Managing Complications of Cirrhosis Marion Peters MD University of California San Francisco

Natural History of ESLD Increasing liver fibrosis Development of HCC Chronic liver disease Compensated cirrhosis Decompensated cirrhosis Death or transplant Alcohol Hepatitis C/B NASH Cholestatic Autoimmune PSC Variceal hemorrhage Ascites Encephalopathy Jaundice HCC, hepatocellular carcinoma; NASH, nonalcoholic steacohepatitis Garcia Tsao CCO Hepatitis.com 2008

Natural History of ESLD Increasing liver fibrosis Development of HCC Chronic liver disease Compensated cirrhosis Decompensated cirrhosis Death or transplant Alcohol Hepatitis C/B NASH Cholestatic Autoimmune PSC Variceal hemorrhage Ascites Encephalopathy Jaundice HCC, hepatocellular carcinoma; NASH, nonalcoholic steacohepatitis Garcia Tsao CCO Hepatitis.com 2008

How to diagnose Cirrhosis Clinically- only useful in late stages Cirrhosis with portal hypertension Low platelets, spider nevi, splenomegaly, ascites Liver Biopsy Imaging Ultrasound- only of value in cirrhosis with portal hypertension Elastography Serum markers

METHODS TO STAGE FIBROSIS Liver Biopsy with Histologic Evaluation Percutaneous Laparoscopic Transjugular Elastography Transient elastography- FibroScan Acoustic Radiation Force Impulse (ARFI) MRI Serum Biomarkers Common Tests Laboratory/ Commercial tests

Transient Elastography

TRANSIENT ELASTOGRAPHY Measures elasticity using sound waves Stiffness determined by multiple factors Degree of Fibrosis Degree of Inflammation- not good for acute hepatitis Degree of Steatosis Not effective in morbidly obese patients >3.5cm Approved in U.S. 4-2013 now have XL probes J Gastrointestin Liver Dis. 2008 Jun;17(2):155-163

Elastography: HCV Fibroscan 2.5 kPa Cholestasis F4 14.5 kPa Affected by weight, access of probe (2 cm), steatosis

Natural history of ESLD Transition to decompensated cirrhosis: 5% to 7% of patients per year. Best predictor of decompensation: hepatic venous pressure gradient (HVPG) > 10 mm Hg HCC can trigger decompensation Tools for predicting disease severity and death in decompensated cirrhosis Child-Turcotte-Pugh (CTP) score Model for End-Stage Liver Disease (MELD) score D’Amico 2006

Child-Pugh-Turcotte Score Points 1 (normal) 2 3 Hepatic encephalopathy None 1-2 3-4 Ascites slight mod Bilirubin <2 2-3 >3 Albumin >3.5 2.8-3.5 <2.8 PT <4 secs  4-6 secs >6 secs or INR <1.7 1.7-2.3 >2.3 A: 5-6; B: 7-9; C: > 9

MELD: Model for End-Stage Liver Disease Bilirubin 2 5 5 5 INR 1.1 2.0 2.0 3.0 Creatinine 1.0 1.0 2.0 2.0 MELD 10 20 27 31

Complications of cirrhosis Portal hypertension Variceal hemorrhage Ascites Encephalopathy Jaundice

Portal Hypertension An increase in the blood pressure around the liver called the portal venous system. Veins coming from the stomach, intestine, spleen, and pancreas merge into the portal vein, which then branches into smaller vessels and travels through the liver

Complications of cirrhosis Variceal hemorrhage Ascites Encephalopathy Jaundice

Risk of Bleeding from Esophageal Varices Cirrhosis 25%-40% Prevalence 35%-80% 50%-70% 30%-50% Survive Die 70% Rebleed 17

Variceal Surveillance All cirrhotics require Esophagogastroduodenoscopy No varices Small varices (< 5 mm), Child B/C Medium or large varices Repeat endoscopy in 3 years (well compensated); in 1 year if decompensated No beta-blocker prophylaxis Child Class A, no red wales: beta blockers Child class B/C, red wales: beta blockers or band ligation Nonselective Beta-blocker prophylaxis Garcia-Tsao G, et al. Hepatology. 2007;46:932-938. 18

Complications of cirrhosis Variceal hemorrhage Ascites Encephalopathy Jaundice

Stages of ascites Diuretic-responsive ascites Refractory ascites Hyponatremia Hepatorenal syndrome (HRS) Each stage reflects a more deranged circulatory state.

Treatment of ascites Diuretic-responsive ascites Refractory ascites Sodium restriction- you have normal amount of Na- too much water Spironolactone (75-100 mg) and furosemide (20-40 mg) Refractory ascites Large volume paracentesis with 25% albumin (50 cc/L) For symptom management TIPS- higher transplant free survival but higher PSE (confusion)

Ascites: LVP Albumin Albumin infusion after large-volume paracentesis (LVP) Meta-analysis of 17 trials involving 1,225 patients showed that albumin improved survival Albumin infusion is recommended when more than 4 Liters of ascitic fluid are removed Albumin infusion may not be necessary for a single paracentesis of less than 4 L (AASLD guidelines) (Bernardi Hepatology 2012)

Hepatorenal syndrome (HRS) Acute renal failure occurs in 14% to 25% of hospitalized patients with cirrhosis Most common form of prerenal failure (accounting for 60% to 80% of the cases)

Hepatorenal syndrome results from vasodilatation and marked reduction in effective arterial blood volume leading to renal vasoconstriction occurs in patients with unresponsive or refractory ascites and/or low sodium (hyponatremia)

HRS treatment OLT Midodrine and octreotide HRS due to extreme splanchnic and systemic vasodilatation Drugs  vasoconstriction Albumin to increase intravascular volume

Spontaneous bacterial peritonitis (SBP) Most common type of bacterial infection in hospitalized cirrhotic patients Clinical suspicion: unexplained encephalopathy, jaundice worsening renal failure <50%: fever, abdominal pain or tenderness, and leukocytosis Diagnose: tap ascites: WCC>500, PMN > 250 cells/mm3 Place ascites in blood culture bottles Start treatment immediately before culture results

Complications of cirrhosis Variceal hemorrhage Ascites Encephalopathy Jaundice

Hepatic Encephalopathy Confusion resulting from the liver not processing toxins from the gut Precipitants Infection- especially SBP or UTI Bleeding Electrolyte imbalance Portal vein thrombosis Worsening liver disease HCC

Hepatic Encephalopathy Treatment aims to reduce production of ammonia from the colon through nonabsorbable disaccharides lactulose, lactitol, and lactose Induce diarrhea Change gut bacteria to sugar from protein nonabsorbable antibiotics neomycin, rifaximin

Hepatic Encephalopathy Protein restriction promotes protein degradation and, if maintained for long periods, worsens nutritional status and decreases muscle mass No longer recommended Night- time snacks

Indications for Liver Transplantation Development of decompensation (liver dysfunction, MELD >12, ascites, variceal bleed, encephalopathy) in patients with cirrhosis HCC that is confined to the liver by Milan criteria: 1 lesion <5 cm or 3 lesions < 3 cm UCSF criteria <6.5 cm total Adherent, no drug use, alcohol, adequate support No extrahepatic disease

Liver Transplantation MELD Serum sodium Underestimated chronic encephalopathy- confusion hepatic hydrothorax- fluid around the lung hepatopulmonary syndrome- low oxygen portopulmonary hypertension- high pressure Recurrent cholangitis- infection

MELD: Model for End-Stage Liver Disease Bilirubin 2 5 5 5 INR 1.1 2.0 2.0 3.0 Creatinine 1.0 1.0 2.0 2.0 MELD 10 20 27 31

Managing complications of cirrhosis Portal hypertension elastography can be used to assess severity of fibrosis/cirrhosis Can measure Portal hypertension Variceal hemorrhage monitor varices with endoscopy

Managing complications of cirrhosis Ascites Need to decrease fluid in body not salt Low salt diet LVP treats symptoms TIPS decreases pressure around liver but increases risk of confusion

Managing complications of cirrhosis Encephalopathy Monitor closely may be subtle Treat infection aggressively Nutrition different in cirrhosis Consider OLT when first liver decompensation occurs