Alcoholic liver disease Flashcards
What is alcoholic liver disease
liver damage caused by excess alcohol intake
Epedemiology of alcoholic liver diease
- M>F prevalence
- ArLD is the foremost health risk in developing countries and ranks third in developed countries.
- The mortality related to liver cirrhosis increases with age.
stepwise progression of alcoholic liver disease
1 alcohol related fatty liver ( steatosis)
2 alcoholic hepatitis
3 cirrhosis
2 main pathways of alcohol metabolisation
alcohol dehydrogenase and cytochrome P450 2E1
Alcohol dehydrogenase pathway
alcohol dehydrogenase (hepatic enzyme) > converts alochol to acetaldehyde > metabolised to acetate by acetaldehyde dehydrogenase
Both enzymes reduce NAD to NADH > inhibits gluconeogenesis and increase fatty acid oxidation which promotes fatty infiltration liver
cytochrome P450 2E1 pathway
generates free radicals through the oxidation of NADPH to NADP. Chronic alcohol use upregulates cytochrome P450 2E1 and produces more free radicals.
What does chronic alcohol exposure also do
activate hepatic macrophages> produce (TNF)-alpha and induce the production of reactive oxygen species in the mitochondria.
Alcoholic hepatitis pathophysiology
acetaldehyde formed from metabolism of alcohol can react with molecules in the liver, forming acetaldehyde adducts
Recognised as foreign > attacked by immune system > inflammation + hepatitis
Leads to activation of stellate cells which causes deposition of extracellular matrix proteins, generation of portal hypertension and fibrosis.
Risk factors of ALD
hep c
chronic alcohol
obesity
age
female
uk recommended alcohol consumption
14 units a week
spread evenly over 3 or more days
describe the CAGE questionnare
C – CUT DOWN? Ever thought you should?
A – ANNOYED? Do you get annoyed at others commenting on your drinking?
G – GUILTY? Ever feel guilty about drinking?
E – EYE OPENER? Ever drink in the morning to help your hangover/nerves
1st line investigations for ALD
- serum AST ; ALT
- serum alkaline phosphotase
- serum bilirubin
Other investigations for ALD
- Full blood count
- Urea & electrolytes
- Liver function tests
- C-reactive protein
- Liver ultrasound
complications of alcohol
- Alcoholic Liver Disease
- Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma
- Alcohol Dependence and Withdrawal
- Wernicke-Korsakoff Syndrome (WKS)
- Pancreatitis
- Alcoholic Cardiomyopathy
signs of liver disease
Jaundice
Hepatomegaly
hand signs
ascites
spider naevi
confusion
What hand signs may occur in ALLD
-palmar erythema
- dupuytrens contracture
What symptoms may be present in alcoholic liver disease
- malaise
- weakness
- weight loss
- abdo pain
- pruritus
What would LFT’s SHOW IN ALD
- raised bilirubin
- AST> ALT ratio
- low albumin
what would bloods show for ALD
elevated bilirubin
decrease in albumin
increase PT
increase ggt
what would fbc show for ALD
-Macrocytic non megaloblastic anaemia
- thrombocytopenia
general management of ALD
- Stop drinking alcohol permanently
- Consider a detoxication regime
- Nutritional support with vitamins
- Steroids improve short term outcomes
- Treat complications of cirrhosis
- Referral for liver transplant in severe disease however they must abstain from alcohol for 3 months prior to referral
- IV Thiamine to prevent Wernicke-Korsakoff encephalopathy
timeline of alcohol withdrawal symptoms
6-12 hours: tremor, sweating, headache, craving and anxiety
12-24 hours: hallucinations
24-48 hours: seizures
24-72 hours: “delirium tremens”
how is thiamine deficiency linked to alcohol
-thiamine is poorly absorbed in the presence of alcohol
-alcoholics tend to have poor diets and rely on the alcohol for their calories
what can thiamine deficiency cause
wernickes encephalopathy
korsakoffs syndrome
Features of Wernicke’s encephalopathy
- Confusion
- Oculomotor disturbances (disturbances of eye movements)
- Ataxia (difficulties with coordinated movements
Features of Korsakoffs syndrome
Memory impairment (retrograde and anterograde)
Behavioural changes
what is non alcoholic fatty liver disease
It is characterised by fat deposited in liver cells. These fat deposits can interfere with the functioning of the liver cells
stage of NAFLD
1-Non-alcoholic Fatty Liver Disease
2-Non-Alcoholic Steatohepatitis (NASH)
3-Fibrosis
4-Cirrhosis
Epidemiology of NAFLD
- Commonest liver disorder in industrialised western countries
- Affects around 3/4’s of all obese individuals
Aetiology of NAFL
- Obesity
- Hypertension
- Diabetes
- Hypertriglyceridemia
- Hyperlipidemia
How does insulin play a role in NAFLD
- insulin receptors are less responsive to insulin so
- excess fat is deposited in liver- less secretion of FA in blood stream
- steatosis occurs (increased synthesis of FFA from blood)
What happens as fat droplets form within hepatocytes
- hepatocytes to swell up with fat and push nuclei to edge of cell.
- Liver appears large, soft, yellow and greasy.
- Unsat FA vulnerable to ROS > form FA radicals which can react with non-radicals like O2
What does the reaction of radicals and non radicals cause?
This ultimately damages lipid membrane, leading to mitochondrial dysfunction and cell death. This generates inflammation. Inflammation + steatosis = steatohepatitis.
S + S of NAFLD
Sometimes symptoms are vague:
- Fatigue
- Malaise
Sufficient damage presents with:
- Hepatomegaly
- Pain in RUQ
- Jaundice
- Ascites
RISK FACTORS FOR nafld
Obesity
Poor diet and low activity levels
Type 2 diabetes
High cholesterol
Middle age onwards
Smoking
High blood pressure
Investigation in Non-Alcoholic Fatty Liver Disease
Serum AST and ALT: Increase in ALT and sometimes AST. (Different to alcoholic liver disease where AST>ALT)
LFT: raised bilirubin, ALP, GGT, prothrombin time, low serum albumin
FBC: anemia and thrombocytopenia due to hypersplenism
Imaging: US, CT, MRI to look for fatty infiltrates
Biopsy: used to diagnose and assess severity
- Differential diagnosis
what would liver US show for NAFLD
WILL show the diagnosis of hepatic steatosis
DDs of NAFLD
- Alcoholic liver disease
- Autoimmune hepatitis
- Hepatitis B and C
- Hemochromatosis
- PSC
- PBC
conservative management of NAFLD
- Weight loss , approx 0.5- 1.0 kg a week through diet and exercise
- limit alcohol intake
- optimise blood pressure
medical management of NAFLD
- orlisat - enteric lipase inhibitor which prevents absorption of fat
- metformin - to improve insulin sensitivity
- antihyperlipidaemics - for patients with hyperlipidaemia
Complications of NAFLD
- Ascites
- Varices and variceal haemorrhage
- Encephalopathy
- Hepatocellular carcinoma
