Download Cirrhosis of the liver

CIRRHOSIS OF THE LIVER: OUTLINE
1. The Case
2. Histology
3. Etiology of Cirrhosis
4. Ecology of Cirrhosis
5. The Care of the Cirrhotic patient
6. Back to the Case
THE CASE
33 YO Female with right upper quadrant abdominal pain
THE CASE
Liver biopsy revealed:
GRANULOMATOUS HEPATITIS CONSISTENT WITH SARCOIDOSIS
Treatment:
Prednisone for one month
Outcome:
She felt well and returned to work as a professional dancer
NORMAL LIVER: HISTOLOGY
WHAT CAUSES CIRRHOSIS?
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Repeated insults  oxidative damage Kupffer and
stellate cell activation  production of excess
collagen and extracellular matrix
Alcoholism
Chronic viral hepatitis
Autoimmune hepatitis
NASH
Biliary cirrhosis (PBC, PSC, autoimmune
cholangiopathy)
Cardiac cirrhosis
Inherited metabolic liver disease (hemochromatosis,
Wilson’s disease, AAT deficiency, CF)
Cryptogenic cirrhosis
CIRRHOTIC LIVER: HISTOLOGY
INJURY
DEGENERATION
FIBROSIS
FORMATION OF FIBRO-VASCULAR
MEMBRANES
• PARENCHYMAL DISSECTION INTO
NODULES
• REARRANGEMENT OF
CIRCULATION
• CIRRHOSIS
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EFFECTS OF CIRRHOSIS: PHYSICAL EXAM
JAUNDICE AND SCLERAL ICTERUS
ASCITES
EDEMA
HEMORRHOIDS
SPLENOMEGALY
FIRM, NODULAR LIVER EDGE
PALMAR ERYTHEMA
SPIDER ANGIOMAS
CAPUT MEDUSAE
PAROTID GLAND ENLARGEMENT
DIGITAL CLUBBING
MUSCLE WASTING
MEN: DECREASED BODY HAIR, GYNECOMASTIA, TESTICULAR
ATROPHY
• WOMEN: METRORRHAGIA OR AMENORRHEA
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HAND FINDINGS IN CIRRHOSIS
EFFECTS OF CIRRHOSIS: LABS
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CAN BE COMPLETELY NORMAL IN EARLY COMPENSATED CIRRHOSIS
• IN ADVANCED LIVER DISEASE…
• ANEMIA: CHRONIC GIB, POOR NUTRITION, HYPERSPLENISM, BONE MARROW
SUPPRESION, ZIEVE’S SYNDROME (HEMOLYTIC ANEMIA WITH SPUR CELLS AND
ACANTHOCYTES)
• THROMBOCYTOPENIA
• NORMAL OR ELEVATED TOTAL BILIRUBIN AND ELEVATED DIRECT BILIRUBIN
• PROLONGED PT
• HYPONATREMIA WITH ASCITES
• TRANSAMINITIS
CARE OF THE CIRRHOTIC PATIENT:
CLASSIFICATION OF SEVERITY
CARE OF THE CIRRHOTIC PATIENT:
CLASSIFICATION OF SEVERITY
CARE OF THE CIRRHOTIC PATIENT:
CLASSIFICATION OF SEVERITY
CARE OF THE CIRRHOTIC PATIENT
FACTORS THAT PREDISPOSE CIRRHOTIC PATIENTS TO
DECOMPENSATE:
• BLEEDING
• INFECTION
• ALCOHOL INTAKE
• MEDICATIONS
• DEHYDRATION
• CONSTIPATION
• OBESITY
CARE OF THE CIRRHOTIC PATIENT: ASCITES
Ascites is the most common complication of cirrhosis
• Caused by Portal Hypertension (hepatic venous
pressure gradient >5mmHg) which is caused by..
• Increased intrahepatic resistance
• Increased splanchnic blood flow due  increased
splanchnic lymph
• Ascites accumulates when…
• Hypoalbuminemia  decreased oncotic pressure
• Sodium retention  perpetuates third spacing
• Labs to obtain when performing paracentesis:
albumin, protein, cell count and diff, culture, gram
stain, AFB, fungal culture, cytology, amylase, lipase,
TGs
CARE OF THE CIRRHOTIC PATIENT: ASCITES
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What is SAAG?
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Ascites can be managed initially with sodium restriction <2g/d
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If moderate ascites, use spironolactone 100-200mg/d and can add furosemide
40-80mg/d
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For refractory ascites, consider repeat LVP or TIPS procedure
• For repeat LVP, always replace albumin if drain > 5L
CARE OF THE CIRRHOTIC PATIENT: SBP
Spontaneous Bacterial Peritonitis
• 25% in-hospital mortality rate
• ‘Spontaneous’ due to bacterial translocation
• Most common organism: Escherichia coli, and gram positives sometimes
found such as Strep viridans, Staph and Enterococcus
• If >2 organisms, consider perforated viscus
How do we diagnose SBP?
 History, PEX, labs
How do we treat SBP?
 2nd generation cephalosporin
Who should use SBP prophylaxis?
 Upper GI Bleed patients
 Previous SBP
 Ascitic fluid protein < 2.0
CARE OF THE CIRRHOTIC PATIENT: GI BLEED
Upper GI bleed secondary to esophageal or gastric varices
PRIMARY PROPHYLAXIS
• All patients diagnosed with cirrhosis should have EGD
• Increased risk: Red wale sign, hmetocystic spots, cherry-red or white-nipple
spots, blue or erythematous
• IR can measure gradient between wedge and free hepatic vein; if >12 mmHg at
risk for variceal hemorrhage
• Nadolol or propanolol
• EVL
SECONDARY PROPHYLAXIS: repeat EVL and beta-blockers
ACUTE VARICEAL BLEED TREATMENT
• IVF, blood products
• Somatostatin
• Balloon tamponade
• Sclerotherapy
• EVL
• GAVE: EVL wont work, perform TIPS
CARE OF THE CIRRHOTIC PATIENT: HRS
Hepatorenal Syndrome
Caused by renal vasoconstriction
Low UOP, low urine sodium
10% patients with advanced cirrhosis, usually those
with large ascites
Type 1 versus Type 2
Treated with midodrine, octreotide, IV albumin
Prognosis for Type 1 is poor unless transplanted
CARE OF THE CIRRHOTIC PATIENT:
ENCEPHALOPATHY
HEPATIC ENCEPHALOPATHY
Caused by gut derived neurotoxins normally removed
by liver
Disturbance in diurnal sleep patterns is an early sign
Brain edema can cause herniation
Asterixis, hyperreflexia
Precipitants of HE: hypokalemia, infection, increased
protein, GIB, dehydration
TREATMENT: Lactulose, rifaximin, zinc
CARE OF THE CIRRHOTIC PATIENT: PULMONARY
COMPLICATIONS
HEPATOPULMONARY SYNDROME
• Platypnea and orthodeoxia
• Triad: liver disease, increased A-a gradient, Intrapulmonary vascular abnormalities
PORTOPULMONARY HYPERTENSION
• Pulmonary hypertension in patients with portal hypertension
• 2% of patients with cirrhosis
• Fatigue, dyspnea, peripheral edema, CP, syncope
HEPATIC HYDROTHORAX
 PLEURAL FLUID IN A PATIENT WITH ASCITES AND NO CARDIOPULMONARY DISEASE
 THROUGH DEFECTS IN DIAPHRAGM
 USUALLY R SIDED
CARE OF THE CIRRHOTIC PATIENT:
CARDIOMYOPATHY
CIRRHOTIC CARDIOMYOPATHY
• Up to 50% of patients with advanced cirrhosis
• Normal to increased CO and contractility at rest but blunted response to stress
• Diastolic dysfunction
• QRS widening
• Caused by abnormalities in the β-adrenergic signaling pathway, altered
cardiomyocyte membrane fluidity, increased myocardial fibrosis, cardiomyocyte
hypertrophy, and ion channel defects
• Acute volume overload (TIPS, transplant) or increased demand for CO (infection)
can lead to heart failure
• Treatment: Beta blockade?
CARE OF THE CIRRHOTIC PATIENT:
COAGULOPATHY
Coagulopathy is almost universal in cirrhotic patients
• Decreased synthesis of clotting factors and impaired clearance of
anticoagulants
• Thrombocytopenia
• Vitamin K requires biliary excretion for subsequent absorption so
this process is diminished
• Decreased hepatic mass means decreased synthesis of
• Which factors are affected?
TREATMENT: IV or IM vitamin K, FFP, platelets
CARE OF THE CIRRHOTIC PATIENT: HCC
Chronic liver disease is the major risk factor for developing HCC.
Most patients with HCC have underlying cirrhosis
Environmental Factors: Food contaminated with aflatoxin and smoking increase
risk
• Corns, soybeans, peanuts
Diabetes is associated with HCC, and treating with metformin decreases risk
Co-infection with HIV increases risk
SURVEILLANCE: HBV carriers and all patients with cirrhosis
• Liver US every 6 mos (+/- AFP level)
• If liver nodule found, <1cm get repeat in 3 mos; if >1cm  further
imaging
TREATMENT:
• OLT for patients who meet Milan criteria (single tumor <5cm or <3 tumors
each <3cm, no macrovascular invasion
• Resection
• TACE
• Ablation
• XRT
• Chemotherapy
BACK TO THE CASE
33 YO F with infiltrative liver disease secondary to sarcoidosis
• Initially treated with course of prednisone for one month, did well
• 5 mos later developed dyspnea after one flight of stairs  stopped
smoking
• 3 mos after that developed melena and syncope
• Finally presented to MGH where she had following workup:
EGD showed varices, gastritis and CT showed hepatosplenomegaly
TTE showed dilated RA + RV and TR
R Heart Cath showed elevated PA pressures not improved with NO
On 6th hospital day after pt developed agitation, AMS, asterixis,
worsening SOB she had cardiac arrest and died
FINAL DIAGNOSIS: HEPATIC CIRRHOSIS DUE TO END STAGE
PRIMARY BILIARY CIRRHOSIS AND PLEXOGENIC PULMONARY
HYPERTENSION DUE TO CIRRHOSIS, WHICH CAUSED COR
PULMONALE
Take care of me and
I’ll take care of you!
That’s all folks,
Thanks!
THE END