ALCOHOLIC LIVER DISEASE

In the last 15 yr, UK alcohol-related deaths have doubled. In 2005, there were 8386 deaths related to alcohol. Death rates in both sexes and all age groups are increasing. Alcohol-related deaths are twice as frequent in males.This review aims to highlight the different subtypes of alcoholic liver disease (ALD) and discuss the management of the various ways in which ALD can present to the intensivist.

ALD is conventionally divided up into three histological types, although features of each may coexist in the same patient.
Steatosis
The metabolism of ethanol causes the accumulation of lipid in liver cells. This is steatosis, or 'fatty liver', estimated to occur in 90–100% of all heavy drinkers.Largely symptom free, it resolves completely within a few months of cessation of alcohol intake.
ALCOHOLIC  HEPATITIS
Ethanol metabolism can generate reactive oxygen species and neo-antigens,promoting inflammation. This 'alcoholic hepatitis' (AH) occurs in 10–35% of heavy drinkers. It may be mild and virtually asymptomatic or it may lead to acute flare ups with all of the signs of the systemic inflammatory response syndrome (SIRS) and subsequent multi-organ failure (MOF). In patients with confirmed AH on biopsy who continue to drink, 40% progress on to cirrhosis.
CIRRHOSIS
Prolonged hepatocellular damage generates myofibroblast-like cells which produce collagen resulting in fibrosis. As hepatocytes are destroyed and liver architecture changes, hepatic function falls and increased resistance to portal blood flow produces portal hypertension. Approximately 8–20% of heavy drinkers will develop cirrhosis, which may be asymptomatic. However, acute episodes of liver failure may be induced by episodes of AH or complications of portal hypertension such as variceal bleeding. In patients whose first presentation is an episode of severe decompensated ALD, 85% will have AH and more than 70% will have cirrhosis.
The single biggest risk factor is the quantity of alcohol ingested, irrespective of what form it is taken in. There is considerable debate as to what constitutes a 'safe' level of alcohol consumption, although it is evident that females are more at risk than males at any individual consumption level. Epidemiological data had initially suggested consumption of 80 g of ethanol per day in men and 60 g in women, for between 10 and 12 yr, is necessary for alcoholic liver damage to occur. However, recently these levels have been questioned, with new figures of 40 g per day in men and 10–20 g per day in women being associated with an increased relative risk of developing liver disease. For comparison, one UK 'unit' of alcohol contains 10–12 g of ethanol.
Other risk factors include obesity and hepatitis C infection. Despite this, it is unknown exactly why ALD only affects a proportion of heavy drinkers, even in the presence of other risk factors.
Patients with ALD may present to the intensive care unit (ICU) with one of the 'acute on chronic' complications of cirrhosis such as encephalopathy or variceal bleeding. Alternatively, they may present with an episode of severe hepatitis which may progress on to MOF. As patients with AH may have coexistent cirrhosis, this group can present with features of both acute and chronic liver disease.
HISTORY
Features in the history include high alcohol intake, history of alcohol abuse, history of alcohol-related diseases (e.g. pancreatitis), and accidents. Additionally, certain jobs (e.g. a publican) increase the likelihood of heavy drinking. In patients in whom dishonesty is suspected, a more accurate alcohol history may be obtained from the family.
EXAMINATION
Although alcoholic patients may have no abnormal examination findings when well, on presentation to ICU, they will have signs of either acute hepatitis, chronic liver disease, or both . In addition to these, there are specific features that should be looked for:

assessment of airway stability;

       signs of chest infection or aspiration at auscultation;

signs of SIRS (pulse, arterial pressure, temperature, etc.);

  assessment of fluid status;

  assessment of GCS and level of encephalopathy;

  assessment for signs of gastrointestinal (GI) bleeding (pallor, melaena on PR   examination);

  examination of input/output charts;

        bowel charts

INVESTIGATIONS
Common investigations requested on patients with ALD are listed in Individual tests are discussed under the different diagnoses subheadings.
GENERAL MANAGEMENT
General supportive care should be instigated in a patient with ALD, irrespective of presentation. Oxygen via a face mask or nasal specs should be commenced, large-bore i.v. access obtained, blood tests taken , and fluid resuscitation commenced. Regular glucose measurements should be taken. Disordered coagulation should only be treated if bleeding has occurred or invasive procedures are planned. Urine output should be closely monitored and oliguria should be aggressively treated. Care should be taken not to rapidly correct severe hyponatraemia which may exist in long-standing cirrhotics due to excess anti-diuretic hormone secretion. However, sodium-containing fluids are not specifically contraindicated in the alcoholic patient in the acute setting as hypotensive organ failure is likely to be more dangerous in this situation than the long-standing sodium retention. Hypokalaemia is also common and should be treated with careful supplementation.
Medications which may provoke hypotension, encephalopathy, or renal dysfunction [diuretics, angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), sedatives, etc.] should be stopped. An appropriate withdrawal regime and ulcer prophylaxis should be started along with vitamin supplementation. Thiamine should be given i.v. before glucose-containing compounds. Suitable antibiotics are required if any infection is suspected. Additionally, prophylactic antibiotics should be started in patients with bleeding.
Nutrition should be commenced early. Malnutrition is common in alcoholic patients and is associated with severity of liver dysfunction and poor outcome. Enteral feeding is preferred over i.v. feeding, and standard feeds can be used. Protein restriction is no longer recommended due to the risk of muscle wasting; however, if encephalopathy supervenes or worsens, then branched chain amino acid feeds should be considered.

Signs of acute hepatitis Jaundice Tender hepatomegaly Fever (<38.50, often sawtooth) Signs of chronic liver disease Leuconychia Palmar erythema Dupytren's contracture Spider naevi Telangactasia Bruising Oedema (hypoalbuminaemia) Parotid swelling Gynaecomastia Hepatomegaly Testicular atrophy Encephalopathy Portal hypertension Ascites Splenomegaly Caput medusae (abdominal varices) Poor nutrition Muscle wasting (back of hands) Weight loss/cachexia Glossitis

 

Blood tests FBC Clotting U+E LFT Other electrolytes (magnesium, calcium, phosphate, etc.) Glucose Group and save/XM Blood cultures Imaging CXR Abdominal ultrasound Other investigations Urine dipstick MSU Diagnostic abdominal paracentesis (if ascites present) Other investigations often indicated Amylase (suspected pancreatitis) Ammonia (encephalopathy) Intra-abdominal pressure (IAP) (hepatorenal syndrome, HRS) Renal tract ultrasound (deteriorating renal function to rule out obstruction) Abdominal CT (suspected perforation) Head CT (encephalopathy, sepsis)
Modified discriminant function (mDF) = Bilirubin (mg dl−1) + [4.6×prolongation of PTT above control (s)] Note: convert bilirubin in micromoles per litre to milligrams per decilitre by dividing by 17.1. Model for end-stage liver disease (MELD) = 3.8×loge bilirubin (mg dl−1) + 11.2×loge INR + 9.6×loge creatinine (mg dl−1) Note: maximum score is 40; values of <1 are given values of 1; recent dialysis requires a creatinine value of 4.0
Child–Pugh score
Criterion	1 point	2 points	3 points
Bilirubin (mmol litre−1)	<34	34–50	>50
Albumin (g litre−1)	>35	28–35	<28
INR	<1.7	1.7–2.2	>2.2
Ascites	None	Controlled	Refractory
Encephalopathy	None	I–II or controlled	III–IV or refractory
Note: Scores 5–6=class A; Scores 7–9=class B; Scores 10–15=class C
Glasgow AH score
Criterion	1 point	2 points	3 points
Age	<50	≥50	—
WCC (109 litre)	<15	≥15	—
Urea (mmol litre)	<5	≥5	—
PT ratio	<1.5	1.5–2.0	>2.0
Bilirubin (mmol litre−1)	<125	125–250	>250
Note: Scores of 9 or above have a >50% 28 day mortality