Alcoholic Liver Disease Flashcards
Alcoholic Liver Disease
Alcoholic liver disease
The STOPAH study (see reference) compared the two common treatments for alcoholic hepatitis, pentoxyphylline and prednisolone. It showed that prednisolone improved survival at 28 days and that pentoxyphylline did not improve outcomes.
Reference:
Thursz et al. Prednisolone or Pentoxifylline for Alcoholic Hepatitis. NEJM. 2015.
Alcoholic Hepatitis and Steroids - Example Question
A 47-year-old lady is admitted to hospital with a 5-day history of abdominal pain, fever, anorexia, and malaise. Her past medical history is remarkable for depression and there is a long history of alcohol excess.
On examination, the patient is jaundiced and unwell. Her temperature is 37.9ºC, her pulse is 106bpm and her blood pressure is 97/61mmHg. Her chest is clear but her abdomen is distended. There is right upper quadrant tenderness on palpation of the abdomen without overt peritonism, and evidence of shifting dullness on percussion. A hepatic bruit is also present.
Her bloods are as follows:
Hb 99 g/l Na+ 128 mmol/l Bilirubin 92 µmol/l
Platelets 113 * 109/l K+ 4.8 mmol/l ALP 138 u/l
WBC 11.2 * 109/l Urea 7.9 mmol/l AST 168 u/l
Neuts 8.7 * 109/l Creatinine 103 µmol/l ALT 82 u/l
Lymphs 2.3 * 109/l γGT 208 u/l
INR 1.8 Albumin 28 g/l
She is started on vitamin supplementation, nutritional support, and oral prednisone.
After 7 days the patient is re-assessed. She remains significantly jaundiced and has become progressively more confused. Her repeat blood tests show:
Na+ 131 mmol/l Bilirubin 127 µmol/l K+ 4.2 mmol/l ALP 172 u/l Urea 11.2 mmol/l ALT 76 u/l Creatinine 134 µmol/l γGT 168 u/l INR 2.3 Albumin 21 g/l
Her Lille score is calculated as 0.52. How should her treatment be altered?
Discontinue prednisolone and add etanercept Discontinue prednisolone and add pentoxifylline Continue prednisolone and add pentoxifylline > Discontinue prednisolone and continue supportive care Palliate
Prednisolone 40mg for 28 days has been shown to increase survival in patients with severe alcoholic hepatitis. However, response to steroid treatment should be re-evaluated at 7 days, as not all patient’s respond and continuing immunosuppressive treatment in patients who are unlikely to benefit may prove deleterious.
As a rule of thumb, an increase in bilirubin over the first 7-days indicates non-response. The Lille score is a more formal method of assessment that takes into account a range of demographic and laboratory values to give a more nuanced evaluation. A Lille score of > 0.45 signifies the failure of prednisolone and justifies its discontinuation. The 6-month survival rate for this group of patients is approximately 25%, so supportive treatment should be continued.
Switching non-responders to pentoxifylline has not been shown to be beneficial.
The inflammatory cytokine TNF-α is thought to be key to the pathophysiology of acute alcoholic hepatitis and several studies have investigated the efficacy of anti-TNF-α therapies in this setting. Unfortunately, a number of studies have shown that infliximab and etanercept are associated with higher mortality rates at 2 and 6 months, largely secondary to the development of acute infection. As a result, these agents are not recommended for use in alcoholic hepatitis.
Alcoholic Hepatitis, Maddrey Discriminant Score and Mx: Example Question
A 48-year-old gentleman presents to the Emergency Department with a 3-day history of fever, nausea, anorexia, and malaise. His past medical history is unremarkable but he admits to drinking heavily for many years. He estimates his present consumption at half-bottle of vodka on 5-6 days of the week.
Examination reveals an unwell and generally tremulous middle-aged man. His temperature is 38.2ºC, his pulse is 113bpm and his blood pressure is 95/57mmHg. Scleral icterus is clearly evident, even from the end of the bed. His abdomen is mildly distended but soft. There is tender hepatomegaly and a bruit is audible on auscultation of the right upper quadrant.
His blood tests are as follows:
Hb 97 g/l Na+ 142 mmol/l Bilirubin 173 µmol/l
MCV 103.1 fl K+ 3.1 mmol/l ALP 184 u/l
Platelets 46 * 109/l Urea 2.1 mmol/l ALT 109 u/l
WBC 15.1 * 109/l Creatinine 51 µmol/l AST 276 u/l
Neuts 13.9 * 109/l γGT 412 u/l
Lymphs 0.6 * 109/l Albumin 24 g/l
INR 1.4
You calculate his Maddrey Discriminant Score (MDS) as 37.7. Given the likely diagnosis, which of the following is the most appropriate treatment strategy?
Pabrinex, nutritional support, prednisolone and pentoxifylline Pabrinex, nutritional support and pentoxifylline Pabrinex and nutritional support only > Pabrinex, nutritional support and prednisolone Pabrinex, nutritional support and N-acetylcysteine
The patient has presented with alcoholic hepatitis, as evidenced by the history of excessive alcohol consumption, macrocytosis, and AST:ALT ratio >2:1. Alcoholic hepatitis almost always presents with clinical jaundice and the presence of a hepatic bruit is particularly suggestive.
An MDS of > 32 is associated with 50% mortality within 2 months and indicates the need for treatment. All patients should receive vitamin replenishment and nutritional support. Patients with alcoholic hepatitis should be encouraged to consume >2000 kcal per day with supplementation via NG feeding if necessary.
Prednisolone has been shown in meta-analyses to confer a significant reduction in 28-day mortality in patients with an MDS >32 or hepatic encephalopathy, however, there was no demonstrable benefit at 90 days or at one year. Pentoxifylline may reduce mortality in the presence of hepatorenal syndrome (HRS) but evidence of efficacy in patients without HRS is lacking.
Combination therapy with prednisolone and pentoxifylline confers no additional benefit over treatment with prednisolone alone, whilst the use of N-acetylcysteine as monotherapy in alcoholic hepatitis is not recommended. In one randomised controlled trial, combination therapy with prednisolone and N-acetylcysteine was shown to be superior to prednisolone monotherapy in reducing mortality at 28 days; largely due to a reduction in the incidence of HRS and superimposed infection.
Alcoholic Hepatitis - Mx to improve Survival - Example Question
A 55-year-old man is seen in the gastroenterology clinic for follow-up of his alcoholic liver disease. He states he has not had an alcoholic drink for many months but following some bad news at work, he went on a binge two days ago and is now feeling very unwell.
On examination he appears mildly jaundiced and clammy. His heart rate is 119 beats per minute and his blood pressure is 105/66 mmHg. He is afebrile. Cardiovascular and respiratory examinations are normal. Examination of the abdomen reveals a tender 2cm liver edge and shifting dullness.
His blood tests are as follows:
Hb 105 g/l Na+ 132 mmol/l Bilirubin 33 µmol/l
Platelets 167 * 109/l K+ 4.4 mmol/l ALP 220 u/l
WBC 10.5 * 109/l Urea 7 mmol/l AST 137 u/l
Neuts 5.7 * 109/l Creatinine 105 µmol/l γGT 505 u/l
INR 1.9 CRP 47 mg/l Albumin 29 g/l
He is diagnosed with alcoholic hepatitis and admitted to hospital.
Which treatment is most likely to improve his survival?
Antibiotics Chlordiazepoxide Human albumin solution Pentoxyphylline > Prednisolone
This gentleman has no evidence of infection and so antibiotics are not indicated at this point.
Although this gentleman claims to have been abstinent prior to his recent alcohol binge, he should be monitored for signs of withdrawal and given chlordiazepoxide if indicated.
Human albumin solution is useful for rehydration in patients with liver disease, particularly in cases of hepatorenal syndrome (HRS). However, this patient does not meet the criteria for HRS and should be rehydrated with crystalloid in the first instance.
Alcoholic Liver Disease - Example Question
A 44-year-old gentleman is referred to the gastroenterology clinic with deranged LFTs. His only symptom is mild fatigue, which does not interfere with his daily activities. He denies itch, nausea, vomiting and recent foreign travel.
His past medical history is remarkable for depression, which is controlled with 20mg citalopram once daily. He has been taking this for the last 6 years. He works long hours as a pastry chef and often eats at unusual times. He admits to drinking a ‘glass of wine or two most nights’ but denies any intravenous drug use.
Examination reveals an overweight gentleman with no obvious jaundice. His abdomen is soft with mild right upper quadrant tenderness on deep palpation. There is no obvious hepatomegaly. Bowel sounds are present.
A set of blood tests are requested:
Hb 143 g/l Na+ 142 mmol/l Bilirubin 24 µmol/l
Platelets 317* 109/l K+ 3.9 mmol/l ALP 176 u/l
WBC 6.4* 109/l Urea 7.1 mmol/l AST 225 u/l
Neuts 4.2* 109/l Creatinine 109 µmol/l ALT 112 u/l
Lymphs 1.7* 109/l γGT 108 u/l
Eosin 0.1* 109/l Albumin 37 g/l
What is the most likely diagnosis?
Haemochromatosis Non-alcoholic fatty liver disease (NAFLD) Cholelithiasis Viral hepatitis > Alcoholic liver disease (ALD)
The patient is overweight and his occupation offers him access to a number of rich foods, making NAFLD a plausible diagnosis. However, closer inspection of his LFTs reveals that the patient’s AST:ALT ratio is > 2:1 and his γGT is double the upper limit of normal. This is more in keeping with ALD, and this is the correct answer.
Haemochromatosis is a common cause of liver dysfunction, but there is no history of skin pigmentation, arthralgia or diabetes mellitus. There is nothing in the history to suggest viral hepatitis whilst one would expect cholelithiasis to present with episodic, severe right upper quadrant pain rather than an incidental finding of deranged LFTs.
AST/ALT Ratio in Liver Disease
The AST/ALT ratio can give clues to the cause of hepatitis. If the ratio is greater than 2 it is suggestive of alcoholic liver disease whereas less than 1 suggests non-alcoholic liver disease e.g. autoimmune hep
Alcoholic liver disease (ALD) = AST:ALT ratio is > 2:1 γGT also elevated significantly
Alcoholic Hepatitis and Prednisolone
Prednisolone 40mg for 28 days has been shown to increase survival in patients with severe alcoholic hepatitis. However, response to steroid treatment should be re-evaluated at 7 days, as not all patient’s respond and continuing immunosuppressive treatment in patients who are unlikely to benefit may prove deleterious.
As a rule of thumb, an increase in bilirubin over the first 7-days indicates non-response. The Lille score is a more formal method of assessment that takes into account a range of demographic and laboratory values to give a more nuanced evaluation. A Lille score of > 0.45 signifies the failure of prednisolone and justifies its discontinuation. The 6-month survival rate for this group of patients is approximately 25%, so supportive treatment should be continued.
Prednisolone has been shown in meta-analyses to confer a significant reduction in 28-day mortality in patients with an MDS >32 or hepatic encephalopathy, however, there was no demonstrable benefit at 90 days or at one year.
Alcoholic Hepatitis Typical Presentation
The patient has presented with alcoholic hepatitis, as evidenced by the history of excessive alcohol consumption, macrocytosis, and AST:ALT ratio >2:1. Alcoholic hepatitis almost always presents with clinical jaundice and the presence of a hepatic bruit is particularly suggestive.
AST: ALT (Assy Alchy)
Role of Pentoxifylline
Pentoxifylline may reduce mortality in the presence of hepatorenal syndrome (HRS) but evidence of efficacy in patients without HRS is lacking.
Combination therapy with prednisolone and pentoxifylline confers no additional benefit over treatment with prednisolone alone.
Switching non-responders to pentoxifylline has not been shown to be beneficial.
Alcoholic Hepatitis - Mx as well as Steroids
An MDS of > 32 is associated with 50% mortality within 2 months and indicates the need for treatment.
All patients should receive vitamin replenishment and nutritional support.
Patients with alcoholic hepatitis should be encouraged to consume >2000 kcal per day with supplementation via NG feeding if necessary.
