1. COMPLICATIONS OF CIRRHOSIS
May 2018
UCI Internal Medicine

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

3. 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.

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

5. HEPATIC ENCEPHALOPATHY: DIAGNOSIS
Cognitive impairment
disturbance in sleep pattern (insomnia, hypersomnia), typical initial symptom
mood changes, attention deficits, slow reaction, coma
Neuromuscular impairment
asterixis (
bradykinesia, hyperreflexia, rigidity, myoclonus, focal deficits
Ammonia elevation
Not required to make diagnosis
video links to youtube of asterixis

6. 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

7. 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 ($44/550mg dose) vs lactulose ($ / 20g dose)

8. 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 mcg 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

9. 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)

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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: /jama
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):