Complications of chronic liver disease

Ascites - Hepatic Encephalopathy - Gastroesophageal Varices – �Spontaneous Bacterial Peritonitis (SBP) - Hepato renal Syndrome - Alcoholic Liver Disease

1. Complications of chronic liver disease PREPARED BY DR . SAYED ZAKI

2. Dr / Sayed Zaki 2 Complications of chronic liver disease Ascites - Hepatic Encephalopathy - Gastroesophageal Varices – Spontaneous Bacterial Peritonitis ( SBP) - Hepato renal Syndrome - Alcoholic Liver Disease

3. Dr / Sayed Zaki 3 Variable Score 1 Point 2 Points 3 Points Encephalopathy Absent Mild-moderate Severe to coma Ascites Absent Slight Moderate Bilirubin (mg/dL) < 2 2–3 > 3 Albumin (g/L) > 3.5 2.8–3.5 < 2.8 Prothrombin time ( seconds above normal) 1–4 4–6 > 6 Scoring Systems for Severity of Liver Disease: Child-Pugh Classification of the Severity of Cirrhosis Class A = total score of 5 or 6 class B = total score of 7–9 class C = total score of 10 or more .

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5. ASCITES Free fluid in the abdominal cavity secondary to resistance within the liver and osmotic pressure within the bloodstream (hypo albuminemia ). Dr / Sayed Zaki 5

6. Dr / Sayed Zaki 6 TREATMENT

7. Dietary sodium restriction (< than 2g/day) fluid restriction to <1.5 L/day if serum sodium is < 120–125 mmol/L furosemide + spironolactone (a ratio of 40 mg of furosemide to every 100 mg of spironolactone is an appropriate starting regimen ) Amiloride 10–40 mg/day may be substituted for spironolactone in patients who develop tender gynecomastia If refractory ascites is present, may consider midodrine 7.5 mg three times daily as add-on therapy to diuretics If tense ascites is present, may use large-volume paracentesis . Administer albumin at a dose of 6–8 g/L of ascitic fluid removed (if more than 5 L is removed at one time ) No upper limit of weight loss if massive edema is present, 0.5 kg/day in patients without edema drugs as NSAIDs. ACE and ARBs should be avoided also to prevent renal failure

8. Dr / Sayed Zaki 8 sodium restriction (< than 2g/day ) fluid restriction to <1.5 L/day if serum sodium is < 120–125 mmol/L 40mg furosemide + 100mg spironolactone patients who develop tender gynecomastia from spironolactone 40mg furosemide+ 10–40 mg Amiloride refractory ascites 40mg furosemide+ 100mg spironolactone + midodrine 7.5 mg tid Tense ascites paracentesis if more than 5 L is removed at one time Albumin at a dose of 6–8 ml/L of ascitic fluid removed Ascites

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11. Dr / Sayed Zaki 11 Hepatic Encephalopathy

12. Dr / Sayed Zaki 12 precipitation factors Constipation& GI bleeding. infection. hypokalemia, dehydration & hypotension. CNS-active drugs (benzodiazepines and narcotics). Hepatic encephalopathy is a brain dysfunction caused by liver insufficiency or portosystemic shunting; it manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma. causes Accumulation of nitrogenous substances (mainly NH3) arising from the gut (mainly). Activation of GABA by endogenous benzodiazepine-like substances. Zinc deficiency, or altered cerebral metabolism.

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14. Lactulose is first-line treatment Metabolized by colonic bacteria to acetic and lactic acid ; NH3 present in the GI lumen is reduced to ammonium ion (NH4 +) through the reduction in pH (“ammonia trapping ”) and is therefore unable to diffuse back into the bloodstream Dose: 15- to 45-mL dose two or three times daily or an enema (300 mL plus 700 mL of water retained for 1 hour, May be continued over the long term to prevent recurrent encephalopathy adverse effects: Flatulence, diarrhea, and abdominal cramping Neomycin or metronidazole may be used; neomycin is considered as effective as lactulose neomycin caution with long-term use in patients with renal insufficiency; long-term metronidazole use may result in peripheral neuropathy . Rifaximin is as effective as lactulose in patients 18 years and older is 550 mg twice daily. Drug cost may be greater. A recent trial showed that polyethylene glycol 3350 4 L given orally or by nasogastric tube over 4 hours resulted in faster improvement in encephalopathy than lactulose Dr / Sayed Zaki 14 Flumazenil is used if the cause is benzodiazepine overdose Zinc is used if the cause is zinc deficiency

15. Dr / Sayed Zaki 15 Lactulose syp 15 to 45mL tid or enema (300 mL lactulose+ 700 mL water for 1hr) Neomycin or metronidazole + + 550 mg Rifaximin bid أو polyethylene glycol 3350 4 L given orally or by nasogastric tube over 4 hours Hepatic Encephalopathy

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18. Dr / Sayed Zaki 18 Gastroesophageal Varices

19. Dr / Sayed Zaki 19 Complications of chronic liver disease

20. Dr / Sayed Zaki 20 Resistance to blood flow within the liver secondary to cirrhosis results in the development of portal hypertension. Collateral blood vessels (e.g., esophageal varices ) are formed because of this increased resistance to blood flow. DEFINITION

21. Dr / Sayed Zaki 21 TREATMENT

22. Nonselective β-blockers primary prophylaxis for patients with cirrhosis and small, medium or large varices and no history of bleeding MOA : block β1 reduces cardiac output,block β2 splanchnic constriction leads to reductions in portal pressure Therapy should aim for a heart rate of 55–60 beats/minute or a 25% reduction from baseline Fluid resuscitation and hemodynamic stabilization.Maintain Hb conc 8 g/Dl Sclerotherapy : Effective in discontinuing bleeding in 80%–90% of patients sclerosing agents include ethanolamine and sodium tetradecyl sulfate Endoscopic variceal band ligation : may be used as an alternative to sclerotherapy Vasopr essin plus nitroglycerin for 3–5 days Vasopressin cause splanchnic vasoconstriction and coronary vasoconstriction / hypertension so nitroglycerin is used to ¯ coronary vasoconstriction /hypertension More adverse effects , less preferable Octreotide ( sandostatin amp ) Works possibly by reducing portal pressure (by reduced splanchnic blood flow ) adverse effects include hyperglycemia and abdominal cramping . dose/ 50 mcg iv bolus then 50mcg/ hr iv for 3-5days patients with cirrhosis and variceal bleeding use a) ( norfloxacin or ciprofloxacin ) orally for 7 days. b) Ceftriaxone 1 g/day i.v may be used if high rates of fluoroquinolone resistance Secondary prophylaxis: combination of endoscopic variceal band ligation + nonselective β-blockers TIPS ( transjugular intrahepatic portosystemic shunt) is very effective at preventing recurrent bleeding; however, it is associated with a 30%–40% incidence of encephalopathy Dr / Sayed Zaki 22

23. Dr / Sayed Zaki 23 مريض عنده liver cirrhosis + varices No bleeding Nonselective β-blockers ( indral ) 1ry prophylaxis bleeding Fluid resuscitation Hb conc 8 g/Dl Sclerotherapy ethanolamine and sodium tetradecyl sulfate or Endoscopic variceal band ligation Vasopressin +nitroglycerin for 3–5 days norfloxacin or ciprofloxacin orally for 7 days Octreotide 50 mcg iv bolus then 50mcg / hr for 3-5days + أو + Ceftriaxone i.v 1 g/day أو + Nonselective β-blockers Secondary prophylaxis Gastroesophageal Varices

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29. Dr / Sayed Zaki 29 Spontaneous Bacterial Peritonitis (SBP)

30. Dr / Sayed Zaki 30 Complications of chronic liver disease

31. Dr / Sayed Zaki 31 Gram-negative Bacilli (50 %) Gram-positive Bacilli (17%) Escherichia coli, 37% Streptococcus pneumoniae, 10% Klebsiella spp., 6% Other streptococci, 6% Other, 7% Staphylococcus aureus , 1% Pathophysiology: The bacteria present are usually enteric pathogens; thus, they may enter the blood because of increases in gut permeability secondary to portal hypertension. gram-negative pathogens are most commonly involved. Definition: Infection of previously sterile ascitic fluid without an apparent intra-abdominal source. Most Commonly Isolated Bacteria Responsible for SBP:

32. Dr / Sayed Zaki 32 TREATMENT

33. The presence of more than 250 polymorphonuclear cells/mm3 (PMN) is diagnostic for SBP 3rd generation cephalosporins : Cefotaxime (2 g every 8–12 hours) or ceftriaxone (2 g/day IV)for 5–10 days. Ofloxacin 400 mg orally twice daily Albumin: 1.5 ml/kg on admission; 1 ml/kg on hospital day 3 Guidelines suggest using this albumin regimen with antibiotics if SCr is >1 mg/dL, BUN > 30 mg/dL, or total bilirubin more than 4 mg/dL Dr / Sayed Zaki 33

34. Dr / Sayed Zaki 34 Cefotaxime 2 g every 8–12 hours for 5–10 days + Ceftriaxone 2 g/day IV for 5–10 days أو Ofloxacin 400 mg orally twice daily + Albumin 1.5 ml/kg on admission; 1 ml/kg on hospital day 3 Indicator for SBP: more than 250 polymorphonuclear cells/mm3 (PMN) SCr > 1 mg/dL BUN > 30 mg/dL total bilirubin > 4 mg/dL Spontaneous Bacterial Peritonitis (SBP)

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38. Dr / Sayed Zaki 38 Hepatorenal Syndrome

39. Development of Renal failure secondary to liver cirrhosis. Primary mechanism responsible for deterioration of renal functions is renal hypo perfusion . Criteria in patients with cirrhosis and ascites: SCr greater than 1.5mg/dL . Subtypes : Type 1: Doubling of SCr to greater than 2.5 mg/dL or a 50% reduction in crcl to less than 20 mL/minute/1.73 m2 in less than 2 weeks. Type 2: Non rapid progression of worsening of renal function. Associated with high mortality Treatment : Albumin + octreotide (200 mcg subcutaneously three times daily ) or midodrine (12.5 mg three times daily maximum) may be considered for type 1 hepatorenal syndrome. Albumin + norepinephrine in ICU = intensive care unit patient Dr / Sayed Zaki 39

40. Dr / Sayed Zaki 40 Albumin + Octreotide 200 mcg S.C tid أو Midodrine 12.5 mg tid لو مريض فى العناية المركزة icu وعنده هذا المرض Albumin + norepinephrine Hepatorenal Syndrome

41. Dr / Sayed Zaki 41 Alcoholic Liver Disease

42. Patients may develop cirrhosis . TREATMENT: 4-week course of prednisolone 40 mg/day, followed by a 2-week taper pentoxifylline 400 mg three times daily, especially if there are contraindications to corticosteroids Dr / Sayed Zaki 42

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