Level of competent 2

Lecture Of Gastroentero-Hepatology System 2012

CASE
INTRODUCTION

 Cirrhosis is a frequent disease worldwide

Diffuse process characterized by fibrosis and

conversion of normal architeture into
structurally abnormal nodules

End stage
of CL Several
damage different cause

Altered Hepatic function Portal hypertension

 Often a poor correlation exists between
histologic findings and the clinical picture.
 Common signs and symptoms may stem
from decreased hepatic synthetic function
(eg, coagulopathy), decreased
detoxification capabilities of the liver (eg,
hepatic encephalopathy), or portal
hypertension (eg, variceal bleeding).
EPIDEMIOLOGY of Liver Cirrhosis

 Prevalence around the world: 100 (25-400)

/100.000 subjects
 WHO report : 796.000 people died in 2001
 The progression of liver injury to cirrhosis may
occur over weeks to years.
ETIOLOGY of Liver Cirrhosis
PATHOPHYSIOLOGY of Hepatic Fibrosis

 Many forms of liver injury are marked by fibrosis.

 Fibrosis is defined as an excess deposition of the
components of extracellular matrix (ie, collagens,
glycoproteins, proteoglycans) within the liver.
 This response to liver injury potentially is reversible.
In contrast, in most patients, cirrhosis is not a
reversible process.
Relationship between cell in the liver
Alteration in the normally balanced processes of extracellular
matrix production and degradation
Hepatic Microvascular
Portal circulation
Vascular changes in cirrhosis
Vascular changes in cirrhosis
Architectural disturbances

Increased hepatic vascular resistence

Garcia-Pagan JC, Grozmann RJ, Bosch J. In Clinical Gastroenterology and Hepatology. 2005; p.709.
PATHOLOGY OF Liver Cirrhosis
CLINICAL PRESENTATION
DIAGNOSTIC METHOD

 Liver biopsy is the gold standard 

 Need to precise stage of fibrosis and grading of
inflammation
 Limitation : sample variation, observer variability,
complication
DIAGNOSTIC METHOD
 Operating characteristics of sign & test in the diagnosis
of CIRRHOSIS

Sign/test Sensitivity Specificity LR+ LR-

% %
Firm liver 89 47 1.67 0.23

Platelet count < 140.000/mmc 59 85 4.0 0.48

AST/ALT ratio >1 53 96 11.7 0.48

USG
-Lack (or reduction to < 30%) of 80 100 - 0.2
respiratory variation of splenic &
mesenteric vein
- liver nodular surface/reduced portal 79 80 3.9 0.26
flow velocity
Endoscopy : esophageal varices 40 99 - 0.6

Liver biopsy 80 100 - 0.2

D”Amico, G Malizia G. In Clinical Gastroenterology and Hepatology. 2005; p.703.

Non-invasive Markers for Predicting Liver Cirrhosis in
Patients with Chronic Hepatitis B

 Alimentary Pharmacology & Therapeutics. 2010;32(11):1343-1350

TREATMENT

 Avoidance of alcohol & hepatotoxic drug

COMPENSATED
CIRRHOSIS (e.g. NSAIDs, isoniazid, valproic acid, erythromycin,
amoxicillin/clavulanate, ketoconazole, chlorpromazine
and ezetimibe)
 Early detection of initial sign of decompensation
 Adequate nutritional : multiple feedings per day, including
breakfast and a snack at night
 Treatment in interuption of fibrogenesis and the
resorption of fibrosis
TREATMENT

DECOMPENSATED
CIRRHOSIS

 Management of complications as they arise

variceal bleeding, ascites, and hepatic
encephalopathy are among the most serious
complications
 Liver transplantation
Treatment of
Portal
Hypertension
Adjunctive therapies

 Zinc sulfate : 220 mg orally twice daily may improve

dysgeusia and can stimulate appetite, muscle
cramps and is adjunctive therapy for hepatic
encephalopathy.
 Cholestyramine , antihistamines (eg,
diphenhydramine, hydroxyzine), ursodeoxycholic
acid, ammonium lactate 12% skin cream : pruritus
 Supplementation with calcium and vitamin D
aminobisphosphonate (eg, alendronate sodium) :
osteoporosis
 Vaccination
PREVENTION

 Routine follow-up monitoring of their complete

blood count, renal and liver chemistries, and
prothrombin time: 3-4 times per year
 Screened for the presence of esophageal varices :
cirrhotic patients with portal vein diameter of ≥ 13
mm and/or platelet count of less than 140,000/mm3
Follow-up endoscopy is performed in 2 years
 Surveillance for HCC with ultrasonography every 6
months
PROGNOSIS

 Survival time within the compensated phase

10-year survival rate is nearly 90%

 Intensity of transtition from compensated to the
decompensated

10-year transitional rate is 50%

 Survival while in the decompensated phase
Kaplan–Meier survival estimates for decompensation in subjects
with compensated alcoholic and non-alcohol-related cirrhosis.
Stage of cirrhosis progression
Correlates with Child-Pugh class

1 2 3
Ascites none Easy control poor
Encephalopathy none Grade I/II Grade III/IV

Bilirubin(mg/dL) <2 2-3 >3

Albumin(g/dL) > 3.5 2.8-3.5 <2.8
PT (seconds increased) <4 4-6 >6

A B C
Total point 5-6 7-9 10-15
1-y survival 100% 81% 45%
2-y survival 85% 57% 35%
Complications
 Ascites
 Portal hypertension and Variceal bleeding
 PHG
 SBP
 Hyponatremia
 Hepatorenal syndrome
 Hepatopulmonal syndrome
 Encephalopaty Hepatic
 Hepatocellulare Carcinoma
 85% ascites caused by cirrhotic (with or without
infection). Runyon BA,et al. Ann Intern Med 1992;
117:215-20.
A Rational basis for treating Ascites

LVP : Large Volume Paraentesis , TP : Total Paraentesis

Management point of ascites

 Grade 1 : USG
 Grade 2 :
 Low sodium diet : 90 mmol/d
 Diuretic :

▪ Spironolactone 100 mg/d and/or

▪ Furosemide 40 mg
 Targeted : weigh loss 500 g/day  increased doses every 5-7 days to gain

 Grade 3 ascites : abdominal distention & refractory ascites

 LVP > 5 L
 Albumin : 8 g/L ascites removed
 TIPS : frequent LVP, <70 yo, no-HE, preserved hepatic function
Initial Approach to ascites

Na Restriction + Diuretic Large Volume paracentesis (LVP)

Treatment algoritme
Esofagogastric Varices (EGV)

 Varices frequently complicate end-stage liver

disease.

 Varices at the time of diagnosis :

 > 30% of compensated cirrhotic
 > 60% of decompensated cirrhotic
 Predictor of Variceal hemorrhage :
 Large Varices  the most important
 Decompensated cirrhosis (Child B/C)
 Red wale marks (endoscopic)
 Variceal hemorrhage does not occur when the HVPG
is reduced to < 12 mmHg.
 HVPG < 12 mmHg or at least 20% from baseline
levels (“HVPG responders”)  lower probability or
risk of developing
 recurrent variceal hemorrhage
 ascites,
 spontaneous bacterial peritonitis
 death
HN : Hyponatremia
VP : Vasopressin
ARB : Angiotensin reeptor blokers
AcEI : AcE Inhibitors
Diagnostic

Clinical Manifestation
 Fever
 Chill
 Abdominal pain
 Rebound abdominaltendernes
 Encephalopathy

Puncti ascites
 PMN > 250 cells/mm3
Management & Prevention of SBP

Therapy
 3rd-gen Cephalosporin : > 5 days
 Cefotaxim 2 gr/8-12h or
Ceftriaxon 1 gr/24h
 Albumin
Prevention
 Gastrointestinal present :  7 days
 Norfloxacin 400 mg/12 h or
 Ceftriaxon 1 gr/24h

 1,5 gr/kg  at the diagnosis of

SBP  Ascites with previous SBP :
1 gr/kg  at 48h later  prevent  Norfloxacin 400 mg/d indefinitely
renal failure
 Norfloxacin 400 mg/d  long-term
 Liver transplantation
prevention
TGF : Transfrming growth factor
VEGF : Vasular endothelial growth factor
ET :endothelin
 Two distinct pulmonary vascular disorders as
complication in hepatic dysfunction and portal
hypertension
 Hepatopulmonary syndrome
 Portopulmonary hypertension
Key Points
Hepatopulmonary syndrome
 Intrapulmonary vasodilataion
 Develops with hepatic synthetic
dysfunction and or portal
hypertension
 Present in 2-8% of pts with cirrhosis
 Liver transplatation generally
curative
Portopulmonary hypertension
 Intrapulmonary vasoconstriction
 Develops in the setting of portal
hypertension
 Present in 3-12 of pts with advanced
liver disease
 Liver transplatation generally
contraindicated
Clinical Presentation
Hepatopulmonary syndrome
 Often asymptomatic
 dyspnea (most common),
 Platypneu
 Signs :
 Spider angiomata
 Digital clubbing
 Cyanosis
 Symptoms/signs may correlate with
severity of underlying cirrhosis
 Hypoxemia common
Portopulmonary hypertension
 Often asymptomatic
 Dyspnea (most common),
 Chest pain,
 Syncope
 Signs :
 Jugular distention,
 Accentuated P2
 Tricuspid regurgitation
 Anasarca
 Symptoms/signs do not correlate with
severity of underlying cirrhosis
 Hypoxemia uncommon
Treatment and Prevention

Hepatopulmonary syndrome Portopulmonary hypertension

No effective medical therapies Medical therapies improve symptoms

 Appropriated interventions :  Appropriated interventions :

 Oxygen therapy (if PaO2 < 60  Referral to specialized centre

mmHg)
 Referral to specialized centre
 Epoprostenol infusion
 Liver transplantation evaluation  Liver transplantation generally
 Liver transplantation only effective contraindicated
treatment modality  No specific prevention available
 No specific prevention available
Resume
 Liver Cirrhosis is a diffuse process characterized by
fibrosis and the conversion of normal liver architecture
into structurally abnormal nodules.
 Cirrhosis is a frequent disease worldwide  main
causes are : VHB, VHC, alcohol abuse & metabolic
 Prognosis fo LC is dictated by development of :
 Portal hypertension related Complication
 Liver failure
 Systemic infections
 The only curative treatment for decompensated LC is
liver transpant