelium after successful EET of BE.
Strong recommendation, low level of evidence

MR10d

ESGE suggests, after successful EET, obtaining fourquadrant random biopsies just distal to a normal-appearing neo-squamocolumnar junction to detect dysplasia in the absence of visible lesions.
Weak recommendation, low level of evidence.

MR10e

ESGE recommends targeted biopsies are obtained where there is a suspicion of recurrent BE in the tubular esophagus, or where there are visible lesions suspicious for dysplasia.
Strong recommendation, very low level of evidence.

MR11

After successful EET, ESGE recommends the following surveillance intervals:

• For patients with a baseline diagnosis of HGD or EAC: at 1, 2, 3, 4, 5, 7, and 10 years after last treatment, after which surveillance may be stopped.
• For patients with a baseline diagnosis of LGD: at 1, 3, and 5 years after last treatment, after which surveillance may be stopped.

Strong recommendation, low quality of evidence.

ABSTRACT

Summary

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification – including weight loss, dietary changes, physical exercise and discouraging alcohol consumption – as well as optimal management of comorbidities – including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated – is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Source file

https://doi.org/10.1016/j.jhep.2024.04.031