Compl ica t ions o f c i r rhos is Var icea l b leed ing

Pathophys io logy Due to splanchnic vasodilation à increase portal venous flow à variceal growth Progress ion No varices à small varices à large varices

R isk fac tor o f b leed ing

1 . HVPG >12mmHg 2. Var ix s ize and locat ion

a) Large esophageal varices (highest risk for first hemorrhage)

b) Small varices in patients with advanced liver failure c) Isolated cluster of varices in fundus of stomach

3 . Var icea l appearance on endoscopy

• Red wale marks à longitudinal streaks on varices

• Cherry – red spots à discrete red raised spots on varices

• Hematocytic spots à discrete red raised spots

4. Degree o f l i ver fa i lu re à child pugh score class C cirrhosis

Prevent ion

Pre – pr imary à preventing the development of varices à no benefit of drug therapy or EBL if no varices Pr imary à preventing bleed when varices present

• NSBB + EBL not superior to beta blocker mono therapy • NSBB = EBL • Beta blocker • Decrease risk of 1st variceal bleed à ARR 9%, NNT = 11

for 2 years § Propranolol 20mg bid § Nadolol 20 - 40 mg daily § Carvedilol 6.25 – 12.5 mg/day

• Nitrates may increase bleeding • Nitrates + NSSB not more effective than NSBB

Secondary à preventing recurrence of hemorrhage

• NSBB + EBL (1st line) better than either alone § Titrate HR 50 – 60 bpm or decrease 25% § Nitrates + BB = NSBB (mortality and bleeding)

T reatment o f

acute var icea l hemorrhage

Genera l management Spec i f i c therapy • IV access and fluid resuscitation • Do not overtransfuse (hemoglobin ~ 8 g/dL) • Antibiotic prophylaxis

• Pharmacological therapy: terlipressin, somatostatin and analogues, vasopressin + nitroglycerin

• Endoscopic therapy: ligation, sclerotherapy • Shunt therapy: TIPS, surgical shunt

Endoscop ic Var icea l Band

L igat ion

• Bleeding controlled in 90%. Rebleeding rate 30% • Compared with sclerotherapy à Less rebleeding, Lower mortality, Fewer complications, Fewer treatment sessions

A l ternat ive/Rescue therap ies

• TIPS – Transjugular Intrahepatic Portosystemic Shunt • Early placement of shunt (within 24-72hrs) associated with improved survival among high-risk patients • Preferred treatment for gastric variceal bleeding (rule out splenic vein thrombosis first)

                           

 Asc i tes

Causes 1. Cirrhosis (most common) 2. Peritoneal malignancy

3. Heart failure 4. Peritoneal TB

5. Others à Pancreatic, Budd – Chiari syndrome, Nephrogenic ascites Pathophysiology from cirrhosis

Physical findings Flank dullness § Set up patient in supine

§ (+) if percussion is tympanic over umbilicus, dull over lateral abdomen and flank Shifting dullness § Set up patient in lying on one side

§ (+) suggesting ascites when area of tympany shifts towards the side of patient facing up Fluid thrill § Set up patient in supine, pressure applied by patient/assistant on mid abdomen

§ Examiner has one hand on either flank § (+) if shock wave of fluid detected with fingertips on one side of flank when a sharp tap is applied on opposite flank

Diagnostic paracentesis

Ind ica t ions Rout ine work up Opt iona l work up 1. New-onset ascites 2. Admission to hospital 3. Symptoms/signs of SBP 4. Renal dysfunction 5. Unexplained encephalopathy

PMN count culture à to rule out SBP

Protein/albumin à to rule out cirrhotic cause

§ Glucose, LDH à to rule out secondary infection

§ Amylase à to rule out pancreatic ascites

§ Cytology à to rule out malignant ascites Diagnosis

Treatment Non – pharmaco log ica l Pharmaco log ica l Mon i tor ing § Avoid hepatotoxins § Alcohol abstinence § Sodium restriction to 200mg/dL

Spironolactone 100mg + Furosemide 40mg Alternative à amiloride, eplerenone

E f f i cacy 1. Pain, decrease over time; monitor daily 2. Weight loss, 0.5kg/day 3. Abdominal girth, decrease Sa fe ty à Hyperkalemia, Hyponatremia, Gyanecomastia

nb Per i toneo-Venous Shunt (PVS) is Use fu l in the Treatment o f Re f rac tory Asc i tes

                       

Spontaneous bacter ia l per i ton i t i s (SBP) Et io logy Most common pathogens à Gram negative Enterobactericeae ( E.Coli, Klebsiella pneumonia)

R isk fac tors

1. Low ascetic fluid albumin concentration (fluid albumin <10g/L) 2. Coexisting GI bleeding 3. Severe hepatic insufficiency

Ear ly D iagnos is o f

SBP

D iagnost ic paracentes is • If symptoms / signs of SBP occur • Unexplained encephalopathy and / or renal dysfunction • At any hospital admission

D iagnos is based on asc i t i c f lu id § PMN count >250/mm3

Acute t reatment

T reatment

• Recommended antibiotics for initial empiric therapy • i.v. cefotaxime, amoxicillin-clavulanic acid • oral norfloxacin (uncomplicated SBP)

• Minimum duration: 5 days • Re-evaluation if ascitic fluid PMN count has not decreased by at least 25% after 2 days of treatment

SBP 2ry prophy lax is

Hepatorena l syndrome

Character is t i cs 1. Renal failure in patients with cirrhosis, advanced liver failure and severe sinusoidal portal hypertension 2. Absence of significant histological changes in the kidney (“functional” renal failure) 3. Marked arteriolar vasodilation in the extra-renal circulation 4. Marked renal vasoconstriction leading to reduced glomerular filtration rate

C r i te r ia to dx

Ma jor cr i ter ia M inor cr i ter ia 1. Advanced hepatic failure and portal hypertension 2. Creatinine > 1.5 mg/dL or creatinine clearance < 40 ml/min 3. Absence of shock, bacterial infection, or nephrotoxic drugs 4. Absence of excessive gastrointestinal or renal fluid loss 5. No improvement in renal function after plasma volume expansion

with 1.5 L of isotonic saline 6. Urinary protein < 500 mg/dL and normal renal ultrasound

Urine Sodium and Urine Volume • Urine sodium <10 mEq/L • Urine osmolality > plasma osmolality • Serum sodium < 130 mEq/L • Urine volume < 500 ml/day • Urine RBCs < 50/HPF

Types

Type 1 Type 2 • Rapidly progressive renal failure (2 weeks) • Doubling of creatinine to >2.5 or halving of creatinine clearance

(CrCl) to <20 ml/min

• More slowly progressive • Creatinine >1.5 mg/dL or CrCl < 40 ml/min • Associated with refractory ascites

Management

Proven e f f i cacy à Liver transplantation Under invest igat ion

• Vasoconstrictor + albumin • Transjugular intrahepatic portosystemic shunt (TIPS) • Vasoconstrictor + TIPS • Extracorporeal albumin dialysis (ECAD)

Ine f fec t ive • Renal vasodilators (prostaglandin, dopamine) • Hemodialysis

   

 Hepat ic encepha lopathy

Pathophys io logy

Types Type A à Associated with Acute liver failure Type B à Associated with porto-systemic Bypass without intrinsic hepatocellular disease Type C à Associated with Cirrhosis and porto-systemic shunting

Character is t i cs

Type A Type C § Rapid onset § Frequently fatal

§ Main cause à cerebral edema

§ Treatment à rarely effective short of liver transplant

§ Gradual onset § Rarely fatal

§ Main cause à shunting / toxin § Precipitant

§ Treatment à usually effective S tages Confusion à drowsiness à somnolence à coma

Nb

Hepatic Encephalopathy Is A Clinical Diagnosis • Clinical findings and history important • Ammonia levels are unreliable • Ammonia has poor correlation with diagnosis • Measurement of ammonia not necessary • Number connection test • Slow dominant rhythm on EEG

T reatment

1. Identify and treat precipitating factor a. Infection b. GI hemorrhage c. Prerenal azotemia d. Sedatives e. Constipation

2. Lactulose (adjust to 2-3 bowel movements/day) 3. Protein restriction, short-term (if at all)