This document discusses a case study of a 55-year-old woman admitted with a variceal bleed from alcoholic liver disease. It then provides background on alcoholic liver disease, its complications including varices, and an overview of the evidence for terlipressin in treating variceal bleeding. The Cochrane review found that terlipressin reduces mortality compared to placebo in acute variceal hemorrhage, though more high-quality studies are needed comparing it to other treatments. Terlipressin is currently the best treatment that can be administered non-invasively.

1. Alcoholic Liver Disease
Lara Gibbs
F1 ACUA

2. Objectives
• Case
• Alcoholic liver disease
• Varices
• Terlipressin – evidence base
• Summary and conclusions

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. 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. 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. 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. Case: Impression
• Variceal bleed
• Possible decompensated ALD
• Need to rule out sepsis
• SBP
• Chest

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. 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. 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. 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. 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. Decompensated ALD
Causes
• Infection – any source
• Bleeding (varices)
• Alcohol – continued excess drinking
• Iatrogenic – drugs

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. 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. Terlipressin: Evidence
Ioannou GN, Doust J, Rockey DC.
Terlipressin for acute esophageal variceal
hemorrhage. Cochrane Database of
Systematic Reviews 2003
(Reviewed 2009)

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. 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. 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. 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

22. 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

23. 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

24. Questions?

25. 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