Cirrhosis Management – A Case Based
Approach to Disease Management
Brenda Appolo PAC, MHS
University of Pennsylvania, Perelman School of Medicine
Causes of Cirrhosis
Hepatitis C
Alcohol
Hepatitis B
Hemochromatosis
Wilson’s Disease
Alpha-1-Antitrypsin
Deficiency
• DILI
•
•
•
•
•
•
• Primary Biliary
Cirrhosis
• Autoimmune chronic
hepatitis
• Primary Sclerosing
Cholangitis
• Cryptogenic
• Non-Alcoholic
Steatohepatitis
Case
• Carl is a 56 M presents to ED with hematemesis
• PMHx:
– HCV infection dx years prior but IFN unwilling
– HTN
• SHx:
– Blood transfusion age
– 2 six packs beer per week; former TOB user; married; FT worker
• Exam:
– BP 90/60; HR 100; BMI 31; No icterus on exam; Abdomen soft;
splenomegaly; +1 pedal edema
• Labs
– Hg 8.0; Hct 25%; 89k; WBC 7.1
– Glu 136; cr 0.57; AlkPhos 114; T bil 1.4; AST 66; ALT 46; INR 1.3
Portal Hypertensive Bleeding
Esophgaeal Varices
Gastric Varices
Portal Hypertensive Gastropathy
Colopathy / Rectal Varices
band ligation
s/p ligation at 4' bleeding stopped w
ethanolamine
bleeding stopped w
ethanolamine
Risk of Esophageal Varices
Bleed
35-80 %
25-40 %
Cirrhosis
50-70 %
Survive
Rebleed
70 %
30-50 %
Die
Esophago-Gastric Varices
• Screening and follow up
• Primary Prophylaxis
Varices diagnosed and what do we do?
• Secondary Prophylaxis
Varices bled and what do we do to prevent rebleeding?
Cirrhosis
Upper Endoscopy
Small varices (< 5 mm),
Child B/C,red wales
No varices
Repeat Endoscopy in 3
years (well compensated);
in 1 year if
decompensated
NO beta-blocker
prophylaxis
Non-selective betablocker prophylaxis
Titrate to HR of 55-60
Medium or
large varices
Child Class A,no red wales-beta
blockers
Child class B/C,red wales-beta
blockers OR band ligation
If prophylaxis not used-repeat
endoscopy in 1-2 years
Gacia-Tsao et al Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis AASLD Practice Guideline: Hepatology
2007;46:922-38
Mechanisms of Action of Various Therapies for
Varices
Treatment
Flow
Vasoconstrictors
(e.g.-blockers)
Venodilators
(nitrates)
Vasoconstrictors +
venodilators
Endoscopic Therapy
TIPS/Shunt Surgery
?
Resistance
Portal Pressure
Case – continued (Carl)
• Carl undergoes serial EGD to obliterate varices;
placed on beta blocker
• Remains IFN unwilling; stopped alcohol
• 2 years later presents with increased
abdominal girth and dyspnea; wife is
concerned about his fatigue and odd behavior
this AM
• Presents to ED; no imaging on file x 1 yr
• Exam –
– BP 90/60; HR 62; Weigh > 20lbs since last ED visit;
+ tense abd; alert and oriented
Ascites
- SBP
Ascites in Cirrhosis : Diagnosis
• Physical Exam/Ultrasound:
– 1.5 - 3 liters: Shifting dullness
– 10 liters: fluid wave
• Paracentesis (1% hematoma)
– No need for FFP or Platelet transfusion
– Helps in differential diagnosis
– 20% prevalence of infection at admission
– Indication: new onset; admitted to hospital with or without
symptoms of abdominal pain, fevers, etc; those who
deteriorate during hospitalization
Management of Ascites
First Line Therapy
Second Line Therapy
Tense ascites
Refractory Ascites 10 %
• Repeated Large volume
paracentesis (LVP)
•TIPS
Paracentesis
• Liver Transplantation
Sodim restriction ( 2 Gm/24 Hrs) and diuretics
•Post paracentesis albumin infusion
may not be necessary for < 5 liters removed
Non-tense ascites
•Diuretics: Spironolactone 100 mg/day, furosemide
40 mg/day or bumetanide 1 mg a day.
•Uptitrate stepwise to spironolactone 400 mg/day,
furosemide 160 mg/day or bumetanide 4 mg/day
as long as it is tolerated
• Albumin infusion of 6-8 gm/liter of fluid
removed is a consideration for repeated LVP
Etiology of Ascites
Congestive Heart Failure Tuberculosis
Other
Malignancy
Cirrhosis
5% Mixed
100
80
Survival 60
(%)
40
20
1
Onset
2
3
Years
4
5
6
Ascites Survival: Only improved by liver transplant
100
80
After Liver Transplant
Survival 60
(%)
40
20
1
Onset
2
3
Years
4
5
6
Ascitic Fluid Analysis
ROUTINE
OPTIONAL
Cell count
Glucose TB smear/culture
LDH
Cytology
Albumin
Gram Stain
Culture
(blood-cultures)
Total Protein
Amylase
UNUSUAL
Ascitic Fluid Infection
• Spontaneous bacterial peritonitis
• Monomicrobial non-neutrocytic bacterascites
• Culture-negative neutrocytic ascites
Spontaneous Bacterial Peritonitis
• PMN count > 250 cells/mL
• Positive ascites culture
• No evidence of intra-abdominal source
requiring surgery
Secondary Bacterial Peritonitis
• PMN count > 250 cells/mL
– (total WBC usually > 10,000)
– Total Protein > 1 g/dL, elevated LDH,
glucose < 50 mg/dL ( 2 of 3 features)
• Positive ascites culture
– (usually multiple organisms)
• Ascites CEA > 5 ng/ml, Alkaline Phophatase > 240 U/L helpful is identifying intra-abdominal surgically treatable
primary source of infection
Overview of Hepatic Encephalopathy
• Encompasses a wide spectrum of neuropsychiatric
abnormalities in patients with liver dysfunction
• Characterized by
– Disturbances in consciousness
– Changes in personality and intellectual capacity
– High blood ammonia (NH3) levels
– Altered neuromuscular activity
– EEG abnormalities
EEG = electroencephalogram.
Abou-Assi et al. Postgrad Med. 2001;109:52-70. Ferenci et al. Hepatology. 2002;35:716-721. Mas et al. J
Hepatol. 2003;38:51-58.
Treatment Options for HE
• Reduction in the nitrogenous load arising from the gut
– Bowel cleansing
– Nonabsorbable disaccharides (lactulose)
– Antibiotics (rifaximin, neomycin, metronidazole)
• Drugs that affect neurotransmission
(flumazenil, bromocriptine)
• Manipulation of the splanchnic circulation
(occlusion of portal-systemic collaterals)
HE = hepatic encephalopathy.
Blei et al. Am J Gastroenterol. 2001;96:1968-1976.
Transjugular Intrahepatic Portosystemic
Shunt and Surgical Shunts
Placement of TIPS
Catheter
Inferior vena cava
Hepatic veins
TIPS
Left gastric vein
Portal vein
Superior mesenteric vein
Inferior mesenteric
vein
Indications and Efficacy of TIPS
Efficacy
Effective
Mortality
Secondary prevention of Variceal Bleeding
Yes
No Effect
Refractory Cirrhotic Ascites
Yes
No Effect
Efficacy in Absence of Another Therapy
Effective
Refractory Acutely Bleeding Varices
Yes
Portal Hypertensive Gastropathy
Yes
Gastric Antral Vascular Ectasia
No
Refractory Hepatic Hydrothorax
Yes
Budd Chiari Syndrome
Yes
Veno-Occlusive Disease
No
Etiology of Hepatocellular Carcinoma in the US
Other
HBV
4%
6%
Cryptogenic
Alcohol
10 %
12
%
29
%
39
%
Marrero JA Hepatology 36;1349-54:2002
HCV + Alcohol
HCV
Screening for Hepatocellular Carcinoma (HCC)
Screening is done with AFP and ultrasound every
6-12 months
• All patients with cirrhosis
• Hepatitis B
- Africans > 20 years
- Asian women > 50 years, men > 40 years
- Family H/O HCC
Guidelines for Diagnosis of HCC
Ultrasound findings
< 1 cm
1-2 cm
> 2 cm
Repeat US every 3-6
mo
Dynamic CT, contrast US
or MRI
Dynamic CT, contrast
US or MRI
2 tests
1 test
Typical = HCC
Typical = HCC
Atypical = biopsy
Atypical = biopsy
Typical features of HCC = vascular nodule on arterial phase
with washout in delayed phases
Bruix J, et al. Hepatology 2005
Current Treatment Options for HCC
Surgical
• Hepatic Resection
• Liver Transplantation
Non-surgical
• Transarterial
Chemoembolization(TACE)
• Ablation Therapy (RFA, PEI)
•Molecular targeted therapy
• Gene Therapy
Liver Transplantation for HCC
Milan Criteria
1 lesion ≤5 cm
3 or less lesions, none >3 cm
+
Absence of Macroscopic Vascular Invasion
Absence of Extra-hepatic Spread
Mazzaferro V, et al. N Engl J Med 1996;334:693–699.
Treatment of HCC
Surgical Resection vs. OLT vs. Ablation
1 yr
5 yr
• Resection
– Survival
74–96%
25–72%
• Liver Transplantation
– Survival
84–90%
69–75%
• Ablation (PEI)
– Survival
87–98%
29–54%
Summary: Complication of Cirrhosis
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•
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•
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Varices
Ascites / Refractory Ascites
Hepatic Encephalopathy
Hepatocellular Carcinoma
Synthetic Dysfunction (jaundice,
coagulopathy)