LIVER CIRRHOSIS AND ITS COMPLICATIONS

1. LIVER CIRRHOSIS AND ITS COMPLICATIONS Jennifer Castillo, MD

2. Features • Final common pathway of many types of chronic liver insults • Irreversible • Chronic • Diffuse, extensive fibrosis central pathogenetic process • Regenerative nodules • Vascular architecture is reorganized by the scarring

3. Classification • Alcoholic – most common • Cryptogenic and posthepatitic • Biliary • Cardiac • Metabolic, inherited, drug-related

4. Pathogenesis • Response of the liver to injurious events: • Degeneration and intracellular accumulation • Necrosis and apoptosis • Inflammation • Regeneration • Fibrosis • Generally irreversible • With continuing fibrosis, the liver is subdivided into nodules of regenerating hepatocytes surrounded by scar tissue, termed CIRRHOSIS

6. Clinical Features

7. Consequences of Parenchymal Failure

8. Peripheral edemaHypoalbuminemia • Differentials • Nutritional and fluid status • Possible renal losses • IV albumin supplements after large volparacentesis in nonedematouspx w/ renal insufficiency. • 6-8g albumin per liter of ascites removed

9. Coagulopathy • Indicates severity of liver dse • Other causes of prolonged PT and PTT • Cholestasis can lead to VitKmalabsorption • Sepsis  Consumptive coagulopathy • HCC  Prod’n of inactive forms of fibrinogen • Tx reserved for active bleeding or about to undergo procedures with high risk of significant bleeding • FFP • Risk: overexpansion of volume, risk of viral infection from contaminated blood

10. Jaundice , Icterisia, and Pruritus • Indicates severity of liver disease • Decreased excretion of B2 into bile (cholestasis) changes the composition of bile and limits its ability to detoxify lipid-soluble wastes • Differentials • Overprodn of bilirubin (e.ghemolysis) • Dec hepatic uptake or conjugation • Mechanical obstruction of bile flow

11. - Nonspecific but of great prognostic significance

12. Renal Failure • Poorly understood • Involves action of circulating factors that reversibly compromise renal perfusion and glomerular function • Secondary to HEPATORENAL SYNDROME • Char by signs of renal failure in the absence of identifiable specific causes of renal dysfunction • Findings: intense renal vasoconstriction, perhaps in response to splanchnic vasodilation in cirrhosis • Urinalysis, pyelography, and biopsy are NORMAL

13. …Hepatorenal Syndrome • Hallmarks: worsening azotemia, hyponatremia and progressive oliguria • Treatment towards optimizing renal blood flow • Treat sepsis, avoid NSAIDs, restore volume, maintain tissue perfusion with inotropes and vasodilators

14. Hyperestrogenemia

15. Consequences of Portal Hypertension

16. Normal Portal Circulation

18. Portal Hypertension • Portal vein pressure > 10mmHg • Ohm’s law: • Change in pressure = blood flow x vascular resistance • Resistance bet right side of heart and splanchnic vessels • Types of obstruction • Prehepatic, intrahepatic or posthepatic • Intrahepatic Obstruction • Presinusoidal - eg portal vein thrombosis • Sinusoidal – eg cirrhosis • Postsinusoidal – eg Budd-chiari syndrome • THUS, although cirrhosis is the most common cause of portal htn, PORTAL HTN CAN OCCUR IN THE ABSENCE OF CIRRHOSIS • Portal vein occlusion – 2nd most common • Assoc with massive hematemesis (GE varices)

20. Portal Vein Pressure • Direct measurement is most reliable • Catheter into the portal vein (via laparotomy) or one of its branches (by percutaneous, transhepatic cannulation of the intrahepatic portal vein branch and advancement of the cannula into the main portal vein) • Indirect method is most commonly used • Catheter into an antecubital or femoral vein and advanced with fluoro guidance into the hepatic vein

23. Collaterals

24. Large esophageal varices Portal hypertensive gastropathy Caput medusae

25. Clinical Complications of Portal Hypertension Gastrointestinal bleeding Hepatic Encephalopathy Ascites Spontaneous Bacterial Peritonitis Hepatopulmonary Syndrome

26. 1. Gastrointestinal Bleeding • Relatively rare: only 1/3 have varices • Other potential sources of bleeding may coexist: • PUD, portal hypertensive gastropathy, portovenous collaterals • Esophageal, gastric, and hemorrhoidal collaterals have the highest propensity to bleed profusely

27. Varices Management • General • Resuscitation: ABC, 2 IV lines, IVF, blood • Platelet transfusion <75; FFP • Specific • IV vasoconstrictors (ocreotide, vasopressin) • Endoscopic banding/sclerotherapy • Varicealtamponade via Balloon NGT • Shunting: Surgical/TIPS • Prevention • Treat underlying disease • Endoscopic banding protocol • B-blockers • Shunt surgery (only if no cirrhosis) • Liver transplantation

28. Treatment • Endoscopic sclerotherapy/banding • Optimal technique for acute mgmt of bleeding and rebleeding • Banding has fewer side effects compared to sclerotherapy (ulceration, pulmo). • Long term control requires periodic endoscopy (q2-4wks then q2-3mos) • Drug therapy • Acute: Direct splanchnic vasoconstrictors • Ocreotide (somatostatin analogue) 50ug/h • Vasopressin + nitroglycerin IV • Chronic • Betablockers - reduces heart rate by 25%, lower pressure in gastric collaterals • Varicealtamponade • Balloon tamponadeNGT(Minnesota or Sengstaken-Blakemore tubes) • Never used >24hrs

29. Surgical • Surgical portosystemic shunts • Most effective means to prevent delayed rebleeding • Selective portosystemic shunt • Mesocaval, distal splenorenal • Nonselective or total shunt • Portacaval • Adequate decompression w/o excessive risk of hepenceph • For px with well-preserved parenchymalfxn who have failed other efforts to prevent bleeding • Transjuglarintrahepaticportosystemic shunting • Can be used in acute bleeding and prevention of rebleeding • Relatively noninvasive and decompresses entire portal system • Theoretically more effective than sclerotherapy and less risky than portosystemic shunt surgery • But has high rate of shunt occlusion (50%)

31. 2. Hepatic encephalopathy • Neuropsychiatric disorder characterized by changes in personality, cognition, motor function, or level of consciousness • Usually reversible • Products that are usually metabolized (or detoxified) by the liver escape into the systemic circulation • Also caused by cirrhosis or portosystemic shunts

33. Clinical Findings

34. Treatment • Goal: control the generation of putative neuroactive toxins • Lactulose • Dec ammonia genesis by enteric flora • Dec ammonia absorption from GIT • S/E: flatulence, diarrhea, acidosis, hypernatremia • Dietary protein intake restriction • Used when lactulose therapy fails • But may induce inc catabolism of muscle protein • Flumanezil • benzodiazepine receptor antagonist

35. 3. Ascites

36. Causes of Ascites • Liver disease: cirrhosis • Right sided heart failure • Kidney disease (nephrotic syndrome) • Low albumin (malnutrition, bowel loss) • Peritonial infection (TB…) • Peritonial cancer

37. Clinical Findings • PE, UTZ, CT, MRI • Diagnostic and Therapeutic Paracentesis • Gross appearance, protein content, albumin level, cell count, and differential cell count; and Gram's and acid-fast stains and culture; cytologic and cell-block exam • Serum-ascites albumin gradient (SAAG) • Parameter to classify ascites = Serum albumin - Ascitic albumin • Chylousascites • turbid, milky, or creamy peritoneal fluid due to the presence of thoracic or intestinal lymph • Sudan-staining fat globules microscopically • Increased TG >2.3 mmol/L (>200 mg/dL) • Result of lymphatic disruption or obstruction from cirrhosis, tumor, trauma, tuberculosis, filariasis, or congenital abnormalities. It may also be seen in the nephrotic syndrome.

39. Treatment • Large amounts of ascites compromises ventilation, increases the risk of ruptured umbilical hernias, impedes venous return, and serves as a source of infection • Diuresis with dietary salt restriction <2g/d • Aldosterone antagonist • Aldactone started at 50mg/d then inc by 50mg q3-4d • Wt loss = 0.5 lb/d • If 300mg is reached w/o satisfactory diuresis, salt reabsorption is avid proximally that sufficient sodium is not reaching the distal nephron, the site of aldactone action (advanced cirrhosis) • Add Furosemide or HCT or both to dec Na reabsorption • Start Furo at 20-40mg/d then inc by 20mg increments q3d • HCT at 25mg/d

40. …Treatment • Paracentesis • 10 or more liters may be removed at a time • Px with renal insufficiency with little peripheral edema, plasma volume-expanders • IV albumin 6-8g per liter of ascites removed • Half infused at the end of paracentesis and remainder 6 hrs later • Risks: bleeding, infection, protein depletion • Shunts, liver transplantation • Hyponatremia due to ascites mobilization • Inc of free water excretion is ineffective • Rapid correction with hypertonic saline can lead to CPM • Thus judicious monitoring of serum electrolytes followed by restriction of free water intake and discontinuation of diuretics until serum sodium = 130meq/L is the best strategy

42. 4. Spontaneous Bacterial Peritonitis • High mortality rate • Caused by a single organism, without an identifiable intra-abdominal source • Peritoneal seeding after bacteremic episodes or possible translocation of gut-derived bacteria • Impaired reticuloendothelial cell clearance of portal blood bacteremias may also contribute • Patients with low levels of total protein in their ascitic fluid (< 1.5 g/dL) are at increased risk for developing SBP because of reduced ascitic complement levels and opsonic activity. • E.coli is most common but other coliforms, Klebsiella, pneumococci, and Enterococcus are also common

43. Clinical Features, Diagnosis, Treatment • May be asymptomatic • Fever, worsening jaundice, abdominal pain (~50%), and confusion are most common • Gram-staining of ascitic fluid is rarely positive • Diagnosis requires peritoneal fluid analysis • WBC >500/uL • Treatment: 3rd gen cephalosporin

44. Other Signs and symptoms: • Hepatorenal Syndrome • Hepatopulmonary Syndrome • Splenomegaly and hypersplenism • Fetor hepaticus

46. Death • Progressive liver failure • Decompensation (stress, infection) • Bleeding • Hepatocellular carcinoma

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