Towards

unbounded
Alcohol related liver disease thinking.

Prof. Hossam GHONEIM

Whatis the definition ofAlcoholism?
Howcommonis Alcoholism? (Males, Females)
HowmuchAlcohol is toomuch?
Whatscreening tools do weuse?

“In the absence of a clear understanding of factors influencing liver

damage, no safe upper limit for alcohol consumption can be
proposed.”
- Robbins
Revised Alcohol Guidelines
Whatare the long term effects of alcoholism?
Alcohol related Liver Disease
• More common in Men Three main conditions
a. Lifetime prevalence
10% males, 4% 1. Hepatic Steatosis
females
• 40s-50s 2. Alcoholic Hepatitis
• 50% of people who drink
heavily have an abnormal 3. Alcohol related
liver Cirrhosis
a. 10-20% cirrhosis
 50%of alcohol
abusers

>90% of heavy 10-35% of

drinkers patients with
(varying degrees) steatosis

8-20% of
alcohol abusers
Carcinoma: 10-20%
of cirrhotic patients
(from alcohol)
 Rising Incidence of Alcohol Related Liver Disease

Williams, Roger et al. "Addressing Liver Disease In The UK: A Blueprint For Attaining Excellence In Health Care And Reducing Premature Mortality
From Lifestyle Issues Of Excess Consumption Of Alcohol, Obesity, And Viral Hepatitis". The Lancet 384.9958 (2014): 1953-1997. Web.
CASE 1
Jeremy, a 42 year old manpresents tohis GP
● Right Upper quadrant pain… ● Lab tests normal except
nothing else ○ Increased MCV
● Obesity- BMI of 32 ○ Increased GGT (500)
● T2DM ○ Increased AST (100), ALT
● Alcoholism- drinks over 40 units (70)
per week
● CAGE- 4 points Refer to Royal Free Hepatology
● O/E- hepatomegaly department- what tests are they
going to do?
Pathology: Hepatic Steatosis
Management
● Alcohol is toxic- when drunk in
excess its metabolism becomes
prioritised
● Stop drinking alcohol
● Cellular energy diverted away from ○ Refer to a specialist CNS nurse
other essential metabolic pathways
e.g. fat metabolism
● Diet control, inc. surveillance of
● Fat accumulates in cytoplasm of liver
cells HbA1c and Lipid profile analysis

● Liver becomes a large greasy organ

● Understand the effects of alcohol.
FATTY CHANGE IS REVERSIBLE!
Case 2
5 Years later: Jeremy, nowa 47 year
Signs O/E
old manpresents to A&E with • Tender hepatomegaly
Jaundice, D&V, Abdo pain and
confusion Observations:
• Increased temperature (37.7)
• High pulse (110)
History
• High RR (25)
• Rapid onset of jaundice
• BP 120/80
• Rt upper quadrant pain
• Dx steatohepatitis 5 years ago
• PMH: DM, Obesity
• Still drinking over 35 units a week
• SH: partner left him due to alcohol
Investigations
• FBC • Microscopy and culture of blood, urine
• ↑WCC, ↑MCV , ↓Platelet count and ascites

• U&E • Ultrasound of liver and biliary tree

• Hyponatraemia
• ↑ serum creatinine • Liver biopsy (not always required)

• Liver biochemistry Most of diagnosis made on clinical

• ↑ALP and ↑AST - disproportionate presentation and liver biochemistry
rise in AST ( AST:ALT ratio >2)
• ↑Bilirubin (300-500 umol/l)
• Low serum albumin
• ↑Prothrombin time and ↑INR
“1 yr after admission for Alcoholic Hepatitis,
40% are dead”
- Oxford Handbook
 Management
Severe alcoholic hepatitis requires admittance and supportive treatment
● Screen for infections +/- ascitic tap and treat for Spontaenous Bacterial Peritonitis

● Stop alcohol consumption (Chlordiazepoxide oral or Lorazepam IM for withdrawal)

● Vitamins: Maddrey’s Discriminant Function >32=

○ Vitamin K 10mg/d IV for 3 days significant disease with a poor
prognosis
○ Thiamine 100mg/d PO
4.6 x (Prothrombin time- control
● Optimise nutrition ( may need NG tube) time) + Bilirubin ug/dL
○ Give >1.2 g/kg/d of protein to prevent ….

● Prednisolone 40mg/d for 5 days tapered over 3 weeks if Maddrey score >32
“80% of patients with alcoholic hepatitis will
go on to develop cirrhosis if drinking
continues”
- Oxford Handbook
Pathology: Alcoholic Hepatitis
• Unclear, but possibly:

• Acetaldehyde (affects lipids by peroxidation and binds proteins →

cytoskeletal & membrane function↓)

• Alcohol (mitochondrial function↓, membrane fluidity↓, cytoskeleton

disruption - Mallory-Denk bodies)

• Reactive Oxygen Species (membrane & protein damage, exacerbated

by neutrophils in hepatocyte necrosis)

• Cytokine-mediated Inflammation (cell injury is a major feature, mainly

TNF stimulated by ROS & gut microbial products)
Case 3: Cirrhosis
6 Years Later: Jeremy, nowa 53 year old manpresents to A&E with
haematemesis

● Increasing abdo distension, increasing somnolence, haematemesis,

confusion
● “Doesn’t drink”

● Cachectic, protuberant abdomen, asterixes, track marks, spider naevi

(42), breast tissue palpable, shifting dullness, palpable spleen, kaput
medusae
● BP-90/60 HR-120 T-36.8 RR-24
 Investigations: Bloods
Hematocrit 25% (high) Alcohol 110 mg/dL

WBC 10 x 109/L Ammonia 150 µmol/L

Prothrombin time 15.8 seconds Amylase 52 iu/dL

(pro-longed)
Lipase 64 iu/L
AST 190 iu/L (very
high) HBsAg negative

ALT 65 iu/L (high) Anti-HBc total - negative

ALP 170 iu/L (high) Anti-HCV positive

Gamma-glutamyl transpeptidase 1510 iu/L (high)

Total bilirubin 74 µmol/L (high)

Total protein 48 g/L (low)

Albumin 28 g/L (low)

Investigations
Endoscopy Imaging
● Dilated blood vessels: distal ● Ultrasound
oesophagus & proximal ● MRI
stomach
Liver biopsy
Abdominal paracentesis ● Confirms clinical diagnosis
● Clear golden yellow fluid
● Total Protein 1.7 g/dL, Albumin
1.0 g/dL, WCC 180/mm3 (10%
neutrophils, 10% lymphocytes)
● MC&S
Management
1. Treat underlying cause

• abstinence & nutrition

2. Manage complications
• ascitic tap, treat encephalopathy, drugs for portal
hypertension
Jeremy’s Self Discharge
6 months later: found unconscious in street
• Anorexia & weight loss
• CT: 6cm homogenous liver mass, Serum Alpha-Fetoprotein: 2500
ng/mL

Death
• post-mortem: cirrhotic liver with a large yellow-green mass and
several smaller irregular masses

• 10-20% of cirrhotic patients develop carcinoma

Take HomeMessages
1. Don’t drink to excess!

2. Try to intervene as soon as possible

3. Identify those at risk with good history taking

4. Be aware that these patients are very ill and need to be

treated acutely
5. Holistic management of patients
Thanks!