CIRRHOSIS AND ITS COMPLICATIONS

1. CIRRHOSIS AND ITS COMPLICATIONS Dr. P. Dienhart, M.D [Gastroenterology] Dr.Padma Poddutoori [PGY3,I.M]

2. Definition • Cirrhosis is a late stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and the formation of regenerative nodules. It is considered to be irreversible in its advanced stages.

3. Etiology of cirrhosis • Alcoholic liver disease • Chronic Hep B,C • PBC • PSC • NASH • Autoimmune hepatitis • Hereditary Hemochromatosis • Alfa1 AT deficiency • Wilsons disease • Cardiac cirrhosis

4. Clinical manifestations and presentation • Stigmata of chronic liver disease discovered on routine PE [spider angioma, palmar erythema, terry’s nails, Muehrcke's nails, clubbing and HOCM, dupuytrens contracture, ascites, splenomegaly, hepatomegaly, caput medusae, testicular atrophy, Cruveilhier-Baumgarten murmur, fetor hepaticus, jaundice and asterexis • Laboratory/ radiologic tests or an unrelated surgical procedure that incidentally uncovered cirrhosis. • Decompensated cirrhosis, which is characterized by the presence of life-threatening complications, such as variceal hemorrhage, ascites, SBP, or hepatic encephalopathy. • Some never come to clinical attention. Cirrhosis is diagnosed at autopsy in ~30- 40% of patients

5. Complications of Cirrhosis • Portal hypertension • Variceal bleeding • Ascites • Splenomegaly leading to thrombocytopenia • SBP • Hepato-renal syndrome • Hepatic encephalopathy • Hepatopulmonary syndrome • Hepatocellular carcinoma

6. Portal Hypertension • Portal venous pressure > 10 mm of Hg • 3 types: presinusoidal[eg:portal vein thrombosis, Schistosomiasis], sinusoidal and postsinusoidal [Budd-Chiari syndrome] • Cirrhosis- most common, 2nd most common- portal vein obstruction • Usually revealed by the appearance of splenomegaly, ascites, encephalopathy, esophageal varices • Treatment- B-blockade with non selective agents like propranolol or nadolol, TIPS • Therapeutic goals-HVPG<12 mm of Hg or by 20% from baseline or reduction of resting pulse by 25%

7. Variceal bleeding • Most common from varices in the GE junction • Factors for bleeding are degree of portal hypertension[>12mm of Hg] and variceal size • Bleeding is painless, massive hematemesis with/without malena can occur • Symptoms/signs could range from mild postural tachycardia to profound shock

8. Management of variceal bleed • Prompt estimation and vigorous replacement of blood loss • Avoid excessive fluid administration-could be deleterious • Close monitoring of central venous pr or pulmonary capillary wedge pr, urine output and mental status is needed • Vasopressors like Somatostatin-250 mcg bolus followed by 250 mcg/hr infusion or octreotide 50-100mcg/hr or vasopressin 0.1-0.4U/min.

9. Management of variceal bleed contd • Balloon tamonade with senstaken blackmore or Minesota tube if endoscopy not available-complications aspiration, esophageal rupture. • EVL controls acute bleed in 90% • Portal systemic shunts-non selective –end to side, side to side PC shunts and proximal SR shunts. Selective-distal SR shunt • TIPS-expandable metal shunt to the hepatic veins to create direct PC shunt • Prevention –prophylactic non-selective B-blockers-propranolol and nadolol-goal to reduce resting HR by 25% or HVPG to 12mm of Hg or 20% below baseline

10. Ascites • Three theories-underfilling, overflow, peripheral arterial vasodilation-splanchnic arteriolar dilation • Portal hypertension plays important role in ascites formation, hypoalbuminemia,reduced plasma oncotic pr also favor. Renal factors also contribute • >500 ml of fluid is needed for ascites to be demonstrated on PE • Salt restriction-800 mg Na or 2 gm NaCl • Fluid restriction of 1 L/day may be necessary to correct hyponatremia. • Spironolactone 100400 and furosemide 40160 • Large volume paracentesis with albumin replacement. • Side-side PC shunt and TIPS

11. SBP-definition and etiology • SBP or primary peritonitis-without an apparent source of contamination • Most commonly in pts with cirrhosis[alcoholic], but also with metastatic malignant disease, postnecrotic cirrhosis, chr.active hepatitis, acute viral hepatitis,CHF,SLE, lymphedema • Hematogenous spread of organisms in pts with diseased liver and altered portal circulation resulting in defect in usual filtration function

12. Presentation and diagnosis • Most common manifestation-fever-80% • Abdominal pain, acute onset of symptoms and peritoneal irritation • Vital to sample peritoneal fluid of any cirrhotic pt with ascites and fever • Diagnosis of SBP- temperature > 37.8[100F] Abd pain and/or tenderness change in MS ascitic fluid PMN >250 • Gm negative org like E.coli, Gm +ve org strep, enterococci and pneumococci

13. Treatment of SBP • Empiric therapy shd cover Gm –ve aerobic bacilli and Gm +ve cocci • Third gen cephalosporins like cefotaxime 2 gm q8, zosyn 3.375 gm q6, ceftriaxone 2gm q24. Pts usually respond in 72 hrs- total 5 days Rx-if rapid improvement and blood cultures are negative, 2 wks Rx if slow improvement or bacteremia • Prevention-70% recurrence. Antibiotics reduce to 20%.ciprofloxacin 750 wkly or noflox 400qd bactrim 1DS qd . • Prolonged prophylaxis (ie, indefinite duration) of patients with cirrhosis and ascitic fluid total protein <1.5 g/dL with a) Child-Pugh >9 points and serum bilirubin >3 mg/dL or b) serum creatinine >1.2 mg/dL or blood urea nitrogen >20 mg/dL or serum sodium <130 mEq/L is recommended.

14. Hepatorenal syndrome • Definition: charecterized by worsening azotemia with avid sodium retention and oliguria in the absence of identifiable causes of renal dysfunction • There is evidence for inappropriate intense renal vasoconstriction, in response to the splanchnic vasodilation • Worsening azotemia, hyponatremia,progressive oliguria and hypotension are the hallmarks • Precipitating factors: severe GI bleed, sepsis or overly vigorous attempts at diuresis or paracentesis • Diagnosis: elevated creatinine >1.5g/dl that fails to improve with volume expansion or withdrawal of diuretics, with a normal urine sediment • Urine sodium is typically <5mmol/l • Some may respond to salt free albumin • Terlipressin, norepinephrine with albumin and octreotide with midodrine have recently emerged • TIPS • Liver transplantation • In SBP, early I.V albumin infusion can prevent HRS in some

15. Hepatic Encephalopathy • Definition: Is a complex neuropsychiatric syndrome ch. by disturbances in consciousness and behaviour, personality changes, fluctuating neurologic signs, asterexis or flapping tremor and distinctive EEG changes. • It could be acute and reversible or chronic and progressive • Pathogenesis: Severe hepatocellular dysfunction and/or intrahepatic and extrahepatic shunting of portal venous blood into systemic circulation, hence bypassing liver Ammonia is the most common one. Others include mercaptans,short chain fatty acids and phenol. Increased concentrations of GABA and direct enhancement of GABA receptor activation by ammonia. Hyperintensity in the basal ganglia by MRI in cirrhotic pts suggests that excessive manganese deposition may contribute

16. Common precipitants of HE • Increased nitrogen load: GI bleeding Excess dietary protein Azotemia Constipation Electrolyte and metabolic imbalance: Hypokalemia Hypoxia Hyponatremia Hypovolemia Alkalosis Drugs: Narcotics, tranquilizers, sedatives Diuretics Others: Infection Surgery Superimposed acute liver disease Progressive liver disease Portal systemic shunts

17. Diagnosis of HE • HE should be considered when 4 major factors are present 1.Acute or chr. hepatocellular disease and/or extensive portal systemic collateral shunts- spontaneous or sec to TIPS 2.Disturbance of awareness and mentation 3.Shifting combinations of neurologic signs inc. asterexis, rigidity, hyperreflexia, extensor plantar signs, seizures 4.Charecteristic symmetric high voltage triphasic slow wave[2-5/sec] pattern on EEG Asterexis: a non rhythmic asymmetric lapse in voluntary sustained position of the extremities, head and trunk. Disturbances of sleep with reversal of sleep/wake cycles are the earliest signs. Fetor hepaticus is the musty odour of the breath and urine due to mercaptans

18. Clinical stages of HE

19. Treatment of HE • Lactulose- a non absorbable disaccharide, acts as an osmotic laxative. Turns Ph acidic and hence converts ammonia to ammonium, may also diminish ammonia production thru direct effects on bacterial metabolism. • Initially 30-60 ml/hr until diarrhea occurs and then 15-30 ml tid-2-4 soft BM • Neomycin 0.5 TO 1gm q 6 hrs • Metronidazole • Hemoperfusion, extracorporeal liver assist devices may bridge pts to recovery or transplantation- yet unproven. Chronic encephalopathy –dietary protein restriction[60 g/d], vegetable protein preferable to animal protein

20. Hepatopulmonary syndrome • Manifest by hypoxemia, platypnea and orthodeoxia • Hypoxia: usually due to R-L intrapulmonary shunts thru dilatations in intrapulmonary vessels detected by contrast enhanced echo or a macro aggregated albumin lung perfusion scan. Endothelin-1 and pulmonary NO correlate with degree of shunting. • Large A-V shunts may be embolized • Liver transplantation

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