… oh the failure

1. … oh the failure Imogen Ketchley Sam Andrews

2. History • 54 yr old • Male • Retired engineer • 1999 – Decompensated Alcoholic Liver Disease • 2000 – Oesophageal Varices Banded

3. Presenting Complaint • Jaundice • Abdominal Swelling • Malaise

4. History of presenting complaint • 3/52 – gradual onset and worsening of presenting symptoms • 1/52 – decreased urine output • 1/52 – hyperpigmentation of urine • 4/7 diarrhoea (no blood, no mucus) • Stools soft and dark (on iron) • No Haemetemesis

5. Drug History • Frusemide – 40mg od • Spironolactone – 50mg od • FeSO4 – 200mg bd • Salbutamol – PRN • Multivitamins - bd

6. Family/Social History • FH: • No liver disease, malignancies or other significant conditions. • SH: • Lives with wife in Colliers Wood • Work: Chauffeur (previously an engineer) • Smoker: 40 pack yrs • Alcohol: “gave up drinking three years ago” • Previously 48 units/wk

7. On examination • CVS: • BP: 148/79 Pulse: 103 (regular) • Sats: 95% (on air) • HS: I + II + 0 • Bilateral Pitting Oedema of ankles and lower calf • Resp: • Fine creps on left and right bases

8. Examination cont. • Abdo: • Spider Naevi • Jaundiced • Gross ascites • Enlarged firm liver edge • No splenomegaly • Abdomen soft and non-tender • Bowel sounds present • Extensive caput medusa • Gynaecomastia present • Neuro: • Grade 1 encephalopathy

9. Blood Results - April 2003 • Hb: 11.5 (13 - 18 g/dL) • WBC: 6.1 (3.8 - 11x109/L) • Platelets: 83 (150 - 450x109/L) • MCV: 99.1 (78 - 96 FL)

10. U’s & E’s and LFT’s - April 2003 • Na: 137 (135 - 145 mmol/L) • K: 3.9 (3.5 - 4.7 mmol/L) • Urea: 3.3 (2.5 - 8.0 mmol/L) • Creatinine: 67 (60 -110 µmol/L) • Bilirubin: 46 (0-17 µmol/L) • Alanine Transaminase: 49 (5 - 40 IU/L) • Albumin: 30 (38-48 g/L) • Gamma GT: 227 (0-60 IU/L)

11. Blood Results on Presentation 7/10/03 • Hb – 12.3 (13-18 g/dL) • WBC – 16.6 (3.8-11x109/L) • Platelets – 77 (150-450x109/L) • MCV – 106 (78-96 FL)

12. U’s & E’s and LFT’s7/10/03 • Na – 126 (135-145 mmol/L) • K – 3.8 (3.5-4.7 mmol/L) • Urea – 15.2 (2.5-8.0 mmol/L) • Creatinine – 369 (60-110 µmol/L) • Bilirubin – 576 (0-17 µmol/L) • Alanine Transaminase – 92 (5-40 IU/L) • Albumin – 21 (38-48 g/L) • Gamma GT – 167 (0-60 IU/L)

13. Abdominal Ultrasound • Liver Cirrhosis • Ascites • Reversal of Portal Vein flow • Normal kidney’s

16. In Summary • 54 year old Male • 4 year history of Alcoholic Liver Disease • Main Problems: • Jaundice due to cirrhosis • Ascites due to decompensated liver disease • Poor renal function

17. Complications of Cirrhosis • Ascites develops late in the course; • Severe portal hypertension • Hepatic insufficiency • Poor survival: 50% mortality in 3 years • Clear indication for liver transplantation • Systemic Haemodynamics + Renal Function: • Better predictors of survival • Severe dysfunction in latest phases • Extremely poor prognosis.

18. Pathogenesis • Complex interaction between: • portal hypertension • circulatory dysfunction • endogenous vasoactive systems • renal dysfunction • Backward Theory of Ascites Formation • Overflow Theory of Ascites Formation • The Peripheral Vasodilatation Hypothesis • The Forward Theory of Ascites Formation

19. Peripheral Arterial Vasodilatation Hypothesis

20. Hepatorenal Syndrome • Occurs in the final phase of the cirrhosis. • Defined as: • ‘The development of renal failure in patients with severe liver disease in the absence of any other identifiable cause of renal pathology’ • Prevelance: • 4% of patients admitted with decompensated cirrhosis.

21. Differential Causes of Renal Failure • Diuretics • Ongoing Bacterial Infection • Spontaneous Bacterial Peritonitis • Nephrotoxic medications: • Aminoglycosides, NSAIDS, ACE inhibitors, platinum derivatives • Circulatory compromise • Variceal haemorrhage • Rapidly progressing glomerulonephritis

22. Diagnostic Criteria • Chronic/acute liver disease with adv hepatic failure and portal hypertension • Creatinine  1.5 mg/dL • or • 24hr Creatinine Clearance < 40 mL/min • No alternative renal pathology • No improvement after diuretic withdrawal and expansion of plasma volume with 1.5 L of isotonic saline • Proteinuria < 500mg/d and no ultrasonographic evidence of obstructive uropathy or parencymal renal disease. • Urine Vol < 500 ml/day • Urine Na+ < 10mEq/L • Urine osmolality greater than plasma osmolality

23. Evolution of Renal Dysfunction • Impaired renal sodium metabolism in compensated cirrhosis • Sodium retention without activation of the RAAS or sympathetic NS • Stimulation of the endogenous vasoconstrictor systems with preserved renal perfusion and GFR • Development of Type-2 HRS • Development of Type-1 HRS

24. Treatment and Management • Bed Rest and Low Sodium Diet • Paracentesis and Fluid Management • Pharmacological Treatment • Terlipressin - Vasopressin Analogue • Parvolex - N-Acetylcysteine • Pentoxyphillin - Peripheral Vasodilator • Ursodeoxycholic acid - Treat 1o biliary cirrhosis • Sando - K - Treat potassium depletion • Multi-vitamins

25. Progress • Improvement in liver function • Improvement in renal function • Although on going electrolyte disturbance • No unwanted effects observed

26. Creatinine Clearance

27. Further Management • The only effective and permanent treatment for HRS is orthotopic liver transplantation • Prognosis: • One year survival rate: 71% • Five year survival rate: 60%