1. Hepatic Decompensations

2. Agenda Hepatic decompensations Hepatic encephalopathy –Treatment/precipitating factors SBP –Differentiate from secondary peritonitis Variceal bleeding (portal HTN bleeding) –Treatment and prophylaxis

3. Hepatic Encephalopathy Neuropsychiatric abnormalities occurring in patients with liver dysfunction –Type A acute liver failure –Type B portosystemic bypass/shunt without cirrhosis –Type C chronic liver disease/cirrhoisis

4. Hepatic Encephalopathy Minimal HE abnormal psychometric testing but normal routine neurologic exam Overt HE: –Stage I personality change, sleep impaired –Stage II asterexis, short attention span –Stage III somnolent but arousable –Stage IV coma Blei AT, Córdoba J. Hepatic Encephalopathy. Am J Gastroenterol. Jul 2001;96(7):1968-76.

5. Management-Identify and precipitating factors GI bleeding Sepsis Medication non- compliance Constipation Protein overload s/p TIPS CNS active drug Development of HCC New liver injury (Hep D infection in chronic Hep B) Uremia Hypokalemia, alkalosis

6. Therapy-Lactulose Synthetic disaccharide-Lactulose start at 30 ml daily/ twice daily (PO/NGT) Reduces colonic pH to 5.0 favors the formation of NH4 from NH3 (decreased plasma concentration of NH3) Titrate to 2-3 BM’s daily Side effects include cramp, diarrhea, flatulence

7. Enema-Lactulose Use of 1-3 liters of 20% Lactulose is more effective than tap water enema Oral therapy preferred by most

8. Therapy- antibiotics Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. Rifaximin 550 mg PO BID approval from FDA March 2010 for reduction of recurrence of Hepatic encephalopathy) Bass et al- 299 patients received either rifaximin 550 mg or placebo BID with lactulose in >90%

9. Rifaximin 58% reduction in the rifaximin group in recurrent HE compared with the placebo group (P <0.0001). Secondary endpoint -- risk of experiencing HE-related hospitalization reduced by 50% with rifaximin (P = 0.0129). Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081.

10. Therapy- antibiotics Metronidazole 250 mg PO QID (short term use-risk of neurotoxicity/antibuse effect) Vancomycin 250 mg PO QID Neomycin 500 mg PO QID (risk of ototoxicity and nephrotoxicity—in general avoid aminoglycosides/NSAIDS in liver patients)

11. Alternative therapy Vegetable-based protein-consider in those who worsen with high protein loads Flumazenil- short term for iatrogenic or endogenous benzo suspected to have precipitated HE Zinc 600 mg daily (especially if deficient). Mixed results Marchesini G, Fabbri A, Bianchi G, et al. Zinc supplementation and amino acid- nitrogen metabolism in patients with advanced cirrhosis. Hepatology. May 1996;23(5):1084-92. Bresci G, Parisi G, Banti S. Management of hepatic encephalopathy with oral zinc supplementation: a long-term treatment. Eur J Med. Aug-Sep 1993;2(7):414-6

12. Non-rx therapy Closure of TIPS Reduction of shunt diameter OLT per AASLD recommend refer for OLT at MELD of 10 or for hepatic decompensation Survival benefit once patient MELD >15

13. Spontaneous Bacterial Peritonitis Positive ascitic fluid culture Nearly always a single organism If polymicrobial consider bowel perforation PMN count of >250 cells/mm3 High risk if h/o SBP, GI bleed, total protein<1 gram/dl

14. Treatment Empirically treat prior to culture results for PMN count > 250 cells/mm3 E. Coli (43%), Streptococcus species (23%) and Klebsiella pneumoniae (11%) Anerobes rare causes of SBP Fungi= SBP only in severe immunodeficiency

15. Treatment Cefotaxime 2 grams IV q 8 hrs (x 5 days) Ceftriaxone 1 gram daily (x 5 days) Most cultures of ascitic fluid become negative after a single dose 5 Day duration= equivalent efficacy rates of cure and relapse to 10 day duration Volume expansion with albumin 1.5 grams/kg day 1 and 1 gram/kg on day 3

16. Prophylaxis Those with prior SBP-indefinitely or until ascities disappears Cirrhotics with GI bleeding-7 days Ascitic fluid TP <1 gram/dl during hospitalization (controversy)

17. Prophylaxis Norfloxacin 400 mg daily (poorly absorbed fluoroqunolone-effective for gram negative enterics) 60% reduction in ascitic fluid infection Bactrim one double strength tablet orally daily

18. Portal HTN bleeding Esophageal, gastric, ectopic varices Portal HTN gastropathy/enteropathy Secondary to distortion of liver architecture Increased flow of splanchnic circulation

19. Esophageal Varices Result of portal hypertension Form when HVPG is >10 mm/hg Bleed with HVPG is >12 mm/hg Consider non- selective b-blockers in those with large varices

20. Conditions associated with cirrhosit –Name the conditions

21. Isolated Gastric Varices Consider: –Splenic vein thrombosis with chronic pancreatitis –Trauma –Malignancy

22. Predictors of bleeding Large varices > 5mm Red color signs-red weals, cherry spots (varices on varices) Hepatic decompensations

23. Variceal prophylaxis B-blockers including propanolol, nadolol Caution with RAD/COPD Caution with hypoglycemic unawareness Goal to reduce HR by 25% HR not less than 55/min Systolic >90 mm/hg

24. Variceal prophylaxis EVBL similar success in preventing first variceal hemorrhage Sclerotherapy for primary prophylaxis TIPS not indicated for primary prophylaxis

25. Acute variceal bleeding Resusitation NG tube or Ewald tube Treat coagulopathy with FFP Transfuse to H/H of 8/24 Intubate for massive bleeds or if compromised mental status ABX x 7 days

26. Variceal Bleeding Both EVBL and sclerotherapy can achieve hemostasis in 80-90% of cases Sclerotherapy may be achieved with ethanolamine, tetradecyl sulfate –Mucosal ulceration->bleed –Esophageal perforation –Mediastinitis –Stricture (dysphagia)

27. Varices-Therapy Varices-Therapy Vasopressin controls bleeding 50% risk of myocardial or mesenteric ischemia (consider addition of nitroglycerin) Octreotide bolus 50-100 mcg with additional 50 mcg/hr (typically 3-5 days) Combination of EVBL with octreotide more effective than either alone

28. Varices-Therapy Balloon tamponade- consider in failure of endoscopic therapy/pharmacologic therapy May inflate only the gastric balloon-do not keep esophageal balloon inflated greater than 24 hrs TIPS as rescue therapy in 10-20% who fail medical therapy (less mortality than surgical shunts)

29. Material covered Hepatic decompensations Hepatic encephalopathy –Treatment/precipitating factors SBP –Differentiate from secondary peritonitis Variceal bleeding (portal HTN bleeding) –Treatment and prophylaxis

30. Questions MCM 30 Oct 2011