Clinical Review

Decompensated alcohol related liver disease: acute management

BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i124 (Published 26 January 2016) Cite this as: BMJ 2016;352:i124
  1. Stuart McPherson, consultant hepatologist1 2,
  2. Michael R Lucey, professor of hepatology3,
  3. Kieran J Moriarty, consultant gastroenterologist4
  1. 1Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  2. 2Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
  3. 3Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
  4. 4Department of Gastroenterology, Royal Bolton Hospital, Bolton, UK
  1. Correspondence to: S McPherson, Liver Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK stuart.mcpherson{at}nuth.nhs.uk

What you need to know

  • Decompensated alcohol related liver disease (ARLD) occurs when there is a deterioration in liver function in a patient with cirrhosis, which presents with jaundice, coagulopathy, ascites, and hepatic encephalopathy

  • The short term mortality rate from decompensated ARLD is high (10-20% at one month)

  • Early aggressive treatment of infections, alcohol related hepatitis, acute kidney injury, gastrointestinal bleeding, and encephalopathy can improve survival in patients with decompensated ARLD

  • All patients admitted with ascites should have a diagnostic tap, since “silent” spontaneous bacterial peritonitis is common. A diagnostic tap can be performed in patients with coagulopathy

  • Every effort must be made to help patients with an episode of hepatic decompensation to achieve long term abstinence, otherwise the prognosis is poor

  • Acute hospitals should establish a consultant led, multidisciplinary alcohol care team

Alcohol related liver disease (ARLD) and liver cirrhosis are complications of long term excessive alcohol use and occur in 10-20% of chronic, heavy drinkers.1 2 Complications, including hepatic decompensation, variceal bleeding, and hepatocellular carcinoma, reduce life expectancy.1 3 Since 1970, there has been a 400% increase in liver related (mainly alcohol related) deaths across all ages in the UK (fig 1).4 5 Liver disease is now the fifth commonest cause of death in the UK. The average age of death from ARLD is 59 years.6

Figure1

Fig 1 Standardised mortality data for major causes of death in UK, 1970-2010. Reproduced with permission of Nick Sheron

In a report of UK hospitals only 47% of patients received “good” hospital care.7 This review provides guidance on the management of patients with decompensated ARLD, focusing on the first 24 hours after hospital admission.

What is decompensated ARLD?

Figure 2 provides a summary of the clinical course of ARLD. Decompensation of cirrhosis occurs when liver function deteriorates, and the disease presents with jaundice and coagulopathy (from reduced hepatic function), ascites and variceal bleeding (from portal hypertension), and hepatic encephalopathy (from portosystemic shunting and liver failure). Box 1 lists the causes of hepatic decompensation. “Acute-on-chronic liver failure” has recently been described as a distinct type of hepatic decompensation, accompanied by extrahepatic organ failure, systemic inflammation, and susceptibility to infection, which can occur in patients with cirrhosis (including ARLD), and carries a particularly high mortality.8 9

Figure2

Fig 2 Clinical course of ARLD1 2 24

Box 1: Causes of hepatic decompensation

  • Infection/sepsis (for example, spontaneous bacterial peritonitis, urinary, chest, cholangitis)

  • Alcohol related hepatitis and alcohol consumption

  • Drugs (non-steroidal anti-inflammatory drugs, others)

  • Gastrointestinal bleeding (variceal and non-variceal)

  • Ischaemic liver injury (sepsis or hypotension)

  • Acute portal vein thrombosis

  • Development of hepatocellular carcinoma

Sources and selection criteria

We electronically searched PubMed and Cochrane reviews using the terms “alcoholic liver disease,” “alcoholic hepatitis,” and “cirrhosis complications.” We also searched personal reference lists and references cited within review articles. Reference was made to relevant guidelines from the National Institute for Health and Care Excellence, European Association for the Study of the Liver, and American Association for the Study of the Liver.

How should a patient with decompensated ARLD be assessed on admission?

A British Society of Gastroenterology endorsed care bundle for the management of patients with decompensated cirrhosis provides a checklist of the key interventions that should be performed (see supplementary information).10 These recommendations are predominantly led from trial data, but where data are not available, recommendations come from international guidelines and expert opinion.

How should patients with decompensated ARLD be managed?

An overview of the management of specific aspects of decompensated ARLD, which often occur simultaneously, follows.

Investigate and manage infection

Cirrhosis is associated with immune dysfunction that can result in life threatening bacterial infections, with particularly high mortality rates (30% at one month).11 12 13 The most common infections are spontaneous bacterial peritonitis, urinary tract infections, pneumonia, Clostridium difficile enterocolitis, and cellulitis.14 15 Patients with cirrhosis do not always display signs typical of an inflammatory response, such as pyrexia.

Perform an infection screen in all patients on admission or if they deteriorate, including culture of ascitic fluid, blood, and urine, and chest radiography.16 17 Enterobacteriaceae and non-enterococccal streptococci cause most spontaneous infections.12 Guidelines by the European Association for the Study of the Liver (EASL) recommend antibiotics, such as β lactams, cephalosporins, or quinolones, with modifications made in light of culture results.12 16

Spontaneous bacterial peritonitis is a primary infection caused by translocation of gut bacteria to the peritoneal fluid, and it is common in those with cirrhotic ascites.16 Patients may have no infective symptoms, although abdominal pain or pyrexia can occur.18 The finding of >250 polymorphonuclear cells per mm3 of ascitic fluid is indicative of spontaneous bacterial peritonitis for which broad spectrum antibiotics are recommended.12 16 19 20

The EASL guidelines recommend intravenous albumin for patients with spontaneous bacterial peritonitis, since a well conducted randomised controlled trial showed that albumin (1.5 g/kg at diagnosis, 1 g/kg at day 3) reduced the incidence of hepatorenal syndrome from 30% to 10% and mortality from 29% to 10%.16 21

Alcohol related hepatitis

Alcohol related hepatitis is a syndrome of rapid onset jaundice (<3 months), liver failure, and systemic inflammation, associated with prolonged, heavy alcohol consumption (typically >12 units/day (120 mL)).22 Clinical features may include tender hepatomegaly, fever, ascites, or encephalopathy. Laboratory investigations typically show increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels 2-6 times the upper limit of normal, with an AST/ALT ratio >2, neutrophilia, hyperbilirubinaemia, and coagulopathy.1 Differentiation between alcohol related hepatitis and other causes of hepatic decompensation, such as sepsis, can be difficult, and a liver biopsy (usually transjugular) should be considered when doubt exists over the diagnosis.23 24

The severity and associated short term mortality risk from alcohol related hepatitis can be assessed by prognostic scores, such as the Maddrey discriminant function, Glasgow alcoholic hepatitis score, and model for end stage liver disease.25 26 27 Although newer scores may more accurately predict mortality from alcohol related hepatitis, the Maddrey discriminant function remains the most widely used, and a score of 32 or more defines “severe” disease, where mortality is increased (30% 28 day mortality) and specific treatment is indicated.25 28

Guidelines recommend oral prednisolone 40 mg daily for four weeks as first line treatment for severe disease, but the efficacy of corticosteroids remains contentious.1 28 29 30 31 32 In the most recent and largest randomised controlled trial, comprising 1103 participants, prednisolone was associated with a trend towards a reduction in 28 day mortality, although this did not reach significance (odds ratio 0.72, 95% confidence interval 0.52 to 1.01, P=0.06).32 In a multivariate analysis, correcting for baseline factors, 28 day mortality was significantly reduced by 40% (0.61, 0.41 to 0.91, P=0.02). However, mortality was not reduced at 90 days or at one year. In a subsequent meta-analysis, including patients from this trial study, corticosteroids reduced short term mortality in severe alcohol hepatitis.33 Overall, data suggest a modest short term survival benefit from corticosteroids and these drugs should remain the first line treatment for severe disease.

The main concern with using corticosteroids for severe alcohol hepatitis is a potentially increased risk of serious infections. Patients should have a negative infection screen or infection treated before starting steroids. Assessment of the Lille score (www.lillemodel.com) at day 7 identifies steroid “non-responders” (score >0.45; approximately 40% of patients), where continued use of steroids may increase the risk of infection.34 35 If there is no clinical response, steroids can be stopped on day 7. Figure 3 shows an algorithm for the use of prednisolone.

Figure3

Fig 3 Algorithm for management of severe alcohol related hepatitis. MDF (Maddrey discriminant function) and Lille score can be calculated at www.lillemodel.com

Pentoxifylline has been recommended as an alternative to corticosteroids,1 29 following a randomised controlled trial that showed a survival benefit in treated patients.36 However, recent trials have failed to show a benefit.32 37 38

Steroid non-responsive severe alcohol hepatitis, with its high mortality, is a research priority. N-acetyl cysteine, combined with prednisolone,39 granulocyte colony stimulating factor,40 and early liver transplantation41 have all shown promise, but further work is needed to define their role.

Acute kidney injury and hepatorenal syndrome

Acute kidney injury occurs in approximately 20% of patients admitted to hospital with cirrhosis42 and is more common in association with spontaneous bacterial peritonitis. Patients with cirrhosis often have low baseline creatinine levels owing to malnutrition. Previous diagnostic criteria used absolute creatinine (>133 µmol/L) for diagnosis,44 but new criteria use changes in creatinine levels to allow more accurate diagnosis of acute kidney injury in these patients.43 45

Perform urinalysis and urine culture, looking for infection or evidence of parenchymal kidney injury. Withdraw diuretics and nephrotoxic drugs and consider other causes, particularly infection.43 Euvolaemia should be achieved with albumin or a crystalloid.43 46 If renal function in a patient with cirrhosis and ascites deteriorates despite initial treatment, the most likely cause is hepatorenal syndrome (box 2). Prompt terlipressin and albumin treatment improves renal perfusion in patients with hepatorenal syndrome. In well conducted randomised controlled trials, treatment has been shown to improve renal function and reduce mortality.47 48

Box 2: Diagnostic criteria for and causes of acute kidney injury in cirrhosis, and diagnostic criteria for hepatorenal syndrome4243

Acute kidney injury
  • Increase in serum creatinine level by ≥26.5 µmol/L within 48 hours or

  • ≥50% increase from baseline, which is known or presumed to have occurred in past seven days

Causes
  • Commonly multifactorial

  • Prerenal (45%):

    • Infections

    • Hypovolaemia (for example, gastrointestinal bleeding, diuresis, diarrhoea)

    • Drugs (for example, vasodilators, non-steroidal anti-inflammatory drugs, iodinated contrast medium)

  • Intrarenal (32%)—acute tubular necrosis and glomerulonephritis

  • Hepatorenal syndrome (23%)

  • Post-renal (<1%)

Hepatorenal syndrome

  • Cirrhosis with ascites

  • Diagnosis of acute kidney injury

  • No response after two consecutive days of diuretic withdrawal and volume expansion with albumin (1 g/kg/day to maximum 100 g/day)

  • Absence of shock

  • No current or recent treatment with nephrotoxic drugs

  • No macroscopic signs of structural kidney injury as defined by:

    • Absence of proteinuria (>500 mg/day)

    • Absence of microhaematuria (>50 red blood cells per high power field)

    • Normal renal ultrasonography

Ascites

Ascites develops in patients with portal hypertension as result of physiological changes leading to sodium retention.49 Patients should start a diet with no added salt.16 In the absence of major renal dysfunction (creatinine levels more than normal range) or hyponatraemia (<130 mmol/L), patients with moderate ascites should start spironolactone 100 mg daily and furosemide (frusemide) 40 mg daily, to achieve 0.5-1.0 kg loss of fluid per day. Doses can be increased every five days, up to a maximum of 400 mg spironolactone and 160 mg of furosemide daily.50 Electrolyte monitoring, at least once weekly for the first month, is essential. Hyponatraemia, hyperkalaemia, hypokalaemia, or increases in serum creatinine levels are common. Once ascites is controlled, reduce diuretic treatment where possible. Randomised controlled trials found that in patients with severe ascites with noticeable abdominal distension, paracentesis with albumin replacement compared with diuretic treatment was associated with shorter hospital stay and fewer complications.16 51

Gastrointestinal bleeding

This should be managed according to recent guidelines.52 53 54

Hepatic encephalopathy

A comprehensive review of the management of hepatic encephalopathy has recently been published.55

Managing nutrition in decompensated ARLD

Malnutrition and sarcopenia occur in 60-70% of patients admitted to hospital with ARLD. Poor nutritional status has an adverse effect on prognosis.56 57 58 Alcohol impairs the intestinal absorption and hepatic storage of thiamine, and heavy drinkers are often deficient. Parenteral thiamine can reduce the risk of alcohol related brain damage, Wernicke’s encephalopathy, and Korsakoff’s syndrome.30 Patients with cirrhosis often require nutritional supplementation and should be assessed by a dietitian.57 Enteral nutrition (oral or nasogastric) improves nutritional status and liver function and reduces complications.59 Daily electrolyte (phosphate, potassium, magnesium, and calcium) monitoring with correction of abnormalities is required until electrolytes are stable, to prevent refeeding syndrome.

Acute alcohol withdrawal and relapse prevention

Hospitals should have an alcohol care team4 7 60 61 (box 3). Acute alcohol withdrawal can occur in alcohol dependent people who suddenly stop drinking. This usually develops 6-24 hours after the last drink. Symptoms include irritability, anxiety, tachycardia, tremors, nausea, vomiting, and pyrexia. Untreated, alcohol withdrawal can progress to seizures, delirium tremens, and death. Patients can be monitored objectively using the revised Clinical Institute Withdrawal Assessment–Alcohol scale.62 If symptoms are present, treatment with short acting benzodiazepines is indicated.63 Patients require close monitoring, which can help to differentiate acute alcohol withdrawal from hepatic encephalopathy. Moreover, benzodiazepines have the potential to precipitate hepatic encephalopathy. Relapse prevention has been discussed in a recent clinical review.64

Box 3: Acute hospital model for an alcohol care team6061

  • A consultant led, multidisciplinary, patient centred alcohol care team to be integrated across primary and secondary care

  • A seven day alcohol specialist nurse service

  • Coordinated policies for the emergency department and acute medical units

  • A rapid assessment, interface, and discharge liaison psychiatry service

  • An alcohol assertive outreach team for frequent attenders to hospital

  • Formal links with local authority, clinical commissioning groups, public health, and other stakeholders

Intensive care

Specialist gastroenterology/liver teams should be involved at the earliest opportunity.7 Patients with worsening physiological variables (increasing early warning score), despite initial treatment, should be considered for escalation to high dependency/intensive care, especially if it is their first presentation and they have a good premorbid performance status.7 Overall mortality outcomes from patients with decompensated cirrhosis are encouraging. One large observational study found that 63% of patients with cirrhosis (most with ARLD), admitted to intensive care units, survived and were discharged.65 Specialist teams monitor progress, using prognostic scores, such as the sequential organ failure assessment score, and after 48-72 hours re-evaluate whether further treatment is appropriate.66

Expected outcomes of acute management of decompensated ARLD

Acute decompensated ARLD is a treatable disorder. Long term abstinence from alcohol is the most important treatment intervention. Those who achieve abstinence have a far better long term prognosis than those who continue to drink. In one observational study, patients with histologically advanced but non-decompensated ARLD who continued drinking had a 5.6-fold increased risk of death/liver transplant after 15 years.67 A comprehensive care plan should include a formal assessment by an alcohol addiction specialist.63 Evidence for the use of drugs to limit drinking in decompensated ARLD is unclear.

A comprehensive care plan should deal with preventable reasons for readmission (table).

Common preventable reasons for early readmission among patients with decompensated cirrhosis, along with potential solutions69

View this table:

However, a subset of patients with decompensated ARLD remains, for whom medical management is futile and a palliative care approach often the most appropriate. Clinical Liver Disease, a free online educational journal of the American Association for the Study of Liver Diseases, is an excellent resource for further short articles and videos on providing palliative care to patients with end stage liver disease (www.cldlearning.com).68

Key research questions

  • What is the optimum treatment for steroid non-responsive alcohol related hepatitis?

  • How do we optimise alcohol relapse prevention?

  • What is the pathophysiology of organ failure in acute on chronic liver failure and how should it be treated?

Additional educational resources

Information for professionals
Information for patients

Tips for non-specialists

  • A care bundle is available for patients admitted with decompensated cirrhosis and provides a checklist of key initial investigations and management that should be conducted in the critical first 24 hours (www.bsg.org.uk/care-bundles/care-bundles-general/index.html)

  • Patients with decompensated ARLD have a high risk of in-hospital death. Specialist gastroenterology/liver teams should be involved at the earliest opportunity

  • Sepsis is a major cause of death in patients with ARLD, who do not always display typical signs of infection. If infection is suspected, have a low threshold for initiating broad spectrum antibiotics

  • Consider early escalation of care to a high dependency/intensive care unit for patients with good preadmission performance status who do not respond to initial treatment, since early aggressive treatment of sepsis, gastrointestinal bleeding, and acute kidney injury saves lives

  • Overall, the most important prognostic factor for survival long term is maintenance of abstinence

How patients were involved in the creation of this article

Patients were not involved in the writing of this review.

Footnotes

  • Competing interests: SM developed the decompensated cirrhosis “care bundle,” which is endorsed by the British Society of Gastroenterology. KJM is the alcohol lead for the British Society of Gastroenterology. All authors contributed to and approved the final manuscript. SM is the guarantor.

References

View Abstract

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