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CIRRHOSIS OF LIVER
Dr.Partha Das
M.E.M. 2nd Year
Fortis Hospital, Kolkata
16-05-2016
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 nodules
Ref : 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 8th
Ed
(*kirros = orange, osis = condition – Greek)
Morphological Classification
 Macronodular (parenchymal nodules >3mm)
 Micronodular (parenchymal nodules <3mm)
Etiology Frequency
Chronic viral hepatitis 10-20%
Wilson’s disease Rare
Alpla1 antitrypsin ↓ Rare
Cryptogenic Common
Various drugs & toxins Rare
Etiology Frequency
Alcohol 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 Cirrhosis
Primary Sclerosing Cholangitis
Autoimmune 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
Cirrhosis of liver
LAB. EVALUATION
Test 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 Score
Measure 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 day
Piptaz 3.375g i/v 6 hourly
Albumin 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 Dose
Terlipressin 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 Features
I 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
Cirrhosis of liver

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Cirrhosis of liver

  • 1. CIRRHOSIS OF LIVER Dr.Partha Das M.E.M. 2nd Year Fortis Hospital, Kolkata 16-05-2016
  • 2. 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)
  • 3. DEFINITION • Cirrhosis is defined as a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules Ref : 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 8th Ed (*kirros = orange, osis = condition – Greek)
  • 4. Morphological Classification  Macronodular (parenchymal nodules >3mm)  Micronodular (parenchymal nodules <3mm) Etiology Frequency Chronic viral hepatitis 10-20% Wilson’s disease Rare Alpla1 antitrypsin ↓ Rare Cryptogenic Common Various drugs & toxins Rare Etiology Frequency Alcohol 60-70% Primary biliary 5% Hemochromatosis 5% Cystic fibrosis Rare
  • 5. CAUSES OF CIRRHOSIS • Alcoholism (Laennec’s Cirrhosis) • Chronic Viral Hepatitis (Hep.B/ Hep.C) • Autoimmune Hepatitis • Biliary Cirrhosis Primary Biliary Cirrhosis Primary Sclerosing Cholangitis Autoimmune Cholangiopathy • Inherited Metabolic Liver Disease ↓alpha-1 antitrypsin Wilson’s Disease • Cardiac Cirrhosis • Cryptogenic Cirrhosis (NAFLD/NASH) • Other causes (parasitic inf, ↑ exposure to toxins)
  • 6. 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
  • 7. Contd… Ref : Robbins’ & Cotran Pathologic Basis of Disease 8th Ed
  • 8. 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
  • 9. 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)
  • 10. 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
  • 12. LAB. EVALUATION Test 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 ↑
  • 13. 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
  • 14. 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
  • 15. 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
  • 16. 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
  • 17. Child-Pugh Score Measure 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%
  • 18. 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
  • 19. 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
  • 20. 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
  • 21. 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
  • 22. 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.
  • 23. 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)
  • 24. 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 day Piptaz 3.375g i/v 6 hourly Albumin 1.5 g/kg i/v at diagnosis and 1 g/kg i/v on 3rd day
  • 25. Contd…  OESOPHAGEAL VARICEAL BLEED • Airway stabilization • Large-bore i/v access – Arrange PRBC & FFP • PharmacoRx Agent Dose Terlipressin 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
  • 26. Contd…  HEPATIC ENCEPHALOPATHY • Lactulose 30ml 4-6 hourly or in the form of enema P/R Stages Features I General apathy II Lethargy, drowsiness, variable orientation, asterixis III Stupor with hyper reflexia, ↑plantars IV Coma
  • 27. 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