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Hepatic Decompensations. Agenda. Hepatic decompensations Hepatic encephalopathy Treatment/precipitating factors SBP Differentiate from secondary peritonitis Variceal bleeding (portal HTN bleeding) Treatment and prophylaxis. Hepatic Encephalopathy.
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Agenda • Hepatic decompensations • Hepatic encephalopathy • Treatment/precipitating factors • SBP • Differentiate from secondary peritonitis • Variceal bleeding (portal HTN bleeding) • Treatment and prophylaxis
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
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.
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 Management-Identify and precipitating factors
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
Enema-Lactulose • Use of 1-3 liters of 20% Lactulose is more effective than tap water enema • Oral therapy preferred by most
Therapy- antibiotics • 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% 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 • 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.
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)
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
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
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
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
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
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)
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
Portal HTN bleeding • Esophageal, gastric, ectopic varices • Portal HTN gastropathy/enteropathy • Secondary to distortion of liver architecture • Increased flow of splanchnic circulation
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 Esophageal Varices
Name the conditions Conditions associated with cirrhosit
Consider: Splenic vein thrombosis with chronic pancreatitis Trauma Malignancy Isolated Gastric Varices
Large varices > 5mm Red color signs-red weals, cherry spots (varices on varices) Hepatic decompensations Predictors of bleeding
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
EVBL similar success in preventing first variceal hemorrhage Sclerotherapy for primary prophylaxis TIPS not indicated for primary prophylaxis Variceal prophylaxis
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
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)
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
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)
Material covered • Hepatic decompensations • Hepatic encephalopathy • Treatment/precipitating factors • SBP • Differentiate from secondary peritonitis • Variceal bleeding (portal HTN bleeding) • Treatment and prophylaxis