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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?

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

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

HAND FINDINGS IN CIRRHOSIS

EFFECTS OF CIRRHOSIS: LABS

• 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: ASCITESAscites 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• What is SAAG?

• Ascites can be managed initially with sodium restriction <2g/d

• If moderate ascites, use spironolactone 100-200mg/d and can add furosemide 40-80mg/d

• 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 BLEEDUpper 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 SyndromeCaused by renal vasoconstrictionLow UOP, low urine sodium10% patients with advanced cirrhosis, usually those with large ascites

Type 1 versus Type 2Treated with midodrine, octreotide, IV albuminPrognosis for Type 1 is poor unless transplanted

CARE OF THE CIRRHOTIC PATIENT: ENCEPHALOPATHYHEPATIC ENCEPHALOPATHY

Caused by gut derived neurotoxins normally removed by liver

Disturbance in diurnal sleep patterns is an early sign

Brain edema can cause herniationAsterixis, hyperreflexiaPrecipitants of HE: hypokalemia, infection, increased protein, GIB, dehydration

TREATMENT: Lactulose, rifaximin, zinc

CARE OF THE CIRRHOTIC PATIENT: PULMONARY COMPLICATIONSHEPATOPULMONARY 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: CARDIOMYOPATHYCIRRHOTIC 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: COAGULOPATHYCoagulopathy 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