&

Oleh:
PROF. DR Dr I DEWA NYOMAN WIBAWA SpPD-KGEH
Div Gastroentero-hepatologi, Lab.I.P. Dalam FK Unud/RS Sanglah
 LIVER CIRRHOSIS

CHARACTERISTIC:
= Formation of regenerative nodule of
liver parenchyme.
= Separated by encapsulated in
fibrotic septa.
= Major angio – architectural changes

Pinzani M, et al: J Hepatol 2005: 42: S25-S36.

 LIVER CIRRHOSIS
 WHO working group (1978):
Cirrhosis is a diffuse process
characterized by fibrosis & the conversion
of normal liver architecture into structurally
abnormal nodule.

• Hemodynamic alteration
• Intrahepatic vascular shunt
Chronic HBV infection: Progression
to cirrhosis
The incidence of cirrhosis

HBeAg pos 2-5 per 100 person year

HBeAg neg 8-15 per 100 person year

Fung SK & Anna SF Lok: J Hepatol 2005;42:S54-S64.

 CHRONIC HCV INFECTION:
COMPENSATED CIRRHOSIS

DISEASES PROGRESSION:

1). Decompensation 3,6%-6,0%/year.

2). Hepatocell Ca. 1,4%-3,3%/year.
3). Death from liver
disease 2,6%-4,0%/year
Everson GT: J Hepatol 2005; 42: S65-S74.
 PROGRESSION OF C.H. TO
CIRRHOSIS
Host factors:
•Difference in handling of metab./toxic load
•Difference in the immune syst.reaction to
infect.agent & AutoAg.
•Difference in management of the chronic
wound healing reaction.

CHRONIC LIVER LIVER

HEPATITIS FIBROSIS CIRRHOSIS

Viral factor:

•Viral load & replicative stage.

•Genotype.
•Quasispecies.
•Co/Super infection
Pinzani M, et al: J Hepatol 2005: 42: S25-S36.
The cellular effector of fibrogenic process

 HSC (Hepatic Stellate Cells).

 Fibroblast & Myofibroblast of the portal
tract.
 Smooth muscle cells in the vessel
walls.
 Myofibroblast arround the
centrolobular vein.
 LIVER CIRRHOSIS
 PATHOGENESIS & PATHOPHYSIOLOGY
HEPATOCELLULAR NECROSIS

Liver responses
Collapse liver lobulus
Liver architecture changes
Diffuse Septal fibrosis
“irreversible”
Regenerative nodular

Distorsion of Intra hepatic blood vessels

Resistance to portal circulation PORTAL HYPERTENSION

HEPATO-CELLULAR FAILURE
 LIVER CIRRHOSIS
 DEFINITION:
chronic liver diseases with diffuse parenchymal lession, changes of
microcirculation, anatomy of large vessels and liver architecture,
caused by diffuse liver fibrosis, accumulation of fibrous collagen
tissue, and regenerative nodule of hepatocyte.

 CLASSIFICATION:
A. Morphologic classification:
A.1 Micronodular cirrhosis
(C. irreguler, septal, uniform, monolobuler, nutritional, Laeneck) : thick
septal, uniform, small nodule < 3cm.
A.2. Macronoduler cirrhosis (post necrotic) :
variable septal, usually wide, variable nodule : 3 - 5 cm.
A.3 Micro + macronoduler cirrhosis:
Combination of 1 and 2, most prevalence.
A.4 Multilobuler cirrhosis : incomplete septal.
 LIVER CIRROSIS
B. Etiologic classification :
B.1 LC caused by chronic hepatitis :
chronic viral hepatitis: HBV, HCV, HDV, HGV.
B.2 Alcoholic cirhhosis
B.3 Cirrhosis in metabolic disorders :
Galactosemia, glycogen storage disease, anti trypsin deficiency,
hemochromatosis, Wilson diseases, diabetes millitus, thyrosinemia.
B.4 Cirrhosis caused by chemical substances: dose-dependent dan non-dose
dependent.
B.5 Nutritional cirrhosis.
B.6 Cirrhosis caused by prolonged cholestatic:
primary and secondary billiary cirrhosis, primary sclerosing cholangitis, billiary
atresia, cystic fibrosis.
B.7 Congestive/ vascular cirrhosis :
Budd-Chiari syndrome, veno-occlusive ds, idiophatic, drug/toxin induced,
and cardiac cirrhosis.
B.8 Cryptogenic cirrhosis.
B.9 Sarcoid cirrhosis (granulomatous).
B.10 Indian childhood cirrhosis.
 ETIOLOGY
 Etiology of LC in Indonesia
1. Hepatitis B Virus (“HBV”)
(40%-50%).
2. Hepatitis C Virus (“HCV”).
(30%-40%).
3. Hepatitis Virus “non-B, non-C“.
(10%-20%).
4. Others (Haemochromatosis,
Alcohol,Wilson ds) ?
 Diagnosis of Liver Cirrhosis
 History/Anamnesis
 Physical examination.

 Liver function test, Immuno-serology, etc.

 Diagnostic imaging: ultrasound, CT scan, MRI, etc.

 Liver biopsy (Gold standar).
 Cirrhotic Ascites

 Portal Hypertension
 Renal retention of sodium

 Splanchnic arterial vasodilatation

 Systemic vascular changes

 Increased splanchnic and hepatic

lymph formation
 Hypoalbuminemia
ASCITES worsens the prognosis, if :
 Large doses of diuretic needed for control
 Refractory ascites
 Hepatorenal-syndrome
 Spontaneous Bacterial Peritonitis
 Clinical classification

Liver cirrhosis:
1. COMPENSATED LIVER CIRRHOSIS.
2. DECOMPENSATED LIVER CIRRHOSIS.
 Clinical classification
 Compensated liver cirrhosis:
Usually encountered on routine physical and laboratory
examination.
Without sign & symptoms of hepatocellular failure and
portal hypertension.
Suspicious of liver cirrhosis if patients with unexplainable
low grade fever, palmar erythema, spider naevi, ankle
oedema, and epistaxis.
 Decompensated liver cirrhosis:
with clinical manifestation of portal hypertension
and hepatocellular failure
Subjective findings (SYMPTOMS)
 Non-specific, depend on the degree of
hepatic lession: ascites, ankle edema,
easy fatique, loss of appetite, early satiety,
loss of body weight, epigastrial discomfort,
bloating, nausea, muscle weakness, right
upper quadrant abdominal pain, melena or
hematemesis.
 Objective findings
I. Hepato-cellular failure
Vascular spider, palmar erythema, icteric,
gynaecomastia, sparse body hair, testical atrophy,
decreased of libido, hepatic encephalopathy,
change fertility in women, anaemia, bleeding,
pleural effusion, hypoproteinaemia, ascites,
oedema.

II. Portal hypertension

Esophageal varices, splenomegaly, caput
meducae, ascites, collateral circulation, and
haemorhhoid.
 cirrhosis complication
coma
jaundice
spider naevi bone marrow change
pectoral alopecia
esophageal varices
gynecomastie
splenomegaly
liver damage
caput medusae
altered hair-distribution ascites
ascites

palmar erythema

testicular atrophy

anemia
anemia
leukopenia
thrombocytopenia

hemorrhagic tendency

odema odema
Child-Pugh Modification criteria
Points
1 2 3
Serum bilirubin < 2.0 2.0-3.0 > 3.0
Serum albumin > 3.5 2.8-3.5 < 2.8
Ensefalopathy None 1&2 3&4
Ascites Absent Slight Moderate
Prothrombin time 1-4* 4-6** >6***

Total points Child Pugh class

5-6 A
7-9 B
10-15 C
LIVER CIRRHOSIS COMPLICATIONS

 Acute complication:
GI bleeding, hepatic encephalopathy,
Spontaneous bacterial peritonitis, Hepato-renal
syndrome, Systemic infection, portal vein
thrombosis

 Chronic complication:
Hepato-pulmonary syndrome, Porto-pulmonary
syndrome, hepatocellular carcinoma.
 LIVER CIRRHOSIS
 Follow up:
DEGREE OF CONSCIOUSNESS,
GI BLEEDING
HEPATIC ENCEPHALOPATHY
DAILY BODY WEIGHT
URINE VOLUME
 MANAGEMENT
Liver cirrhosis:
1. COMPENSATED LIVER CIRRHOSIS.
2. DECOMPENSATED LIVER CIRRHOSIS.
 Treatment of Compensated LC
1. Management of Chronic Hep B.
2. Management of Chronic Hep C.
3. Treatment of NAFLD ( “Non Alcoholic Faty Liver
Disease”).
4. Treatment of Haemochromatosis, Wilson ds, etc.
5. Treatment of Liver fibrosis.
Management of
Management of Decompensated
Decompensated LC
LC

1. Treatment of ascites
2. Treatment of hepatorenal syndrome
3. Management of hepatic encephalopathy
4. Management of portal hypertension
5. Treatment of Spontaneous bacterial
peritonitis.
6. Upper GI bleeding.
7. MARS
8. Liver transplantation
 Management of ascites in LC
- Abstain from alcohol consumption.
- First line treatment: sodium restriction 88 mmol=2
gram/day and Diuretics: - oral spironolactone 100-
400 mg/day and furosemide 40-160 mg/day
- Spironolactone: Minimal ascites
- Tense ascites : abdominal paracentesis + diuretics.
- Fluid restriction: unless serum sodium less than
120-125 mmol/l (Grade III)
- Liver transplantation

AASLD Practice guideline, Hepatology 39, 2004.

 Refractory ascites

1. Large volume paracentesis: 4 – 6 L

2. Transjugular intrahepatic portosystemic
shunt (TIPS)
3. Peritoneovenous Shunt (PV).
4. Orthotopic Liver Transplantation. (OLT).
 Albumin indication in liver
cirrhosis
 SBP
 HRS type 1
 Paracentesis > 5 liter
 Albumin level < 2.5 g/dl with complication.

National Consensus 2001

 HEPATOCELLULAR CARCINOMA
 DEFINITION: a malignant tumor of hepatocytes

 CLASSIFICATION
 HISTOPHATOLOGY:
1. solitary: = massive, usually with central necrosis:
64,4%
2. nodular: 23%
3. diffuse: 12,6%

 OTHER CLASSIFICATION:
1. Infiltrative type.
2. Expansive type.
3. Mixed type between infiltrative and expansive.
4. Diffuse type.
Primary tumor of the liver
Benign Malignant
Hepatocellular Adenoma HCC
Fibro-lamellar
Hepatoblastoma

Billiary Adenoma Cholangiocarcinoma

Cystadenoma Combined hepato-cellular carcinoma and
Papillomatosis cholangiocarcinoma

Mesodermal Haemangioma Angiosarcoma

(Haemangio-endothelioma)
Epithelioid
Haemangio-endothelioma
Sarcoma

Other Mesenchymal
Hamartoma
Lipoma
Fibroma
 
Global Epidemiology of
Hepatocellular Carcinoma

 320,000-400,000 deaths related to

HCC/year
 Represents 5% of all cancer cases
 Great variability according to gender,
age, and geographic areas

Kiyosawa, Jpn J Inf Dis, 2002

 Hepatitis B and Risk of HCC
12
Cumulative Incidence of HCC (%)

HBsAg+, HBeAg+
10

4
HBsAg+, HBeAg-
2
HBsAg-, HBeAg-
0
0 1 2 3 4 5 6 7 8 9 10
Year

Yang, HI, et al. N Engl J Med. 2002;347:168-174.

Hepatitis C and Hepatocellular
Carcinoma (HCC) in the US

 Chronic HCV infection substantially increases the risk of

HCC

 HCV accounts for 60% of HCC cases

 5- to 7-fold higher risk for developing HCC for HCV-

positive patients

EASL International Consensus Conference, J. Hepatology, 1999

Di Bisceglie, Semin Liver Dis,1995
Prevalence of HCV Positivity
in HCC

El Serag and A. Mason, NEJM, 1999

Yoshizawa et al, Oncology 2002
Yao et al, Curr Treat Options Oncol 2001
Bruix J, et al.
 HCV/HBV Activation of oncogenes

Initiation Promotion Progression

Chemical carcinogens Inactivation

of tumor suppressor genes
 CIRRHOSIS
Suppressor gene Integration
mutation

TGF- Disorganized DNA

Transactivation
(HBx)
CANCER
CLINICAL PRESENTATION

 Ranges from catastrophic tumor rupture into the

peritonium to incidental cancer diagnosed by
abdominal imaging.
 Most common symptoms are abdominal pain
(right upper quadrant) and weight loss.
 HCC may lead to hepatic insufficiency.
 Extention to the portal vein thrombosis.
 Paraneoplastic symptoms, such as diarrhea,
polycythemia, hypercalcemia,hypoglycemia,
and ferminization, rarely occur.

Med Clin N Am 2005; 89:345-369.

CLINICAL PRESENTATION

HCC should be suspected in any cirrhotic

patient presenting with worsening hepatic
function manifested by increased jaundice,
encephalopathy, or portal hypertension (ie,
ascites, variceal bleeding).

Med Clin N Am 2005; 89:345-369.

 DIAGNOSIS
HCC in cirrhotic patients is diagnosed by:
1. Alpha feto protein (AFP).
2. Imaging studies.
3. Histologic diagnosis

Med Clin N Am 2005; 89:345-369.

 DIAGNOSIS
EASL : Hepatocellular carcinoma
diagnostic criteria:
1. Cytohistopathologic diagnosis or
2. > 2-cm arterial hypervascular lesion detected
by two coincident imaging techniques in the
setting of cirrhosis or
3. >2-cm arterial hypervascular lesion detected
by one imaging technique with serum AFP >
400ng/ml in the setting of cirrhosis.
Bruix J, et al.
NATURAL HISTORY OF HCC

1. Early stage HCC.

2. Intermediate-advanced HCC
3. End-stage HCC
Hepatology 2005; 42: 1208-36.
 RECOMMENDED HCC TREATMENT

T4

TACE Supportive care

Chemotherapy
Experimental therapies
T3
Resection

T2 Resection Transplantation

Transplantation RFA / PEI

RFA/PEI
T1

Child’s A Child’s B Child’s C

Based on Child-Pugh status and TNM stage. Med Clin N Am 2005; 89:345-369.
Hepatology 2005; 42: 1208-36.
MATUR SUKSMA