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Alcoholic Liver Disease and Terlipressin use in Variceal bleeds

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Alcoholic Liver Disease and Terlipressin use in Variceal bleeds

  1. 1. Alcoholic Liver Disease Lara Gibbs F1 ACUA
  2. 2. Objectives • Case • Alcoholic liver disease • Varices • Terlipressin – evidence base • Summary and conclusions
  3. 3. Case Study • Mrs A, 55 • Background:  Known ALD  Discharged from CGH 2/52 ago with decompensated disease  Still drinking (6 – 7 glasses wine/day)  Uncontrolled extensive psoriasis
  4. 4. Case: History Admitted GRH Presenting Complaint: • Found collapsed at home by friend – covered in melaena • Nauseated but no vomiting • Alcohol – still problem • Numerous previous admissions for detox and decompensated ALD, ascitic drains, LRTI, prev OGD: no varices.
  5. 5. Case: Examination HR 110, BP 128/90, Sats 96% on air • General: Uncomfortable and distressed, extensive psoriasis (all limbs, chest, abdomen, genitalia) • Hands: Clubbing • Eyes: No jaundice • Chest: Spider naevi • Abdomen: Caput medusae, ascites, tender epigatrium, no organomegaly • PR: bleeding perianal psoriatic lesions, melaena
  6. 6. Case: Blood Results Date Hb WCC Neut PT APTT Na Urea Creat 2/10/9 5.0 14.5 11.2 18 32.4 135 13.6 59 12/10/ 9 10.6 7.6 5.43 17 37.9 135 3.8 62
  7. 7. Case: Impression • Variceal bleed • Possible decompensated ALD • Need to rule out sepsis • SBP • Chest
  8. 8. Case: Management • ABC • Bloods and Cultures, Ascitic tap, CXR • Blood 4 units • Terlipressin • Booked urgent OGD • Ascitic Tap – later grew lactobacillus lacti (unexpected organism) • IV Tazocin • B vitamins
  9. 9. Case: Admission • OGD: • Oesophagus : 2 bleeding varices – banded • Stomach: Full of blood, no varices • Duodenum: No varices • Ascitic tap: WCC > 500 • IV Tazocin • Developed pulmonary oedema: • Oxygen, Spironolactone, careful fluid balance, • Developed LRTI • Plan for ascitic drain in near future • Home with B vitamins, SBP prophylactic Cipro
  10. 10. Alcoholic Liver Disease • Fatty liver – macrovesicular steatosis (dose related) • Alcoholic hepatitis – steatonecrosis (not dose related) • Cirrhosis – fibrosis and altered liver architecture, 5 year survival 50% If drinking continues • Encephalopathy – build up of glutamine and fluid shift
  11. 11. ALD: Signs • Clubbing • Leuconychia • Splinter haemorrhages • Palmar erythema • Dupuytren’s contractacture • Jaundice • Spider naevi • Gynaecomastia • Caput medusae • Ascites • Large or small liver • Splenomegaly, • Testicular atrophy • Loss of body hair
  12. 12. ALD: Complications • Deranged clotting (INR) • Hypo-albuminaemia • Sepsis • Spontaneous bacterial peritonitis – 10 – 30% of hospitalised patients with ascites • Hypoglycaemia • Portal hypertension – porto-systemic anastomoses – varices – bleeding – anaemia • Hepatorenal syndrome – 18% cirrhotic patients with ascites • HRS Type I – rapid progression – med survival 2 weeks • HRS Type II – steady progression – med survival 6 months • Treatment – Albumin and Terlipressin (arterial vasocontrictors)
  13. 13. Decompensated ALD Causes • Infection – any source • Bleeding (varices) • Alcohol – continued excess drinking • Iatrogenic – drugs
  14. 14. Bleeding varices Mortality 20 – 50%1 Rockall score • Prediction of bleeding and mortality • Based on findings pre and post endoscopy Child-Pugh • Grades severity of cirrhosis and risk of variceal bleeding • Based on blood results and presence or absence of ascites and encephalopathy
  15. 15. Terlipressin • Synthetic Vasopressin (Anti-diuretic hormone). Used in variceal bleeds and hepatorenal syndrome • Mechanism of action: Slowly cleaved to vasopressin + intrinsic vasoconstrictor effect of its own • Dose: 2mg IV followed by 1 – 2mg every 4 – 6 hours, until bleeding is controlled, for up to 72 hours • Contraindications: Vascular disease (esp coronaries), Chronic nephritis. (Caution in asthma, epilepsy, migraine, renal impairment, pregnancy) • Side Effects: Fluid retention, pallor, tremor, headache, nausea, vomiting, coronary artery constriction, peripheral ischaemia, hypersensitivity reactions • Alternatives/additional therapies: Vasopressin, Octreotide, Sclerotherapy, Balloon tamponade, Band ligation, TIPS
  16. 16. Terlipressin: Evidence Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database of Systematic Reviews 2003 (Reviewed 2009)
  17. 17. Cochrane Systematic Review • Objective: “To determine if treatment with terlipressin improves outcome in acute oesophageal variceal haemorrhage and is safe” • Methods: selected RCTs comparing: a) Placebo or no treatment, b) Balloon tamponade, c) Endoscopic treatment, d) Octreotide, e) Somatostatin and f) Vasopressin, … in the setting of acute variceal haemorrhage.
  18. 18. Cochrane Review Outcomes • Primary outcome: Mortality • Secondary outcomes: • Failure of initial haemostasis, • Rebleeding, • Procedures required for uncontrolled bleeding or rebleeding, • Transfusion requirements • Length of hospitalisation
  19. 19. Cochrane Review Conclusions Terlipressin Comparison Studies Results/Conclusion Placebo 7 (5) Terlipressin reduced mortality RR 0.66 (0.49 – 0.88) Somatostatin 3 (2) No statistically significant difference in any outcomes Endoscopic Treatment 1 Vasopressin, Octreotide, Balloon tamponade Few, poor quality
  20. 20. Terlipressin V Placebo: Conclusions • Terlipressin reduced all cause mortality Vs Placebo (no statistical hetergeneity) • All studies found reduced risk of failed initial haemostasis (BUT there was statistical heterogeneity between studies) • Blood transfusion requirements were lower with terlipressin than placebo in all studies • No difference between re-bleeding rates between terlipressin and placebo • Reduced number of endoscopic procedures needed • Number need to treat 8.3
  21. 21. Flaws in the data • Few good quality large RCTs comparing main competitors of Terlipressin • Time until start of treatment and duration of treatment differed between studies • Study protocols differed – some automatically offered sclerotherapy or balloon tamponade on admission – compared Terlipressin + sclerotherapy to Sclerotherapy alone • Cost effectiveness analysis
  22. 22. Conclusions • Terlipressin currently the only treatment modality that can be administered by non specialised personnel, quickly • Different bioavailability means it can be given in IV boluses rather than by infusion • Much lower incidence of severe side effects than vasopressin • No other single study has shown other vaso active agents to be as effective • Insufficient data to reliably compare it to the alternatives • Cost: 1mg = £19.44 • Need more research
  23. 23. Questions?
  24. 24. References • Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database of Systematic Reviews 2003 • Oxford University Press. Oxford Handbook of Clinical Medicine. 7th Edition • Wikiepdia.org

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