CIRRHOSIS OF LIVER

Dr.Partha DasM.E.M. 2nd YearFortis Hospital, Kolkata16-05-2016

IMPACT OF CIRRHOSIS

• 11th-leading cause of death by disease in the US

• About 25,000 people die from the complications of cirrhosis/year; almost half of these are alcohol related

• A/c to the latest WHO data published in may 2014 Liver Disease Deaths in India reached 216,865 or 2.44% of total deaths.

(http://www.worldlifeexpectancy.com/india-liver-disease)

DEFINITION• Cirrhosis is defined as a diffuse process

characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodulesRef : Robbins’ & Cotran Pathologic Basis of Disease 8th Ed

• Cirrhosis is a generic term for an end stage of CLD characterized by destruction of hepatocytes & replacement of normal hepatic architecture with fibrotic tissue & regenerative nodules

Ref : Rosen's Emergency Medicine - Concepts and Clinical Practice 8 th Ed

(*kirros = orange, osis = condition – Greek)

Morphological Classification Macronodular (parenchymal nodules >3mm)

Micronodular (parenchymal nodules <3mm)

Etiology FrequencyChronic viral hepatitis 10-20%

Wilson’s disease Rare

Alpla1 antitrypsin ↓ Rare

Cryptogenic Common

Various drugs & toxins Rare

Etiology FrequencyAlcohol 60-70%

Primary biliary 5%

Hemochromatosis 5%

Cystic fibrosis Rare

CAUSES OF CIRRHOSIS• Alcoholism (Laennec’s Cirrhosis)• Chronic Viral Hepatitis (Hep.B/ Hep.C)• Autoimmune Hepatitis• Biliary Cirrhosis

Primary Biliary CirrhosisPrimary Sclerosing CholangitisAutoimmune Cholangiopathy

• Inherited Metabolic Liver Disease↓alpha-1 antitrypsin Wilson’s Disease

• Cardiac Cirrhosis• Cryptogenic Cirrhosis (NAFLD/NASH)• Other causes (parasitic inf, ↑ exposure to toxins)

PATHOGENESIS Death of Hepatocytes Extracellular matrix deposition Vascular reorganization

Three main characteristics of Cirrhosis :-• Involvement of most/all of the liver• Bridging fibrous septa• Parenchymal nodules of senescent &

replicating hepatocytes

Contd…

Ref : Robbins’ & Cotran Pathologic Basis of Disease 8th Ed

CLINICAL FEATURES & COMPLICATIONS• Fatigue• Generalized pruritus• Loss of appetite & weight• Intermittent jaundice• Loss of libido & testicular atrophy (men)• Gynecomastia• Menstrual abnormalities (females)• Bleeding tendencies (↓protein for clotting)• Ecchymoses• Edema & ascites (↓intravascular colloidal

pressure & ↑capillary hydrostatic pressure)• Fetor hepaticus

Contd…• Asterixis (flapping hand tremors)• Portal HTN (scar tissue blocks normal flow

of blood & ↑pressure in the portal vein)• GI bleed (d/t esophageal varices

/hemorrhoids)• SBP (d/t long-standing ascites)• Splenomegaly (portal HTN can cause

spleen to enlarge & retain WBCs & platelets)

• Hepatic encephalopathy (↑accumulation of toxins like Ammonia in the brain)

• Gallstones & CBD stones (d/t biliary stasis)

Contd…• Insulin resistance & Type 2 DM• Metabolic bone diseases• Palmar erythema• Pigmentation• Digital clubbing• Caput medusae• Spider angioma• Hepatorenal syndrome• Hepatopulmonary syndrome• Hepatic Hydrothorax• Hepatocellular carcinoma

LAB. EVALUATIONTest category Serum measurement

Hepatocyte integrity AST ↑ (AST/ALT ratio >1)ALT ↑LDH ↑

Biliary excretory function S.Bil ↑ (total/direct)Urine Bil. ↑S. Bile acids ↑S. GGT ↑S. 5-nucleotidase ↑S.ALP ↑

Hepatocyte function S. Albumin ↓PT ↑S. Ammonia ↑

Radiological Evaluation Ultrasound• Surface nodularity• Coarse & heterogenous echotexture• Segmental hypertrophy/atrophy• Signs of Portal HTN

Enlarged p/vein (>13 mm)Slow portal venous flow (<15cm/sec)Portal vein thrombosis

• Splenomegaly• Ascites• Fatty change• Cork screw appearance of hepatic arteries

Contd… CT Scan• Surface nodularity (regenerative>siderotic)• Fatty change• Segmental hypertrophy/atrophy• Signs of portal HTN

MRI• Morphologic changes (same as USG & CT)• Regenerative or cirrhotic nodules

Other Ix Transient Elastography (Fibro-scan)• New, non‐invasive, rapid & reproducible method• In cirrhotic patients, liver stiffness measurements

range from 12.5 to 75.5 kPa Liver Biopsy

• regenerative nodules of hepatocytes surrounded by fibrous connective tissue that bridges between portal tracts

• Mallory's hyaline material within hepatocytes

Radiological Differentials

• Widespread (miliary type) liver mets• Chronic Budd-Chiari syndrome• Fulminant hepatic failure• Pseudocirrhosis• Congenital hepatic fibrosis• Hepatic sarcoidosis• Idiopathic portal HTN• Nodular regenerative hyperplasia of liver

Child-Pugh ScoreMeasure 1 point 2 points 3 points

T.Bil (mg/dl) <2 2-3 >3

S.Albumin (g/dl)

>3.5 2.8 – 3.5 <2.8

PT <4.0 4.0 – 6.0 >6.0

Ascites None Mild Mod to Sev.

Hep.Encph. None Grade I-II Grade III-IV

Points Class 1 yr survival 2 yr survival

5-6 A 100% 85%

7-9 B 81% 57%

10-15 C 45% 35%

MELD Score• The Model for End-Stage Liver Disease,

or MELD, is a scoring system for assessing the severity of CLD (e.g. Cirrhosis).

• Useful in determining prognosis and prioritizing for receipt of a liver transplant.

• MELD = 3.78×ln[serum Bil. (mg/dl)] + 11.2×ln[INR] + 9.6×ln[serum Creat. (mg/dl)] + 6.43

• *If the patient has been dialyzed twice within the last 7 days, then the value for serum Creat. used should be 4.0

Contd…• In interpreting the MELD Score in

hospitalized patients, the 3 month mortality is:

40 or more 71.3% mortality

30-39 52.6% mortality

20-29 19.6% mortality

10-19 6.0% mortality

<9 1.9% mortality

Milan Criteria

• Applied as a basis for selecting patients with Cirrhosis & HCC for liver transplantation

• The Milan criteria state that a patient is selected for transplantation when he or she has:• One lesion <5cm• Upto 3 lesions <3cm• No extra hepatic manifestations• No vascular invasion

MANAGEMENT GENERAL MEASURES• Avoid NSAIDs (may worsen hepatotoxicity

& GI bleed)• Avoid sedatives & hypnotics (may cause

CNS & respiratory depression if patient is in danger of hepatic coma)

• Thiamine replacement (50-100mg/day)• Iron & folate (if anemic)• BCAA supplementation (In

encephalopathy)• Vit.K 10mg s/c (in case of ↑PT)• 2000-3000 calorie diet with 1g protein/kg

MANAGEMENT PORTAL HTN• Pharmacologic : Beta blockers

(Propranolol, Nadolol)• Endoscopic procedures : sclerotherapy

and variceal ligation to prevent the recurrence of variceal bleed

• Surgical care : decompressive shunts, devascularization procedures & liver transplantation.

Contd… ASCITES• Water restriction (effective in dilutional ↓

Na+)• Spironolactone 100-200mg/day (monitor

u/o, abdominal girth, BUN, weight)• Paracentesis (S/E transient hypovolemia,

hypotension, ARF, hemoconcentration,shock)

• Send ascitic fluid for lab studies(WBC count, glucose, protein, c/s, Gm stain, cytology, albumin, LDH, tumour markers)

Contd… SBP

Clinical setting Cirrhosis with ascites

Presentation Fever, ↑abd.pain & tenderness, worsening encephalopathy

Diagnosis Ascitic fluid

WBC>1000/ml

PMN>250/ml

Treatment Ceftriaxone 2g i/v per dayPiptaz 3.375g i/v 6 hourlyAlbumin 1.5 g/kg i/v at diagnosis and 1 g/kg i/v on 3rd day

Contd… OESOPHAGEAL VARICEAL BLEED• Airway stabilization• Large-bore i/v access – Arrange PRBC &

FFP• PharmacoRx

Agent DoseTerlipressin 2mg 6 hourly X 1st 24 hours,

1mg 6 hourly for the 2nd 24 hours

Octreotide 50mcg IV bolus, then 50mcg/hr i/v infusion

Somatostatin 250–500mcg i/v bolus, then 250–500mcg/hr i/v infusion

Contd… HEPATIC ENCEPHALOPATHY• Lactulose 30ml 4-6 hourly or in the form of

enema P/R

Stages FeaturesI General apathy

II Lethargy, drowsiness, variable orientation, asterixis

III Stupor with hyper reflexia, ↑plantars

IV Coma

REFERENCES

• Rosen's Emergency Medicine - Concepts and Clinical Practice 8th Ed

• Tintinalli’s Emergency Medicine 6th Ed• Robbins’ & Cotran Pathologic Basis of

Disease 8th Ed• http://radiopaedia.org/articles/cirrhosis• Mudit Khanna Self Assessment & Review

(Medicine)• Ferrell, Liver update on staging of Fibrosis

& Cirrhosis, 2013