LIVER CIRRHOSIS AND ITS

COMPLICATIONS

Jennifer Castillo, MD

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

Classification

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

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

Clinical Features

Consequences of Parenchymal

Failure

Peripheral edemaHypoalbuminemia

• Differentials• Nutritional and fluid status• Possible renal losses

• IV albumin supplements after large vol paracentesis in nonedematous px w/ renal insufficiency. • 6-8g albumin per liter of ascites removed

Coagulopathy

• Indicates severity of liver dse• Other causes of prolonged PT and PTT– Cholestasis can lead to VitK malabsorption– 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

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.g hemolysis)– Dec hepatic uptake or conjugation– Mechanical obstruction of bile flow

- Nonspecific but of great prognostic significance

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

…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

Hyperestrogenemia

Consequences of Portal Hypertension

Normal Portal Circulation

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)

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

Collaterals

Clinical Complications of

Portal Hypertension

Gastrointestinal bleedingHepatic Encephalopathy

AscitesSpontaneous Bacterial

PeritonitisHepatopulmonary

Syndrome

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

Varices Management• General– Resuscitation: ABC, 2 IV lines, IVF, blood– Platelet transfusion <75; FFP

• Specific– IV vasoconstrictors (ocreotide, vasopressin)– Endoscopic banding/sclerotherapy– Variceal tamponade via Balloon NGT– Shunting: Surgical/TIPS

• Prevention– Treat underlying disease– Endoscopic banding protocol– B-blockers– Shunt surgery (only if no cirrhosis)– Liver transplantation

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 • Variceal tamponade

– Balloon tamponade NGT (Minnesota or Sengstaken-Blakemore tubes)

– Never used >24hrs

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 hep enceph– For px with well-preserved parenchymal fxn who have failed other

efforts to prevent bleeding• Transjuglar intrahepatic portosystemic 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%)

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

Clinical Findings

CLINICAL STAGE

INTELLECTUAL FUNCTION NEUROMUSCULAR FUNCTION

Subclinical Normal exam but work or driving may be impaired

Subtle changes on psychometric or number connection tests

Stage 1 Impaired attention, irritability, depression or personality change

Tremor, incoordination, apraxia

Stage 2 Drowsiness, behavioral changes, poor memory and computation, sleep disorders

Asterixis, slowed or slurred speech, ataxia

Stage 3 Confusion and disorientation, somnolence, amnesia

Hypoactive reflexes, nystagmus, clonus and muscular rigidity

Stage 4 Stupor and coma Dilated pupils and decerebrate posturing; oculocephalic reflex; absence of response to stimuli in advanced stages

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

3. Ascites

Causes of Ascites1. Liver disease: cirrhosis2. Right sided heart failure3. Kidney disease (nephrotic

syndrome)4. Low albumin

(malnutrition, bowel loss)5. Peritonial infection (TB…)6. Peritonial cancer

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

• Chylous ascites – 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.

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

…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

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

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

Other Signs and symptoms:

• Hepatorenal Syndrome• Hepatopulmonary Syndrome• Splenomegaly and hypersplenism• Fetor hepaticus

Points Class One year survival Two year survival

5-6 A 100% 85%

7-9 B 81% 57%

10-15 C 45% 35%

Death

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

END…