COMPLICATIONS OF CIRRHOSIS May 2018 UCI Internal Medicine

OBJECTIVES: Describe the most common complications of cirrhosis Hepatic Encephalopathy Esophageal/gastric Varices Ascites Hepatocellular Carcinoma Hepatorenal Syndrome

Case 57 year old male with recently diagnosed alcoholic cirrhosis presenting to the ED with 1 day of melena. On exam, he appears confused & disoriented. He is a jaundiced male with icteric sclera and his abdomen is distended with a fluid wave. His labs are notable for a Hgb of 8 (baseline 11) and creatinine of 2.3 (baseline 1.0). What are possible causes of the melena? What are possible causes of his AKI? What can be done regarding his confusion? Think about this case, we will return to it later.

MAJOR COMPLICATIONS Hepatic Encephalopathy Esophageal & Gastric varices Ascites Hepatocellular carcinoma Hepatorenal syndrome

HEPATIC ENCEPHALOPATHY: DIAGNOSIS Cognitive impairment disturbance in sleep pattern (insomnia, hypersomnia), typical initial symptom mood changes, attention deficits, slow reaction, coma Neuromuscular impairment asterixis (https://www.youtube.com/watch?v=9Oog_w2xNq0) bradykinesia, hyperreflexia, rigidity, myoclonus, focal deficits Ammonia elevation Not required to make diagnosis video links to youtube of asterixis https://musculoskeletalkey.com/screening-for-hepatic-and-biliary-disease/

HEPATIC ENCEPHALOPATHY: PRECIPITATING FACTORS GI bleed Infection Metabolic derangements Renal failure Hypovolemia Medications / Medication nonadherence Constipation Other Gi bleed: variceal, PUD, or other causes of GI bleed. Infection: SBP, UTI, bacteremia, etc. Metabolic derangements: hypokalemia, other electrolyte disturbances, alkalosis, hypoxia, hypoglycemia Medications such as sedatives Others include HCC, portal or hepatic vein thrombosis

HEPATIC ENCEPHALOPATHY: TREATMENT Nutrition support, avoid dehydration & electrolyte abnormalities Correct precipitating cause Lactulose (20-30g 3-4x daily, titrate to 2-3 BM) +/- rifaximin (400mg TID or 550mg BID) Initially lactulose. If no improvement in 48 hours, add Rifaximin (or consider another cause) Lactulose + Rifaximin has been shown to improve mortality and decrease hospital stay vs lactulose alone (Sharma et al, 2013) Rifaximin is very expensive though ($44/550mg dose) vs lactulose ($0.10-0.20/ 20g dose)

ESOPHAGEAL/GASTRIC VARICES Due to portal hypertension High risk for bleeding, and can be brisk as it is a higher pressure system If none, have low threshold to treat ABCs (airway, breathing, circulation) PPI Octreotide (bolus of 50-100mcg followed by continuous 25-50mcg/hr x 72 hours) Ceftriaxone (shown to improve mortality, rebleeding risk, hospital days) Up to 20% of variceal bleeders have infection at time of presentation Up to 50% will develop an infection Transfuse no to goal Hgb of 8 Endoscopic intervention banding, sclerotherapy, Blakemore tube Assess for prior screening EGD but still have high suspicion in cirrhotic with GI bleed, especially if brisk bleed Terlipressin (instead of octreotide as somatostatin analog) used in Europe with improved mortality Other antibiotics: norfloxacin (not available but studied) & ciprofloxacin (use oral cipro if need to complete course of treatment) Transfusion >8 associated with increasing portal pressure, therefore increasing rebleeding rates

VARICEAL BLEED PROPHYLAXIS Given to those with high risk varices (“red wale”) OR Child-Pugh class B or C OR those with medium/large varices Nonselective Beta blockers Propanolol Nadolol Endoscopic Variceal Ligation (banding) risk for bleeding from banding site ulcerations Red wale (up to date)

ASCITES Most common complication of cirrhosis Due to portal hypertension On initial presentation, will need a diagnostic paracentesis Cell counts, SAAG, total protein SAAG >1.1, Total Protein <2.5 Spontaneous Bacterial Peritonitis: PMN >250 Treat with diuretics Aldactone:furosemide typically starting at 100mg:40mg typically some form of 5:2 dosing -wikipedia

HEPATOCELLULAR CARCINOMA All cirrhotic patients should be screened Annual incidence in cirrhotic patients in 1.5 percent Approach to surveillance per AASLD guidelines: Ultrasound every 6 months Sensitivity for US alone: 78% for HCC at any stage, 45% for HCC at early stage Alpha fetoprotein (AFP) every 6 months Increases sensitivity to 97% for HCC at any stage, 63% for HCC at early stage AASLD = American Association of Liver Diseases New data puts into question whether surveillance actually decreased mortality

HEPATORENAL SYNDROME One of many causes of AKI in cirrhosis Rise in creatinine, low urine sodium (<10), no proteinuria, oliguria Exclude other causes of AKI (i.e. a diagnosis of exclusion) Treatment: If critically ill: norepinephrine + albumin (1g/kg/day x2d) If not critically ill: Midodrine + Octreotide + albumin in other countries, Terlipressin + albumin

Case 57 year old male with recently diagnosed alcoholic cirrhosis presenting to the ED with 1 day of melena. On exam, he appears confused & disoriented. He is an obese, jaundiced male with icteric sclera and his abdomen is distended with a fluid wave. His labs are notable for a Hgb of 8 (baseline 11) and creatinine of 2.3 (baseline 1.0). What are possible causes of the melena? What are possible causes of his AKI? What can be done regarding his confusion? gastroesophageal varices, PUD, gastropathy, AVMs, mallory weiss, cancer Hypovolemia, medicorenal disease, medication effects, HRS Check ammonia, but would likely treat with lactulose (+/- rifaximin) even if normal

Summary Hepatic encephalopathy has many precipitating factors Many of complications of cirrhosis are due to portal hypertension e.g. varices, ascites There are many causes of GI bleeds & AKI in cirrhotic patients Variceal bleeds can be brisk and dangerous, always ensure ABCs are addressed first New onset ascites should be assessed with paracentesis

RESOURCES Up-to-date Udell JA, Wang CS, Tinmouth J, et al. Does This Patient With Liver Disease Have Cirrhosis?. JAMA.2012;307(8):832–842. doi:10.1001/jama.2012.186 https://www.cdc.gov/nchs/fastats/liver-disease.htm Sharma, Barjesh Chander, et al. "A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy." The American journal of gastroenterology 108.9 (2013): 1458. Garcia‐Tsao, Guadalupe, et al. "Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis." Hepatology 46.3 (2007): 922-938.