Learning Points

1. Alcohol cessation is the single most important intervention for patients with alcohol-related cirrhosis and alcohol-related hepatitis.
2. Patients with decompensated alcohol-related cirrhosis and alcohol-related hepatitis have complex medical needs requiring specialist, multidisciplinary input. 
3. Patients with decompensated disease and at least 3 months of alcohol abstinence should be considered for liver transplantation. 

Introduction

Alcohol remains the most common cause of liver disease in the UK[1]. The prevalence of this condition has risen sharply in the context of the COVID 19 pandemic and rise of co-factors which contribute to its severity, including mental health issues, obesity, and diabetes. In the past 20 years the number of premature deaths (age<75) in England from alcohol-related liver disease (ALD) has increased by 74%[2]. 

ALD describes a spectrum of illness. This article focuses on the most severe manifestations: ALD cirrhosis and alcohol-related hepatitis (AH). Many of the management principles apply to any patient with cirrhosis. This article will highlight those considerations which are specific to, or particularly important for patients with ALD. 

Managing alcohol use

Over 70% of patients with ALD cirrhosis admitted to our hospital are actively drinking alcohol. In our clinic 60% reported drinking at some point in the previous 12 months[3]. Ongoing alcohol use is clearly associated with a worse prognosis for patients with cirrhosis [4, 5] and following an episode of AH[6]. 

Alcohol use disorder (AUD) is intrinsically linked with ALD and describes a spectrum of illness defined by an impaired ability to stop or control alcohol intake. It can be identified using a validated tool, such as the AUD identification test- C (AUDIT-C) or fast alcohol screening test (FAST)[7].  A key characteristic is ongoing alcohol consumption despite negative health or social consequences[8] and by this definition, any patient with ALD who continues to drink alcohol has AUD. 

Alcohol cessation is the single most important intervention for patients with ALD cirrhosis and AH. Psychological interventions and pharmacotherapies to treat alcohol use disorder have been shown to be effective in improving clinical endpoints for these patients [9-12]. Although pharmacotherapies for AUD in this population are under-researched, Baclofen has been shown to be effective and safe[13-15]. Acamprosate is metabolised via the kidneys and also appears to be safe for patients with AH and ALD cirrhosis[16]. All patients should be strongly encouraged to engage with these interventions and referred to a specialist addiction/alcohol practitioner.[7]  

What is alcohol-related hepatitis?

AH describes an acute presentation with jaundice, malaise and liver decompensation occurring in a patients with ALD and recent or active alcohol consumption[17]. Patients with AH usually consume large amounts of alcohol (typically more than 7-10 units per day) and have alcohol use disorder. Of those who are not cirrhotic at presentation, 70% will go on to develop cirrhosis[18]. Of patients with established cirrhosis, about 40% will develop AH and this combination is a poor prognostic indicator[19].

The following characteristics are now widely accepted in clinical practice[20]: 

• Bilirubin ≥50 
• History of excess alcohol within 2 months
• Duration of clinically apparent jaundice <3 months (without other cause) 
• AST and ALT <400  (AST:ALT >2:1)

Biopsy is rarely necessary for diagnosis. In circumstances when the alcohol history is not clear, a wider range of formal tests for recent alcohol use are now available (Table 1)[21].

Management of decompensated alcohol related cirrhosis and alcohol-related hepatitis

Patients who present with decompensated ALD and/or AH are often very unwell. Decompensated chronic liver disease describes a deterioration in liver function in a patient with cirrhosis, presenting most commonly with jaundice, encephalopathy, ascites, and GI bleeding. AH is a common cause for decompensation in patients with ALD cirrhosis, but other causes include infection and variceal haemorrhage. 

 Clinicians should follow the guidance for the management of all patients with decompensated cirrhosis, in particular the decompensated cirrhosis care bundle[22]. Similarly, guidance is available for the diagnosis and management of acute on chronic liver failure which frequently develops in this cohort[23, 24]. 

The following points are particularly relevant to patients with decompensated ALD including those with AH:

• Alcohol withdrawal syndrome should be managed (ideally) using a symptom driven approach. In patients with severe liver impairment, short-acting benzodiazepines (lorazepam, oxazepam) should be considered in order to prevent excessive sedation[7, 25, 26].
• Any patient who is suspected or confirmed to be actively drinking should receive high dose intravenous B vitamins with ascorbic acid for the prevention of Wernicke’s encephalopathy[25]. 
• Nutrition
  1. Malnutrition is common in patients with ALD[27]. All decompensated patients should have input from a dietician. 
  2. Adequate nutrition is one of the only interventions with evidence base for improving outcomes in AH[28]. A calorie intake of 35-40kcal/kg is recommended.

In addition to the above the following points are relevant where a diagnosis of AH is suspected or confirmed:

• Severity Scoring – A Glasgow Alcoholic Hepatitis Score[29] of >9 or a Maddrey’s Discriminant Function score[30] >32 defines severe AH and predicts worse outcomes. 
• Vigilance for infection is key in this condition - infection is common in patients with AH and is associated with worse outcomes particularly if acquired during hospital admission[31, 32]. AH alone is sufficient to produce a systemic inflammatory response (including fevers and raised inflammatory markers)[17]. Nevertheless a low threshold should always exist for seeking out and treating infections. 
• Corticosteroids - European and American guidelines currently recommend corticosteroids (e.g, prednisolone 40 mg daily for four weeks) for patients with severe AH[33, 34]. The following should be considered:
  1. Clear diagnosis of severe alcohol-related hepatitis (above). 
  2. Absence of active/uncontrolled infection.
  3. A MELD 25-39 predicts the best response to steroids [35] as dose a baseline neutrophil: lymphocyte ratio of 5-8[36]. 
  4. Response to steroids should be assessed using a Lille score at either day 7[37] or day 4[38].
• N-acetylcysteine – when used in addition to the above measures, N-acetylcysteine was shown to improve mortality at 1-month but not beyond this[39]. Its use is portrayed as optional in current guidelines, and it is very unlikely to cause harm. 

Intensive Care

Patients with decompensated ALD cirrhosis and AH frequently develop organ failure which would necessitate support in the intensive care unit. 

The NCEPOD report “Measuring the Units” in 2013 identified that patients with ALD were ‘at times inappropriately denied treatment in critical care’ [40]. The update to this report, released in 2022, found that 30% of liver specialists felt that it was more challenging to get patients admitted to intensive care if they had alcohol as the cause of their liver disease. 

Gastroenterologists should foster good working relationships with colleagues in intensive care and make collaborative decisions about patient escalation strategies in discussion with the patient and their family. Further guidance to aid in these decisions in contained within the recently published European guidance for the management of acute on chronic liver failure.[24]

Liver transplant

UK guidance around liver transplantation for ALD cirrhosis has recently been updated[41]. As a summary we would highlight two points:

1. Any patient with decompensated ALD cirrhosis and at least three months of reported abstinence should be considered for liver transplant.

2. Early referral of such patients to a liver transplant unit for formal consideration is encouraged. 

Of note, although early liver transplantation for severe AH is used in a sub-group of patients in a number of countries including the USA. At present, AH is a contra-indication for liver transplant in the UK. 

Palliative Care

Referral to palliative care services should be considered for all patients with ALD who have an estimated prognosis of <12 months[7]. In particular this advice would apply to patients who remain decompensated despite abstinence from alcohol and/or those who are not candidates for liver transplantation. 

Table 1: Alcohol testing in patients with liver disease. Adapted from Arnts et al 2021 [21]

Author Biographies

Dr Chris Oldroyd

Dr Christopher Oldroyd is a Hepatology Specialist Registrar and Senior Research Fellow at the Cambridge Liver Unit. He was awarded an NIHR Doctoral Fellowship to complete a PhD at the University of Cambridge. His focus is the development of a complex intervention for alcohol use disorder targeted at patients with cirrhosis or alcohol associated hepatitis."

Dr Michael Allison

Consultant Hepatologist, Cambridge University Hospitals NHS Trust.