Alcoholic Liver Disease

Lara Gibbs F1 ACUA

Objectives

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

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

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.

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

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

Case: Impression

• Variceal bleed

• Possible decompensated ALD

• Need to rule out sepsis• SBP• Chest

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

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

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

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

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)

Decompensated ALD

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

Bleeding varicesMortality 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

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

Terlipressin: Evidence

Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal

hemorrhage. Cochrane Database of Systematic Reviews 2003

(Reviewed 2009)

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.

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

Cochrane Review Conclusions

Terlipressin Comparison

Studies Results/Conclusion

Placebo 7 (5) Terlipressin reduced mortalityRR 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

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

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

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

Questions?

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