Alcoholic Liver Disease

Alcoholic liver disease
Straight to the point of care
Last updated: Aug 24, 2021

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Case history 7
Diagnosis 8
Approach 8
History and exam 14
Risk factors 16
Investigations 18
Differentials 22
Management 26
Approach 26
Treatment algorithm overview 30
Treatment algorithm 31
Emerging 38
Primary prevention 38
Secondary prevention 38
Patient discussions 39
Follow up 40
Monitoring 40
Complications 41
Prognosis 42
Guidelines 44
Diagnostic guidelines 44
Treatment guidelines 45
Online resources 47
References 48
Images 60
Disclaimer 62
Alcoholic liver disease Overview
Summary
Alcoholic liver disease accounts for 3 million deaths annually worldwide.
Caused by chronic heavy alcohol ingestion. About 40 to 80 g/day in men and 20 to 40 g/day in women for 10
OVERVIEW
to 12 years is sufficient to cause liver damage in the absence of other liver diseases.
Clinical presentations are highly variable. There is no specific laboratory test to identify alcohol as a cause
of liver damage. Liver biopsy, in the context of a history of alcohol abuse, is diagnostic but is not absolutely
indicated in all patients.
Alcohol abstinence is the first line of treatment, with periodic liver enzyme tests to monitor ongoing liver
damage. Abstinence is also the key to prevention of alcoholic liver diseases.
Complications include oesophageal or gastric variceal bleeding, ascites, coagulopathy, hepatic

encephalopathy, and liver cancer.
Definition
Alcoholic liver disease (ALD) has 3 stages of liver damage: fatty liver (steatosis), alcoholic hepatitis
(inflammation and necrosis), and alcoholic liver cirrhosis. All are caused by chronic heavy alcohol ingestion.
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Aug 24, 2021.
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3
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Alcoholic liver disease Theory
Epidemiology
Alcohol consumption is a significant cause of mortality, morbidity, and social problems, accounting for
approximately 5% of deaths (3 million deaths) worldwide.[1] [2]
THEORY
A US modelling study of high-risk alcohol drinking patterns suggests that age-standardised deaths due to
alcohol-related liver disease are expected to increase from 8.2 per 100,000 person-years in 2019 to 15.2 per
100,000 person-years in 2040.[3]
In 2018, the US National Survey on Drug Use and Health reported that 14.4 million adults aged ≥18 years
(5.8% of this age group) had alcohol-use disorder.[4] [5] Of these, 9.2 million were men (7.6% of men in this
age group).[4] [5]
Between 2006 and 2010, approximately 38,600 deaths annually were attributable to chronic excessive
alcohol use in the US (26,800 males and 11,800 females), making alcohol a leading cause of preventable
death.[6]
The prevalence of alcohol use and binge drinking increased significantly among middle-aged and older US
adults between 2000 and 2016 (e.g., average annual increase in binge drinking of 2.7% for ages 50-64,
and 3.4% for individuals aged 65 and over), and may be contributing to increasing rates of alcohol-related
morbidity and mortality.[7]
In the US, the prevalence of ALD has remained relatively stable at 8.8% to 8.1% from 2001-2002 to
2015-2016. However, the proportion of ALD patients with stage ≥3 fibrosis has increased from 2.2% to
6.6%.[8] From 2007 to 2017, the total number of adults with ALD listed for liver transplant increased by
63.4% and the proportion with concurrent hepatocellular carcinoma increased by 178%.[8]
In the UK, hospital admissions for ALD have significantly increased from 32.0 per 100,000 population
(16,360 admissions) in 2013/2014 to 38.5 per 100,000 people (20,202 admissions) in 2016/2017.[9]
Aetiology
The common aetiological denominator in ALD is chronic, heavy alcohol ingestion. Alcohol is a risk factor
for advanced liver disease and cirrhosis; however, the threshold of consumption at which risk emerges is
unclear. One systematic review found evidence of increased risk of mortality from cirrhosis among men and
women drinking >12 to 24 g and >0 to 12 g of ethanol per day, respectively.[10]
Alcohol abuse or alcohol dependence alone are not suggestive of clinically important ALD. Only about 10%
to 20% of chronic heavy drinkers develop severe forms such as alcoholic hepatitis or cirrhosis.[11] [12] In
patients with co-existent liver diseases related to hepatitis C or obesity, alcohol-related liver damage can
occur with much lower alcohol consumption.[11] [13] The risk of ALD is at least 2 times higher in patients
who are overweight.[14] [15] Smoking is common among heavy drinkers; not only is the progression of
fibrosis in patients with ALD faster in those who smoke,[16] but smoking encourages the development of
hepatocellular carcinoma in patients with alcoholic cirrhosis.[17] These behaviours are modifiable, and afford
an opportunity to significantly alter the adverse impact of ALD.
Meta-analyses of observational data indicate that a number of cytokine and alcohol-metabolising enzyme
gene polymorphisms may be associated with increased risk for ALD:[18] [19] [20]
• Tumour necrosis factor-alpha 238G>A polymorphism
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Aug 24, 2021.
• Interleukin-6 gene polymorphisms (G [rs1800795], C [rs1800796] or G [rs1800797] allele or
genotypes)
• Patatin-like phospholipase domain protein 3 (PNPLA3) gene polymorphism (rs738409 C>G).
Associations may vary with ethnicity. Further, more rigorous research is required to delineate the relationship
THEORY
between specific polymorphisms and risk for ALD.
Pathophysiology
Alcohol is metabolised mainly in the liver, through 2 main pathways: alcohol dehydrogenase and cytochrome
P-450 2E1.
Alcohol dehydrogenase is a hepatic enzyme that converts alcohol to acetaldehyde, which is subsequently
metabolised to acetate by the mitochondrial enzyme acetaldehyde dehydrogenase. Alcohol dehydrogenase
and acetaldehyde dehydrogenase reduce nicotinamide adenine dinucleotide (NAD) to NADH (reduced form
of NAD). Excessive NADH in relation to NAD inhibits gluconeogenesis and increases fatty acid oxidation,
which in turn promotes fatty infiltration in the liver.
The cytochrome P-450 2E1 pathway generates free radicals through the oxidation of NADPH (reduced form
of nicotinamide adenine dinucleotide phosphate) to NADP. Chronic alcohol use upregulates cytochrome
P-450 2E1 and produces more free radicals.
Chronic alcohol exposure also activates a third site of metabolism: hepatic macrophages, which
produce tumour necrosis factor (TNF)-alpha and induce the production of reactive oxygen species in the
mitochondria.
People with alcohol-use disorder are usually deficient in antioxidants, such as glutathione and vitamin E.
Therefore, oxidative stress promotes hepatocyte necrosis and apoptosis in these patients. Free radicals
can also induce lipid peroxidation, which can cause inflammation and fibrosis. The alcohol metabolite
acetaldehyde, when bound to cellular protein, produces antigenic adducts and induces inflammation. Alcohol
also affects the barrier function of intestinal mucosa, producing endotoxaemia, which leads to hepatic
inflammation.
Other pathways may have a role in the pathogenesis of ALD.[21]
Liver biopsy showing the typical histological changes of alcoholic steatosis (fatty liver)
From the collection of Dr McClain; used with permission
5
THEORY Alcoholic liver disease Theory
Liver biopsy showing the typical histological changes of alcoholic steatohepatitis

Liver biopsy showing alcoholic cirrhosis

Case history
Case history #1
THEORY
A 50-year-old man presents to his general practitioner with complaints of fatigue for 2 months. He also
notes distension of his abdomen and shortness of breath beginning 2 weeks ago. His wife reports that
the patient has been having episodes of confusion lately. The patient has a significant medical history of
chronic heavy alcohol consumption of about half a pint of vodka daily for around 20 years. On physical
exam the patient is noted to have scleral icterus, tremors of both hands, and spider angiomata on the
chest. There is abdominal distension with presence of shifting dullness, fluid waves, and splenomegaly.
Laboratory examination shows low haemoglobin, low platelets, low sodium, aspartate aminotransferase
(AST) elevation > alanine aminotransferase (ALT) elevation, and high prothrombin time (PT) and
international normalised ratio (INR). Ultrasound of the abdomen shows liver hyperechogenicity, portal
hypertension, splenomegaly, and ascites.
Case history #2
A 38-year-old man presents to the emergency department for severe alcohol abuse with nausea and
vomiting. He has a significant medical history of chronic heavy alcohol consumption of about one bottle
of wine each day for about 5 years until 1 year ago; since then he has had severe intermittent binge
alcohol intake. He reports no other significant medical problems. The patient is confused and slightly
obtunded, and hepatomegaly is discovered on physical exam. His body mass index is 22. Pertinent
positive laboratory values show low haemoglobin, AST elevation > ALT elevation, normal PT and INR,
and very high serum alcohol level. Ultrasound of the abdomen shows fatty infiltration in the liver.
7
Alcoholic liver disease Diagnosis
Approach
A detailed history of the quantity and duration of alcohol ingestion, together with a physical exam and
appropriate laboratory tests, is essential in the diagnosis of ALD. Key risk factors include prolonged heavy
alcohol consumption, presence of hepatitis C, and female sex.
Asymptomatic elevation of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) in a

person consuming alcohol in excess is a common mode of presentation. It is important to emphasise that
the signs, symptoms, histological stages, and severity of liver disease are variable among individuals with
ALD. In addition, relatively asymptomatic patients may have histologically advanced liver disease. Clinical
decompensation carries a poor prognosis regardless of the histological stage of ALD. Patients with ALD may
have more than one pattern of alcoholic liver damage simultaneously. For example, they may have alcoholic
hepatitis on a background of cirrhosis.
History
A thorough history of alcohol consumption from patients and sometimes their family members is critical.
Popular questionnaires used to assess the presence of alcohol dependency are AUDIT (Alcohol Use
Disorders Identification Test), AUDIT-C, and CAGE.[29] [30] [31] The CAGE questionnaire is easier to
use, but AUDIT and AUDIT-C are more reliable.
AUDIT (Alcohol Use Disorders Identification Test) questionnaire
The AUDIT questionnaire, developed by the World Health Organization, consists of 10 questions. A
score of 8 or more (≥7 for age >65 years) indicates alcohol-use disorder and alcohol dependence with
sensitivity >90% and specificity >80%, while a score of >3 in a man or >2 in a woman indicates alcohol-
use disorder with sensitivity >80%. An overall score of >4 in men or >2 in women identifies 84% to 86% of
patients with an alcohol-use disorder.[32] The American College of Gastroenterology and the European
Association for the Study of the Liver both recommend the AUDIT questionnaire.[11] [33]
AUDIT-C 3-item alcohol screen

DIAGNOSIS
Identifies people who are hazardous drinkers, or who have alcohol-use disorder. It is a modified version
of the 10-question AUDIT questionnaire. AUDIT-C comprises three questions asking about frequency of
alcohol use, typical amount of alcohol use, and occasions of heavy use. AUDIT-C takes approximately 1
to 2 minutes to administer.
CAGE questionnare
The CAGE questionnaire takes its name from its 4 simple questions and is a useful screening tool for
alcohol abuse or dependency:
• C: Have you ever felt you needed to CUT down on your drinking?
• A: Have people ANNOYED you by criticising your drinking?
• G: Have you ever felt GUILTY about drinking?
• E: Have you ever felt you needed a drink first thing in the morning (EYE-OPENER) to steady your
nerves or get rid of a hangover?
Two or more positive answers indicate alcohol dependency with sensitivity of 70% to 96% and specificity
of 91% to 99%.[30] [31]
Symptoms
Do not directly reflect the presence or severity of ALD, and clinical manifestations may vary. Typical
symptoms include:
• Fatigue
• Anorexia
• Weight loss
• Jaundice
• Fever
• Nausea and vomiting
• Right upper quadrant abdominal discomfort.
In advanced liver disease, patients may present with symptoms of severe hepatocellular failure, such as:
• Abdominal distension and weight gain (ascites)

• Confusion (hepatic encephalopathy)
• Haematemesis or melaena (gastrointestinal bleeding)
• Asterixis
• Leg swelling.
Fever in the absence of infection can occur in patients with ALD.[33]
Physical examination
Ambulatory patients with early-stage ALD often do not have major findings on physical examination,
or may have only hepatomegaly, mild jaundice, or low-grade fever (even in the absence of infection).
Patients with advanced ALD may have signs of portal hypertension, including:
• Ascites
• Splenomegaly
• Venous collateral circulations.
The consequences of ascites are related not only to aesthetic body shape changes but also to the high
risk of spontaneous infection of the fluid, development of abdominal hernias, difficulty in breathing,
DIAGNOSIS
decreased food intake, and progressive malnutrition, as well as decreased physical activity with loss of
muscular mass.[34]
Signs of significant or severe hepatic involvement include:
• Confusion (hepatic encephalopathy)

• Cutaneous telangiectasias
• Palmar erythema
• Finger clubbing (often from hypoxaemia due to hepatopulmonary syndrome)
• Dupuytren's contracture
• Parotid gland enlargement
• Feminisation (gynaecomastia, hypogonadism)
Poor nutritional status, muscle wasting, peripheral neuropathy, dementia, or cardiomyopathy may co-
exist with ALD because of chronic alcohol abuse. Hepatic mass is an ominous finding suggesting
hepatocellular carcinoma (HCC). It should be noted that most of the symptoms and signs listed are
common to all chronic liver diseases and are not specific for ALD.
9
Initial blood tests
Liver-related biochemical tests (AST, ALT, gamma-GT, ALP, albumin, bilirubin)
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are markers of alcohol-
induced liver injury. However, it is important to note that AST and ALT can be normal in the absence of
significant liver inflammation (a reassuring sign) or in advanced cirrhosis (in which there are few viable
hepatocytes left to produce the transaminases, a sign of end-stage disease).[35]
In patients with ALD, the AST level is almost always elevated (usually above the ALT level). The classic
ratio of AST/ALT >2 is seen in about 70% of cases.[36] Reversal of the ratio suggests the concomitant
presence of viral hepatitis, or possibly non-alcoholic fatty liver disease.
Gamma glutamyl transferase (gamma-GT) is frequently elevated in heavy drinking, but is not specific for
alcohol use. It is helpful in identifying patterns of alcohol abuse. Elevated alkaline phosphatase (ALP) may
represent cholestasis associated with ALD. Concomitant elevated GGT and ALP indicates the liver as the
source of the ALP, because GGT is not significantly present in bone.[37]
Albumin and bilirubin are markers of hepatocellular function. Low albumin reflects impaired liver synthetic
function; elevated bilirubin, in the absence of biliary obstruction, is typically due to parenchymal liver
disease.
Full blood count
Anaemia is common in ALD and has multiple causes including iron deficiency, gastrointestinal bleeding,
folate deficiency, haemolysis, and hypersplenism. Leukocytosis may be from an alcoholic hepatitis-related
leukemoid reaction or an associated infection. Thrombocytopenia may be secondary to alcohol-induced
bone marrow suppression, folate deficiency, or hypersplenism. A high mean corpuscular volume (MCV)
may also indicate liver disease.
Basic metabolic panel (sodium, potassium, chloride, bicarbonate, urea, creatinine)
Hyponatraemia is usually present in patients with advanced liver cirrhosis. Hypokalaemia and
DIAGNOSIS
hypophosphataemia are common causes of muscle weakness in ALD.
Magnesium and phosphorus
Hypomagnesaemia can cause persistent hypokalaemia and may predispose patients to seizures during
alcohol withdrawal. Hyperphosphataemia predicts poor recovery in advanced liver disease.
Coagulation profile (PT, INR)
Prolonged prothrombin time (PT) and international normalised ratio (INR) indicate diminished hepatic
synthetic function in advanced liver disease with cirrhosis or liver failure in patients with ALD.
Coagulopathy is an obvious complicating factor in cases of gastrointestinal bleeding from varices or

gastropathy.
Subsequent laboratory tests to rule out co-existing diseases

Serum laboratory tests to rule out other significant diseases and comorbidities that may co-exist with ALD
include the following.
Viral hepatitis serological panel (for hepatitis A, hepatitis B, hepatitis C)
All patients should be screened for hepatitis A total antibody and hepatitis B surface and total-core
antibodies, in order to plan for immunisations. To exclude co-existent viral hepatitis, patients can be tested
for immunoglobulin M (IgM) anti-hepatitis A, hepatitis B surface Ag, and IgM anti-hepatitis B core, and for
hepatitis C RNA by polymerase chain reaction (PCR).
Iron studies (for haemochromatosis) and copper studies (for Wilson's disease)
Elevated ferritin is common because it is an acute-phase reactant, and sometimes due to secondary iron
overload.[38] Iron distribution in tissue, hepatic iron index, and genetic studies for haemochromatosis can
help to clarify the co-existence of ALD with haemochromatosis.
Increased urinary copper, very high liver copper, and decreased serum ceruloplasmin indicate Wilson's
disease.
Ammonia level and folate
The serum ammonia level may be elevated but does not always correlate with the presence or severity of
hepatic encephalopathy (unless it is extremely high). Therefore, a finding of elevated serum ammonia is
not required to diagnose ALD or hepatic encephalopathy.
Reduced intake and increased requirements of folate in hepatic disease may lead to folate deficiency.
Anti-mitochondrial antibody, anti-nuclear antibody, and anti-smooth muscle antibody
Anti-mitochondrial antibody (AMA) is used to test for co-existent primary biliary cirrhosis. ANA (anti-
nuclear antibody) and ASMA (anti-smooth muscle antibody) are used to rule out the presence of
associated autoimmune hepatitis.
Alpha-1 antitrypsin
Alpha-1 antitrypsin phenotype may need to be investigated if there is a personal or family history of
DIAGNOSIS
emphysema.
Other serum laboratory tests that may indirectly reflect the

presence of alcohol abuse
Among these are carbohydrate-deficient transferrin (CDT) and mitochondrial AST.
When clinical suspicion is high but the patient persists in denial of alcohol abuse, a positive CDT test may
be helpful to establish alcohol misuse. This is particularly true in young men with alcohol ingestion >60 g/
day.[39] [40]
Mitochondrial AST is a specific isoform of the AST enzyme released from hepatocytes at high levels in
diseases associated with alcohol abuse.[41]
Routine use of CDT and mitochondrial AST is not necessary.
Imaging
Ultrasound should be performed among patients with harmful alcohol use, as it helps diagnose alcoholic
fatty liver disease in patients with hepatic steatosis.[11]
11
Ultrasound (or computed tomography [CT] scan) of the abdomen is useful to exclude alternative
diagnoses, such as cholecystitis, biliary obstruction, portal or hepatic vein thrombosis, and liver mass
when clinically indicated.
Common CT scan and magnetic resonance imaging (MRI) findings include irregular liver margins and
intrahepatic hypervascularity. Non-contrast plus triphasic contrast CT scan (four phase study) or four-
dimensional phase contrast MRI of the abdomen are useful further investigations to evaluate a liver mass
detected by ultrasound. They are also used to search for a tumour in patients with an elevated alpha-
fetoprotein and high clinical suspicion of HCC whose ultrasound is negative.
The choice between CT scan and MRI depends on factors such as availability, expertise, quality of
equipment, and previous radiation exposure.
Non-invasive markers of chronic ALD

A number of non-invasive laboratory tests are used to assess liver fibrosis in patients with alcoholic
liver disease, including enhanced liver fibrosis (ELF), fibrosis-4 (FIB-4), and AST to platelet ratio index
(APRI).[42]
The enhanced liver fibrosis test uses specific molecular markers of fibrogenesis, while other tests
use combinations of routinely collected blood tests (e.g., FIB-4, APRI). The utility of these markers is
predominantly for excluding severe fibrosis, with normal values being reassuring. They do not perform
well at differentiating intermediate stages of fibrosis.
Imaging tests to detect fibrosis
Transient elastography is an ultrasound-based technique for detecting hepatic fibrosis without the need
for liver biopsy. Transient elastography may help to rule out severe fibrosis (F3 or worse) in patients with
ALD.[43]
Liver biopsy
Liver biopsy is diagnostic, and useful for grading ALD, when there is a history of excessive alcohol
DIAGNOSIS
consumption, but is not necessary in every patient.[11] [33]
Liver biopsy is indicated in patients with atypical presentation to evaluate possible co-existing liver
diseases (e.g., haemochromatosis, Wilson's disease, autoimmune hepatitis), to determine the histological
severity of liver disease (i.e., presence of liver cirrhosis), and in patients with clinical evidence of severe
alcoholic hepatitis when medical therapy is contemplated.[11] [33] [44]
The presence of fatty infiltration in the liver in the absence of inflammation indicates early-stage ALD with
steatosis.[11] Inflammation with necrosis and presence of Mallory bodies indicates alcoholic hepatitis.[11]
[33] Severe fibrosis (usually micronodular, but sometimes mixed macro- and micronodular) starting from
the central vein and extending into the portal triad occurs in alcoholic cirrhosis.[11] [33] The presence of
polymorphonuclear cells on liver biopsy may be prognostic for survival of patients with severe alcoholic
hepatitis.[45]
Biopsy findings in alcoholic and non-alcoholic steatohepatitis, some drug-induced liver injuries, and
Wilson's disease may be identical; thus, the history of alcohol use and appropriate laboratory tests is
critical for proper interpretation of the liver biopsy. Special stains and quantitative measurement of copper
or iron in tissue can be extremely helpful when the history or laboratory testing raises the question of
alternative or co-existing illness.
Liver biopsy showing the typical histological changes of alcoholic steatosis (fatty liver)
DIAGNOSIS
Liver biopsy showing the typical histological changes of alcoholic steatohepatitis

13
Liver biopsy showing alcoholic cirrhosis

History and exam

Key diagnostic factors
presence of risk factors (common)
• Key risk factors include prolonged heavy alcohol consumption, presence of hepatitis C, and female
DIAGNOSIS
sex.
abdominal pain (common)

• Right upper abdominal discomfort is most common in patients with acute alcoholic hepatitis.
hepatomegaly (common)
• May be present in patients with alcoholic fatty liver (steatosis) or alcoholic hepatitis. Hepatomegaly
may be an ominous sign in liver cirrhosis patients, suggesting the presence of hepatocellular
carcinoma.
haematemesis and melaena (uncommon)

• Signs of gastrointestinal bleeding, possibly related to oesophageal or gastric varices, gastric irritation,
and coagulopathy.
venous collaterals (uncommon)

• Engorged para-umbilical veins (caput medusae), present in advanced alcoholic liver disease.
splenomegaly (uncommon)
• May be present in advanced liver disease patients with portal hypertension.
hepatic mass (uncommon)

• Ominous sign; may portend presence of hepatocellular carcinoma.
jaundice (uncommon)
• Common in severe alcoholic hepatitis and in decompensated severe alcoholic cirrhosis. Uncommon
in compensated alcoholic cirrhosis or alcoholic steatosis. However, co-existent intra- or extrahepatic
cholestasis should also be considered.
palmar erythema (uncommon)

• Affects the thenar and hypothenar eminences while sparing the central portions of the palm. It may be
present in patients with advanced alcoholic liver disease.
cutaneous telangiectasia (uncommon)

• Vascular spiders with central arteriole flanked by smaller vessels. Usually seen on the trunk, face, and
upper limbs. It may be present in patients with advanced alcoholic liver disease.
asterixis (uncommon)
• Flapping motions of outstretched, dorsiflexed hands; quick test for encephalopathic state. It is one of
the manifestations of hepatic encephalopathy present in advanced alcoholic liver disease.
Other diagnostic factors

ascites (common)
• Very common clinical complication of cirrhosis. It can be evaluated by the presence of shifting dullness
or fluid wave examination.
weight loss (common)

• High tumour necrosis factor (TNF)-alpha and inflammatory response is associated with ALD and can
DIAGNOSIS
lead to loss of appetite and weight loss.
weight gain (common)

• Ascites and/or oedema can cause gradual unintentional weight gain in ALD patients with portal
hypertension.
malnutrition and wasting (common)

• May manifest as loss of weight and muscle mass, or as vitamin deficiency.
anorexia (common)
• High tumour necrosis factor (TNF)-alpha and inflammatory response is associated with ALD and can
lead to loss of appetite.
fatigue (common)
• Common in patients with co-existing chronic hepatitis. Due to over-expression of tumour necrosis
factor (TNF)-alpha, causing fatigue.
confusion (uncommon)
15
• Hepatic encephalopathy in advanced liver cirrhosis may manifest as impaired mentation.[46]
• Agitation, loss of concentration, and impaired judgement may be part of mental confusion.
• Thiamine deficiency associated with ALD can lead to mental confusion and neurological
complications, such as Wernicke-Korsakoff syndrome.
pruritus (uncommon)
• Present in association with jaundice due to accumulation of bile salts in the skin layers. It may be
significant enough to cause sleep disturbances.
fever (uncommon)
• Low-grade fever can be present in alcoholic hepatitis patients in the absence of infection.[33]
nausea and vomiting (uncommon)

• May be due to gastric irritation from alcohol- or cirrhosis-associated gastroparesis.
finger clubbing (uncommon)

• Distal portion of digit takes on drumstick appearance.
Dupuytren's contracture (uncommon)

• Characteristic palmar fascia contracture and thickening associated with severe liver disease.
leg swelling (uncommon)

• Peripheral oedema commonplace in both renal and liver disease from salt retention,
hypoalbuminaemia, osmotic changes.
parotid gland enlargement (uncommon)

• Fatty infiltration of the gland with fibrosis and oedema, probably due to the extrahepatic toxicity of
alcohol.
gynaecomastia (uncommon)
DIAGNOSIS
• Present in nearly two-thirds of patients; manifestation of altered sex hormone metabolism.
hypogonadism (uncommon)
• Multifactorial in nature, and a common finding in advanced alcoholic liver disease.
dementia (uncommon)
• Warrants careful evaluation for thiamine deficiency.
peripheral neuropathy (uncommon)

• Focal defects, including altered reflexes, may be present.
• Peripheral neuropathy might be associated with the direct toxic effect of alcohol on nerve tissue but is
more likely to be associated with nutritional deficiencies.
Risk factors
Strong
prolonged and heavy alcohol consumption
• The quantity of alcohol ingested is the single most important risk factor for ALD development.
• Although alcohol-induced liver injury is somewhat dose dependent,[10] there is no set alcohol
consumption threshold that reliably predicts the development of ALD.
• Most heavy alcohol drinkers will never develop clinical liver disease. Only about 10% to 20% of chronic
heavy drinkers develop severe forms of ALD, such as alcoholic hepatitis or cirrhosis.[11] [12]
hepatitis C
• ALD patients with hepatitis C infection have more severe histological features, decreased survival,
disease development at a younger age, and a higher incidence of hepatocellular carcinoma.[22] [23]
female sex
• ALD develops more rapidly and occurs at lower drinking levels in women than in men.[24] [10] [25]
• However, most patients with ALD are male.
Weak
cigaret te smoking
• Fibrosis progresses more rapidly in patients with ALD who smoke.[16]
obesity
• The risk of ALD is at least 2 times higher in patients with obesity than in patients with a normal body
mass index.[14] [15] Even if abstinent, obese people are at an increased risk of fatty liver. Obesity
seems to be an independent risk factor for both alcoholic hepatitis and alcoholic cirrhosis.[14]
age >65 years

• Alcohol metabolism and distribution change with age. An older person's liver is more susceptible to
alcohol-related toxicity. However, within the spectrum of ALD, the symptoms and signs are similar in
patients of all ages. Prognosis for ALD in older people (age >65 years) is poor.[26]
DIAGNOSIS
Hispanic ethnicity
• Age-adjusted mortality from cirrhosis is greater among patients of Hispanic ethnicity compared with
white non-Hispanics and black non-Hispanics.[27] [28]
genetic predisposition
• A number of cytokine and alcohol-metabolising enzyme gene polymorphisms (tumour necrosis factor-
alpha 238G>A polymorphism, interleukin-6 gene polymorphisms, patatin-like phospholipase domain
protein 3 gene polymorphism rs738409 C>G) may be associated with increased risk for ALD.[18] [19]
[20]
17
Investigations
1st test to order
Test Result
serum aspartate aminotransferase (AST), alanine men: >30 units/L; women:
aminotransferase (ALT) >19 units/L
• AST (sensitivity 50%, specificity 82%) and ALT (sensitivity 35%,
specificity 86%) are elevated in ALD when alcohol use >50 g/day.[47]
• True upper limits of normal for AST and ALT are considered to be
30 units/L for men and 19 units/L for women.[48] AST and ALT can
be normal either in the absence of significant liver inflammation or in
advanced cirrhosis with few viable hepatocytes to produce AST or
ALT.[35]
• AST and ALT both elevated to <300 units/L, unless associated with
paracetamol abuse or certain other complicating liver diseases.[49]
serum AST/ALT ratio ratio >2
• In patients with ALD, AST level is almost always elevated (usually
above ALT level). The classic ratio of AST/ALT >2 is seen in about
70% of cases.[36]
• Reversal of the ratio, ALT > AST, suggests concomitant presence of
viral hepatitis or possibly non-alcoholic fatty liver disease as the major
cause of liver injury in alcoholic patients.
serum alkaline phosphatase normal or elevated
• If elevated may represent cholestasis associated with ALD.
serum bilirubin elevated
• Elevated bilirubin reflects impaired metabolic function of the liver in
the absence of biliary obstruction.
• Elevated bilirubin has prognostic utility in ALD patients in the absence
of biliary obstruction.
• Both conjugated and unconjugated bilirubin are increased in varying
DIAGNOSIS
proportion.
serum albumin, protein low
• Low albumin reflects impaired synthetic function of the liver.
serum gamma glutamyl transferase (gamma-GT) elevated
• Increase in this liver microsomal enzyme represents enzyme
activation, which can be induced by alcohol and certain drugs.
• Increased in cholestasis along with alkaline phosphatase (ALP).
• GGT is not significantly present in bone, such that concomitant
elevated GGT and ALP indicates the liver as the source of the ALP.
• Gamma-GT is more sensitive (sensitivity 69% to 73%) than AST or
ALT for heavy alcohol use and liver injury.[39]
FBC anaemia, leukocytosis,
thrombocytopenia, high
• Anaemia in ALD is likely to be due to multiple causes such as iron
mean corpuscular volume
deficiency, gastrointestinal bleeding, folate deficiency, haemolysis,
(MCV)
and hypersplenism.
• Leukocytosis is likely from alcoholic hepatitis-related leukaemoid
reaction or associated infection.
• Thrombocytopenia may be secondary to alcohol-induced bone
marrow suppression, folate deficiency, or hypersplenism.
Test Result
• MCV, as a diagnostic tool for alcohol abuse, lacks sensitivity (27% to
52%) but is reasonably specific (85% to 91%) for alcohol use >50 g/
day in the absence of vitamin B12 or folic acid deficiency.[39]
serum electrolytes, magnesium, phosphorus normal or low sodium,
potassium, magnesium,
• Hyponatraemia is frequently present in patients with advanced liver
phosphorus
cirrhosis.
• Hypokalaemia and hypophosphataemia are common causes of
muscle weakness in ALD.
• Hypomagnesaemia can cause persistent hypokalaemia and may
predispose patients to seizures during alcohol withdrawal.
serum urea and creatinine normal or elevated
• Elevated urea in the presence of normal creatinine suggests active
gastrointestinal bleeding; elevated urea and creatinine is present in
hepatorenal syndrome.
serum prothrombin time (PT), INR normal or prolonged
• Useful to evaluate synthetic function of the liver. An elevated PT/
INR indicates advanced liver cirrhosis or liver failure in ALD patients.
Elevated PT has prognostic utility in ALD patients.
hepatic ultrasound may show hepatomegaly,
• Ultrasound should be performed among patients with harmful alcohol fat ty liver, liver cirrhosis,
liver mass, splenomegaly,
use.[11]
• It is also used to screen for hepatocellular carcinoma (HCC) every 6 ascites, evidence of portal
to 12 months in ALD patients with cirrhosis. hypertension
• Sensitivity of ultrasound for HCC detection is about 70% to >90% and
specificity is >90%.[50]
DIAGNOSIS
19
Other tests to consider
Test Result
viral hepatitis serology absence of hepatitis
• HBV surface antigen, IgM anti-HBc, IgM anti-HAV, IgG anti-HCV, and B virus (HBV) surface
antigen, immunoglobulin
PCR for HCV RNA are used to exclude concomitant hepatitis A, B,
M (IgM) anti-hepatitis B
and C infection.
core (anti-HBc), IgM anti-
• Anti-hepatitis surface and core antigens, total anti-HBc, and total
hepatitis A virus (anti-
anti-HAV are used to detect previous exposure to hepatitis B
HAV), IgG anti-hepatitis C
(natural or immunisation mediated) and hepatitis A, in order to plan
virus (anti-HCV), and HCV-
immunisations.
RNA PCR
serum iron, ferritin, transferrin normal or elevated serum

iron, ferritin
• Used to rule out the presence of associated haemochromatosis.
• Elevated ferritin is common because it is an acute-phase reactant,
and sometimes due to secondary iron overload.[38]
• Iron distribution in tissue, hepatic iron index, and genetic
studies for HFE can help clarify the co-existence of ALD with
haemochromatosis.
urine copper (24-hour collection) normal
• Samples should be collected in trace element-free containers.
• Levels >40 micrograms/24 hours raise the possibility of Wilson's
disease.
serum ceruloplasmin normal or elevated
• In ALD, the ceruloplasmin level is usually normal (20 to 35 mg/dL
[200 to 350 mg/L]) or elevated due to acute injury.
• With low or low-normal ceruloplasmin, liver biopsy with copper
quantitation is needed to differentiate ALD from Wilson's disease.
serum anti-mitochondrial antibody (AMA) normal
• Normal AMA will help to exclude presence of primary biliary cirrhosis.
serum anti-nuclear antibody (ANA) and anti-smooth muscle absent ANA and ASMA
DIAGNOSIS
antibody (ASMA)
• Used to rule out the presence of associated autoimmune hepatitis.
• Liver biopsy is needed to establish the diagnosis of autoimmune
hepatitis.
serum alpha-1 antitrypsin level normal
• Used to screen for the presence of alpha-1 antitrypsin deficiency.
serum ammonia normal or elevated
• Elevated ammonia level does not correlate with severity of hepatic
encephalopathy alone. Therefore, its routine use in diagnosis of
hepatic encephalopathy is not always necessary.
serum folate normal or low
• Increased requirements for folate in hepatic disease, and decreased
intake, may lead to folate deficiency.
non-invasive tests of liver elasticity serological marker
and ultrasound-based
• Transient elastography is an ultrasound-based technique for
elastography evidence of
detecting hepatic fibrosis without the need for liver biopsy. Transient
fibrosis.
elastography may help to rule out severe fibrosis (F3 or worse) in
patients with ALD.[43]
Test Result
• A number of non-invasive laboratory tests are used to assess liver
fibrosis in patients with alcoholic liver disease, including enhanced
liver fibrosis (ELF), fibrosis-4 (FIB-4), and AST to platelet ratio index
(APRI).[42]
• The enhanced liver fibrosis test uses specific molecular markers of
fibrogenesis, while other tests use combinations of routinely collected
blood tests (e.g., FIB-4, APRI).
• The utility of these markers is predominantly for excluding severe
fibrosis, with normal values being reassuring.
CT abdomen, MRI abdomen may show hepatomegaly,
splenomegaly, ascites,
• Non-contrast plus triphasic contrast CT scan (four phase study) or
portal vein engorgement
four-dimensional phase contrast MRI of the abdomen are useful
further investigations to evaluate a liver mass detected by ultrasound.
• The choice between CT scan and MRI depends on factors such as
availability, expertise, quality of equipment, and previous radiation
exposure.
liver biopsy steatosis, inflammation-
• Sensitivity is 91%, positive predictive value is 88%, specificity is 96%, neutrophil infiltrate,
ballooning hepatocytes,
and negative predictive value is 97% in diagnosis of ALD and/or
Mallory hyaline bodies,
alcoholic cirrhosis.[44]
pericellular fibrosis
Emerging tests
Test Result
serum carbohydrate-deficient transferrin test elevated
• Relatively specific (82% to 92%) but not sensitive (58% to 69%) test
to detect current alcohol abuse.[47]
• In the presence of denial of alcohol abuse when clinical suspicion is
high, a positive test may be helpful, particularly in young men with
alcohol ingestion >60 g/day.[39] [40]
DIAGNOSIS
serum mitochondrial AST elevated
• A specific mitochondrial isoform of the AST enzyme released from
hepatocytes at high levels is associated with alcohol abuse.[41]
21
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Hepatitis B virus (HBV) • Often asymptomatic. • Serum test positive for
infection • History may reveal high- hepatitis B surface antigen
risk behaviour (e.g., illicit (HBsAg), hepatitis B virus
intravenous drug use, DNA, or anti-hepatitis B core
multiple sexual partners) and antigen-IgM antibody.
absence of chronic heavy • In patients with co-
alcohol use. existing ALD and HBV, but
• May present as acute without cirrhosis, alanine
hepatitis B infection in adults aminotransferase (ALT) is
and sometimes can be fatal usually higher than aspartate
from complications such as aminotransferase (AST).
acute liver failure.
• Patients with chronic
hepatitis B may develop
complications such as
cirrhosis, hepatocellular
carcinoma, or liver failure.
Hepatitis C virus (HCV) • History may reveal high- • Serum test positive for anti-
infection risk behaviour (e.g., illicit hepatitis C virus antibody
injection drug use) and and hepatitis C virus RNA
absence of chronic heavy PCR.
alcohol use. • Most patients have
• Most patients are fluctuating elevation of
asymptomatic. alanine aminotransferase
• In advanced disease, (ALT) and aspartate
patients exhibit signs and aminotransferase (AST).
symptoms related to chronic • In patients with co-existing
liver injury from hepatitis C ALD and HCV but without
such as jaundice, ascites, cirrhosis, ALT is usually
DIAGNOSIS
spider angiomata, and higher than AST.

constitutional complaints.
Hepatitis A virus • History suggestive of • Serum test positive for

infection exposure (e.g.,use of anti-hepatitis A virus-IgM
contaminated food/water, antibody with marked
travel to endemic area, men elevation of serum
who have sex with men) and transaminases.
absence of binge alcohol
use.
• Symptomatic patients may
present with abrupt-onset
fever, abdominal pain,
malaise, and jaundice.
Common examination
findings are hepatomegaly
and clinical jaundice.
Cholecystitis • Acute right upper quadrant • Ultrasound of gallbladder is

abdominal pain, with positive the initial test.
Murphy's sign (pain with • Nuclear medicine
hepatobiliary scan may

symptoms
inspiration beneath palpation be helpful in cases where
at costal margin). diagnosis is unclear.
Hepatic vein thrombosis • Variable chronicity of • Ultrasound of liver with

presentation but classic Doppler study can show
triad of abdominal pain, obstruction, thrombosis,
hepatomegaly, and ascites is collaterals, and hyperechoic
seen. cords replacing normal
venous architecture.
• CT abdomen with contrast
might be more precise for
this diagnosis.
Acute liver failure • Patient with acute • Severe elevation of

symptoms and signs of aspartate aminotransferase
acute fulminant hepatic (AST) and alanine
deterioration, coagulopathy, aminotransferase (ALT)
encephalopathy, and with prolonged INR and
sometimes cerebral oedema. prothrombin time (PT).
• Often related to ingestion • Serum ammonia may be
of hepatotoxic drug (e.g., dramatically elevated.
paracetamol). • Liver biopsy may be
diagnostic but is contra-
indicated in coagulopathy,
unless done by transjugular
approach.
Haemochromatosis • Presenting features include • High iron saturation (>45%

fatigue, arthralgias, and transferrin saturation) and
diabetes mellitus. high ferritin.
• Characteristic skin bronzing • Positive haemochromatosis
may be present. gene mutation.
• Liver biopsy shows
excessive iron deposition in
DIAGNOSIS
hepatocytes.
• High hepatic iron index.
Wilson's disease • Patients may have • Increased urinary

neurological manifestations copper, decreased serum
similar to parkinsonism, and ceruloplasmin.
psychological manifestations • Liver biopsy shows
such as psychosis. excessive copper deposition
• Kayser-Fleischer rings may by copper measurement.
be present on slit-lamp eye
examination.
Drug- or toxin-induced • History of exposure to • Liver biopsy may show

hepatitis hepatotoxic drugs or toxins. evidence of hepatocellular
• Examination may range from injury or cholestatic or mixed
mild and non-specific to pattern of liver injury.
fulminant hepatic failure.
Autoimmune hepatitis • History of immune • There may be positive

dysregulation, genetic or elevated anti-nuclear
predisposition, or female antibody, anti-smooth
sex. muscle antibody, or anti-
23

symptoms
• Constitutional symptoms are LKM antibody (anti-liver/anti-
similar to those of alcoholic kidney microsome antibody).
liver injury. • Liver biopsy shows
evidence of hepatocellular
inflammation with plasma
cell infiltrates and interface
hepatitis with plasma cell
infiltrates.
Wernicke's • Usually presents with abrupt • Clinical diagnosis.

encephalopathy symptoms of confusion,
short-term memory loss,
eye movement disorders
(nystagmus, gaze palsies,
and ophthalmoplegia)
in a patient with chronic
malnutrition.
• Low thiamine intake.
Biliary obstruction • Symptoms associated • Ultrasound abdomen (also

with biliary obstruction CT or MRI of abdomen) may
may include right upper show dilation of biliary tract.
quadrant pain, fever/chills,
jaundice, pruritus, nausea,
and vomiting.
Screening
Alcohol misuse screening
The US Preventive Services Task Force recommends screening for unhealthy alcohol use in primary care
settings in adults 18 years and older.[51] A thorough history of alcohol use should be obtained, and standard
DIAGNOSIS
screening questionnaires performed.[11]
Standard, validated questionnaires are more effective in the detection and diagnosis of ALD than any
routine clinical or laboratory evaluations.[52] Popular questionnaires used to assess the presence of alcohol
dependency are AUDIT (Alcohol Use Disorders Identification Test), AUDIT-C, and CAGE.[29] [30] [31] The
CAGE questionnaire is easier to use, but AUDIT and AUDIT-C are more reliable.
AUDIT (Alcohol Use Disorders Identification Test) questionnaire
The AUDIT questionnaire, developed by the World Health Organization, consists of 10 questions. A score of
8 or more (≥7 for age >65 years) indicates an alcohol-use disorder and alcohol dependence with sensitivity
>90% and specificity >80%, while a score of >3 in a man or >2 in a woman indicates alcohol-use disorder
with sensitivity >80%. An overall score of >4 in men or >2 in women identifies 84% to 86% of patients with an
alcohol-use disorder.[32] The American College of Gastroenterology and the European Association for the
Study of the Liver both recommend the AUDIT questionnaire.[11] [33]
AUDIT-C 3-item alcohol screen
Identifies people who are hazardous drinkers, or who have alcohol-use disorder. It is a modified version of
the 10-question AUDIT questionnaire. AUDIT-C comprises three questions asking about frequency of alcohol
use, typical amount of alcohol use, and occasions of heavy use. AUDIT-C takes approximately 1 to 2 minutes
to administer.
CAGE questionnaire
The CAGE questionnaire takes its name from its 4 simple questions and is a useful screening tool for alcohol
abuse or dependency:
C: Have you ever felt you needed to CUT down on your drinking?
A: Have people ANNOYED you by criticising your drinking?
G: Have you ever felt GUILTY about drinking?
E: Have you ever felt you needed a drink first thing in the morning (EYE-OPENER) to steady your nerves or
get rid of a hangover?
Two or more positive answers indicate alcohol dependency with sensitivity of 70% to 96% and specificity of
91% to 99%.[30] [31]
Hepatocellular carcinoma screening

Serial imaging studies such as ultrasound have been used for hepatocellular carcinoma (HCC) screening in
patients with alcoholic cirrhosis. Ultrasound of the abdomen every 6 to 12 months is used to screen for HCC
in ALD patients with liver cirrhosis.[11] [53] [54] The sensitivity of ultrasound for HCC detection is about 70%
to >90% and specificity is >90%.[50]
DIAGNOSIS
25
Alcoholic liver disease Management
Approach
The main goal of treatment is to reduce liver injury due to excessive alcohol use and prevent progression of
liver disease.
Other treatment goals are to reduce symptoms and prevent complications related to ALD. It is important
that clinicians consider the continuous long-term management of ALD in addition to treatment of the acute
symptomatic episodes of alcoholic hepatitis.
Treatment by a multi-disciplinary team is the ideal approach.[29] A medicine specialist (internist,

gastroenterologist, or hepatologist), a mental health specialist (psychiatrist, substance abuse expert), and a
nutrition expert (dietician, gastroenterologist) should work together to improve the long-term prognosis of the
patient.[55]
Alcohol abstinence and alcohol withdrawal

The importance of alcohol abstinence needs to be continually emphasised in the management of ALD.
Abstinence or even reducing the amount of alcohol consumed improves projected survival in ALD,[11]
[33] even in the presence of cirrhosis with decompensation.[56] Alcohol abstinence reduces steatosis,
fibrosis, and possibly the risk of hepatocellular carcinoma.[56] [57] Complete alcohol abstinence is
associated with improved long-term survival in patients with alcoholic hepatitis.[58]
Abstinence from alcohol may lead to the development of alcohol withdrawal syndrome (AWS). Light or
moderate AWS can develop within 6 to 24 hours after the patient's last alcoholic drink, and may progress
to more severe forms.[11] [33] Alcohol withdrawal symptoms include:
• Mild AWS
• Hypertension and tachycardia

• Anorexia, anxiety, emotional lability, insomnia, irritability, diaphoresis, headache, and fine
tremor
• Moderate AWS (worsening mild AWS, plus):
• Agitation and coarse tremor

• Severe AWS/delirium tremens (worsening moderate AWS, plus):
• Confusion/delirium
• Generalised tonic-clonic seizures (this may be the first manifestation of AWS for some
patients)
• Auditory, visual, or tactile hallucinations
• Hyperthermia subsequent to psychomotor agitation.
Pharmacotherapy for alcohol withdrawal syndrome
Benzodiazepines are the most commonly used drugs to treat AWS.[11] Long-acting benzodiazepines
MANAGEMENT
(e.g., diazepam) provide greater protection against seizures and delirium; shorter-acting benzodiazepines
(e.g., oxazepam, lorazepam) are safer in older adults and those with hepatic dysfunction.[11] High doses
of benzodiazepines may trigger or worsen hepatic encephalopathy.[11]
Once abstinence has been achieved, the combination of counselling plus pharmacotherapy may be
considered to improve the likelihood of long-term abstinence. See our Alcohol withdrawal topic for detailed
information.
Weight reduction
Weight reduction is important in obese patients to slow the progression of ALD.[14] [59]
Caution is required if using orlistat to reduce weight in ALD, due to reports of acute liver failure, and other
significant complications such as cholelithiasis and cholestatic hepatitis.[60] [61]
Smoking cessation
Smoking cessation is beneficial in reducing the progression of ALD.[33] Smoking cessation is also helpful
in initiating alcohol abstinence and maintenance.
Cessation may be facilitated by efforts as modest as a simple recommendation by a physician during

routine consultation with the patient.
Immunisations
Influenza and pneumococcal vaccine are recommended in patients with chronic ALD. If hepatitis B
surface antibody and hepatitis A immunoglobulin G (IgG) antibody are negative, then hepatitis A and
hepatitis B immunisation should be considered in all stages of ALD.[11] [62]
Nutrition
The prevalence of malnutrition is extremely high in ALD. ALD is associated with a high risk of
complications including infection, ascites, encephalopathy, hepatorenal syndrome, and overall
mortality.[63] [64] [65]
Guidelines recommend evaluation of nutritional status, with consideration for nutritional supplementation
to ensure sufficient caloric intake and to correct specific deficits.[11] [33] [29] Nutritional therapy should
be instituted during hospitalisations for acute decompensation of ALD, including calories, vitamins, and
micronutrients (including zinc).[33] These patients require frequent-interval feeds; nitrogen balance can
be improved by a night-time snack and a morning feed.[66] [67]
Nutritional supplementation
May reduce overall mortality in some malnourished patients with ALD, especially those with alcoholic
hepatitis or cirrhosis, but a consistent improvement in survival has not been demonstrated.[11] [68] [69]
[70] Systematic reviews indicate that adjunctive nutritional support (parenteral or enteral nutrition, or
nutritional supplements) does not confer a survival benefit in patients with ALD, but encephalopathy may
be ameliorated.[71] [72] [73] [74] Randomised controlled clinical trials are required.
Enteral nutrition is preferred.[11] [33] [29] If the patient cannot achieve adequate caloric intake orally, then
an enteral feeding tube should be considered.[33]
MANAGEMENT
Routine use of specialised formulations
Not indicated, unless standard formulations cannot be tolerated at amounts necessary to satisfy
nutritional requirements.[75] [76] Branched chain amino acid (BCAA) formulations are used for patients
who cannot tolerate the necessary amount of standard amino acids without precipitating encephalopathy.
27
Protein feeding
Is usually well tolerated, and there is no reason to routinely restrict protein in patients with alcoholic
hepatitis. Patients with severe alcoholic hepatitis need a daily protein intake of 1.2 to 1.5 g/kg and caloric
intake of 35 kcal/kg.[11]
Re-feeding syndrome
Alcoholic patients are at high risk of developing re-feeding syndrome and should have close surveillance
for development of severe hypokalaemia, hypophosphataemia, and hypomagnesaemia.
Micronutrient supplementation
Long-term oral zinc supplementation for ALD cirrhosis patients has shown beneficial effects on both
nutritional parameters and liver metabolic function including in liver fibrosis (cirrhosis).
Thiamine and other vitamin supplements should be considered if necessary.[11]
Pharmacotherapy
Clinical trials have focused on patients with alcoholic hepatitis.
Corticosteroids
Meta-analysis of individual patient data from four controlled studies of severe alcoholic hepatitis found
that corticosteroid reduced risk of death within 28 days compared with placebo (hazard ratio [HR] 0.64;
95% confidence interval [CI] 0.48-0.86) or pentoxifylline (HR 0.64; 95% CI 0.43-0.95).[77] Corticosteroid
efficacy reduced with time; 6-month mortality did not differ between corticosteroid and placebo or
corticosteroid and pentoxifylline.[77]
A subsequent meta-analysis found that corticosteroids did not statistically reduce mortality in patients
with alcoholic hepatitis compared with placebo or no intervention (relative risk 0.90, 95% CI 0.70 to 1.15)
up to 3 months following randomisation.[78] However, in a subgroup of patients with poor prognosis
(Maddrey discriminant function score 32 or hepatic encephalopathy), corticosteroid use improved short-
term survival, but there was no long-term health benefit.[79] [80]
An early decline in serum bilirubin at day 7 of treatment is a strong prognostic factor for a response
to corticosteroids and a higher survival rate at 6 months after treatment.[81] Along with prothrombin
time, and other parameters, it is included in the calculation of the Lille score used to identify patients
who are not responding to corticosteroids.[82] In one meta-analysis, the only patients who benefited
from corticosteroids (28-day survival) were those with Lille scores of ≤0.16 (complete responders) or
between 0.16 and 0.56 (partial responders).[80] Those with higher Lille scores should discontinue
corticosteroids.[29] The American College of Gastroenterology recommends discontinuing corticosteroids
in patients with a Lille score >0.45, while the European Association for the Study of the Liver recommends
discontinuation in patients with a Lille score ≥0.56.[11] [33]
Prednisolone is preferred to prednisone in acute alcoholic hepatitis.[11] [29] Corticosteroids should be

MANAGEMENT
avoided in ALD patients with gastrointestinal bleeding requiring transfusion, in active infection, and in
hepatorenal syndrome.[83] [84]
Corticosteroids do not appear to increase the occurrence of, or mortality from, bacterial infections in
patients with severe alcoholic hepatitis.[85]
Pentoxifylline
Guidelines do not recommend pentoxifylline for the treatment of severe alcoholic hepatitis.[11] [33] [29]
Prospective studies are required to determine if subgroups of patients with alcoholic hepatitis may
potentially benefit from pentoxifylline.[11] There are insufficient data to assess whether other anti-tumour
necrosis factor (TNF) therapies are beneficial in ALD.[86] [87]
Treatment of ascites
Patients with ascites should undergo diagnostic paracentesis to exclude spontaneous bacterial
peritonitis.[11] [88]
The kidneys avidly retain sodium in patients with alcoholic hepatitis and cirrhosis. The goal of treatment
is to attain negative sodium balance. Patients with less-severe disease may respond to moderate dietary
salt restriction alone (2 g of sodium daily). More severe restriction usually leads to compliance problems,
as the diet will be unpalatable and the patient may reduce food intake.[88] [89] [90] Only 10% to 15% of
patients respond to diet management alone.[88]
As liver function deteriorates, patients need diuretics in combination with a sodium-restricted diet in
order to induce adequate sodium excretion in the urine. The most commonly used diuretic regimen is a
combination of furosemide and spironolactone.[88] Using this combination, successful therapy can be
reached in up to 90% of patients.[88] In patients who are refractory to salt restriction and diuretics (usually
<10% of those with cirrhosis), large-volume paracentesis or transjugular intrahepatic portosystemic shunt
(TIPS) therapy may be required.[34] [88] [89] [90]
The use of daily oral fluoroquinolone in selected high-risk liver cirrhosis patients with low ascites fluid
protein (<1.5 g/dL) has been shown to reduce the risk of developing first episode of spontaneous bacterial
peritonitis and risk of mortality in meta-analysis.[95] Primary prophylaxis with oral fluoroquinolone should
be considered in appropriate high-risk (ascites fluid protein <1.5 g/dL) alcoholic liver cirrhosis patients.
Treatment of co-existing hepatitis C

The decision to use antiviral therapy in patients with ALD with hepatitis C infection should be determined
on an individual basis. Use of interferon or other antiviral agents in patients with active alcohol abuse
cannot generally be recommended because efficacy may be reduced.[96] Alcohol abstinence followed by
antiviral therapy may potentially improve the efficacy of antiviral therapy.[97]
Current treatment for chronic hepatitis C in abstinent patients is almost exclusively with combinations
of direct antiviral agents. Recommended regimens for the treatment of hepatitis C are frequently
updated by the American Association for the Study of Liver Diseases. [AASLD: HCV guidance] (http://
hcvguidelines.org)
End-stage disease
Patients with end-stage ALD should be considered for liver transplantation. Patients with ALD must
be screened for alcohol-related comorbid disease, and are required by most transplant centres to
MANAGEMENT
have at least a 6-month period of confirmed abstinence.[98] [99] Other criteria should be taken into
consideration.[11] [33] [100]
Priority for receiving liver transplantation depends on the model for end-stage liver disease (MELD)
score. Other factors include acuteness of liver disease, associated complications, other medical and
29
psychiatric comorbidities, family support, alcohol dependence, and risk of recidivism. The model is based
on a composite scoring of serum creatinine, serum bilirubin, and international normalised ratio. A higher
score indicates worse prognosis. It has been validated as an independent predictor of patient survival in
candidates for liver transplantation. A MELD score of 21 had a sensitivity of 75% and a specificity of 75%
in predicting 90-day mortality in acute alcoholic hepatitis.[101]
Patients with acute alcoholic hepatitis are usually not considered for transplantation until they have
recovered from the acute illness and can demonstrate rehabilitation and sustained abstinence. However,
there is growing evidence that, using stringent criteria, liver transplantation can be successful in a select
group of patients with alcoholic hepatitis.[102] [103] Risk of alcohol relapse does not differ significantly
between patients with alcoholic hepatitis and patients with alcoholic cirrhosis who underwent elective liver
transplantation.[102]
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Ongoing ( summary )
all patients
1st alcohol abstinence ± alcohol withdrawal

management
plus weight reduction + smoking cessation
plus nutritional supplementation +

multivitamins
plus immunisation
adjunct corticosteroids
adjunct sodium restriction ± diuretics
2nd liver transplant
plus alcohol abstinence ± alcohol withdrawal

management
MANAGEMENT
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
MANAGEMENT
31
Ongoing
all patients
1st alcohol abstinence ± alcohol withdrawal

management
Primary options
» oxazepam: 15-30 mg orally three to four

times daily
OR
» diazepam: 10 mg intravenously initially,

followed by 5-10 mg every 3-4 hours when
required
More frequent dosing may be required. A
variety of dosing regimens may be used;
consult local protocols for guidance on dose.
Secondary options
» lorazepam: 2-6 mg/day orally given in 2-3

divided doses
» Measures include alcohol abstinence

counselling, brief intervention psychotherapy,
Alcoholics Anonymous, alcohol rehabilitation
programmes, and behaviour modification for
cessation of alcohol, smoking, and drug use.
Also close monitoring for, and treatment of,
symptoms of alcohol withdrawal.
» Benzodiazepines are the most commonly used

drugs to treat alcohol withdrawal syndrome.[11]
Long-acting benzodiazepines (e.g., diazepam)
provide greater protection against seizures and
delirium; shorter-acting benzodiazepines (e.g.,
oxazepam, lorazepam) are safer in older adults
and those with hepatic dysfunction.[11] [33] High
doses of benzodiazepines may trigger or worsen
hepatic encephalopathy.[11]
» Once abstinence has been achieved,

the combination of counselling plus
pharmacotherapy may be considered to improve
the likelihood of long-term abstinence. See our
Alcohol withdrawal topic for detailed information.
plus weight reduction + smoking cessation
Treatment recommended for ALL patients in
selected patient group
MANAGEMENT
» Weight reduction is important in obese patients

to slow the progression of ALD.[14] [59] Caution
is required if using orlistat to reduce weight
in ALD, due to reports of acute liver failure,
and other significant complications such as
cholelithiasis and cholestatic hepatitis.[60] [61]
Ongoing
» Smoking cessation is beneficial in reducing the
progression of ALD.[33] Smoking cessation is
also helpful in initiating alcohol abstinence and
maintenance. Cessation may be facilitated by
efforts as modest as simple recommendation by
a physician during routine consultation with the
patient.
plus nutritional supplementation +
multivitamins
» The prevalence of malnutrition is extremely
high in ALD.[63] [64] [65]
» Guidelines recommend evaluation of nutritional

status, with consideration for nutritional
supplementation to ensure sufficient caloric
intake and to correct specific deficits.[11] [33]
[29] Nutritional therapy should be instituted
during hospitalisations for acute decompensation
of ALD, including calories, vitamins, and
micronutrients (including zinc).[33] These
patients require frequent-interval feeds; nitrogen
balance can be improved by a night-time snack
and a morning feed.[66] [67]
» Nutritional supplementation may reduce overall

mortality in some malnourished patients with
ALD, especially those with alcoholic hepatitis
or cirrhosis, but a consistent improvement in
survival has not been demonstrated.[11] [68] [69]
[70] Systematic reviews indicate that adjunctive
nutritional support (parenteral or enteral nutrition,
or nutritional supplements) does not confer
a survival benefit in patients with ALD, but
encephalopathy may be ameliorated.[71] [72]
[73] [74] Randomised controlled clinical trials are
required.
» Enteral nutrition is preferred.[11] [33] If the

patient cannot achieve adequate caloric intake
orally, then an enteral feeding tube should be
considered.[33] [29]
» Routine use of specialised formulations is

not indicated, unless standard formulations
cannot be tolerated at amounts necessary
to satisfy nutritional requirements.[75] [76]
Branched chain amino acid (BCAA) formulations
are used for patients who cannot tolerate the
MANAGEMENT
necessary amount of standard amino acids

without precipitating encephalopathy.
» Protein feeding is usually well tolerated, and

there is no reason to routinely restrict protein in
patients with alcoholic hepatitis. Patients with
33
Ongoing
severe alcoholic hepatitis need a daily protein
intake of 1.2 to 1.5 g/kg and caloric intake of 35
kcal/kg.[11]
» Alcoholic patients are at high risk of developing

're-feeding syndrome' and should have
close surveillance for development of severe
hypokalaemia, hypophosphataemia, and
hypomagnesaemia.
» Long-term oral zinc supplementation for ALD

cirrhosis patients has shown beneficial effects on
both nutritional parameters and liver metabolic
function including in liver fibrosis (cirrhosis).
» Thiamine and other vitamin supplements

should be considered if necessary.[11]
plus immunisation
» Influenza and pneumococcal vaccine are
recommended in patients with chronic ALD.
If hepatitis B surface antibody and hepatitis A
immunoglobulin G (IgG) antibody are negative,
then hepatitis A and hepatitis B immunisation
should be considered in all stages of ALD.[11]
[62]
adjunct corticosteroids
Treatment recommended for SOME patients in
Primary options
» prednisolone: 40 mg orally once daily
Secondary options
» prednisone: 40 mg orally once daily
Tertiary options
» methylprednisolone: 30-36 mg/day orally

given in 3 divided doses
» Meta-analysis of individual patient data from

four controlled studies of severe alcoholic
hepatitis found that corticosteroid reduced
risk of death within 28 days compared with
placebo (hazard ratio [HR] 0.64; 95% confidence
interval [CI] 0.48-0.86) or pentoxifylline (HR 0.64;
MANAGEMENT
95% CI 0.43-0.95).[77] Corticosteroid efficacy

reduced with time; 6-month mortality did not
differ between corticosteroid and placebo or
corticosteroid and pentoxifylline.[77]
Ongoing
» Suitable for ALD patients with a Maddrey's
discriminant function (MDF) score of 32 or more,
or hepatic encephalopathy.
» MDF is based on a composite scoring of

prothrombin time and total bilirubin.[79] [80]
» If bilirubin falls during the first week, treatment

is continued until acute decompensation
resolves.
» Corticosteroids are stopped if there is no

improvement in serum bilirubin at seventh day of
treatment. Those with higher Lille scores should
discontinue corticosteroids.[29]
» The American College of Gastronterology

recommends discontinuing corticosteroids
in patients with a Lille score >0.45, while the
European Association for the Study of the Liver
recommends discontinuation in patients with a
Lille score of ≥0.56.[11] [33]
» Prednisolone is preferred to prednisone in

acute alcoholic hepatitis.[11] [29]
» Corticosteroids should be avoided in

patients with gastrointestinal bleeding
requiring transfusion, in active infection, and in
hepatorenal syndrome.[83] [84] Corticosteroids
do not appear to increase the occurrence of, or
mortality from, bacterial infections in patients
with severe alcoholic hepatitis.[85]
adjunct sodium restriction ± diuretics
Treatment recommended for SOME patients in
Primary options
» furosemide: 40-160 mg orally once daily in

the morning
-and-
» spironolactone: 100-400 mg orally once
daily in the morning
» For patients with less severe ascites a 2 g daily

sodium diet is required. Commonly prescribed
'no added' salt diets usually contain about 4 g
sodium daily. The target weight loss should be
no more than 0.5 kg per day in patients without
peripheral oedema (those with oedema may lose
up to 1 kg per day).
MANAGEMENT
» As liver function deteriorates, patients will need

diuretics in combination with a sodium-restricted
diet in order to induce adequate sodium
excretion in the urine. The most commonly used
diuretic regimen is a combination of furosemide
35
Ongoing
and spironolactone. Using this combination,
successful therapy can be reached in up to 90%
of patients.[88]
» In patients who are refractory to salt restriction

and diuretics (usually <10% of those with
cirrhosis), large-volume paracentesis or
transjugular intrahepatic portosystemic shunt
(TIPS) therapy may be required.[34] [88] [89]
2nd liver transplant
» Patients with end-stage ALD should be

considered for liver transplantation. Patients
with ALD must be screened for alcohol-related
comorbid disease, and are required by most
transplant centres to have at least a 6-month
period of confirmed abstinence.[98] [99]
» Other criteria should be taken into

consideration.[11] [33] [100]
» Priority for receiving liver transplantation

depends on the model for end-stage liver
disease (MELD) score. Other factors include
acuteness of liver disease, associated
complications, other medical and psychiatric
comorbidities, family support, alcohol
dependence, and risk of recidivism. The model
is based on a composite scoring of serum
creatinine, serum bilirubin, and international
normalised ratio. A higher score indicates
worse prognosis. It has been validated as an
independent predictor of patient survival in
candidates for liver transplantation. A MELD
score of 21 had a sensitivity of 75% and a
specificity of 75% in predicting 90-day mortality
in acute alcoholic hepatitis.[101]
» Patients with acute alcoholic hepatitis are

usually not considered for transplantation until
they have recovered from the acute illness and
can demonstrate rehabilitation and sustained
abstinence. However, there is growing evidence
that, using stringent criteria, liver transplantation
can be successful in a select group of patients
with alcoholic hepatitis.[102] [103] Risk of
alcohol relapse does not differ significantly
between patients with alcoholic hepatitis and
patients with alcoholic cirrhosis who underwent
elective liver transplantation.[102]
plus alcohol abstinence ± alcohol withdrawal
MANAGEMENT
management
Primary options
Ongoing
» oxazepam: 15-30 mg orally three to four
times daily
OR
» diazepam: 10 mg intravenously initially,

followed by 5-10 mg every 3-4 hours when
required
More frequent dosing may be required. A
variety of dosing regimens may be used;
consult local protocols for guidance on dose.
Secondary options
» lorazepam: 2-6 mg/day orally given in 2-3

divided doses
» Measures include alcohol abstinence

counselling, brief intervention psychotherapy,
Alcoholics Anonymous, alcohol rehabilitation
programmes, and behaviour modification for
cessation of alcohol, smoking, and drug use.
Also close monitoring for, and treatment of,
symptoms of alcohol withdrawal.
» Benzodiazepines are the most commonly used

drugs to treat alcohol withdrawal syndrome.[11]
Long-acting benzodiazepines (e.g., diazepam)
provide greater protection against seizures and
delirium; shorter-acting benzodiazepines (e.g.,
oxazepam, lorazepam) are safer in older adults
and those with hepatic dysfunction.[11] [33] High
doses of benzodiazepines may trigger or worsen
hepatic encephalopathy.[11]
» Once abstinence has been achieved,

the combination of counselling plus
pharmacotherapy may be considered to improve
the likelihood of long-term abstinence. See our
Alcohol withdrawal topic for detailed information.
MANAGEMENT
37
Emerging
Granulocyte-colony stimulating factor (G-CSF)
G-CSF is a glycoprotein that stimulates the bone marrow to release neutrophils and stem cells (CD34+)
into the bloodstream. One open-label study of 57 patients with severe alcoholic hepatitis found that G-
CSF improves liver function and increases survival times compared with an 800 to 2000 kcal/day diet
plus pentoxifylline.[104] Larger studies are needed to better define the utility of G-CSF in severe alcoholic
hepatitis.
Extracorporeal cellular therapy

In an extracorporeal cellular therapy (ELAD) study, hepatoblastoma-derived C3A cells (that express anti-
inflammatory proteins and growth factors) failed to improve overall survival in patients with severe alcoholic
hepatitis.[105] Subgroup analysis suggested that further investigation of ELAD in younger patients (<46.9
years) with a model for end-stage liver disease (MELD) score of less than 28 may be warranted.
Faecal microbiota transplantation (FMT)

In a pilot study, one week of FMT (from healthy donors) improved indices of liver disease and survival (at 12
months) among patients with severe alcoholic hepatitis who were ineligible for corticosteroid therapy.[106]
Larger controlled studies with long-term follow-up are needed.
Prednisolone plus acetylcysteine

In one randomised controlled trial of patients with severe acute alcoholic hepatitis, the combination of
prednisolone plus acetylcysteine improved 1-month survival compared with corticosteroid alone.[107]
However, 6-month mortality, the primary endpoint, did not differ between groups.[107] Results from a network
meta-analysis suggest that corticosteroid plus acetylcysteine may reduce the risk of short-term mortality,
compared with corticosteroid alone, in patients with severe alcoholic hepatitis.[108]
Primary prevention
Alcohol abstinence can prevent development of ALD.
Social support through Alcoholics Anonymous, inpatient and outpatient rehabilitation programmes, and
individual counselling should be provided to alcohol-dependent patients.
The American College of Gastroenterology recommends that people who drink heavily (i.e., >3 drinks per
day in men and >2 drinks in women) for >5 years should be counselled about the increased risk for ALD.[11]
Secondary prevention
Social support through Alcoholics Anonymous, inpatient and outpatient rehabilitation programmes, and
individual counselling should be provided to alcohol-dependent patients. All patients with ALD should be
screened for:
• Hepatitis A total or IgG antibodies

• Hepatitis B surface antibodies and hepatitis B core total and IgG antibodies
MANAGEMENT
• Hepatitis C antibodies.
If patients are not immune, they should be vaccinated against hepatitis A. In addition, the Advisory
Committee on Immunization Practices in the US recommends that all patients with chronic liver disease and
an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level greater than twice the upper
limit of normal should be vaccinated against hepatitis B.[120] If the patient has active hepatitis C or fulfils
criteria for therapy for hepatitis B, they should be offered treatment. Immunisation against Pneumococcus
and influenza is also advisable. If cirrhosis is present, screening for development of liver cancer is also
recommended. Weight reduction in obese patients and smoking cessation are both influential and positive
steps towards reducing the risk and progression of ALD.
All medications should be evaluated for potential hepatotoxicity. If a medication may be hepatotoxic, an
alternative drug should be considered. Caution and close observation is recommended if hepatotoxin use
is absolutely necessary. Patients should be made aware of symptoms of liver injury. Periodic liver-related
biochemical tests should be obtained at baseline before starting hepatotoxins, followed by every 2 weeks for
the first month, every month for the next 3 months, and every 3 months thereafter. Hepatotoxic medication
should be discontinued if measured laboratory values increase to >2 times the baseline levels or the patient
develops liver-related symptoms.[121] Patients with ALD should be asked specifically about their use of
alternative therapies. Patients should be instructed to avoid potentially hepatotoxic herbal preparations.
Patients with ALD can safely use paracetamol at a dosage of up to 2 g/day, if they are eating regularly.
ALD patients with cirrhosis should avoid using non-steroidal anti-inflammatory drugs (NSAIDs), owing to
enhanced nephrotoxicity and worsening of ascites.
Patient discussions
Patients should avoid drinking alcohol or limit the amount of alcohol use, because alcohol consumption
facilitates ALD progression. They should discuss with their healthcare provider various methods to stop
drinking alcohol.
A periodic physical check-up with laboratory tests is essential to evaluate the progression of liver disease.
Vaccines, such as for hepatitis A, hepatitis B, influenza, and pneumonia, can prevent infections and
reduce comorbidities. Patients should keep a written list of their medicines, their amounts, and when
and why to take that medication. The list of medicines or the pill bottles should be brought to follow-up or
hospital visits. All medications should be taken regularly as directed by the physician. Patients with ALD
can safely use paracetamol at a dosage of up to 2 g/day, if they are eating regularly.
Patients should take more protein and calories, which may improve their illness. Having a snack between
breakfast and lunch and at bedtime may increase daily calorie intake. The amount of salt intake should be
limited to prevent fluid retention in the abdomen.
Patients should seek help immediately if they have a fever or experience abdominal pain, shortness of
breath, fast heart rate or breathing, a dizzy feeling, black stool or blood in stool, or blood or coffee-ground
material in the vomit.
MANAGEMENT
39
Alcoholic liver disease Follow up
Monitoring
Monitoring
FOLLOW UP
ALD can be monitored through periodic liver function tests and visits to the healthcare provider. It is
important to evaluate any worsening of signs and symptoms. Healthcare providers should monitor
compliance with treatment and alcohol abstinence. Models such as the Child-Turcotte-Pugh index, which
includes a combination of clinical and laboratory variables, can be useful to assess disease severity
and set a baseline for future reference. Patients with advanced liver disease should be screened for
oesophageal varices and treated with prophylactic non-selective beta-blockers (e.g., propranolol, nadolol,
or carvedilol) if they have oesophageal varices 5 mm or more in size. Prophylactic endoscopic banding
can be utilised if the patient has oesophageal varices of 5 mm or more and is intolerant to beta-blockers
or not deemed appropriate for beta-blocker therapy. If oesophageal varices are not found, or if they are <5
mm, then surveillance at 1- to 2-year intervals is indicated until a therapeutic decision is reached.
Complications
Complications Timeframe Likelihood
FOLLOW UP
hepatic encephalopathy long term high
Hepatic encephalopathy is a common and serious complication of severe liver damage from alcohol use.
It occurs due to a build-up of harmful toxins in blood, particularly ammonia, and from an imbalance of
amino acids that affect brain function. It can be checked by the confusion assessment method (CAM), a
brief questionnaire that assesses, among other things, attention, memory, organisation, and sleep and
wakefulness. [Confusion Assessment Method instrument (CAM)] (https://www.islandhealth.ca/sites/
default/files/2018-05/cam-short-form.pdf)
Early symptoms include forgetfulness, difficulty in concentrating, and rapid changes in mental state,
including agitation or confusion. Bad fruity-smelling breath and tremor may be associated clinical
findings. Late-stage presentation of encephalopathy is stupor and eventually coma. Lactulose is used
to prevent and to treat this condition in susceptible ALD patients. The earliest stage is 'minimal hepatic
encephalopathy', which impairs fitness to drive and can be diagnosed with the computerised Inhibitory
Control Test.[113]
portal hypertension long term high
In alcoholic cirrhosis, liver cell damage slows down intrahepatic blood flow, causing a back-up of blood
through the portal vein (portal hypertension). This produces secondary complications such as variceal
bleeding, ascites, splenomegaly, and secondary thrombocytopenia. Progression of portal hypertension is
not reversible without liver transplantation or prolonged alcohol abstinence.
gastrointestinal (GI) bleeding long term medium
GI bleeding occurs secondary to the development of gastro-oesophageal varices, haemorrhoids, and

portal hypertensive gastropathy or enteropathy, along with the presence of coagulopathy from reduced
synthetic function of the liver and the presence of thrombocytopenia secondary to splenomegaly. Patients
with cirrhosis and GI bleeding should receive antibiotic prophylaxis to reduce mortality, infections, re-
bleeding, and length of hospital stay.[114]
Patients with advanced liver disease should be screened for oesophageal varices and treated with
prophylactic non-selective beta-blockers such as propranolol, nadolol, or carvedilol if they have
oesophageal varices of 5 mm or more. Prophylactic endoscopic banding can be utilised if oesophageal
varices are 5 mm or more and the patient is intolerant to beta-blockers or not deemed appropriate for beta-
blocker therapy. If oesophageal varices are not found, or if they are <5 mm, then surveillance at 1- to 2-
year intervals is indicated until a therapeutic decision is reached.[115] The utility of antacids in reducing
variceal bleeding in cirrhotic patients is inconclusive in the absence of proper randomised controlled
trials.[116]
Restrictive blood transfusion (only when Hb ≤7 g/dL [≤70 g/L] with target of 7-9 g/dL [70-90 g/L]) is
preferred over liberal blood transfusion (when Hb is ≤9 g/dL [≤90 g/L] with target of 9-11 g/dL [90-110 g/
L]) because liberal blood transfusion increases portal hypertension, while restrictive transfusion decreases
re-bleeding rate in all patients with cirrhosis, and decreases mortality in patients with Child-Pugh A and B
cirrhosis.[117]
coagulopathy long term medium
Coagulopathy occurs from reduced synthetic function of coagulation factors in the liver due to liver
cirrhosis.
41
Complications Timeframe Likelihood

renal failure long term medium
FOLLOW UP
Renal impairment is a secondary complication from portal hypertension and high renin-angiotensin system
activity.
Non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk for kidney failure.
hepatorenal syndrome long term medium
Hepatorenal syndrome occurs if the kidneys significantly reduce their own blood flow distribution in
response to the altered blood flow in the liver, which decreases mean arterial pressure because of extreme
vasodilation. Hepatorenal syndrome is a life-threatening complication. It presents as acute kidney failure in
the absence of other kidney diseases and is associated with high mortality.
Medical management options also include albumin with norepinephrine (noradrenaline), and albumin with
midodrine plus octreotide.[118] Surgical procedures such as transjugular intrahepatic portosystemic shunt
can be used to bridge until liver transplantation. A meta-analysis concluded that terlipressin reverts type 1
hepatorenal syndrome. Terlipressin is not yet commercially available in the US.[119]
hepatocellular carcinoma long term low
Liver cirrhosis greatly increases the risk for liver cancer. Liver cancer has a high risk of mortality.
Serial imaging studies such as with ultrasound of the abdomen can be used to screen for liver cancer.
Radiofrequency ablation, transarterial chemo-embolisation (TACE), transarterial microsphere embolisation,
sorafenib, and liver transplantation can be used to treat liver cancer.
sepsis variable medium
Bacterial infections are extremely common in advanced cirrhosis and may increase the risk for bleeding.
Patients have higher risk of bacterial infections in ascites fluid and in the urinary, respiratory, and
gastrointestinal tracts, from repeated hospital admissions.
Prognosis
The short-term outlook for patients with alcoholic fatty liver is excellent, as alcoholic fatty liver usually reverts
to normal with alcohol abstinence. Longer follow-up has found that cirrhosis develops more commonly in
alcohol abusers with fatty liver changes than in those with normal liver histology.
Natural history
It is important to emphasise that the signs, symptoms, histological stages, and severity of liver disease
are variable among people with ALD. In addition, relatively asymptomatic patients may have histologically
advanced liver disease. Clinical decompensation carries a poor prognosis regardless of the histological stage
of ALD.
Fatty liver may result from acute alcohol abuse. In long-term heavy alcohol consumers, about 90% to 100%
develop fatty liver, 20% to 35% develop alcoholic hepatitis, and 8% to 20% develop alcoholic cirrhosis. Liver
cirrhosis from severe and prolonged liver damage used to be considered an irreversible outcome. However,
studies in patients with liver disease have shown some degree of reversibility. The 5-year survival rate for
FOLLOW UP
people with cirrhosis who stop drinking is about 90%, compared with 70% of those who do not stop drinking.
However, for late-stage cirrhosis (e.g., jaundice, ascites, or gastrointestinal bleeding), the survival rate is only
60% for those who stop drinking and 35% for those who do not.[109] For those patients with decompensated
alcoholic cirrhosis who undergo liver transplantation, 5-year survival is about 70%.
Predictive models
Maddrey discriminant function (MDF) and model for end-stage liver disease (MELD)
MDF is a model based on a composite scoring of prothrombin time (PT) and total bilirubin. A higher score
indicates a worse prognosis. MDF score >32 indicates high mortality of around 35% to 45%.[79] [110]
Patients with MDF <32 have short-term survival rates of 90% to 100%.
The 30-day mortality in patients with alcoholic hepatitis ranges from 0% to 50%.[79] Both the MDF score and
the model for end-stage liver disease (MELD) score can be used to predict short-term mortality in alcoholic
hepatitis patients.[111] Three-year survival approaches 90% in abstainers, whereas it is <70% in active
drinkers.[110]
Glasgow alcoholic hepatitis score (GAHS)
GAHS is based on a composite scoring of age, serum urea (mmol/L), serum bilirubin (mmol/L), PT, and WBC
count. A higher score indicates a worse prognosis. GAHS score on day 1 had an overall accuracy of 81%
when predicting 28-day outcome in alcoholic hepatitis patients.[112]
Lille model
The Lille model is based on a composite scoring of age, serum albumin (g/L), serum creatinine above or
below 1.3 mg/dL, bilirubin, change in bilirubin from day 0 to day 7, and PT. A score of >0.45 predicts a 6-
month survival of 25%, versus 85% survival when the score is <0.45.[82]
Child-Turcotte-Pugh index
The Child-Turcotte-Pugh index includes a combination of clinical and laboratory variables and can be useful
to assess disease severity and set a baseline for future reference.
43
Alcoholic liver disease Guidelines
Diagnostic guidelines
United Kingdom
Guidelines on the management of ascites in cirrhosis (ht tps://

www.bsg.org.uk/resource-type/clinical-resources/guidelines)
Published by: British Society of Gastroenterology Last published: 2020
Guidelines on the use of liver biopsy in clinical practice (ht tps://

www.bsg.org.uk/resource-type/clinical-resources/guidelines)
Published by: British Society of Gastroenterology; Royal College of Last published: 2020
Radiologists; Royal College of Pathology
Guidelines for the diagnosis and treatment of hepatocellular carcinoma

(HCC) in adults (ht tps://www.bsg.org.uk/resource-type/clinical-resources/
guidelines)
GUIDELINES
Europe
EASL clinical practice guidelines: management of alcohol-related liver

disease (ht tps://easl.eu/publications/clinical-practice-guidelines)
Published by: European Association for the Study of the Liver Last published: 2018
International
Diagnosis and treatment of alcohol‐related liver diseases (ht tps://www.journal-

of-hepatology.eu/article/S0168-8278(18)32581-9/fulltext)
Published by: The American Association for the Study of the Liver Last published: 2019
North America
ACG clinical guideline: alcoholic liver disease (ht tps://gi.org/guidelines)

Published by: American College of Gastroenterology Last published: 2018
Evaluation of abnormal liver chemistries (ht tps://gi.org/guidelines)

Latin America
Alcohol-related liver disease: clinical practice guidelines (ht tps://

www.sciencedirect.com/science/article/pii/S1665268119300419)
Published by: The Latin American Association for the Study of the Liver Last published: 2019
Treatment guidelines
United Kingdom
Guidelines on the management of ascites in cirrhosis (ht tps://

www.bsg.org.uk/resource-type/guidelines)
Indications for referral and assessment in adult liver transplantation: a

clinical guideline (ht tps://www.bsg.org.uk/resource-type/guidelines)
Alcohol-use disorders: diagnosis and management of physical complications

(ht tps://www.nice.org.uk/guidance/cg100)
Published by: National Institute for Health and Care Excellence Last published: 2017
GUIDELINES
UK guidelines on the management of variceal haemorrhage in cirrhotic
patients (ht tps://www.bsg.org.uk/clinical/bsg-guidelines.html)
Guidelines for the diagnosis and treatment of hepatocellular carcinoma

(HCC) in adults (ht tps://www.bsg.org.uk/resource-type/guidelines)
Europe
EASL clinical practice guidelines: management of alcohol-related liver

disease (ht tps://easl.eu/publications/clinical-practice-guidelines)
EASL recommendations on treatment of hepatitis C (ht tps://easl.eu/

publications/clinical-practice-guidelines)
Clinical guidelines on nutrition in chronic liver disease (ht tps://easl.eu/

publications/clinical-practice-guidelines)
EASL clinical practice guidelines on the management of ascites,

spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis
(ht tps://easl.eu/publications/clinical-practice-guidelines)
45
North America
Testing, evaluation, and monitoring of hepatitis C (ht tps://

www.hcvguidelines.org/evaluate)
Published by: American Association For the Study of Liver Diseases; Last published: 2020
Infectious Diseases Society of America
Diagnosis and treatment of alcohol‐related liver diseases (ht tps://www.journal-

of-hepatology.eu/article/S0168-8278(18)32581-9/fulltext)
Published by: The American Association for the Study of the Liver Last published: 2019
Use of cannabis in gastroenterological and hepatic disorders (ht tps://

academic.oup.com/jcag/article/2/1/37/5166404)
Published by: Canadian Association of Gastroenterology Last published: 2018
ACG clinical guideline: alcoholic liver disease (ht tps://gi.org/guidelines)

GUIDELINES
Medical management of severe alcoholic hepatitis (ht tps://

www.ncbi.nlm.nih.gov/pmc/articles/PMC5172399)
Published by: American Gastroenterological Association Last published: 2017
Management of adult patients with ascites due to cirrhosis: an update

(ht tps://www.aasld.org/publications/practice-guidelines)
Published by: American Association for the Study of Liver Diseases Last published: 2012
Latin America
Alcohol-related liver disease: clinical practice guidelines (ht tps://

www.sciencedirect.com/science/article/pii/S1665268119300419)
Published by: The Latin American Association for the Study of the Liver Last published: 2019
Alcoholic liver disease Online resources
Online resources
1. AASLD: HCV guidance (http://hcvguidelines.org) (external link)
2. Confusion Assessment Method instrument (CAM) (https://www.islandhealth.ca/sites/default/

files/2018-05/cam-short-form.pdf) (external link)
ONLINE RESOURCES
47
Alcoholic liver disease References
Key articles
• Heimbach J, Kulik LM, Finn R, et al. AASLD guidelines for the treatment of hepatocellular
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bleeding. N Engl J Med. 2013 Jan 3;368(1):11-21. Full text (http://www.nejm.org/doi/full/10.1056/
NEJMoa1211801#t=article) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/23281973?
118. Karwa R, Woodis CB. Midodrine and octreotide in treatment of cirrhosis-related hemodynamic
complications. Ann Pharmacother. 2009 Apr;43(4):692-9. Abstract (http://www.ncbi.nlm.nih.gov/
119. Sagi SV, Mittal S, Kasturi KS, et al. Terlipressin therapy for reversal of type 1 hepatorenal syndrome:
A meta-analysis of randomized controlled trials. J Gastroenterol Hepatol. 2010 May;25(5):880-5.
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Mortal Wkly Rep. 2017 Feb 10;66(5):136-8. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC5657965) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/28182599?tool=bestpractice.bmj.com)
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North Am. 1995 Dec;24(4):1047-64. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8749911?
59
Alcoholic liver disease Images
Images
Figure 1: Liver biopsy showing the typical histological changes of alcoholic steatosis (fatty liver)
IMAGES
Figure 2: Liver biopsy showing the typical histological changes of alcoholic steatohepatitis
Alcoholic liver disease Images
IMAGES
Figure 3: Liver biopsy showing alcoholic cirrhosis
61
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63
Contributors:
// Authors:
Craig McClain, MD
Professor
Chief of Research Affairs, Associate Vice President for Health Affairs/Research, Division of
Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of
Medicine, Louisville, KY
DISCLOSURES: CM acts as a consultant for Nestlé, Durect, Allergan, Intercept and DISCUS. He works
for the Veterans Administration on a part time basis, has received grants from the NIH and VAMC, and is
working on the update of the AGC nutritional guideline..
Luis Marsano, MD
Professor and Director of Hepatology
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville
School of Medicine, Louisville, KY
DISCLOSURES: LM is on the speaker bureau for Salix (maker of Rifaximin - Xifaxan); Rifaximin is part of
the therapy (supported by practice guidelines) of hepatic encephalopathy. He is also on the speaker bureau
of Grifols (one of the makers of albumin for intravenous infusion); albumin is used as part of the treatment of
spontaneous bacterial peritonitis (supported by practice guidelines).
// Acknowledgements:
Dr Craig McClain and Dr Luis Marsano would like to gratefully acknowledge Dr Mihir Patel, a previous
contributor to this topic.
DISCLOSURES: MP declares that he has no competing interests.
// Peer Reviewers:
Lorenzo Leggio, MD, MSc

Postdoctoral Research Associate
Center for Alcohol and Addiction Studies, Brown University, Providence, RI
DISCLOSURES: LL declares that he has no competing interests.
Nancy Reau, MD
Assistant Professor of Medicine
University of Chicago, Center for Liver Disease, Chicago, IL
DISCLOSURES: NR declares that she has no competing interests.
Nick Sheron, MD, FRCP

Head of Clinical Hepatology and Senior Lecturer
Division of Infection, Inflammation and Immunity, University of Southampton Medical School, Southampton
General Hospital NHS Trust, Southampton, UK
DISCLOSURES: NS has received research grants from the Medical Research Council (MRC), Wellcome
Trust, British Liver Trust, Alcohol Education Research Council, and various other funding bodies. He has
undertaken paid consultancy work and received travelling expenses from pharmaceutical companies
developing drugs for the treatment of inflammatory bowel disease and liver disease. He has been paid for
medico-legal work in the areas of hepatitis C and alcohol-related liver disease. The following memberships
Contributors:
and advisory work are unpaid apart from travelling expenses: EU Alcohol Forum, EU Alcohol Marketing
Taskforce, Royal College of Physicians Alcohol Committee, Alcohol Health Alliance UK. NS has undertaken
advisory and media work for the UK Department of Health, Home Office, Department of Transport, Cross
Cabinet Strategy Committee, National Institute for Health and Care Excellence, Southampton City Council,
UK Police, and British Liver Trust, and various other NGOs, local government, and other bodies. NS is an
unpaid trustee of the Drinkaware Trust, an independent body set up by the UK Government to use industry
resources to reduce alcohol-related harm. The Trust is funded entirely by the alcohol industry, with a board
of trustees comprising 5 industry members, 5 members with alcohol-related health expertise, and 3 lay
members.
Alastair MacGilchrist, MD, FRCP

Consultant Hepatologist
Royal Infirmary of Edinburgh, Edinburgh, UK
DISCLOSURES: AM declares that he has no competing interests.

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Alcoholic Liver Disease

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Alcoholic liver disease

Straight to the point of care

Last updated: Aug 24, 2021

Complications include oesophageal or gastric variceal bleeding, ascites, coagulopathy, hepatic

• Tumour necrosis factor-alpha 238G>A polymorphism

Other pathways may have a role in the pathogenesis of ALD.[21]

Liver biopsy showing the typical histological changes of alcoholic steatohepatitis

Liver biopsy showing alcoholic cirrhosis

Asymptomatic elevation of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) in a

AUDIT (Alcohol Use Disorders Identification Test) questionnaire

AUDIT-C 3-item alcohol screen

• Abdominal distension and weight gain (ascites)

Signs of significant or severe hepatic involvement include:

• Confusion (hepatic encephalopathy)

Full blood count

Basic metabolic panel (sodium, potassium, chloride, bicarbonate, urea, creatinine)

hypophosphataemia are common causes of muscle weakness in ALD.

Magnesium and phosphorus

Coagulation profile (PT, INR)

Coagulopathy is an obvious complicating factor in cases of gastrointestinal bleeding from varices or

Subsequent laboratory tests to rule out co-existing diseases

Ammonia level and folate

Anti-mitochondrial antibody, anti-nuclear antibody, and anti-smooth muscle antibody

Other serum laboratory tests that may indirectly reflect the

Routine use of CDT and mitochondrial AST is not necessary.

Non-invasive markers of chronic ALD

Imaging tests to detect fibrosis

consumption, but is not necessary in every patient.[11] [33]

Liver biopsy showing the typical histological changes of alcoholic steatohepatitis

Liver biopsy showing alcoholic cirrhosis

History and exam

abdominal pain (common)

haematemesis and melaena (uncommon)

venous collaterals (uncommon)

hepatic mass (uncommon)

palmar erythema (uncommon)

cutaneous telangiectasia (uncommon)

Other diagnostic factors

weight loss (common)

weight gain (common)

malnutrition and wasting (common)

nausea and vomiting (uncommon)

finger clubbing (uncommon)

Dupuytren's contracture (uncommon)

leg swelling (uncommon)

parotid gland enlargement (uncommon)

• Present in nearly two-thirds of patients; manifestation of altered sex hormone metabolism.

peripheral neuropathy (uncommon)

age >65 years

Other tests to consider

serum iron, ferritin, transferrin normal or elevated serum

Condition Differentiating signs / Differentiating tests

spider angiomata, and higher than AST.

Hepatitis A virus • History suggestive of • Serum test positive for

Cholecystitis • Acute right upper quadrant • Ultrasound of gallbladder is

Condition Differentiating signs / Differentiating tests

Hepatic vein thrombosis • Variable chronicity of • Ultrasound of liver with

Acute liver failure • Patient with acute • Severe elevation of

Haemochromatosis • Presenting features include • High iron saturation (>45%

Wilson's disease • Patients may have • Increased urinary

Drug- or toxin-induced • History of exposure to • Liver biopsy may show

Autoimmune hepatitis • History of immune • There may be positive

Condition Differentiating signs / Differentiating tests

Wernicke's • Usually presents with abrupt • Clinical diagnosis.