Skip to main content

Main menu

  • Home
  • Our journals
    • Clinical Medicine
    • Future Healthcare Journal
  • Subject collections
  • About the RCP
  • Contact us

Clinical Medicine Journal

  • ClinMed Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Author guidance
    • Instructions for authors
    • Submit online
  • About ClinMed
    • Scope
    • Editorial board
    • Policies
    • Information for reviewers
    • Advertising

User menu

  • Log in

Search

  • Advanced search
RCP Journals
Home
  • Log in
  • Home
  • Our journals
    • Clinical Medicine
    • Future Healthcare Journal
  • Subject collections
  • About the RCP
  • Contact us
Advanced

Clinical Medicine Journal

clinmedicine Logo
  • ClinMed Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Author guidance
    • Instructions for authors
    • Submit online
  • About ClinMed
    • Scope
    • Editorial board
    • Policies
    • Information for reviewers
    • Advertising

How I treat… alcohol-related liver disease

Luke D Tyson and Heather Lewis
Download PDF
DOI: https://doi.org/10.7861/clinmedicine.19-1-43
Clin Med January 2019
Luke D Tyson
AImperial College Healthcare NHS Trust, London, UK
Roles: NIHR academic clinical fellow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: luke.tyson@nhs.net
Heather Lewis
BImperial College Healthcare NHS Trust, London, UK
Roles: consultant hepatologist
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
Loading

ABSTRACT

Age-standardised mortality from liver disease in the United Kingdom has risen by 400% since 1970, with three-quarters of deaths from alcohol-related liver disease (ARLD). The 2013 National Confidential Enquiry into Patient Outcome and Death report found that only 47% of the patients dying in hospital from liver disease experienced ‘good’ care. We discuss common complications in the care of patients with ARLD and the evidence-based best practice that can improve patient outcomes, with a focus on the initial management of patients presenting acutely to the medical take.

KEYWORDS
  • Alcohol
  • cirrhosis
  • decompensation
  • withdrawal
  • ­dependence
  • best practice

Introduction

Since the Gin Acts of the 18th century, alcohol has been a recognised major cause of morbidity and mortality in the United Kingdom: a fact inescapable to the practicing general physician. The extent of the problem cannot be overstated – since 1970 the age-standardised mortality from liver disease in the UK has risen by 400%, in contrast to the gradual and significant reductions in mortality from circulatory, ischaemic heart, cerebrovascular, neoplasm, respiratory, endocrine and metabolic disease. Three-quarters of these deaths are from alcohol related liver disease (ARLD).1 Public Health England (PHE) estimates that there were 23,000 alcohol-related deaths in England in 20142 with most patients dying under the age of 65.3 It is estimated that alcohol abuse costs the NHS £3.5 billion each year.1

Concerningly, while deaths from cirrhosis are rising in England, they are falling in most other EU countries.1 Furthermore, the problem affects the most deprived members of our society disproportionally – PHE found the alcohol-related mortality of the most deprived lifestyle group to be 65% higher than the average.2 In addition, the 2013 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report found that only 47% of the patients dying in hospital from ARLD experienced ‘good’ care. Simple interventions such as prompt treatment of sepsis and good fluid management were, in some instances, lacking.4

In response to the NCEPOD report, stakeholders including the British Association for the Study of the Liver (BASL) and the British Society of Gastroenterology (BSG) developed the Decompensated Cirrhosis Care Bundle to optimise recognition of common complications and prompt early intervention in this high-mortality condition (see supplementary material S1).5 Our aim is to expand on this guidance and to describe what we consider to be current evidence-based best practice when treating patients with ARLD.

Alcohol

Alcohol withdrawal

Alcohol withdrawal is a common occurrence on the acute medical take, both in patients with and without liver disease. It is treated primarily with benzodiazepines. Many units routinely use fixed-dose chlordiazepoxide regimens. However, caution must be taken with patients with cirrhosis as chlordiazepoxide clearance is reduced in these patients6 and hence chlordiazepoxide can accumulate and cause drowsiness and respiratory depression. In patients with cirrhosis and at risk of alcohol withdrawal, it is felt safer and equally efficacious to use oral lorazepam in a symptom-triggered manner as dictated by regular assessment of the patient’s Clinical Institute Withdrawal Assessment Scale for Alcohol score.7

Alcohol dependence

An admission due to alcohol provides a unique opportunity to change a patient’s clinical course by undertaking a brief intervention aimed at stopping or reducing a patient’s alcohol use. A 2010 Cochrane review highlighted that alcohol consumption is reduced following a brief intervention. In addition, the reviewers note mortality was reduced at 6 months and 1 year in these patients compared to their controls.8 We would encourage the use of a dedicated alcohol liaison service to deliver these interventions using established frameworks; for example, the Paddington Alcohol Test is used in the emergency department to identify patients misusing alcohol and to facilitate brief advice from an emergency physician or nurse, as well as the offer of an appointment with an Alcohol Liaison Nurse (ALN) for a brief intervention. A pragmatic, single-blind randomised clinical trial demonstrated that a reattendance is avoided for every two patients that accept the offer of an ALN appointment.9

Once a patient has been treated acutely for alcohol withdrawal, of equal importance is assisting them to maintain this withdrawal. Although not currently licensed in the UK for the treatment of alcohol dependence, there is evidence of a significant increase (29% to 71%) in maintenance of abstinence in alcohol-dependent cirrhotics treated with baclofen 10 mg three times a day versus placebo (double-blind randomised controlled trial).10 Acamprosate also shows a reduction in drinking and an increase of abstinence in a Cochrane meta-analysis,11 although this is untested in liver disease. Naltrexone is also efficacious12 but can cause hepatocellular injury. Disulfiram should be avoided as it has been linked to cases of fulminant hepatic failure.13 Close links between the alcohol liaison service and a specialist with an interest in ARLD can help patients with alcohol dependence access suitable medication to maintain alcohol cessation.

Infection

As highlighted in the 2013 NCEPOD report, treatment of infection was often delayed.3 Infection increases mortality significantly in patients with cirrhosis14 and every hour that appropriate antibiotics are delayed will further increase mortality.15 We would recommend adopting a low threshold for the instigation of broad-spectrum antibiotics in patients with decompensated cirrhosis, followed by rationalisation once a source of infection is definitively identified.

In patients who fail to respond to antibiotics, we must also consider fungal infections, seen to occur in up to 10% of critically unwell cirrhotic patients with septic shock.15 In the presence of ascites, diagnostic paracentesis is mandatory on admission – with prompt treatment for spontaneous bacterial peritonitis with antibiotics and human albumin solution16 should the ascitic neutrophil count be greater than 250 /mm3. Diagnostic paracentesis should be repeated should the patient deteriorate during their admission, as part of a broader ‘septic screen’.

Fluid balance

Fluid management in patients with cirrhosis is historically an area where there is heterogeneity of practice. Patients with decompensated cirrhosis are often on high doses of diuretics and are at high risk of acute kidney injury (AKI), often complicated by hyponatraemia. Treating clinicians may have concerns regarding salt balance, and about precipitating a worsening of existing ascites. However, this must be weighed against the increased mortality should AKI develop.17

The consensus highlighted in the Decompensated Cirrhosis Care Bundle5 is that if there is evidence of an AKI (based on modified risk of renal dysfunction; injury to the kidney; failure of kidney function, loss of kidney function and end-stage kidney disease criteria), there is hyponatraemia (defined as serum sodium <125 mmol/L) or the patient is clinically dehydrated, then one should suspend all diuretics and nephrotoxic drugs and fluid resuscitate with 250 mL boluses of 5% albumin or 0.9% saline aiming to restore a mean arterial pressure >80 mmHg and a urine output of >0.5 mL/kg/h based on dry weight. Locally, many clinicians will use 0.9% saline in the first instance as it is readily and promptly available in an acute situation.

Frequently, one or two litres of fluid will correct the patient’s losses. However, should the patient worsen or should they fail to achieve targets within the first 6 hours, escalation to a higher level of care must be considered for further resuscitation guided by central venous pressure monitoring and for consideration of inotropes.

Alcoholic hepatitis

Alcoholic hepatitis (AH) is a clinical syndrome characterised by jaundice and an acute deterioration of liver function in an actively drinking patient. AH can be diagnosed clinically in patients with recent alcohol excess and a short history of jaundice (less than 3 months), in the absence of other causes of liver failure. Characteristically the serum aspartate aminotransferase (AST): serum alanine transaminase (ALT) ratio is >2:1 although an AST >500 IU/L or an ALT >300 IU/L should prompt consideration of an alternative diagnosis.

For those with severe AH (Maddrey’s Discriminant Function >32) mortality remains high – approximately 56% at 1 year in a recent trial including more than 1000 patients;18 many of these patients have underlying cirrhosis. Liver biopsy for histological confirmation of AH is considered for patients with severe AH as these patients may be treated with corticosteroids, which are associated with an increased number of infections;18 as such, it is desirable to limit corticosteroids only to those who may benefit.

Steroids or pentoxifylline?

Historically, patients with AH and a poor prognostic score (Maddrey’s Discriminant Function >32; Glasgow Alcoholic Hepatitis Score ≥9) have been treated with corticosteroids. More recently, pentoxifylline was suggested as an alternative or additive treatment. Both were shown to reduce short term mortality in severe AH in a network meta-analysis.19

The Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial was a large multicentre, double blind, randomised trial designed to evaluate the effect of treatment with prednisolone or pentoxifylline or both compared to placebo. It was designed to settle the controversy around steroid treatment. 1053 patients were included in the final analysis. The STOPAH trial found that pentoxifylline did not improve survival in patients with AH and that prednisolone was associated with a reduction in 28-day mortality that did not reach significance. There was no improvement in mortality at 90 days or 1 year. However, in a secondary analysis adjusting for baseline determinants of prognosis, prednisolone had a significant survival benefit at 28 days. A higher rate of infection was seen in patients treated with prednisolone, but the mortality attributed to infection did not vary between those who did and did not receive steroids.18

A recent meta-analysis, subsequent to STOPAH, found that corticosteroids reduced risk of death at 28 days but not at 6 months.20 Consequently, clinicians continue to use steroids in the treatment of AH in patients with a poor prognostic score. Other treatments (for example, N-acetylcysteine, obeticholic acid and interleukin-22) are currently undergoing evaluation. We would advise consulting a specialist before starting steroids in a patient with AH.

Infection

Patients with AH who show evidence of infection have a lower survival at 6 months.21 Infection accounted for 24% of the deaths in the STOPAH trial.18 Recently, infection has been found to be an independent risk factor for developing acute on chronic liver failure (ACLF) during the medical management of patients with AH. The presence of ACLF significantly increased mortality in this cohort.22 We would encourage prompt treatment of suspected infection in patients with AH.

Nutrition

There has long been an awareness of the importance of good nutrition in patients with decompensated cirrhosis.16 Numerous randomised controlled trials report that enteral and parenteral nutrition reduce mortality in AH and cirrhosis compared to no intervention. However, when looked at systematically, these trials were judged at high or unclear risk of bias.23 Our view is that enteral nutrition (oral or nasogastric) is low risk when managed by appropriately trained professionals. Given the potential benefit of nutritional therapy in these high-risk patients, we would encourage early referral of patients with AH and cirrhosis to dietetic services.

Transplantation

Transplantation in AH has proved controversial.24 Patients with severe AH who are failing to respond to steroids can be identified by the Lille score calculated at day seven. If a patient’s Lille score is >0.45, 6-month survival is estimated at 25%, compared to 85% survival for a Lille score of <0.45.25 Mathurin et al selected patients with AH failing to respond to medical therapy from seven French and Belgian centres using strict criteria (no previous AH, supportive family, no severe co-morbidities, commitment to alcohol abstinence) for early transplant and compared them to matched controls. Less than 2% of patients met their criteria. Twenty six patients were transplanted with a 6-month survival of 77.8% compared to 23.8% in the control group. Three resumed alcohol intake at 720, 740 and 1,140 days post-transplant.26

There is increasing international experience in, and acceptance of, early liver transplant in carefully selected patients with AH as a first presentation of ARLD.24,26 The UK pilot programme began in 2014, aiming to recruit 20 patients. Two of the seven UK transplant centres declined to participate.27 The pilot programme did not meet recruitment targets and was closed.

End stage ARLD

In contrast to AH, liver transplant in end-stage ARLD is widely accepted. ARLD is currently the most common indication for liver transplant, accounting for approximately 30% of transplants in the UK.28 Abstinence from alcohol is required, traditionally for 6 months29 and many centres send serum alcohol levels routinely during patient contacts. Urinary ethyl glucuronide is an alternative marker of alcohol consumption that is detectable for up to 5 days after alcohol ingestion.

Post-transplant, the 5-year risk-adjusted survival after liver transplant for ARLD is 84.4%. This is comparable to other indications for liver transplant.28 Alcohol use post-transplant is independent of the indication for the liver transplant.30 In common with other aetiologies of end stage liver disease, significant milestones in a patient’s clinical course (development of hepatic encephalopathy, development of ascites, first decompensation) and a qualifying United Kingdom Model for End-Stage Liver Disease score should prompt consideration of referral to a transplant centre for patients with ARLD who have shown a commitment to alcohol abstinence.

Conclusion

Mortality from ARLD is rising in the UK. In contrast, deaths from cirrhosis are falling in other European countries. Historically, there are areas of practice that we can improve. Management decisions during the first 24 hours are critical. We believe that simple evidence-based interventions, for example adoption of the Decompensated Cirrhosis Care Bundle, can improve mortality from these common, yet deadly, conditions.

Supplementary material

Additional supplementary material may be found in the online version of this article at www.clinmed.rcpjournal.org :

S1 – BSG – BASL Decompensated Cirrhosis Care Bundle – First 24 Hours.5 www.bsg.org.uk/resource/bsg-basl-decompensated-cirrhosis-care-bundle.html [Accessed 22 August 2018].

  • © Royal College of Physicians 2019. All rights reserved.

References

  1. ↵
    1. Williams R
    , Aspinall R, Bellis M, et al. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet 2014;384:1953–97.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Public Health England
    . The public health burden of alcohol and the effectiveness and cost-effectiveness of alcohol control policies: An evidence review. London: Public Health England, 2016. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/733108/alcohol_public_health_burden_evidence_review_update_2018.pdf [Accessed 14 July 2018].
  3. ↵
    1. Office for National Statistics
    . Alcohol related deaths 1994–2015. Newport: Office for National Statistics, 2017. www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/previousdefinitionofalcoholrelateddeaths [Accessed 14 July 2018].
  4. ↵
    1. National Confidential Enquiry into Patient Outcome and Death (NCEPOD)
    . Alcohol-related liver disease: measuring the units. NCEPOD, 2013. www.ncepod.org.uk/2013arld.html [Accessed 14 July 2018].
  5. ↵
    1. McPherson S
    , Dyson J, Austin A, Hudson M. Response to the NCEPOD report: development of a care bundle for patients admitted with decompensated cirrhosis-the first 24 h. Frontline Gastroenterol 2016;7:16–23.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Greenblatt DJ
    , Shader RI, MacLeod SM, Sellers EM. Clinical pharmacokinetics of chlordiazepoxide. Clin Pharmacokinet 1978;3:381–94.
    OpenUrlPubMed
  7. ↵
    1. McKeon A
    , Frye MA, Delanty N. The alcohol withdrawal syndrome. J Neurol Neurosurg Psychiatry 2008;79:854–862.
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. McQueen J
    , Howe TE, Allan L, et al. Brief interventions for heavy alcohol users admitted to general hospital wards. Cochrane Database Syst Rev 2011;8:CD005191.
    OpenUrlPubMed
  9. ↵
    1. Crawford MJ
    , Patton R, Touquet R, et al. Screening and referral for brief intervention of alcohol misusing patients in an emergency department: a pragmatic randomised controlled trial. Lancet 2004;364:1334–9.
    OpenUrlCrossRefPubMed
  10. ↵
    1. Addolorato G
    , Leggio L, Ferrulli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet 2007;370:1915–22.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Rösner S
    , Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010a;9:CD004332.
    OpenUrlPubMed
  12. ↵
    1. Rösner S
    , Hackl-Herrwerth A, Leucht S, et al. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 2010b;12:CD001867.
    OpenUrlPubMed
  13. ↵
    1. Watts TE
    , Pandey RA, Vancil TJ. Fatal fulminant hepatic failure related to the use of disulfiram. J Ark Med Soc 2014;110:280–3.
    OpenUrl
  14. ↵
    1. Arvaniti V
    , D’Amico G, Fede G, et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology 2010;139:1246–56.e5.
    OpenUrlCrossRefPubMed
  15. ↵
    1. Arabi YM
    , Dara SI, Memish Z, et al. Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis. Hepatology 2012;56:2305–15.
    OpenUrlPubMed
  16. ↵
    1. Moore KP
    , Aithal GP. Guidelines on the management of ascites in cirrhosis. Gut 2006;55(Suppl 6):vi1–12.
    OpenUrlFREE Full Text
  17. ↵
    1. Belcher JM
    , Garcia-Tsao G, Sanyal AJ, et al. Association of AKI with Mortality and Complications in Hospitalized Patients with Cirrhosis. Hepatology 2013;57:753–62.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Thursz MR
    , Richardson P, Alison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015;372:1619–28.
    OpenUrlCrossRefPubMed
  19. ↵
    1. Singh S
    , Murad MH, Chandar AK, et al. Comparative effectiveness of pharmacological interventions for severe alcoholic hepatitis: A systematic review and network meta-analysis. Gastroenterology 2015;149:958–70.e12.
    OpenUrlPubMed
  20. ↵
    1. Louvet A
    , Thursz MR, Kim DJ, et al. Corticosteroids reduce risk of death within 28 days for patients with severe alcoholic hepatitis, compared with pentoxifylline or placebo – a meta-analysis of ­individual data. Gastroenterology 2018;155:458–468.e8.
  21. ↵
    1. Rudler M
    , Mouri S, Charlotte F, et al. Prognosis of treated severe alcoholic hepatitis in patients with gastrointestinal bleeding. J Hepatol 2015;62:816–21.
    OpenUrlPubMed
  22. ↵
    1. Serste T
    , Cornillie A, Njimi H, et al. The prognostic value of acute-on-chronic liver failure during the course of severe alcoholic ­hepatitis. J Hepatol 2018;69:318–24.
    OpenUrl
  23. ↵
    1. Fialla AD
    , Israelsen M, Hamberg O, Krag A, Gluud LL. Nutritional therapy in cirrhosis or alcoholic hepatitis: a systematic review and meta-analysis. Liver Int 2015;35:2072–8.
    OpenUrl
  24. ↵
    1. Lee BP
    , Terrault NA. Early liver transplantation for severe alcoholic hepatitis: moving from controversy to consensus. Curr Opin Organ Transplant 2018;23:229–36.
    OpenUrl
  25. ↵
    1. Louvet A
    , Naveau S, Abdelnour M, et al. The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology 2007;45:1348–54.
    OpenUrlCrossRefPubMed
  26. ↵
    1. Mathurin P
    , Moreno C, Samuel D, et al. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med 2011;365:1790–800.
    OpenUrlCrossRefPubMed
  27. ↵
    1. NHS Scotland
    . Edinburgh transplant unit: Annual report 2013-2014. Edinburgh: NHS Scotland, 2014. www.edren.org/media/TPunit/Edinburgh_Transplant_Unit_Annual_Report__2013.pdf [Accessed 17 July 2018].
  28. ↵
    1. NHS Blood and Transplant
    . Annual report on liver transplantation: report for 2016/2017 (1 April 2007 – 31 March 2017). Watford: NHS Blood and Transplant, 2017. https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/5007/annual_liver_transplantation_report_2017.pdf [Accessed 17 July 2018].
  29. ↵
    1. Parker R
    , Holt A. Transplanting patients with alcohol-related liver disease in the national health system: New rules and decisions. Alcohol Alcohol 2018;53:145–50.
    OpenUrl
  30. ↵
    1. Russ KB
    , Chen N-W, Kamath PS, et al. Alcohol use after liver ­transplantation is independent of liver disease etiology. Alcohol Alcohol 2016;51:698–701.
    OpenUrlCrossRefPubMed
Back to top
Previous articleNext article

Article Tools

Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Citation Tools
How I treat… alcohol-related liver disease
Luke D Tyson, Heather Lewis
Clinical Medicine Jan 2019, 19 (1) 43-46; DOI: 10.7861/clinmedicine.19-1-43

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
How I treat… alcohol-related liver disease
Luke D Tyson, Heather Lewis
Clinical Medicine Jan 2019, 19 (1) 43-46; DOI: 10.7861/clinmedicine.19-1-43
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • ABSTRACT
    • Introduction
    • Alcohol
    • Infection
    • Fluid balance
    • Alcoholic hepatitis
    • End stage ARLD
    • Conclusion
    • Supplementary material
    • References
  • Figures & Data
  • Info & Metrics

Related Articles

  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Personalised future prescribing using pharmacogenomics: A resumé of a joint Royal College of Physicians / British Pharmacological Society working party report
  • Digital tools in neurosurgical pathways: considerations for the future
  • Patient and public understanding of the concept of ‘personalised medicine’ in relation to cancer treatment: a systematic review
Show more Review

Similar Articles

FAQs

  • Difficulty logging in.

There is currently no login required to access the journals. Please go to the home page and simply click on the edition that you wish to read. If you are still unable to access the content you require, please let us know through the 'Contact us' page.

  • Can't find the CME questionnaire.

The read-only self-assessment questionnaire (SAQ) can be found after the CME section in each edition of Clinical Medicine. RCP members and fellows (using their login details for the main RCP website) are able to access the full SAQ with answers and are awarded 2 CPD points upon successful (8/10) completion from:  https://cme.rcplondon.ac.uk

Navigate this Journal

  • Journal Home
  • Current Issue
  • Ahead of Print
  • Archive

Related Links

  • ClinMed - Home
  • FHJ - Home
clinmedicine Footer Logo
  • Home
  • Journals
  • Contact us
  • Advertise
HighWire Press, Inc.

Follow Us:

  • Follow HighWire Origins on Twitter
  • Visit HighWire Origins on Facebook

Copyright © 2021 by the Royal College of Physicians