CirrhosisCirrhosisNormalNormal

NodulesNodules

Irregular surfaceIrregular surface

GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVERGROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER

Causes of Liver Disease: CirrhosisCauses of Liver Disease: Cirrhosis

Viral Hepatitis: B and C Genetic Liver Disease:

Hemochromatosis, Wilson’s Disease Alcohol NASH (non alcoholic steatohepatitis) Autoimmune Liver Disease Cryptogenic

Viral Hepatitis: B and C Genetic Liver Disease:

Hemochromatosis, Wilson’s Disease Alcohol NASH (non alcoholic steatohepatitis) Autoimmune Liver Disease Cryptogenic

Two aspects of Liver Disease

•Synthetic Function:measured by Bilirubin, albumin and INR

•Portal Hypertension

Normal Vascular Anatomy

Hepatic vein

Hepatic vein

SinusoidSinusoid

Portal vein

Portal vein

Hepatic arteryHepatic artery

LiverLiver

Splenic veinSplenic vein

Coronary veinCoronary vein

Inferiorvena cava

Inferiorvena cava

Inferior mesenteric veinInferior mesenteric vein

Superiormesenteric vein

Superiormesenteric vein

NORMAL VASCULAR ANATOMY OF THE LIVER

Portal systemic collaterals

Portal systemic collaterals

Distorted sinusoidal

architectureleads to

increased resistance

Distorted sinusoidal

architectureleads to

increased resistance

Portal vein

Portal vein

Cirrhotic Liver

SplenomegalySplenomegaly

ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCEINTRAHEPATIC RESISTANCE

Complications of Cirrhosis:

Esophageal and gastric Varices Ascites Hepatic Encephalopathy Hepatorenal Syndrome

CAT Scan in CirrhosisCAT Scan in Cirrhosis

Liver with an irregular surfaceLiver with an irregular surface SplenomegalySplenomegalyCollateralsCollaterals

DIAGNOSIS OF CIRRHOSIS – CAT SCANDIAGNOSIS OF CIRRHOSIS – CAT SCAN

Small varicesSmall varices Large varicesLarge varicesNo varicesNo varices

7-8%/year7-8%/year 7-8%/year7-8%/year

Varices Increase in Diameter Progressively

Varices Increase in Diameter Progressively

Merli et al. J Hepatol 2003;38:266Merli et al. J Hepatol 2003;38:266

VARICES INCREASE IN DIAMETER PROGRESSIVELYVARICES INCREASE IN DIAMETER PROGRESSIVELY

Predictors of hemorrhage: Variceal size Red signs Child B/C

Predictors of hemorrhage: Variceal size Red signs Child B/C

NIEC. N Engl J Med 1988; 319:983NIEC. N Engl J Med 1988; 319:983

Variceal hemorrhageVariceal hemorrhage Varix with red signsVarix with red signs

PROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGEPROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGE

Acute Variceal Bleeding

Initial ManagementAssessment of severity/resuscitation

•airway protection for massive bleed or if agitated

•Blood and fluid replacement

Pharmacology therapy

•Octreotide

Endoscopy for diagnosis and therapy

•Variceal ligation

•Sclerotherapy

•Balloon tamponade

Acute Variceal Bleeding

Endoscopic Ligation•Bleeding controlled in 90%

•Rebleeding rate reduced to 30%

•Band to “obliteration”

Acute Variceal Bleeding

Sclerotherapy•Bleeding controlled in 80-95%

•Rarely used now- massive bleeds?

Gastric VaricesGastric Varices

Pretreatment cyanoacrylatePretreatment cyanoacrylate Post-treatment cyanoacrylate

Post-treatment cyanoacrylate

ENDOSCOPIC IMAGES OF GASTRIC VARICESENDOSCOPIC IMAGES OF GASTRIC VARICES

Treatment of Varices / Variceal Hemorrhage

Treatment of Varices / Variceal Hemorrhage

RecurrenthemorrhageRecurrent

hemorrhage

Varicealhemorrhage

Varicealhemorrhage

Medium/ large varicesNo hemorrhage

Medium/ large varicesNo hemorrhage

Small varicesNo hemorrhage

Small varicesNo hemorrhage

No varicesNo varices

1) -blockers (propranolol, nadolol) indefinitely

2) Endoscopic variceal ligation in patients intolerant to -blockers

1) -blockers (propranolol, nadolol) indefinitely

2) Endoscopic variceal ligation in patients intolerant to -blockers

MANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES WITHOUT PRIOR HEMORRHAGEMANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES WITHOUT PRIOR HEMORRHAGE

Variceal Bleeding

Bleeding Ectopic Varices

Tips

Transjugular Intrahepatic

Portosystemic Shunt

MildMild

Mild and Severe Portal Hypertensive GastropathyMild and Severe Portal Hypertensive Gastropathy

SevereSevere

Mosaic patternMosaic pattern Mosaic pattern + red spotsMosaic pattern + red spots

Carpinelli et al. Ital J Gastroenterol Hepatol 1997; 29:533Carpinelli et al. Ital J Gastroenterol Hepatol 1997; 29:533

ENDOSCOPIC IMAGES OF MILD AND SEVERE PORTAL

HYPERTENSIVE GASTROPATHY

ENDOSCOPIC IMAGES OF MILD AND SEVERE PORTAL

HYPERTENSIVE GASTROPATHY

Ascites

Malignancy

Heart Failure

Turberculosis

Miscellaneous• Nephrogenic

• Pancreatic

• Fulminant Hepatic Failure

• Biliary Leak

ChronicLiverDisease

Ascites

Ascites

Pathogenesis: HypothesesUnderfill Overflow Vasodilati

onCirrhosis

Portal Hypertension

Ascites

Effective Intravascular

volumeRenal sodium

retention

Primary renal sodium

retention (? Stimulus)

Blood volume

Peripheral arterialvasodilation

Effective Intravascular

volume

Renal sodiumretention

Ascites

Ascites

Diagnosis Paracentesis

Indications•New-onset ascites

•Admission to hospital

•Clinical deterioration

•Fever

Contraindications

•None

Ascites

Fluid Analysis

Routine•Cell count

•Culture

•Albumin

•Protein

•Glucose

•LDH

•Amylase

•Gram stain

Optional•TB smear and culture

•Cytology

•Triglyceride

High (> 11 g/L)

•Cirrhosis; alcoholic hepatitis

•Cardiac disease

•Massive liver metastases

•Fulminant hepatic failure

•Hepatic outflow block

•Portal vein thrombosis

Ascites

Serum-Ascites Albumin Gradient[Albumin] –

[Albumin]Serum Ascites

Low (< 11 g/L)

•Peritoneal carcinomatosis

•Tuberculous peritonitis

•Pancreatic duct leak

•Biliary leak

•Nephrotic syndrome

•Serositis

Ascites

Ascites

Sodium restriction

Diuretics

•Spironolactone +/- furosemide

•Stepwise increase as needed to maximal doses

Large volume paracentesis (for tense ascites)

Ascites

Initial Therapy

Ascites

Therapy of Refractory Ascites

Ascites

Complications

Spontaneous Bacterial Peritonitis (SBP)

Spontaneous Bacterial Peritonitis:SBP Usually caused by gram-negative bacteria

and usually only one organism: only 50% of cultures positive

If neutrophil count high in ascites: ie > 250/cc-treat with IV Cefotaxime, even if culture negative

Prophylaxis for SBP or recurrent SBP controversial: high resistance rates develop

Survival After Development of Spontaneous Bacterial Peritonitis

Survival After Development of Spontaneous Bacterial Peritonitis

Probability of survival

(%)

Probability of survival

(%)

MonthsMonths00

1.01.0

.8.8

.4.4

.2.2

.6.6

33 66 1212 2424 363600

Tito et al., Hepatology 1988; 8:27Tito et al., Hepatology 1988; 8:27

SURVIVAL AFTER DEVELOPMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)SURVIVAL AFTER DEVELOPMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

•Reversible neuropsychiatric abnormalities

•Asterixis and abnormal EEG

•Hepatic failure and/or portosystemic shunting

Hepatic Encephalopathy

Hepatic Encephalopathy

“Blood ammonia levels cause as much confusion in those

requesting the measurement as in the patients in whom they are

being measured”

“Blood ammonia levels cause as much confusion in those

requesting the measurement as in the patients in whom they are

being measured”Adrian ReubenHepatology 2002;35:983

Adrian ReubenHepatology 2002;35:983

BLOOD AMMONIA LEVELS ONLY LEAD TO CONFUSIONBLOOD AMMONIA LEVELS ONLY LEAD TO CONFUSION

Hepatic Encephalophathy

Hepatic Encephalophathy

Precipitants

Hepatic Encephalophathy

Actions of Lactulose

Hepatorenal Syndrome•Identify other causes

•Establish circulatory volume

•Avoid nephrotoxic agents

•Consider hemodialysis

•Evaluate for liver transplatation

Hepatorenal Syndrome

Evidence for a Functional Disorder

Hematologic Manifestations of Cirrhosis Mild Anemia and Macrocytosis Neutropenia secondary to splenic

sequestration Thrombocytopenia secondary to splenic

sequestration Prolonged INR secondary to decreased

production of clotting factors by liver

Hepatocellular Carcinoma

Other names are Hepatoma, Primary Liver Cell Cancer

Develop in Cirrhotic livers especially Hepatitis B and C

May produce a protein tumour marker: alphafetoprotein

Ultrasound screening every 6 months for early detection

Complications of Cirrhosis

Child-Pugh Criteria

1 point 2 points

3 points

Bilirubin (mg/dL)

Albumin (g/L)

PT (sec prolonged)

Ascites

Encephalopathy

<2

>35

1-3

none

none

2-3

28-35

4-6

Slight

1-2

>3

<28

>6

Moderate

3-4

Grades: A = 5-6 points; B = 7-9 points; C = 10-15

Causes of death

in Cirrhosis•Infection

•Variceal bleeding

•Hepatic encephalopathy

•Hepatocellular carcinoma

Spontaneous Bacterial Peritonitis (SBP) is the Most Common Infection in

Cirrhotic Patients

Spontaneous Bacterial Peritonitis (SBP) is the Most Common Infection in

Cirrhotic Patients

00

2525

5050

7575

100100

125125

150150

UTIUTI PneumoniaPneumoniaSBPSBP

BacteremiaBacteremia

Procedure-related

Procedure-related

SpontaneousSpontaneous

# Hospitalized cirrhotic patients

# Hospitalized cirrhotic patients

Fernández et al., Hepatology 2002; 35:140Fernández et al., Hepatology 2002; 35:140

SPONTANEOUS BACTERIAL PERITONITIS (SBP) IS THE MOST COMMON INFECTION IN CIRRHOTIC PATIENTSSPONTANEOUS BACTERIAL PERITONITIS (SBP) IS THE MOST COMMON INFECTION IN CIRRHOTIC PATIENTS

60604040 8080 100100 120120 140140 16016000

4040

6060

8080

2020

202000

100100

MonthsMonths

Probability of survival

Probability of survival

All patients with cirrhosisAll patients

with cirrhosis

Decompensated cirrhosis

Decompensated cirrhosis

180180

Decompensation Shortens SurvivalDecompensation Shortens Survival

Gines et. al., Hepatology 1987;7:122Gines et. al., Hepatology 1987;7:122

Median survival~ 9 years

Median survival~ 9 years

Median survival~ 1.6 years

Median survival~ 1.6 years

SURVIVAL TIMES IN CIRRHOSISSURVIVAL TIMES IN CIRRHOSIS

Liver TransplantationLiver Transplantation

Only proven treatment for advanced cirrhosis

Long waiting list: insufficient donors Allocation by MELD score (Bilirubin,

creatinine, INR) Patients with recent alcohol or drug

abuse, extrahepatic malignancies or other major co-morbidities excluded

Only proven treatment for advanced cirrhosis

Long waiting list: insufficient donors Allocation by MELD score (Bilirubin,

creatinine, INR) Patients with recent alcohol or drug

abuse, extrahepatic malignancies or other major co-morbidities excluded

Treatment of Fulmimant Liver Failure

Treatment of Fulmimant Liver Failure

Supportive measures Transfer to transplant centre if

encephalopathic ?Mars Improve with time or need liver

transplant 1st on Waiting list for Transplant

Supportive measures Transfer to transplant centre if

encephalopathic ?Mars Improve with time or need liver

transplant 1st on Waiting list for Transplant

CirrhosisCirrhosisNormalNormal

NodulesNodules

Irregular surfaceIrregular surface

GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVERGROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER

Causes of Liver Disease: CirrhosisCauses of Liver Disease: Cirrhosis

Viral Hepatitis: B and C Genetic Liver Disease:

Hemochromatosis, Wilson’s Disease Alcohol NASH (non alcoholic steatohepatitis) Autoimmune Liver Disease Cryptogenic

Viral Hepatitis: B and C Genetic Liver Disease:

Hemochromatosis, Wilson’s Disease Alcohol NASH (non alcoholic steatohepatitis) Autoimmune Liver Disease Cryptogenic