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Cirrhosis: The good, the bad, and the ugly

Cirrhosis: The good, the bad, and the ugly. Dr. Homayon Iraninezhad DO GFW-SGNA 25 th Annual Educational Symposium March 2013. Homayon Iraninezhad, DO. I have no financial relationships to disclose within the past 12 months relevant to my presentation AND

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Cirrhosis: The good, the bad, and the ugly

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  1. Cirrhosis: The good, the bad, and the ugly Dr. Homayon Iraninezhad DO GFW-SGNA 25th Annual Educational Symposium March 2013

  2. Homayon Iraninezhad, DO I have no financial relationships to disclose within the past 12 months relevant to my presentation AND My presentation does not include discussion of off-label or investigational use

  3. objectives • Natural history of cirrhosis • Compensated and decompensated cirrhosis are two distinct entities • HCC may occur along the whole course of the disease and significantly worsens outcome • Pathophysiology of portal HTN • Esophageal varices • Hepatic encephalopathy • Cirrhosis and infection

  4. CASE A 62 - year - old man presents to the emergency room (ER) at 6:00am with complaints of vomiting blood 1 hour ago. He denies any retching or abdominal pain. His last bowel movement was the previous night and was softer than his usual and dark in color. He does have a past history of alcohol consumption up to six cans of beer a day for 30 years but he quit 6 months ago. He also has multiple tattoos, some of which he got when he was in the Far East. He denies ever being ill in the past and in fact does not even have a primary care physician. On examination, he is afebrile, pulse 95, blood pressure 90/68. He appears mildly anxious. Skin examination reveals scleralicterus and multiple spider nevi on the front and back of the chest. Heart and lung examinations reveal no abnormality. There is no palpable hepatomegaly. However, the tip of the spleen is palpable 2 cm below the costal margin. There is dullness to percussion in both flanks. In the ER, he has another emesis and dark - red blood is noted in the pan. • What would be the next step?

  5. Functions of the Liver: A Brief Overview • Largest organ in body, integral to most metabolic functions of body, performing over 500 tasks • Only 10-20% of functioning liver is required to sustain life • Removal of liver will result in death within 24 hours

  6. Functions of the Liver • Main functions include: • Metabolism of CHO, protein, fat • Storage/activation vitamins and minerals • Formation/excretion of bile • Steroid metabolism, detoxifier of drugs/alcohol • Action as (bacteria) filter • Conversion of ammonia to urea • Gastrointestinal tract significant source of ammonia • Generated from ingested protein substances that are deaminated by colonic bacteria • Ammonia enters circulation via portal vein • Converted to urea by liver for excretion

  7. Cirrhosis • Important cause of morbidity and mortality • ~ 800,000 people die of cirrhosis annually worldwide • In the U.S., it is the 12 leading cause of death overall and the 7th among individuals between 25-64 years of age • Increasing incidence over the next decade

  8. Hepatic Stellate Cell

  9. Natural history of cirrhosis

  10. PORTAL HTN 5 mm Hg PORTAL VEINIVC

  11. Esophageal VaricesNatural history and epidemiology • ½ patients with cirrhosis at time of diagnosis (highest in CPC C) • GE varices occur at rate of 7% per year • 1 year rate of a first esophageal variceal hemorrhage is 12% • High risk patients at risk for variceal hemorrhage: • Variceal size • CPC B or C • Red wale marks

  12. Formation of varices • HVPG > 10 mm Hg • varices form • HVPG > 12 mm Hg • bleeding risk • HVPG > 20 mmHg • continued bleeding and failure of medical therapy in acute variceal hemorrhage • Variceal rupture • wall tension exceeds the elastic limits of variceal wall

  13. The acute variceal bleeding episode • High risk of re-bleeding • 25% during first week* and 62% at 2 years • Variceal bleeding is not just first 24 hours! * The time from for the acute bleeding episode is 5-days (Baveno IV)

  14. Mortality from acute variceal bleed • 1981 (Graham et al..)  ~50% • 2003 (D’amico et al..)  ~ 20% • Reason • Endoscopic band ligation • Prophylactic antibiotics • Mortality has a correlation to CPC C patients

  15. Therapies to reduce portal pressure • Splanchnic vasoconstrictors  vasopressin and somatostatin, octreotide • Non-selective beta blockers  nadolol, propranolol • B1-blockade = reduction of cardiac output • B2-blockade = splanchnic vasoconstriction

  16. Local therapies without portal pressure decrease • Endoscopic procedures: • Elastic banding on variceal columns • Injecting Sclerosing agents • Tissue adhesives • Balloon tamponade • Expandable esophageal stents

  17. Prevention of varices and a first variceal hemorrhage • No varices = no beta blockers! • Small varices without red wale marks and in absence of severe liver disease = optional to give non selective beta blocker • Small varices with high risk of hemorrhage = recommend non selective beta blockers • Medium or large varices = either give non selective beta blockers or endoscopic variceal ligation

  18. Advantage of beta blockade over endoscopic variceal ligation • Cost is low • Don’t need expertise • Prevent other complications • Portal HTN gastropathy • Ascites • SBP • Disadvantage • Side effects: fatigue and SOB

  19. Treatment of acute variceal hemorrhage • CPC A or HVPG < 20 mm Hg = • octreotide (2-5 days) plus • endoscopic therapy < 12 hour • Prophylactic antibiotics (norfloxacin or ceftriaxone) • CPC B or C or an HVPG > 20 mm Hg • Early TIPS procedure patient who fails conservative therapy • Blakemore tube

  20. Gastric varices • Occur in 20% of cirrhotic • More severe and higher rate of death • Endoscopic variceal obturation • Adhesive = N-butyl-2-cyanoacrylate (not in USA) • Off-label = 2-octyl cyanoacrylate • TIPS

  21. Prevention of recurrent variceal hemorrhage • Combination nonselective beta blocker plus endoscopic variceal ligation • Combination helps with re-bleeding rates but not with overall survival • TIPS • Goal = decrease HVPG < 12 or 20% reduction from baseline

  22. Special situations • Portal HTN gastropathy • Seen in patient with GE varices and high CPC • Progression correlates with high CPC • Higher among patients that have undergone endoscopic ligation • MCC presentation = slow chronic hemorrhage resulting in anemia • Treatment = non selective beta blockade and iron supplementation  TIPS

  23. Blood loss increase with blood transfusion in a rat model of portal HTN bleeding • Transfusions should be very conservative in variceal bleeding and cirrhosis • Concept  in portal HTN the more you transfuse the more you bleed • Why? • During bleeding  hypovolemia causes splanchnic vasoconstriction directed to send blood to vital organs and this lowers the splanchnic blood flow • with transfusion you offset this reflex and this leads to an increase in portal pressure *Castaneda et al. Hepatology 2001, 33:821-825

  24. Cautious transfusion improves outcomes in cirrhotic patients with GI hemorrhage • Hemoglobin failures were lower with cautious transfusion. • Treatment  Hemoglobin goal ~ 7 = 16% treatment failure; whereas hemoglobin ~ 9 = 28% failure. • 6 week mortality  Hemoglobin ~7 = 12%; Hemoglobin ~ 9 = 16%. • Colomo A et al. AASLD 2008

  25. Coagulopathy correction in acute variceal bleed • Factor VIIA • Variceal bleeders and CPC B/C  results of a second double-blind RCT in 256 CPC B/C patients with active variceal bleeding did not show significant effects on 5-day failure, but lower 6 week mortality • No firm indication of use of factor VIIA Bosch et al, Hepatology 2008

  26. Summary • General measures • Avoid over transfusion (keep Hgb 7-8 g/dL) • Antibiotics  IV cephalosporins in patients with advanced cirrhosis in setting of high prevalence of quinolone-resistance • Protect the airway • Hemostatic treatment: vasoactive drugs + EBL • rFVIIa not recommended • Early TIPS: could be first choice in CPC C patients

  27. TIPS • Transjugularinrahepaticportasystemic shunt • 1st line treatment for bleeding esophageal varices when earlier-mentioned methods fail • Performed in IR • Success rates 90-100% • Significant complication is hepatic encephalopathy

  28. TIPS • Technically feasible • Complications 9 - 50% Infection Intraperitoneal Bleeding Congestive Failure Subcapsular Hematoma Acute Renal Failure Hemobilia • Mortality (30 day) 3 - 13% • RoschHepatology 1992;16:884

  29. Problems with TIPS • Encephalopathy minimum 15% • Occlusion 33 - 73% @ one year • Re-bleeding 18% @ one year* 19% @ 4.7 months** • *RossieNEJM 1994;330:165, **RoschHepatology1992;16:884.

  30. The role of tips • Refractory bleeding • Bridge to transplant • Child C • ??? refractory ascites • Relative contraindication: Poor f/u

  31. 0 / 10 A 56y/o male with known alcoholic cirrhosis is admitted to the hospital for treatment of refractory ascites. He has noted a 15lb weight gain over the past month since his last large-volume paracentesis. A decision is made to place a transjugular intrahepaticportosystemic shunt for treatment of his ascites. He tolerates the procedure well, and is discharged home on the same medication regimen he was taking prior to admission. Three days later he arrives to the hospital via ambulance after being found at home confused and lethargic. On exam he is afebrile, BP 123/76, RR 15. He is arousable but confused, and has asterixis. He has stigmata of chronic liver disease and is anicteric. Which of the following is the most likely diagnosis? • Hepatorenal syndrome • Encephalopathy secondary to TIPS procedure • DIC • SBP • Septic shock Labs WBC 6.2 Hgb 12.0 Plt 201 BUN 11 Cr 1.2 Ascitic fluid analysis WBC 5 RBC 2 SAAG: 2.6

  32. What is Hepatic Encephalopathy? • Broadly defined • All neurological and psychological symptoms in patients with liver disease that cannot be explained by presence of other pathologies • Brain and nervous system damage secondary to severe liver dysfunction (most often chronic disease) resulting from failure of liver to remove toxins • Multifactorial pathogenesis with exact cause unknown • Symptoms vary from nearly undetectable, to coma with decerebration • Characterized by various neurologic symptoms • Cognitive impairment • Neuromuscular disturbance • Altered consciousness • Reversible syndrome

  33. Incidence & Prognosis • Incidence • 10-50% of cirrhotic pts and portal-systemic shunts (TIPS) experience episode of overt hepatic encephalopathy • True incidence/prevalence of HE unknown • Lack of definitive diagnosis • Wide spectrum of disease severity • Prognosis • 40% survival rate 1 year following first episode • 15% survival rate 3 years following first episode T or F: H.E. can occur in patients with normal liver tests?

  34. Clinical Manifestations of HE • Cerebral edema • Brain herniation • Progressive, irreversible coma • Permanent neurologic losses (movement, sensation, or mental state) • Increased risk of: • Sepsis • Respiratory failure • Cardiovascular collapse • Kidney Failure

  35. Variants of Hepatic Encephalopathy • Acute HE • Associated with marked cerebral edema seen in patients with the acute onset of hepatic failure (FHF) • Hormonal disarray, hypokalemia, vasodilation (ie, vasopressin release) • Quick progression: coma, seizures, and decerebrate rigidity • Altered mental function attributed to increased permeability of the blood-brain barrier and impaired brain osmoregulation • Results in brain cell swelling and brain edema • Can occur in cirrhosis, but usually triggered by precipitating factor • Precipitating factors usually determine outcome

  36. Variants of Hepatic Encephalopathy • Chronic HE • Occurs in subjects with chronic liver disease such as cirrhosis and portosystemic shunting of blood (Portal Systemic Encepalopathy [PSE]) • Characterized by persistence of neuropsychiatric symptoms despite adequate medical therapy. • Brain edema is rarely reported • Refractory HE • Recurrent episodes of an altered mental state in absence of precipitating factors • Persistent HE • Progressive, irreversible neurologic findings: dementia, extrapyramidal manifestations, cerebellar degeneration, transverse cordalmyelopathy, and peripheral neuropathy • Subclinical or “Minimal HE” • Most frequent neurological disturbance • Not associated with overt neuropsychiatric symptoms • Subtle changes detected by special psychomotor tests

  37. Precipitants of Hepatic Encephalopathy • Drugs • Benzodiazepines • Narcotics • Alcohol • Portosystemic Shunting • Radiographic or surgically placed shunts • Spontaneous shunts • Vascular Occlusion • Portal or Hepatic Vein Thrombosis • Dehydration • Vomiting • Diarrhea • Hemorrhage • Diuretics • Large volume paracentesis • Increased Ammonia Production, • Absorption or Entry Into the Brain • Excess Dietary Intake of Protein • GI Bleeding • Infection • Electrolyte Disturbances (ie., hypokalemia) • Constipation • Metabolic alkalosis Primary Hepatocellular Carcinoma

  38. Asterixis (“flapping tremor”) Hx. liver disease Impaired performance on neuropsychological tests Visual, sensory, brainstem auditory evoked potentials Fetor Hepaticus Increased DTR’s Unilateral or bilateral Babinski’s Slowing of brain waves on EEG Elevated serum NH3 Stored blood contains ~30ug/L ammonia Elevated levels seen in 90% pts with HE Not needed for diagnosis Diagnostic Criteria

  39. Stages of Hepatic Encephalopathy = Conns score With Stage III,IV  intubate Asterixis: usually with stage II, III, sometimes I

  40. Asterixis • Patient extends there arms with wrists flexed backward and fingers open for 30 seconds

  41. Treatment • Identify and treat the precipitating factor • Medications: • Lactulose • Rifaximin • Metronidazole • Neomycin • Zinc • Bromocriptine

  42. Bacterial infections are common in hospitalized cirrhotic patients • Prevalence of infections in hospitalized patients: • 10%  normal patients • 33%  patients with cirrhosis • 50%  patients with cirrhosis & GI hemorrhage

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