Cirrhosis Management – A Case Based Approach to Disease Management

1. Cirrhosis Management – A Case Based Approach to Disease Management Brenda Appolo PAC, MHS University of Pennsylvania, Perelman School of Medicine

2. Hepatitis C Alcohol Hepatitis B Hemochromatosis Wilson’s Disease Alpha-1-Antitrypsin Deficiency DILI Primary Biliary Cirrhosis Autoimmune chronic hepatitis Primary SclerosingCholangitis Cryptogenic Non-Alcoholic Steatohepatitis Causes of Cirrhosis

3. Case • Carl is a 56 M presents to ED with hematemesis • PMHx: • HCV infection dx years prior but IFN unwilling • HTN • SHx: • Blood transfusion age • 2 six packs beer per week; former TOB user; married; FT worker • Exam: • BP 90/60; HR 100; BMI 31; No icterus on exam; Abdomen soft; splenomegaly; +1 pedal edema • Labs • Hg 8.0; Hct 25%; 89k; WBC 7.1 • Glu 136; cr 0.57; AlkPhos 114; T bil 1.4; AST 66; ALT 46; INR 1.3

4. Portal Hypertensive BleedingEsophgaeal Varices Gastric Varices Portal Hypertensive Gastropathy Colopathy / Rectal Varices

5. band ligation s/p ligation at 4' bleeding stopped w ethanolamine bleeding stopped w ethanolamine

6. Risk of Esophageal Varices Bleed 35-80 % 25-40 % Cirrhosis 50-70 % 30-50 % Survive Die Rebleed 70 %

7. Esophago-Gastric Varices • Screening and follow up • Primary Prophylaxis Varices diagnosed and what do we do? • Secondary Prophylaxis Varices bled and what do we do to prevent re- bleeding?

8. Cirrhosis Upper Endoscopy Small varices (< 5 mm), Child B/C,red wales No varices Medium or large varices Non-selective beta-blocker prophylaxis Titrate to HR of 55-60 Repeat Endoscopy in 3 years (well compensated); in 1 year if decompensated NO beta-blocker prophylaxis Child Class A,no red wales-beta blockers Child class B/C,red wales-beta blockers OR band ligation If prophylaxis not used-repeat endoscopy in 1-2 years Gacia-Tsao et al Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis AASLD Practice Guideline: Hepatology 2007;46:922-38

9. Mechanisms of Action of Various Therapies for Varices ?

10. Case – continued (Carl) • Carl undergoes serial EGD to obliterate varices; placed on beta blocker • Remains IFN unwilling; stopped alcohol • 2 years later presents with increased abdominal girth and dyspnea; wife is concerned about his fatigue and odd behavior this AM • Presents to ED; no imaging on file x 1 yr • Exam – • BP 90/60; HR 62; Weigh > 20lbs since last ED visit; + tense abd; alert and oriented

11. Ascites - SBP

12. Ascites in Cirrhosis : Diagnosis • Physical Exam/Ultrasound: • 1.5 - 3 liters: Shifting dullness • 10 liters: fluid wave • Paracentesis (1% hematoma) • No need for FFP or Platelet transfusion • Helps in differential diagnosis • 20% prevalence of infection at admission • Indication: new onset; admitted to hospital with or without symptoms of abdominal pain, fevers, etc; those who deteriorate during hospitalization

13. Management of Ascites First Line Therapy Second Line Therapy Tense ascites • Repeated Large volume paracentesis (LVP) Refractory Ascites 10 % Paracentesis • TIPS • Liver Transplantation Sodim restriction ( 2 Gm/24 Hrs) and diuretics • Post paracentesis albumin infusion • may not be necessary for < 5 liters removed • Albumin infusion of 6-8 gm/liter of fluid • removed is a consideration for repeated LVP Non-tense ascites • Diuretics: Spironolactone 100 mg/day, furosemide 40 mg/day or bumetanide 1 mg a day. • Uptitrate stepwise to spironolactone 400 mg/day, furosemide 160 mg/day or bumetanide 4 mg/day as long as it is tolerated

14. Etiology of Ascites Tuberculosis Congestive Heart Failure Other Malignancy Cirrhosis 5% Mixed

15. 100 80 Survival (%) 60 40 20 5 6 1 2 4 3 Years Onset

16. Ascites Survival: Only improved by liver transplant 100 After Liver Transplant 80 Survival (%) 60 40 20 5 6 1 2 4 3 Years Onset

17. Ascitic Fluid Analysis OPTIONAL ROUTINE UNUSUAL Cell count Glucose TB smear/culture Albumin LDH Cytology Amylase Gram Stain Culture (blood-cultures) Total Protein

18. Ascitic Fluid Infection • Spontaneous bacterial peritonitis • Monomicrobial non-neutrocytic bacterascites • Culture-negative neutrocytic ascites

19. Spontaneous Bacterial Peritonitis • PMN count > 250 cells/mL • Positive ascites culture • No evidence of intra-abdominal source requiring surgery

20. Secondary Bacterial Peritonitis • PMN count > 250 cells/mL • (total WBC usually > 10,000) • Total Protein > 1 g/dL, elevated LDH, glucose < 50 mg/dL ( 2 of 3 features) • Positive ascites culture • (usually multiple organisms) • Ascites CEA > 5 ng/ml, Alkaline Phophatase > 240 U/L - helpful is identifying intra-abdominal surgically treatable primary source of infection 

21. Overview of Hepatic Encephalopathy Encompasses a wide spectrum of neuropsychiatric abnormalities in patients with liver dysfunction Characterized by Disturbances in consciousness Changes in personality and intellectual capacity High blood ammonia (NH3) levels Altered neuromuscular activity EEG abnormalities EEG = electroencephalogram. Abou-Assi et al. Postgrad Med. 2001;109:52-70. Ferenci et al. Hepatology. 2002;35:716-721. Mas et al. J Hepatol. 2003;38:51-58.

22. Treatment Options for HE Reduction in the nitrogenous load arising from the gut Bowel cleansing Nonabsorbable disaccharides (lactulose) Antibiotics (rifaximin, neomycin, metronidazole) Drugs that affect neurotransmission (flumazenil, bromocriptine) Manipulation of the splanchnic circulation (occlusion of portal-systemic collaterals) HE = hepatic encephalopathy. Blei et al. Am J Gastroenterol. 2001;96:1968-1976.

23. Transjugular Intrahepatic Portosystemic Shunt and Surgical Shunts

24. Placement of TIPS Catheter Inferior vena cava Hepatic veins TIPS Left gastric vein Portal vein Inferior mesenteric vein Superior mesenteric vein

25. Indications and Efficacy of TIPS

26. Etiology of Hepatocellular Carcinoma in the US Other Alcohol HBV 4 % 10 % 6 % HCV + Alcohol 12 % 29 % Cryptogenic HCV 39 % Marrero JA Hepatology 36;1349-54:2002

27. Screening for Hepatocellular Carcinoma (HCC) Screening is done with AFP and ultrasound every 6-12 months • All patients with cirrhosis • Hepatitis B - Africans > 20 years - Asian women > 50 years, men > 40 years - Family H/O HCC

28. Guidelines for Diagnosis of HCC Ultrasound findings Typical features of HCC = vascular nodule on arterial phase with washout in delayed phases Bruix J, et al. Hepatology 2005

29. Current Treatment Options for HCC Surgical Non-surgical • Hepatic Resection • Liver Transplantation • Transarterial • Chemoembolization(TACE) • Ablation Therapy (RFA, PEI) • Molecular targeted therapy • Gene Therapy

30. Liver Transplantation for HCC Milan Criteria 1 lesion ≤5 cm 3 or less lesions, none >3 cm + Absence of Macroscopic Vascular Invasion Absence of Extra-hepatic Spread Mazzaferro V, et al.N Engl J Med 1996;334:693–699.

31. 1 yr 5 yr Resection Survival 74–96% 25–72% Liver Transplantation Survival 84–90% 69–75% Ablation (PEI) Survival 87–98% 29–54% Treatment of HCCSurgical Resection vs. OLT vs. Ablation

32. Summary: Complication of Cirrhosis • Varices • Ascites / Refractory Ascites • Hepatic Encephalopathy • Hepatocellular Carcinoma • Synthetic Dysfunction (jaundice, coagulopathy)