Oleh:

Fransiska M.C., S.Farm., Apt.

LEARNING OBJECT

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• Anatomy-Physiology of Liver
• Cirrhosis
Definition
Etiology & Pathopysiology
Clinical Manifestation
Disfunction Type
Laboratory Data
Complication and Therapy

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 FISIOLOGI HEPAR
• Albumin, • Vitamins,
coagulation mineral,
factors carbohydrates
etc

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• Carbohydrate,
Fat & Protein
SYNTHESIS
& STORAGE
METABOLISM

PROTEKSI
SECRETORY
& &
DETOXIFICATION
EXCRETORY
• Toxins, • Bile, Bile
ammonia, etc acids, salts &
• Bilirubin, drugs, pigments
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hormon
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DEFINITION

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Diffuse, irreversible distortion of the liver
architecture due to fibrosis and nodular
regeneration
Sustained wound-healing response to chronic
liver injuries with hepatocellular necrosis;
progressive
A common end-stage from a variety of causes
Decreased secretory and biochemical function,
liver failure
Interferes with blood flow through the liver,
causing portal hypertension 7
WHAT HAPPENING IN CIRRHOSIS??

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•Parasetamol
•amiodarone
•isoniazid (INH)
ETIOLOGY

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•methotrexate
•Methyldopa
•oxyphenisatin
•perhexiline maleat
•vitamin A

•Virus Hepatitis B
•Virus Hepatitis C

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PATHOPYSIOLOGY

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Slow, insidious, progressive, chronic
Fibrous bands replace normal liver structure
Cell degeneration occurs
Liver attempts to regenerate cells but cells are
abnormal and disorganized
Causes abnormal blood and lymph flow
Results in more fibrous tissue formation

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PROGRESSION OF LIVER DISEASES

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 HISTOPATOLOGI

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NORMAL CIRRHOSIS

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STEATOSIS
THE EFFECT OF THE LIVER NODULE

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 • Lelah, mual, muntah,

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kehilangan nafsu makan,
BB turun
• Jaundice, urin gelap,
muntah darah

GEJALA
EKSTRAHEPATIK
• palmar eritema
• ginekomastia,
• atropi testikular,
• spider angioma
• koagulopati
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• menstruasi yg
iregular
SPIDER ANGIOMAS

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Caput Medusa
GYNAECOMASTIA

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Jaundice

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DIAGNOSA

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Abdominal x-ray → hepatomegaly
Upper GI, EGD → esophageal varices, ulcers
Angiography → identify arterial bleeding sites
Abdominal CT → amount of ascites
Liver biopsy → true definitive test for cellular
changes
Nuclear scan → measure liver wall thickening
and presence of masses

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DATA LAB

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↑ SGOT-SGPT (ALT-AST) tdk signifikan
↑ Bilirubin
↓ Albumin
PT (protrombin time) >> WHY..??
?
↓ Clotting factor
Darah lengkap ↓
↑ Amonia

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Laennec’s (alcoholic) Postnecrotic
•Also called alcoholic cirrosis •Caused by viral hepatitis or hepatotoxins

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•Alcohol causes inflammation to liver cells •Scar tissue destroys liver lobes
•Leads to fatty deposits and hepatomegaly •Liver initially enlarges but then shrinks in

TYPES OF
•Scarring formed and liver cells destroyed size
•Malnutrition and more alcohol accelerate •10 – 30% of all cirrhoses
the damage

CIRRHOS
IS
Biliary Cardiac
•Caused by chronic biliary obstruction or
•Seen with right sided heart failure
stasis of bile, biliary inflammation, or hepatic
•Liver is engorged with venous blood
fibrosis
•Becomes enlarged, edematous, and dark
•Excessive bile leads to liver cell destruction
•Venous congestion results in anoxia
and formation of nodules in the lobes
•Cell necrosis results
•5 – 10% of all cirrhoses
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ALCOHOLIC FATTY LIVER (STEATOSIS)

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Fatty Liver Cirrhosis

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MORPHOLOGIC CLASSIFICATION

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CHILD-PUGH SCORE
score 1 2 3

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Albumin >3.5 3.5-2.8 <2.8
Bilrubin <2 2-3 >3
Ascites Absent Mild- Severe/
Moderate Refractory
HE Absent Mild (I-II) Severe (III-
IV)
PT <4 sec. 4-6 sec. >6 sec.
prolongation (<1.7) (1.7-2.3) (>2.3)

Interpretation: 23

Class A: 5-6 Class B: 7-9 Class C: 10-15

MELD SCORE

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 DISFUNCTION TYPE

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DISFUNGSI
HEPATOSIT-LOBULUS

GANGGUAN FUNGSI
FIBROSIS NORMAL HATI

DISFUNGSI
SIRKULASI

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HIPERTENSI PORTAL
 JAUNDICE-

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IKHTERUS
ASITES + PALMAR
ERITEMA-
EDEMA SPIDER
PERIFER ANGIOMA

LOSS
FUNCTION
KOAGULOPATI OF GINEKOMASTI
HEPATOSIT

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 VARISES
ESOFAGEAL

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HEPATIC HT ASITES
ENCHEPALOPATY
PORTAL -SBP

SPLENOMEGALI/
HIPERSPLENISME
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HT PORTAL ???

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Splanchnihc
Vasodilation

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Bosch. 2008. Falk Symposium: Pathophysiology of Portal Hipertension. University of Barcelobna
MANAGEMENT OF HT PORTAL

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 β-Blocker non selektif
ex. Propanolol 20 mg 2dd1, nadolol 20-40 mg 1dd1, kmd
titrasi sampai dosis maksimal yg dapat ditoleransi. Why
non selektif?
Target : to achieve a resting heart rate of 55 beats per
minute or a reduction of 25% from the base-line rate.
 Isosorbide mononitrate (Sekarang tidak lagi
direkomendasikan..!!!)  higher mortality
 Kombinasi β-Blocker non selektif +
ISMN/spironolacton)  insufficient evidence to support

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TIPS

Transjugular Intrahepatic Portal-systemic

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
Shunt

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PATOGENESIS AND MANAGEMENT OF PORTAL HT

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BRTO: Balloon-occluded retrograde transvenous obliteration; NSBBs: Non-selective -blocker

SMT: somatostatin; VP: Vasopresin
1st Complication

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Normal

Variceal Bleeding

Varises
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 Goal therapy
 Menurunkan tekanan
vena porta
 Cegah bleeding
 Bleeding → Atasi
pendarahan & cegah
rebleeding
AASLD PRACTICE GUIDELINES
PREVENTION AND MANAGEMENT OF GASTROESOPHAGEAL
VARICES AND VARICEAL HEMORRHAGE IN CIRRHOSIS
No specific therapy
No VARICES

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Repeat Endoscopy in 2-3 years

VARICES no β-Blocker non selective (prevention),

HEMORRHAGE Repeat Endoscopy

β-Blocker
Large VARICES no
EVL (Endoscopic Variceal Ligation)
HEMORRHAGE
Resusitasi cairan,transfusi darah
Ab profilaksis (max 7 days)
VARICEAL
Somatostatin, vassopresin
HEMORRHAGE
Sclerotherapy
TIPS
Recurrent
HEMORRHAGE β-Blocker + EVL 36
TIPS
2nd Complication

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Tanda & gejala lain yg
menyertai
Udem, rasa tidak enak di perut,
kaki bengkak, susah bernafas,
anoreksia, malaise, BB turun

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 SIROSIS

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↑Aldosteron
Pe↓ Albumin Plasma ↑Tek. Portal dan ADH

Pe↓ Tek Pe↑Tek Retensi Na

onkotik Plasma Hidrostatik kapiler dan Air

TRANSUDAT+EKSUDAT CAIRAN

Akumulasi cairan dlm rongga peritoneal

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ASCITES + EDEMA PERIFER
ALBUMIN

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GUIDELINE THERAPY

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(AASLD, 2012)
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GUIDELINE THERAPY
 Based on AASLD (2012)

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 Terapi non farmakologi
◦ Penghentian alkohol
◦ Pembatasan garam 2g/hari (tdk boleh < 120mEq/L)

 Diuretik
◦ Spioronolacton 100mg & furosemid 40mg 1.dd.1
◦ Target: penurunan BB max 0,5 kg/hari pd pasien tanpa
edema, dan tidak ada batasan pada pasien dg udema
◦ Peningkatan dosis dpt dilakukan max 400mg spironolacton &
160mg furosemid
◦ Monitor: elektrolit (Na, K)

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REFRACTORY ASCITES

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 Repeat large volume paracentesis
◦ IV albumin use controversial, but may be beneficial if
>5L fluid removed (6-8g per L fluid removed), no
benefit if <4L fluid removed)
 TIPS can be considered but has not been shown
to be superior to repeat large volume
paracentesis
 Vaptans are under investigation
 Liver transplantation should be considered

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GUIDELINE TERAPI
Berdasarkan EASL (2010)

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

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SBP
Patogenesis

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
◦ Overproduksi bakteri, gangguan imun dan peningkatan
permeabilitas usus .
◦ Translokasi bakteri (migrasi transmural bakteri dari usus)
dan adanya endotoksin dalam cairan ascites)
 Bakteri gram (-) Enterobacteriaceae
(ex: E. coli, K. pneumoniae, S. pneumoniae)
 Diagnosa
◦ PMN ≥ 250 sel/mm3
◦ kultur (+)
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◦ tanda-tanda infeksi
THERAPY

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 Antibiotika spektrum luas
◦ Cefotaxim 2g iv , 3 times daily (1st choice)
◦ Fluoroquinolon iv (norfloxacin 400mg once daily or
ciprofloxacin 750mg weekly) / Amoxicilin-
as.klavulanat iv
◦ Ciprofloxacin (500 mg twice daily for 7 days) atau
trimethoprim-sulfamethoxazole p.o 1.dd.1 u/
profilaksis

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3rd Complication

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•All neurological and psychological
symptoms in patients with liver
disease
•Characterized by various neurologic
symptoms
—Cognitive impairment
—Neuromuscular disturbance
—Altered consciousness
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 NH3-

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OTA
K

FALS
E NT
↑
HE GAB
A↑

Other
BBB↑ Zinc defficiency 48
Manganese deposits
METABOLISME AMONIA

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PE ↑
BBB

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 Batasi intake protein
LAKTULOSA (me↓ pH + efek
katartik)
Rifaximin 550 mg twice daily
(kombinasi dg Laktulosa) NH3-

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Hilangkan bakteri penghasil urease OTAK Hambat
(lactobacillus acidophylus, enterococcus
reseptor GABA-
faecum) : NEOMISIN, METRONIDAZOL)
BDZ :
FLUMAZENIL

Me ↑ asupan
FALSE
NT ↑ HE GABA
↑

BCAA ex :
Aminoleban
L-ornitin L-
aspartat
(LOLA) i.v.
BBB↑ 52
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OTHER COMPLICATION
(SELF STUDY….OK!!!)

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 Koagulopati
 Slenomegali-hipersplenisme

 Sindrom hepatorenal

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SEE U IN TUTORIAL N EXAM!!

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