Cirrhosis Management – A Case Based Approach to Disease Management

Brenda Appolo PAC, MHSUniversity 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 VaricesPortal Hypertensive GastropathyColopathy / Rectal Varices

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

bleeding stopped w ethanolamine

Cirrhosis

35-80 %

Risk of Esophageal Varices

25-40 %

Die

30-50 %50-70 %

Survive

Rebleed70 %

Bleed

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?

Cirrhosis

Upper Endoscopy

No varices

Repeat Endoscopy in 3 years (well compensated);

in 1 year if decompensated

NO beta-blocker prophylaxis

Small varices (< 5 mm), Child B/C,red wales

Non-selective beta-blocker 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

Gacia-Tsao et al Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis AASLD Practice Guideline: Hepatology 2007;46:922-38

If prophylaxis not used-repeat endoscopy in 1-2 years

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

?

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

• 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

• 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

Ascites in Cirrhosis : Diagnosis

Management of Ascites

First Line Therapy Second Line Therapy

Tense ascites

Paracentesis

Sodim restriction ( 2 Gm/24 Hrs) and diuretics

Non-tense ascites

• Repeated Large volume paracentesis (LVP)

• TIPS

• Liver Transplantation

Refractory Ascites 10 %

• 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

• 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

Etiology of Ascites

Cirrhosis

Malignancy

Congestive Heart Failure Tuberculosis

Other

5% Mixed

20

40

60

80

100

1 2 3 4 5 6YearsOnset

Survival(%)

20

40

60

80

100

1 2 3 4 5 6YearsOnset

Survival(%)

Ascites Survival: Only improved by liver transplant

After Liver Transplant

Ascitic Fluid AnalysisAscitic Fluid Analysis

ROUTINE OPTIONAL UNUSUAL

Cell count Glucose TB smear/cultureAlbumin LDH Cytology

Gram StainCulture(blood-cultures)

Amylase

Total Protein

Ascitic Fluid InfectionAscitic Fluid Infection• Spontaneous bacterial peritonitis

• Monomicrobial non-neutrocytic bacterascites

• Culture-negative neutrocytic ascites

• Spontaneous bacterial peritonitis

• Monomicrobial non-neutrocytic bacterascites

• Culture-negative neutrocytic ascites

Spontaneous Bacterial PeritonitisSpontaneous Bacterial Peritonitis

• PMN count > 250 cells/mL

• Positive ascites culture

• No evidence of intra-abdominal source requiring surgery

• PMN count > 250 cells/mL

• Positive ascites culture

• No evidence of intra-abdominal source requiring surgery

Secondary Bacterial PeritonitisSecondary 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

• 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

Hepatic veins

TIPS

Portal vein

Superior mesenteric vein

Inferior mesenteric vein

Left gastric vein

Inferior vena cava

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

HCV39 %

29 %

Cryptogenic

HCV + Alcohol12 %

Alcohol

10 %

HBV6 %

4 %

Other

Marrero JA Hepatology 36;1349-54:2002

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

< 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

Dynamic CT, contrast US or MRI

1 test

Typical = HCC

Atypical = biopsy

Typical features of HCC = vascular nodule on arterial phase with washout in delayed phases

Typical features of HCC = vascular nodule on arterial phase with washout in delayed phases

Ultrasound findingsUltrasound findings

Bruix J, et al. Hepatology 2005Bruix J, et al. Hepatology 2005

Current Treatment Options for HCC

Surgical Non-surgical

• Hepatic Resection• Liver Transplantation

• Transarterial Chemoembolization(TACE) • Ablation Therapy (RFA, PEI)• Molecular targeted therapy• Gene Therapy

+Absence of Macroscopic Vascular Invasion

Absence of Extra-hepatic Spread

1 lesion ≤5 cm 3 or less lesions, none >3 cm

Liver Transplantation for HCC Milan Criteria

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

• Varices• Ascites / Refractory Ascites• Hepatic Encephalopathy• Hepatocellular Carcinoma• Synthetic Dysfunction (jaundice,

coagulopathy)