Alcoholic Hepatitis

Question 1

Define alcoholic hepatitis

Answer 1

Alcoholic hepatitis is a clinical syndrome due to progressive alcohol-mediated liver inflammation and injury

Question 2

Alcoholic hepatitis typically occurs at what age?

Answer 2

Alcoholic hepatitis generally refers to the acute onset of symptomatic hepatitis due to heavy alcohol consumption. It can occur at any age, but is more likely in middle-aged patients (e.g. 40-50 years) who have drank excess amounts of alcohol for many years. It is part of a wider spectrum of conditions known as alcohol-related liver disease (discussed below).

Question 3

Severe alcoholic hepatitis requiring hospital admission is associated with … short-term survival. However, the true prevalence of alcoholic hepatitis is difficult to ascertain because many mild cases can be asymptomatic.

Answer 3

Severe alcoholic hepatitis requiring hospital admission is associated with poor short-term survival. However, the true prevalence of alcoholic hepatitis is difficult to ascertain because many mild cases can be asymptomatic.

Question 4

Typically, alcohol consumption >… g per day for 15-20 years increases the risk of alcoholic hepatitis.
Approximately … g of pure ethanol is equal to 1 unit. This refers to approximately 12.5 units per day (87.5 units per week).

Answer 4

Typically, alcohol consumption >100 g per day for 15-20 years increases the risk of alcoholic hepatitis.
Approximately 8 g of pure ethanol is equal to 1 unit. This refers to approximately 12.5 units per day (87.5 units per week).

Question 5

Typically, alcohol consumption >100 g per day for …-… years increases the risk of alcoholic hepatitis.
Approximately 8 g of pure ethanol is equal to 1 unit. This refers to approximately 12.5 units per day (87.5 units per week).

Answer 5

Typically, alcohol consumption >100 g per day for 15-20 years increases the risk of alcoholic hepatitis.
Approximately 8 g of pure ethanol is equal to 1 unit. This refers to approximately 12.5 units per day (87.5 units per week).

Question 6

Alcoholic … is part of a spectrum of alcohol-related liver diseases due to the excess ingestion of alcohol.

Answer 6

Alcoholic hepatitis is part of a spectrum of alcohol-related liver diseases due to the excess ingestion of alcohol.

Question 7

Alcohol-related liver disease (ArLD) refers to a spectrum of conditions that result from alcohol-mediated liver damage. ArLD refers to what three conditions?

Answer 7

Alcoholic fatty liver: metabolism of alcohol leads to deposition of excess fat in the liver. May occur with or without inflammation.
Alcoholic hepatitis: severe inflammation of the liver. Generally refers to acute symptomatic hepatitis.
Cirrhosis: irreversible scarring of the liver associated with numerous complications

Question 8

Define alcoholic fatty liver disease

Answer 8

Alcoholic fatty liver: metabolism of alcohol leads to deposition of excess fat in the liver. May occur with or without inflammation.

Question 9

Define alcoholic hepatitis

Answer 9

Alcoholic hepatitis: severe inflammation of the liver. Generally refers to acute symptomatic hepatitis.

Question 10

Define cirrhosis

Answer 10

Cirrhosis: irreversible scarring of the liver associated with numerous complications

Question 11

Only … in 10 patients who drink excess alcohol will develop cirrhosis.

Answer 11

Only 1 in 10 patients who drink excess alcohol will develop cirrhosis.

Question 12

Patients with cirrhosis who continue to drink may develop …. on chronic liver failure or acute … cirrhosis due to alcoholic hepatitis. Alternatively, patients with only alcoholic fatty liver may develop alcoholic hepatitis. These patients are at risk of subsequently developing ….

Answer 12

Patients with cirrhosis who continue to drink may develop acute on chronic liver failure or acute decompensated cirrhosis due to alcoholic hepatitis. Alternatively, patients with only alcoholic fatty liver may develop alcoholic hepatitis. These patients are at risk of subsequently developing cirrhosis.

Question 13

… accounts for the majority of liver disease within the UK

Answer 13

Alcohol accounts for the majority of liver disease within the UK

Question 14

It is estimated that 90-100% of patients who chronically abuse alcohol develop … .… liver. Continued intake increases the risk of alcoholic steatohepatitis, which could lead to severe alcoholic hepatitis.

Answer 14

It is estimated that 90-100% of patients who chronically abuse alcohol develop alcoholic fatty liver. Continued intake increases the risk of alcoholic steatohepatitis, which could lead to severe alcoholic hepatitis.

Question 15

Severe alcoholic hepatitis is associated with a high morbidity and mortality. In those who develop severe alcoholic hepatitis and survive, relapse is estimated at …% after one year.

Answer 15

Severe alcoholic hepatitis is associated with a high morbidity and mortality. In those who develop severe alcoholic hepatitis and survive, relapse is estimated at 25% after one year.

Question 16

Alcoholic hepatitis is due to heavy alcohol consumption over many years (typically >… g per day).

Answer 16

Alcoholic hepatitis is due to heavy alcohol consumption over many years (typically >100 g per day).

Question 17

The liver is the primary site of ethanol metabolism. Ethanol and its metabolites are toxic to the liver and can cause … injury.

Answer 17

The liver is the primary site of ethanol metabolism. Ethanol and its metabolites are toxic to the liver and can cause hepatocyte injury.

Question 18

Deficiency or reduced activity of … … can lead to the flushing reaction seen in certain Asian populations when they consume alcohol. This is due to a build up of ….

Answer 18

deficiency or reduced activity of acetaldehyde dehydrogenase can lead to the flushing reaction seen in certain Asian populations when they consume alcohol. This is due to a build up of acetaldehyde.

Question 19

Alcohol metabolism:

Ethanol is taken to the liver where it is metabolised via different pathways.

… metabolism: Ethanol is converted to acetaldehyde by action of alcohol dehydrogenase. Acetaldehyde is subsequently converted to acetate by the action of acetaldehyde dehydrogenase.
… enzyme … system: Ethanol is converted to acetaldehyde by the cytochrome system. Important in the biotransformation of foreign compounds.

Answer 19

Ethanol is taken to the liver where it is metabolised via different pathways.

Oxidative metabolism: Ethanol is converted to acetaldehyde by action of alcohol dehydrogenase. Acetaldehyde is subsequently converted to acetate by the action of acetaldehyde dehydrogenase.

Microsomal enzyme oxidative system: Ethanol is converted to acetaldehyde by the cytochrome system. Important in the biotransformation of foreign compounds.

Question 20

The development of alcoholic hepatitis is multifactorial related to immunological dysfunction, disruption of the liver-gut axis with alteration in the microbiome (group of microorganisms living within the gut), increased gut permeability with translocation of bacterial … (e.g. LPS) and direct toxic effects of ethanol metabolism leading to … damage and a pro-… response.

Answer 20

The development of alcoholic hepatitis is multifactorial related to immunological dysfunction, disruption of the liver-gut axis with alteration in the microbiome (group of microorganisms living within the gut), increased gut permeability with translocation of bacterial endotoxins (e.g. LPS) and direct toxic effects of ethanol metabolism leading to oxidative damage and a pro-inflammatory response.

Question 21

A marked inflammatory response with neutrophilic infiltration and hepatocyte death is classic of alcoholic hepatitis. This inflammatory response can also lead to the activation of stellate cells, which causes deposition of extracellular matrix proteins, generation of … … and f…

Answer 21

A marked inflammatory response with neutrophilic infiltration and hepatocyte death is classic of alcoholic hepatitis. This inflammatory response can also lead to the activation of stellate cells, which causes deposition of extracellular matrix proteins, generation of portal hypertension and fibrosis.

Question 22

Alcoholic hepatitis is characterised by …., anorexia, … and tender ….

Answer 22

Alcoholic hepatitis is characterised by jaundice, anorexia, fever and tender hepatomegaly.

Question 23

Symptoms of alcoholic hepatitis

Answer 23

Jaundice
Fever: important to rule out infection
Anorexia
Abdominal pain
Abdominal distention (ascites)
Muscle wasting
Confusion: seen in encephalopathy and alcohol withdrawal

Question 24

Signs of alcoholic hepatitis

Answer 24

Jaundice
Tender hepatomegaly
Ascites
Asterixis: flapping tremor secondary to encephalopathy
Tremor: seen in alcohol withdrawal
Bruising (coagulopathy)
Stigmata of chronic liver disease: spider naevi, palmar erythema, gynaecomastia, leukonychia

Question 25

What are the stigmata of chronic liver disease?

Answer 25

Spider naevi, palmar erythema, gynaecomastia, luekonychia

Question 26

In alcoholic hepatitis, there may be features of underlying chronic liver disease/cirrhosis due to chronic alcohol ingestion. Patients may also present with features of … … (sweating, tremor, nausea, vomiting, altered mental status, agitation) or have overt signs of … (confusion, asterixis, coma).

Answer 26

There may be features of underlying chronic liver disease/cirrhosis due to chronic alcohol ingestion. Patients may also present with features of alcohol withdrawal (sweating, tremor, nausea, vomiting, altered mental status, agitation) or have overt signs of encephalopathy (confusion, asterixis, coma).

Question 27

Characteristic clinical features and laboratory findings in the context of heavy alcohol consumption is usually enough to make a diagnosis of alcoholic hepatitis. A liver …. is usually reserved for severe cases of alcoholic hepatitis. It helps to assess severity, look for underlying cirrhosis and exclude alternative causes of liver disease.

Answer 27

Characteristic clinical features and laboratory findings in the context of heavy alcohol consumption is usually enough to make a diagnosis of alcoholic hepatitis. A liver biopsy is usually reserved for severe cases of alcoholic hepatitis. It helps to assess severity, look for underlying cirrhosis and exclude alternative causes of liver disease.

Question 28

Routine tests for alcoholic hepatitis

Answer 28

Full blood count
Urea & electrolytes
Liver function tests
Bone profile
C-reactive protein
Magnesium
Coagulation (INR)
Non-invasive liver screen (see below)
Liver ultrasound
\+/- septic screen (e.g. blood cultures, urines, ascitic cultures, chest x-ray)

Question 29

Any patient with acute hepatitis requires a full liver screen including a liver ultrasound with …. to assess the architecture of the liver and exclude portal vein thrombosis or …-Chiari (i.e. hepatic vein thrombosis).

Answer 29

Any patient with acute hepatitis requires a full liver screen including a liver ultrasound with dopplers to assess the architecture of the liver and exclude portal vein thrombosis or Budd-Chiari (i.e. hepatic vein thrombosis).

Question 30

What is a liver screen?

Answer 30

A liver screen refers to a series of non-invasive investigations to determine possible causes of liver disease (e.g. autoimmune hepatitis, viral hepatitis). In alcoholic hepatitis, it is essential to exclude other causes of acute hepatitis.

Question 31

Laboratory features suggestive of alcoholic hepatitis include:

Moderately elevated … (< 300 IU/L)
…/… ratio >2 (other liver diseases rarely cause this ratio)
Elevated … (usually > 86 umol/L)
… gamma-glutamyl transferase (GGT)
Elevated … count (typically < 20.0 x10^9/L)
… INR (usually due to impaired synthesis of coagulation factors with severe inflammation)

Answer 31

Moderately elevated transaminases (< 300 IU/L)
AST/ALT ratio >2 (other liver diseases rarely cause this ratio)
Elevated bilirubin (usually > 86 umol/L)
Elevated gamma-glutamyl transferase (GGT)
Elevated neutrophil count (typically < 20.0 x10^9/L)
Elevated INR (usually due to impaired synthesis of coagulation factors with severe inflammation)

Question 32

: an AST/ALT ratio > 2 is secondary to deficiency of pyridoxal 5’-phosphate in hepatocytes, which is needed as a cofactor for ALT activity. This is low in patients who chronically .. …

Answer 32

AST/ALT ratio > 2 is secondary to deficiency of pyridoxal 5’-phosphate in hepatocytes, which is needed as a cofactor for ALT activity. This is low in patients who chronically abuse alcohol.

Question 33

Liver biopsy - involves taking a sample of hepatic tissue to assess the underlying architecture. It can be completed … or …. The latter is usually preferred in patients with deranged clotting, significantly elevated bilirubin or ascites.

Answer 33

liver biopsy involves taking a sample of hepatic tissue to assess the underlying architecture. It can be completed percutaneously or transjugular. The latter is usually preferred in patients with deranged clotting, significantly elevated bilirubin or ascites.

Question 34

Liver biopsy potential findings

Answer 34

Findings at biopsy may be non-specific, but features can include:

Steatosis (fat in the liver)
Neutrophil infiltration
Hepatocyte ballooning
Fibrosis
Cholestasis
Mallory-Denk bodies: eosinophilic accumulations of proteins within the cytoplasms of hepatocytes. No pathological role in disease but a marker of alcohol-induced liver disease.

Question 35

What are Mallory-Denk bodies?

Answer 35

eosinophilic accumulations of proteins within the cytoplasms of hepatocytes. No pathological role in disease but a marker of alcohol-induced liver disease.

Question 36

The clinical and laboratory features of alcoholic hepatitis are similar to … cirrhosis

Answer 36

The clinical and laboratory features of alcoholic hepatitis are similar to decompensated cirrhosis. Decompensated cirrhosis occurs when the liver is unable to carry out its normal function leading to ascites, encephalopathy, jaundice, coagulopathy and GI bleeding. All of these features can also occur in severe alcoholic hepatitis with/without cirrhosis.

Question 37

Severity of alcoholic hepatitis:

Answer 37

The Maddrey discriminant function (DF), Model for End-stage Liver Disease (MELD) and Glasgow alcoholic hepatitis score (GAH) can all be used to assess the severity of alcoholic hepatitis. These scores are predominantly based on laboratory parameters.

Question 38

Maddrey discriminant function

Answer 38

The DF score has been traditionally use to assess the severity of alcoholic hepatitis. It is based on serum bilirubin and prothrombin time.

DF = (4.6 x [prothrombin time (sec) - control prothrombin time (sec)]) + (serum bilirubin/17.1)

Serum bilirubin (umol/L)

Severe alcoholic hepatitis is defined as a DF score ≥ 32. The 28 day (one month) mortality among patients with a DF ≥32 ranges from 25-45%. Patients with a score < 32 have mild-to-moderate alcoholic hepatitis, which has a <10% mortality at 1-3 months.

Question 39

Glasgow alcoholic hepatitis score

Answer 39

The GAH is a newer scoring system, which also predicts mortality among patients with alcoholic hepatitis. It is a slightly more complex score based on age, white blood cell count, urea, bilirubin and prothrombin time.

A score ≥ 9 is consistent with severe alcoholic hepatitis and associated with a poor 28-day and 84-day survival (46% and 40%, respectively).

Question 40

Management of alcoholic hepatitis - overview

Answer 40

Management is largely supportive with nutritional support, haemodynamic support and treating alcohol withdrawal.

Question 41

The key principles for all patients with alcoholic hepatitis include:

Managing … …:
Alcohol … : important on discharge and follow-up
H….:
Nutrition: dietitian input, … threshold for NG feeding and vitamin supplementation (i.e. high dose Pabrinex).
… treatment of infections:
Pharmacological therapy: patients with severe alcoholic hepatitis (DF ≥…, GAH ≥…) can be treated with pharmacological therapies including …. (e.g 40 mg prednisolone for 28 days) or newer agents as part of a clinical trial.

Answer 41

Managing alcohol withdrawal: CIWA scoring, benzodiazepines, alcohol team input
Alcohol cessation: important on discharge and follow-up
Hydration: cautious fluid resuscitation, especially in patients with acute kidney injury. Consider the use of albumin to reduce the risk of worsening ascites, hyponatraemia and precipitating GI bleeding.
Nutrition: dietitian input, low threshold for NG feeding and vitamin supplementation (i.e. high dose Pabrinex). The majority of patients with severe alcoholic hepatitis have evidence of malnutrition on admission.
Aggressive treatment of infections: patients with alcoholic hepatitis are at increased risk of life-threatening infections due to immune dysfunction. Investigations (e.g. blood cultures, chest radiograph, ascites culture) should be completed in any patient with suspected infection. Antifungals may be needed in addition to antibacterials in severe cases.
Pharmacological therapy: patients with severe alcoholic hepatitis (DF ≥32, GAH ≥9) can be treated with pharmacological therapies including corticosteroids (e.g 40 mg prednisolone for 28 days) or newer agents as part of a clinical trial.

Question 42

Patients with severe alcoholic hepatitis (DF ≥…, GAH ≥…) can be treated with pharmacological therapies including corticosteroids (e.g 40 mg prednisolone for 28 days) or newer agents as part of a clinical trial.

Answer 42

patients with severe alcoholic hepatitis (DF ≥32, GAH ≥9) can be treated with pharmacological therapies including corticosteroids (e.g 40 mg prednisolone for 28 days) or newer agents as part of a clinical trial.

Question 43

Mild to moderate alcoholic hepatitis - management

Answer 43

Patients with mild-to-moderate alcoholic hepatitis (DF <32, GAH <9) are usually managed conservatively with good nutrition, attention to adequate hydration and managing alcohol withdrawal.

It is important to screen for underlying chronic liver disease, but the mainstay of treatment is alcohol cessation.

Question 44

Patients with severe alcoholic hepatitis (DF ≥32, GAH ≥9) can be extremely unwell with multi-organ failure and require referral to an intensive care unit (ICU). It is important to manage complications as they arise, which can include infections, …. bleeding, …. or …. … injury.

Answer 44

Patients with severe alcoholic hepatitis (DF ≥32, GAH ≥9) can be extremely unwell with multi-organ failure and require referral to an intensive care unit (ICU). It is important to manage complications as they arise, which can include infections, GI bleeding, encephalopathy or acute kidney injury.

Question 45

Patients with severe alcoholic hepatitis should be considered for …. therapy.

Answer 45

Patients with severe alcoholic hepatitis should be considered for corticosteroid therapy. The use of corticosteroids should be guided by hepatologists. They are typically given as a 28-day course of prednisolone at 40 mg daily with a short taper at the end.

Question 46

The use of corticosteroids in severe alcoholic hepatitis should be guided by hepatologists. They are typically given as a 28-day course of prednisolone at … mg daily with a short taper at the end. If there is no significant improvement within 7 days of starting steroids cessation of treatment should be considered because of the risk associated with systemic steroids. The Lille score can be used to identify patients not responding to steroids.

Answer 46

The use of corticosteroids should be guided by hepatologists. They are typically given as a 28-day course of prednisolone at 40 mg daily with a short taper at the end. If there is no significant improvement within 7 days of starting steroids cessation of treatment should be considered because of the risk associated with systemic steroids. The Lille score can be used to identify patients not responding to steroids.

Question 47

Due to the complex pathological mechanisms involved in alcoholic hepatitis, a number of treatment options are being explored for the treatment of severe cases. Examples include:

Answer 47

Anti-IL-22: felt to be anti-inflammatory and induce hepatic regeneration
G-CSF (filgastrim): increases neutrophils and stimulates hepatic regeneration
IL-1 receptor antagonist (Anakinra)
Faecal transplant: alters the gut microbiome

Patients presenting with severe alcoholic hepatitis may be eligible to enter into a clinical trial at a tertiary hepatology unit or transplant centre.

Question 48

Liver transplant for alcoholic hepatitis ? Is it possible

Answer 48

In the UK, alcoholic hepatitis is not an indication for liver transplantation. In fact, due to the ‘6-month rule’, which means patients need to be abstinent from alcohol for 6 months prior to transplantation, alcoholic hepatitis is a contraindication. Nevertheless, the interest in transplantation for severe alcoholic hepatitis is increasing because of the effectiveness of therapy.

Question 49

Severe alcoholic hepatitis is associated with a … …-term survival.

Answer 49

Severe alcoholic hepatitis is associated with a poor short-term survival.

Question 50

Patients with alcoholic hepatitis and underlying cirrhosis may develop severe decompensation with associated … …. This is typically referred to as acute on chronic liver failure that is associated with a high ….

Answer 50

Patients with alcoholic hepatitis and underlying cirrhosis may develop severe decompensation with associated organ failure. This is typically referred to as acute on chronic liver failure that is associated with a high mortality.

Question 51

During the course of alcoholic hepatitis, particularly severe cases, patients are at increased risk of numerous complications.

Answer 51

Hepatic encephalopathy
Systemic infection: including spontaneous bacterial peritonitis
GI bleeding: variceal bleeding (oesophageal/rectal)
Coagulopathy and thrombocytopaenia
Ascites: can develop even in the absence of decompensated cirrhosis and portal hypertension
Multi-organ failure