1

LIVER CIRRHOSIS

leonardo dairi

Departemen Penyakit Dalam

DEFINITION ANATOMICALLY AS A DIFFUSE PROCESS WITH FIBROSIS AND NODULE FORMATION

CLASSIFICATION:

MICRONODULAR CIRRHOSIS

MACRONODULAER CIRRHOSIS

MIXED

2

3

Causes of Cirrhosis• Viral hepatitis; B, D, and C

• Alcohol

• Metabolic

Haemochromatosis

Wilson’s disease

Alpha-1-antitrypsin deficiency

• Chronic biliary obstruction

Extrahepatic biliary obstruction

Intrahepatic biliary obstruction

• Venous outflow obstruction

Veno-occlusive disease

Budd-Chiari syndrome

Cardiac failure

• Autoimmune chronic active hepatitis

• Drug and toxins

DIAGNOSIS.

1.SPIDER NAEVI

2.ERITHEMA PALMARIS

3.COLLATERAL VEIN

4.ASITES

5.SPLENOMEGALI

6.INVERTED ALBUMIN GLOBULIN

7.HEMATEMESIS/MELENA

4

CLINICAL CIRRHOSIS

IN CLINICAL TERM,COMPENSATED AND DECOMPENSATED

CLINICAL APPERANCE RESULT,

���� HEPATOCELLULER FAILURE

���� PORTAL HYPERTENSION

CHRONIC ACTIVE HEPATITIS and

EARLY CIRRHOSIS ���� NON SPECIFIC,

DECOMPENSATED CIRRHOSIS

INVESTIGATION:

1. HAEMATOLOGY

- HAEMOGLOBIN,LEUCOCYTE,

PLATELET COUNT and PROTHROMBIN

TIME.

2. BIOCHEMICAL

BILLIRUBIN,TRANSAMINASE

(ALT/AST),ALKALINI

PHOSPATASE,ALBUMIN

GLOBULIN,IMMUNOGLOBULINT,

GAMMA GT,

5

- ASCITES PRESENT,

SERUM SODIUM,POTASSIUM,

BICARBONATE,CHLORIDE,UREA AND

CREATININE LEVEL,WEIHLY DAILY AND 24

HOUR URINE VOLUME

3.USG,HEPATIC CT SCAN

4.LEVER BIOPSY GOLD STANDART

5.ENDOSCOPY

6.EEG IF

EXMINATION:

NURITION,FEVER,FETOR HEPATICUS,JAUNDICE,PIGMENTATION,PURPURA,FINGER CLUBBING,WHITE NAILS,SPIDER NAEVI,PALMAR ERYTHEMA,GYNECOMASTIA,TESTICULAR ATROPHY,DISTRIBUTION OF BODY HAIR,PAROTID ENLARGMENT,DUPUYTREN CONTRACTURE,BLOOD PRESSURE

ABDOMEN ���� ASCITES, COLLATERAL VEIN, LIVER, SPLEEN

PERIPHERAL OEDEMA

NEUROLOGICAL CHANGES ���� MENTAL FUNCTIONS, STUPOR, TREMOR.

6

MODIFIED CHILD-PUGH CLASSIFICATION

OF THE SEVERITY LIVER DISEASE

CHILD A B C

BILIRUBIN < 2 gr % 2,0 - 3,0 gr % > 3,5 gr %.

KADAR ALBUMIN > 3,5 gr % 2,8 - 3,5 gr % < 2,8 gr %.

ASCITES - SLIGHT MODERATE

ENSEFALOPATI - GRADE 1/2 GRADE 3/4

PROTHROMBINE 1 – 3 4 - 6 >6

TOTAL SCORE ,! – 6 (grade A), 7 – 9(grade B), 10 – 15(grade C)

Continuing Liver damage

Nodular regeneration

Fibrosis

Increased sinusoidalpressure

Portal Hypertension

Splancnic vasodilatation Increased gastroesophagealcollateral

Formation ofoesophagogastric varices

Decreased effective bloodvolume

Variceal rupture

Variceal bleeding

Increased sodium retention

Ascites

PORTAL HYPERTENSI

7

8

9

MANAGEMENT

TERGANTUNG STADIUMNYA.

1. STD. KOMPENSASI

- KONTROL TERATUR, ISTIRAHAT CUKUP,

DIET TINGGI KALORI / PROTEIN, LEMAK

SECUKUPNYA, DIIT HATI III/IV

- HINDARI FAKTOR PENYEBAB ( ALKOHOL,

OBAT ).

- LIVER PROTEKTIF.

2. STAD. DEKOMPENSATA:

- ISTIRAHAT TOTAL.

- BATASI MASUKKAN CAIRAN < 1000 cc / HARI.

- DIURETIK HEMAT KALIUM /

SPIRONOLAKTON.

BILA GAGAL ���� + FUROSEMID.

- DIET RENDAH GARAM : 0,5 gr / HR.

- BILA TERJADI ENSEFALOPATI ���� PROTEIN ����.

- BERI LIVER PROTEKTIF.

- HINDARKAN PENYEBAB PENCETUS

ENSEFALOPATI.

10

PROGNOSA :

PROGNOSA JELEK,

1. ASITES REFRAKTER.

2. BILIRUBIN MENETAP > 1,5 - 2 gr %.

3. KADAR ALBUMIN < 2,5 gr %.

4. HATI MENGECIL.

5. MASA PROTROMBIN RENDAH.

6. KADAR NATRIUM DARAH RENDAH.

7. TERJADI PSCA.

8. GANGGUAN KESADARAN.

MORTALITAS PENDERITA S.H. BERDASARKAN

KRITERIA CHILD PADA OPERASI:

A : 10 – 15 %.

B : 30 %.

C : DIATAS 60 %.

PENYEBAB KEMATIAN :

- 43 % ���� DARI LUAR HATI.

- 57 % ���� DARI HATI.

11

Causes of death

• Variceal hemorrhage

• Spontaneous bacterial peritonitis

• Sepsis

• Liver failure

• Hepatic coma

• Functional renal failure

• Hepatocelluler carcinoma

Complications of Cirrhosis

• Variceal bleeding

• Ascites, refractory ascites

• Hepatorenal syndrome(HRS),HPS

• Hepatic encephalopathy

• Spontaneous bacterial peritonitis

• Hepatocelluler carcinoma

12

Variceal Bleeding

A.A. BleedingBleeding fromfrom –– varisesvarises isis reportedreported inin aboutabout 2020 –– 6060%% ofof casecase wwithith cirrhosiscirrhosis..

B.B. MortalityMortality ofof thethe firstfirst bleedingbleeding episodeepisode isis aroundaround 5050%%

C.C. UpUp toto 7070 %% OfOf PatientPatient wwhoho dodo notnot receivereceive treatmenttreatmentdiedie withinwithin 11 yearyear ofof thethe initialinitial bleedingbleeding episodeepisode

PreventiPreventionon measuremeasuress rationalrational to avoid development to avoid development of Varices bleeding (Primary propof Varices bleeding (Primary prophhylaylaxxis).is).

The Efforts in preventing bleeding seems to be The Efforts in preventing bleeding seems to be crucial (secondary, prophylaxis)crucial (secondary, prophylaxis)

13

Consensus in Portal Hypertension Baveno IIIConsensus in Portal Hypertension Baveno III

Monitoring for the Development of Varices in thePortal Hypertensive Patient.1. All cirrhotic patients should be screened for the

presence of varices at the time of the initialdiagnosis of cirrhosis.

2. In compensated patients without varices, endoscopyshould be repeated at 2-3 year intervals toevaluate the development of varices.

3. In compensated patients with small varices,endoscopy should be repeated at –2 year intervalsto evaluate progression of varices.

4. There is no indication for subsequent evaluationsonce large varices are detected.

Algorithm for cirrhosis Without Bleeding

Algorithm For

Cirrhosis Without

Bleeding

CirrhosisEstablished

Reguler Interval

Usually one week

Upper Endoscopy

No varices Small or Medium

VaricesLarge Varices

Observe Observe(1 – 2 years Evaluation)

Primary BleedingProphylaxis

� Non Selectne Blockers

(and /or long actmy Nitrates)

� Ligation

(2 – 3 years Evaluation)

14

Algorithm For Bleeding Cirrhotis

Algorithm For

Bleeding Cirrhotis�Resuscitae

� Begin Octreotide

(or Vasopressin)

Early endoscopy

Non-PortalHypertensiveCause

Gastric Varices Esophagel

VaricesPortal

Hypertensive

Gastropathy

Treat appropriatelyContinue octreotide 5 daysBegin beta-blocker when stable

Band ligation or injection

Sclerotheraphy

Ballon Tamponade

Rebleeding No rebleeding

Shunt (Child A)

TiPSS. or

Liver transplantation (Child B or C)

Continue treatment

Preventation of Rebleeding• Pharmacological Treatment

• Ligation /SclerotheraphyReguler Interval

Usually one week

Repeated Endoscopy

3 – 6 month

Eradication

Shunt (Child A)

TIPSS or Liver transplantation

(Child B or C)

Rebleeding

Dosis dan cara pemberian obat-obat vasoaktif pada

perdarahan varisesObat Cara pemberian Dosis Lama

pemberian

Vasopressin

(VP) +

Nitroglyserin

(NG)

VP: i.v infus

NG:

percutaneus,

bolus

VP:

0,4UU/menit

48 jam

Terlipressin i.v, bolus 2 mg/4 jam

selama 24-48

jam pertama,

kemudian 1

mg/ 4 jam

2-5 hari

Somatostatin i.v bolus dan

infus

250 ug diikuti

250-500 ug/jam

2-5 hari

Octreotide i.v, bolus dan

infus

50 ug diikuti

50 ug/jam

2-5 hari

15

ASCITES

Splanchnic arteriolar vasodilatation

"Forward" increase of

splancnic capillary pressureand permeability

Arterial vascular underfilling

and activation of sodiumretaining mechanism

Sodium and water retentionLymph formation > lymph

return

Ascites

Portal Hypertension

Pathophysiology of Ascites

16

Management of cirrhotic patients with moderate

uncomplicated ascites

• Start with a low sodium diet (80 mmol /day) and anti

aldosteronic drug (100-200 mg/day) ⌫ monitoring body

weight

• Low doses of furosemide (20-40 mg/day, in case of poor

response to the anti aldosteronic drug.

• The goal of treatment : weight loss of 500 g /day in

patients without peripheral edema, and 1 kg/day in

patients with peripheral edema.

• Maximum dose of anti aldosteronic drug 400 mg/day, and

160 mg of furosemide.

• Sodium restriction.

Management of cirrhotic patients with tense or large

uncomplicated ascites

• Total paracentesis is the most effective and safest

procedures to mobilize large ascites

• Blood volume with intravenous albumin (8 g/L of ascite

removed) is required if the volume of ascites is more than

5 liter.

• Start with a low sodium diet and diuretics soon after

paracentesis

17

Management of refractory ascites

• Paracentesis

• Peritovenous shunt

• Transjugular intrahepatic porto-systemic

stent-shunt (TIPSS)

• Liver Transplantation

18

Hepatic Encephalophathy

Common Precipitant of Hepatic encephalopathy

• Increased Nitrogen Load

Gastrointestinal bleeding

Excess dietary protein

Azotemia

Constipation

• Electrolyte and Metabolic Imbalance

Hypokalemia

Alkalosis

Hypoxia

Hyponatremia

• Drugs

Narcotics, transquilizers, sedatives, Diuretics.

• Miscellaneous

Infection, Surgery, Superimposed liver disease

19

Clinical Stages of Hepatic Encephalopathy

Stage Mental status Asterixis EEG

I Euphoria or depression,

mild confusion, slured

speech, disordered speech

+/- Normal

II Lethargy, moderate

confusion

+ Abnormal

III Marked confusion,

incoherent speech, sleeping

but arousable

+ Abnormal

IV Coma, initially responsive

to noxious stimuli, later

unresponsive

- Abnormal

Initial Evaluation

* Exclude other causes of disordered mentation* Identify precipitant and correct* Determinant electrolytes, BUN, creatinine, NH3,

Glucose

Protein restriction

Laxative, e.g., Lactulose 30-120 ml, 1 to 4 timesdaily until 4 stools/day

Inadequate response?

Broad-spectrum antibiotics (e.g., neomycin 500mg qid, or metronidazole 250 mg tid)

Inadequate response?

Consider liver transplatation

Approach to the patient with hepatic encephalopahty

20

Spontaneus Bacterialis

Peritonitis

Cirrhotic patients at high risk of SBP

• Cirrhotic patients with gastrointestinal hemorrhage

• Cirrhotic patients with low ascitic fluid total protein (< 1

g/dL) and / or high serum bilirubin (>2.5 mg/dl)

• Survivors of an episode of SBP.

• Hospitalized cirrhotic patients with ascites and low ascitic

fluid total protein (< 1 g/dl)

21

Pasien sirosis hati dengan asites

Nyeri perut panas Gejala menyertai:Syok, perdarahan, gangguan

kesadaran, gangguanmotilitas, hipotensi, dllAsimtomatik.

Pungsi asites

Pungsi asites:

periksa: PMNKultur

Sel PMN > 250 Sel PMN < 250

BMNN(Bakterasites Monomikrobial

Non-Neutrosistik)

Kultur + Monomikrobial

PBS

Kultur + Monomikrobial

Ulangi pungsi24 jam

Diagnosis Peritonitis Bakterialis Spontan

PBS simtomatik Profilaksis PBS

Ofloksasin

SiprofloksasinDosis standar

5-7 hari

Antibiotik pilihan :Sefotaksim 1-2 gram/hari selama 5-7 hari

Amoksisilin+Asam klavulanat selama 5-7 hari

Parasentesis ulang setelah 24 jamantibiotik

Sel PMN Sel PMN

Ganti antibiotikAntibiotikditeruskan

Penatalaksanaan Peritonitis Bakterialis Spontan

22

HEPATORENAL SYNDROME

Cirrhosis

Splanchnic vasodilatation

Arterial underfilling

Baroreceptor-mediatedactivation of systemic

Vasoconstriction factors

Renal vasoconstriction

Hepatorenal syndrome

Reduced renalvasodilator factors

Increased intrarenalvasoconstriction

factors

Sinusoidal portalhypertension

Pathogenesis of Hepatorenal Syndrome

23

HEPATOCELLULAR

CARCINOMA

• Treatment of HCC depends on

1. Local resources

2. Stage of the disease

3. Presence of cirrhosis

• Liver Transplantation

• Hepatic resection � treatment of choice for the

few patients with HCC and normal liver.

• Trans Arterial Chemo Embolization

• Cytostatica

• Interferon

24

Five years survival of pts with HCC treated by transplantation

in 82 Europeans centers between 1988 and june 1994

• Indication to transplantation Patients % Alive

HCC with Cirrhosis 361 46

HCC without cirrhosis 446 34

Cirrhosis with HCC 176 54

p = 0.0004

from European Transplantation Register