1. Cirrhosis Management – A Case Based Approach to Disease Management
Brenda Appolo PAC, MHS
University of Pennsylvania, Perelman School of Medicine

2. Causes of Cirrhosis Hepatitis C Primary Biliary Cirrhosis 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

3. Case Carl is a 56 M presents to ED with hematemesis PMHx: SHx: Exam:
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

4. Portal Hypertensive Bleeding. Esophgaeal Varices. Gastric Varices
Portal Hypertensive Bleeding Esophgaeal Varices Gastric Varices Portal Hypertensive Gastropathy Colopathy / Rectal Varices

5. band ligation
s/p ligation at 4' bleeding stopped w ethanolamine
bleeding stopped w ethanolamine

6. Risk of Esophageal Varices
Bleed
35-80 %
25-40 %
Cirrhosis
50-70 %
30-50 %
Survive
Die
Rebleed
70 %

7. 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 re- bleeding?

8. Cirrhosis Upper Endoscopy No varices Medium or large varices
Small varices (< 5 mm), Child B/C,red wales
No varices
Medium or large varices
Non-selective beta-blocker prophylaxis
Titrate to HR of 55-60
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
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

9. Mechanisms of Action of Various Therapies for Varices
Treatment
Flow
Resistance
Portal Pressure
Vasoconstrictors
(e.g.-blockers)
Venodilators
(nitrates)
Vasoconstrictors + venodilators
Endoscopic Therapy
TIPS/Shunt Surgery ?

10. 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

11. Ascites - SBP

12. Ascites in Cirrhosis : Diagnosis
Physical Exam/Ultrasound:
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

13. Management of Ascites Paracentesis
First Line Therapy
Second Line Therapy
Tense ascites
Repeated Large volume paracentesis (LVP)
Refractory Ascites 10 %
Paracentesis
TIPS
Liver Transplantation
Sodim restriction ( 2 Gm/24 Hrs) and diuretics
Post paracentesis albumin infusion
may not be necessary for < 5 liters removed
Albumin infusion of 6-8 gm/liter of fluid
removed is a consideration for repeated LVP
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

14. Etiology of Ascites Malignancy Cirrhosis 5% Mixed Other
Congestive Heart Failure
Tuberculosis
Other
Malignancy
Cirrhosis
5% Mixed

15. 100 80
Survival
(%) 60 40 20 1 2 3 4 5 6
Onset
Years

16. Ascites Survival: Only improved by liver transplant
100 80
After Liver Transplant
Survival
(%) 60 40 20 1 2 3 4 5 6
Onset
Years

17. Ascitic Fluid Analysis
ROUTINE
OPTIONAL
UNUSUAL
Cell count
Glucose
TB smear/culture
Albumin
LDH
Cytology
Amylase
Gram Stain
Culture
(blood-cultures)
Total Protein

18. Ascitic Fluid Infection
Spontaneous bacterial peritonitis
Monomicrobial non-neutrocytic bacterascites
Culture-negative neutrocytic ascites

19. Spontaneous Bacterial Peritonitis
PMN count > 250 cells/mL
Positive ascites culture
No evidence of intra-abdominal source requiring surgery

20. 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 

21. 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: Ferenci et al. Hepatology. 2002;35: Mas et al. J Hepatol. 2003;38:51-58. 21

22. 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: 22

23. Transjugular Intrahepatic Portosystemic Shunt and Surgical Shunts

24. Placement of TIPS Catheter Inferior vena cava Hepatic veins TIPS
Left gastric vein
Portal vein
Inferior mesenteric vein
Superior mesenteric vein

25. Indications and Efficacy of TIPS
Effective
Mortality
Secondary prevention of Variceal Bleeding
Yes
No Effect
Refractory Cirrhotic Ascites
Efficacy in Absence of Another Therapy
Refractory Acutely Bleeding Varices
Portal Hypertensive Gastropathy
Gastric Antral Vascular Ectasia No
Refractory Hepatic Hydrothorax
Budd Chiari Syndrome
Veno-Occlusive Disease

26. Etiology of Hepatocellular Carcinoma in the US
Other
Alcohol
HBV
4 %
6 %
10 %
HCV + Alcohol
12 %
29 %
Cryptogenic
HCV
39 %
Marrero JA Hepatology 36; :2002

27. 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

28. 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
2 tests
Typical = HCC
Atypical = biopsy
1 test
Typical = HCC
Typical features of HCC = vascular nodule on arterial phase
with washout in delayed phases
Bruix J, et al. Hepatology 2005

29. Current Treatment Options for HCC
Surgical
Non-surgical
Hepatic Resection
Liver Transplantation
Transarterial
Chemoembolization(TACE)
Ablation Therapy (RFA, PEI)
Molecular targeted therapy
Gene Therapy

30. 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.

31. Treatment of HCC Surgical Resection vs. OLT vs. Ablation
1 yr yr
Resection
Survival –96% 25–72%
Liver Transplantation
Survival 84–90% 69–75%
Ablation (PEI)
Survival 87–98% 29–54%

32. Summary: Complication of Cirrhosis
Varices
Ascites / Refractory Ascites
Hepatic Encephalopathy
Hepatocellular Carcinoma
Synthetic Dysfunction (jaundice, coagulopathy)