FARMAKOTERA

PI S

IROSIS HEPATIK

Budi Suprapti
Departemen Farmasi Klinis
Fakultas Farmasi Universitas
Surabaya
Airlangga

EPIDEMIOLOGI
WHO 2011 : Indonesia
- 45.000 kasus
Asia tenggara : Kematian 280.000/th
30% - kematian global
Sirosis Hepatik 3,5% pasien rawat inap IPD
47,4% pasien rawat inap penyakit
Etiologi-HCV
26%
(Sease, 2008)
HBV-HDV 15%
Dunia : Hepatitis B 2 Milyar 240

liver

juta HB kronis

Hepatitis C - 170 juta

kematian 1,5 juta/tahun
Indonesia: Hepatitis B - 23 juta
Hepatitis C 2 juta
Riskesdas 2007:
Pemeriksaan biomedis 9,4%

POSITIP HBsAg
(Kemenkes RI, 2012)

SIROSIS HEPATIK
. Chirose-warna orange-kuning orange hati / liver

. Kerusakan difuse irreversibel dari liver

dikarakterisasi oleh hilangnya architecture
liver normal secara lengkap
diganti oleh fibrosis yang ekstensif dengan
nodul-2 regenerasi parenchim
(Dipiro, 2011)

ETIOLOGI SIROSIS HEPATIK

Konsumsi alkohol kronik

Hepatitis viral kronis (tipe B, C, D)

Penyakit metabolik liver:
Penyakit hemokromatosis
Penyakit Wilson
Defisiensi -1 antitripsin
Nonalkoholik steatohepatitis
(fatty liver)
Penyakit immunologi
Cystic fibrosis
Hepatitis autoimmun, sirosis bilier primer
Penyakit vaskular: Budd chiari, gagal jantung
Obat-obat:
INH, metildopa, amiodaron, metotrexat,
tamoxifen, retinol, PTU, didanosin

Dipiro, 2011

FUNGSI LIVER - NORMAL

-Energi-

interkonversi substrat
Metabolisme KH, prot., lipid
- Sintesis-sekresi prot.plasma,
clotting factor
- Solubilisasi, transpor, storage :
. Sirkulasi empedu
. Lipoprotein-transpor lipid
. Vitamin, glycogen
- Protektif + klirens
. Fagositosis
. Metabolisme ammonia
. Sintesis glutathion
. Metabolisme obat, hormon (Ganong, 2010)

(Torotora, 2003)

(Torotora, 2003)
7

Features of Clinically important hepatitis viruses (Dipiro)

Virus
Genome
Incubation
( days )
Transmission
oral

Hepatitis A

Hepatitis B

Hepatitis C

Hepatitis D

HAV
ssRNA
14-45

HBV
dsDNA
40-180

HCV
ssRNA
35-84

HDV
ssRNA
40-180

Fecal-oral

Parenteral

Parenteral

Sexual
Perinatal
Mucous
membrane

Sexual
Perinatal
Mucous
membrane

Serologic markers
Antigens
HAVAg
HDVAg
N/A

Abtibodies

HBsAg

Parenteral

Hepatitis E
HEV
ssRNA
14-60
Fecal-

Sexual(?)
Perinatal

HCVAAg

HBcAg
HBeAg
Anti-HAV Anti-HBs
HDV
N/A

Anti-HCV

Anti-

Anti-HBc
AntiHBe
Viral markers HAVRNA
Hepatocellular
Ca No
No
Hepatocellular
Ca
DNA polymerase

HBV DNA
Yes
Yes

HCVRNA
Yes
Yes

HDVRNA
Yes
Yes

N/A
No
No (McPhee,
(McPhee, 2006)

Clincal syndromes associated with viral hepatitis (Ganong)

Hepatitis Vruses
- HAV
- HBV
- HCV
- Delta
- HEV

Infection

Subclinical
Hepatitis

Acute
Hepatitis

Chole static
Hepatitis

Chronic
Chronic
rsistent
Hepatitis
P
( Carrier
state )
e

Fulminant
Hepatitis
( massive
necrosis )

Active
Hepatitis
( continuing
Necrosis )

(
Cirrhosis
Recovery
( with normal
Appearing,
Regenerated
liver )

Hepato
Cellular
carcinoma

Death

(McPhee, 2006)

SIKLUS REPLIKASI VIRUS HEPATITIS B

RESPONS IMMUN SELULAR TERHADAP VIRUS HEPATITIS B

TANDA DAN GEJALA

HAV: sangat bervariasi, tidak
HBV

spesifik

Demam
Nyeri sendi. otot
kelelahan
Mual, muntah kembung
anoreksia
Gejala kuning, gatal
BAK seperti teh

BAB pucat
HCV : > 90% asimptomatik

Kemenkes, 2012
12

LIVER NORMAL
13

14

15

16

17

Tipe disfungsi liver

. Disfungsi

hepatosit-lobulus
. Disfungsi sirkulasi (HT portal)

18

(Torotora, 2003)
19

LIVER FAILURE - COMPLICATION

HypoAlbuminemia

Portal
Hypertension

Cholestasis

NH4+ + HCO3-

Fat Abs.
Ascites

Exudative
enteropathy

Varices

Hyperaldo
Steronism
Hypokalemia

Vitamin K
deficiency

Urea

Clotting factors
GI Bleeding
Aromatic AA

Renal NH4+
Production

Enteric AA
Break down
Hyper Ammonemia
Alkalosis

False Neuro
transmiters
Hypervent.

Encephalopathy

(Silbernagi, 2000)
20

Manifestasi klinik sirosis

(McPhee, 2006)
21

Manifetasi - data laboratorium

Hipoalbumin
Prothrombin time
Trombositopeni
Alkali fosfatase
Peninghkatan
AST,

ALT, GGT
(Dipiro, 2011)
22

Managemen terapi

23

PENDEKATAN TERAPI
Identifikasi-eliminasi penyebab
sirosis
Profilaksis / Tx variceal bleeding
Asites farmakologi/paracentesis
Tx
SBP
HE
Monitor

hepatorenal syndrome
(Dipiro, 2011)

HT portal-variceal bleeding
1. cegah perdarahan profilkasis
2. Tx acute variceal hemorrhage
3. Cegah rebleeding-profilaksis sekunder
NOTE:
Varises 5% pasien sirosis 1 th
28% pasien sirosis 3 tahun
Acute variceal bleeding terjadi pada 25 40% pasien
dengan tingkat kematian 30%
Rebleeding dalam 10 hari I : 50%
(Dipiro, 2011, ACCP
2013)

Ad. 1Mencegah perdarahan variceal

. Me portal inflow + tekanan portal
.

Adrenergik blocker HR 25% (55-60

bpm)

propanolol 3 dd 10 mg (40-320mg/d)
nadolol 1 dd 20 mg
EVL Endoscopy variceal ligation
.
(Dipiro, 2011, ACCP
2013)

Ad.2. TX ACUTE VARICEAL BLEEDING

. Resusitasi cairan cukup & stabilisasi hemodinamika
cairan kristaloid, FFP, platelet, PRC
. Kendalikan bleeding
Octreotide 50 mcg iv bolus 50 mcg/jam (3-5 hari)
Somatostatin 250 mcg iv bolus 250-500 mcg/hari
(3-5 hari)
. Antibiotika
. Kuinolon
. Ceftriaxon
. PPI, H2RA, Sucralfat
(Dipiro, 2011, ACCP 2013)

!! Hindari peningkatan vol.intravask. berlebihan

Ad.3 Cegah rebleeding-profilaksis sekunder

. Blocker long acting
. Propanolol 3 x 20 mg
Nadolol 1 x 20 40 mg
Lakukan titrasi mingguan dicapai HR 55-60 bpm
atau turun 25% normal
. EBL
. EIS
. TIPS
(Dipiro, 2011, ACCP
2013)

ASITES
Terjadi pada 30% pasien SH 5 tahun
Diet garam < 2 g/hari (!! Na dlm mkn, ob)
Batasi air bila Na serum < 120-125 mg/dL
Diuretik
Spironolakton 100 mg/hari (max 400 mg/hari)
Furosemid 40 mg/hari (max 160 mg/hari)
?? Capaian
?? Monitoring
. Asites >>-- paracentesis
bila cairan asites yang dihilangkan > 5 L
komb. Albumin 6-8 g/L cairan asites
Hindari NSAID

(Dipiro, 2011, ACCP 2013)

Spontaneous Bacterial Peritonitis

Terjadi pada 10-30 pasien rawat inap-SH-asites
mortalitas 20-40%
Bakteri penginfeksi:
E coli, EKlebsiella
sp, streptococcus
coli, Klebsiella
sp, streptococcus pneumoniae
lainnya
AB broad spectrum terutama gram negatif
. Cefotaxim 1-2 g/8-12 jam
. Ceftriaxon 2 g/hari
. Kuinolon dapat digunakan
. Hindari aminoglikosida
AB diberikan sampai 5-10 hari
AB profilaksis pasien SH- perdarahan saluran
cerna
Ofloxacin, ciprofloxacin atau komb TMP/smz
(Dipiro, 2011, ACCP 2013)

HEPATIC ENCHEPHALOPATY (HE)

Semua gejala neurologik dan psikologik penyakit liver
5 tahap HE
Kesadaran :
Normal Absent minded drowsy sleeping but
arousable coma
Intelectual function:
Actional IQ reduced calculation impaired loss of time
orientation loss of spatial orientation loss of self
Behaviour :
Normal accentuate of normal behaviour disinhibition,
apathy delusi, aggresion
Neuromuscular function
psychomotor test impaired handwriting impaired
(asterixis) asterixis, ataxia pyramidal sign muscular
rigidity dilated pupil
(Gerber 2000, Dipiro, 2011, ACCP
ECG
2013)

31

Hepatic enchephalopaty (HE)

Common precipitants of HE
Increased nitrogen load
. GI bleeding
. Excess dietary protein
. Azotemia
. Constipation
Electrolyte imbalance
. Hypokalemia
. Alkalosis
. Hypoxia
. Hypovolemia
Drugs
. Opioids, tranqulizer, sedatives
. Diuretics
Micellaneous
. Infection
. Surgery
. Progressive liver disease
(Gerber 2000, Dipiro, 2011, ACCP
2013)

32

Hepatic enchephalopaty (HE)

Terapi patogenesis
Batasi protein intake 1-1,5 g/kg hari sumber nabati stlh HE teratasi
Laktulosa - Me ammonia darah
Awali 30-60 ml po/1-2jam sampai pergerakan BAB modah
turunkan 4 dd 15-30 ml
jangka panjang
Neomisin 3-6 g/hari dosis terbagi 3-4 x
Antagonis reseptor benzodiazepin : Flumazenil
Supplemen Zinc
Infus Asam Amino Cabang False
neurotransmiter

( Dipiro, 2011, ACCP 2013)