Alcoholic Liver Disease

1. Alcoholic Liver Disease Hannah Leaver

2. anatomy

3. Alcohol metabolism NAD+ NADH + H+ NAD+ NADH + H+

4. ↑NADH:NAD+ ratio • Fatty liver – Steatitis • Inhibition of fatty acid β-oxidation • β-oxidation requires NAD+ • Instead of FAs being metabolised, they are re-esterified to triglycerides • TGs incorporated into VLDLs which cumulate in the liver and blood • Alcoholic Ketoacidosis • FAs that are oxidised are converted to acetylCoA • Enough NADH is generated from oxidation of ethanol and FAs so less acetylCoA enters TCA cycle • AcetylCoAenters pathway for ketone body synthesis • KBs normally absorbed from blood to muscle, but acetate is a preferred fuel

5. Lactic Acidosis • Due to ↑NADH:NAD+, pyruvate from glycolysis is converted to lactate, instead of acetylCoA • Responsible for muscle pain after drinking • ↑ lactate, causes ↓ uric acid excretion excretion, leading to hyperuricaemia • Hypoglycaemia • ↑NADH:NAD+ prevents precursors entering gluconeogenesis, causing ↓ glucose blood levels.

6. Meos pathway • Converts Ethanol to Acetaldehyde, using cytochrome P450 enzyme CYP2E1 • CYP2E1 has a higher affinity for ethanol than ADH but it’s supply is limited • In moderate drinkers – 10-20% ethanol oxidised by MEOS • Accumulation of Acetaldehyde causes free radical damage by inhibiting protective

7. Features of alcoholic liver disease • Steatohepatits • Acute alcoholic disease • Cirrhosis

8. Signs and symptoms • Acute Alcoholic Hepatitis • Sudden onset jaundice • Anorexia • Nausea • Malaise • Fever • Neutrophil leucocytosis

9. Signs and symptoms • Decompensated Chronic Liver Disease • Reduced liver cell mass • Encephalopathy • ↓ muscle and adipose body mass • Coagulopathy • Portal hypertension • Varices (GI bledding) • Ascites – due to Na+ retention as a result of ↑portal pressure and low albumin • Hypersplenism • Hepato and spleno-megaly

10. Others • Jaundice • Dupuytren’s contracture • Spider Naevi • Palmar Erythema • Ascites • Xanthelasma • Gynaecomastia • Asterrixis

11. investigations • Alcohol History • Random alcohol level • LFTs • Liver USS • Biopsy – assess degree of disease

12. complications • CV – arrhythmias, HTN, cerebrovascular disease, CHD, alcoholic cardiomyopathy, atherosclerosis • Neuro– seizures, peripheral neuropathy, associated psychiatric disorders, insomnia, alcoholic cerebellar degeneration • Muscle/skeletal – gout, osteoporosis, avascular necrosis • Endocrine – Oestrogen and testosterone metabolism disrupted – loss of body hair, testicular atrophy, spider naevi, gynaecomastia, palmar erythema. Diabetes, alcohol induced pseudo Cushings syndrome. • GI – pancreatitis, ulcers, Mallory-Weis syndrome, reflux oesophagitis, malnourishment • Resp– immune suppression and self-neglect →LRTI. Aspiration of vomit → pneumonia, bronchiectasis. • Cancers- ↑risk of oropharyngeal, laryngeal, oesophageal, liver, breast and colorectal cancer.

13. Psychosocial management • FRAMES • Feedback about patients risk • Emphasise patient’s responsibility to make changes • Advice to reduce/stop drinking • Menu of alternative strategies to drinking • Empathy • Self-efficacy of patient enhanced

14. Psychosocial management • Alcoholic abstinence • Relapse prevention • CBT • Motivational interviewing • Debt, housing and social support • AA – 12 step approach

15. Medical management • Prednisolone given for alcoholic hepatitis • Regular surveillance for HCC • Disulfiram – blocks ALDH, causing accumulation of acetaldehyde → anxiety, flushing, nausea, and headache. • Acamprosate – enhances GABA transmission and reduces glutamate surge associated with reward and addiction system

16. pr0gnosis • 5 year survival rates • 70% in abstinent patients • 35% in continued drinkers • Hepatocellular Carcinoma occurs in 15% of people with alcoholic cirrhosis

17. Useful definitions • Tolerance – when increasing administration of the drugs leads to decreasing effect • Dependence – Compulsions, impaired control, physiological withdrawal symptoms, tolerance, preoccupation and persistence. ≥3 of these features for at least 1 month. • Withdrawal – symptoms or signs occurring when the substance is stopped