LAYANAN KEFARMASIAN

PADA

PENYAKIT HATI
PENYAKIT HATI
•  ACUTE LIVER DISEASE: Hepatitis, Toksisitas obat atau alkohol
•  CHRONIC LIVER DISEASE
•  END STAGE LIVER DISEASE
ANATOMI
HEPATOMEGALI
PROBLEM MEDIK UMUM
l Seringkali asimtomatik meskipun tes lab tak normal
l Komplikasi:
§  Ascites, Spontaneous Bacterial Peritonitis (SBP)
§  Oedema
§  Hipertensi Portal
§  Hepatic Encephalopathy
§  Gangguan Koagulasi
§  Hepatorenal syndrome
COMMON DRP
•  Pemilihan obat yang kurang tepat
•  Tak ada penyesuaian dosis
•  ADR : HE, peningkatan Transaminase
•  DILD (Drug Induced Liver Disease)
ASSESSMENT OF LIVER FUNCTION
l  Tdk ada tes yg dpt mengkuantifikasi fs hati
l  Marker Nekrosis Hepatoseluler :
§  SGOT(AST)
§  SGPT(ALT)
§  ALP
§  GGT
§  Bilirubin
l  Marker Kapasitas Sintetis Hepar:
§  Albumin,
§  Prothrombin Time
ACUTE LIVER DISEASE
•  Manifestasi: Hepatitis, Drug intoxication, alcohol
toxication
•  Sign: Transaminase ↑ minimal 2x nilai normal,
dpt disertai pe ↑ GGT, ALP
•  Symptom: mual, muntah, nyeri perut kuadran
kanan bawah, jaundice
•  Dapat menyebabkan Acute or Chronic Hepatic
Failure
ACUTE HEPATIC FAILURE
•  May be fulminant (mortality rate 80%, Tierney) or subfulminant
•  Fulminant: HE dlm 8 mgg setelah hepatitis, coagulopathy
•  Subfulminant: HE > 8 mgg paska hepatitis
•  Cause: Hepatitis B, Hepatitis C, drug-induced (Paracetamol),
idiosyncratic drug reaction, poisonous mushrooms, malignancy
(lymphomas), Wilson’s disease, Reye’ syndrome, shock
•  Presentation: jaundice minimal, SIRS, GI symptoms, hemorrhagic
phenomenon, lab test ( severe hepatocellular damage)
ACUTE HEPATIC FAILURE
l  Characteristics:
§  Short course ( < 8 weeks)
§  Rare portal hypertension
§  Hepatic encephalopathy
§  Cerebral oedema
§  Reversible (regeneration)
TREATMENT
l  Goal: correcting metabolic abnormalities, preventing coma
l  Treatment include:
o  Coagulation defects with Vit K, Fresh Frozen Plasma, Trombocyte Concentrate
o  Imbalance acid-base, fluid and electrolyte
o  Renal failure
o  Hypoglycemia with Dextrose 40% or 10%
o  Encephalopathy: avoid drugs that alter mental status, lactulose is not effective in this
setting
o  Prophylactic antibiotics reduce the risk of infection
o  Acetyl cystein for Pamol toxicity ( 140mg/kg followed by 70mg/kg every 4 hours for 17
doses)
o  Avoidance to drug induced liver failure
o  Liver Transplant
CHRONIC LIVER DISEASE
Characteristics
l Long course (months-years)
l Portal hypertension
l Hepatic encephalopathy
l Rare cerebral oedema
l Irreversible (scar formation)
l Forms:
§  CIRRHOSIS HEPATIC
§  PRIMARY BILLIARY CIRRHOSIS
CLD SEVERITY ASSESMENT
Child–Pugh Score, predictor severity of CH,survival,risk
variceal bleeding, dosage adjustment

Score 1 2 3

Bilirubin(mg/dl) 1-2 2-3 >3

Albumin (mg/dl) >3,5 2.8-3.5 <2.8

Ascites None Mild Moderate

Prothrombin Time 1-4 4-6 >6

CIRRHOSIS HEPATIC

v Progressive loss of basic hepatocyte function

v Loss of enzymes →↓drugs & toxin handling
v Findings: jaundice, gynecomastia, spider navy,
splenomegaly, erytema palmaris.
v Manifestasi: Hepatic encephalopathy, coagulopathy,
Portal hypertension, Ascites, SBP, oesophageal/gastric
varices, hepatorenal syndrome.
CIRRHOSIS HEPATIC
CH TREATMENT
l Ascites management
l Koreksi nutritional deficiency (hati-hati dg iron
replacement).
l Treatment of coagulopathy (Vit K / transfusi)
l Imunitas ↓→terapi infeksi agresif, profilaksis
l Terapi portal hypertension (bila+) dg propanolol
l Variceal Bleeding: Octreotide, somatostatin, TIPS,
sclerotherapy
 CH TREATMENT
Gastroenterol (2016) 51:629–650 639

diuretic-resistant or diuretic-intractable ascites

Small moderate amount of ascites
spironolactone 25 100mg
furosemide 20 80mg p.o. Therapeutic paracenteses
(+albumin infusion)
resistant
cell-free and concentrated ascites reinfusion therapy (CART)

Massive ascitis Admission

Sodium restriction 5 7g/day resistant
spironolactone/furosemide < 70 years of age
tolvaptan 3.75 7.5mg Child-Pugh score 11

transjugular intrahepatic
peritoneovenous shunt
portosystemic stent-shunt
(PVS)
(TIPS)
pottasium canrenoate 200 600mg impossible impossible
furosemide 20 100mg i.v.
Serum T. Bil 10mg/dL , respiratory
beginning with 20mg,
failure, DIC, SBP, gastrointestinal
be increased, if necessary bleeding, peritoneal adhesion,
albumin infusion untreated risky varices Liver transplantation

Serum Cr 1.0mg/dL
Spontaneous bacterial Third generation BUN 30mg/dL + Albmin infusion
Peritonitis (SBP) cephalosporins i.v. or (1.5g/kg b.w.)
T. Bil 4.0mg/dL

Fig. 4 Therapeutic algorithm for cirrhotic ascites. The first-choice after large-volume paracentesis has been proved to be useful for the
diuretic for a small to moderate amount of ascites is spironolactone prevention of paracentesis-induced circulatory disturbance, although
25–100 mg/day). If it is not effective, furosemide (20–80 mg/day this is restricted in the public medical insurance systems in Japan
orally) is added. Patients with massive or nonresponsive ascites Patients with spontaneous bacterial peritonitis (SBP) should receive
PRIMARY BILLIARY CIRRHOSIS (PBC)
•  Characteristic: autoimmune destruction of intrahepatic bile ducts and
cholestasis
•  Insidious onset, progressive
•  More women aged 40-60
•  Complication: steatorrhea, xanthomas, xanthelasma, osteoporosis,
osteomalacia, portal hypertension
•  Presentation: jaundice, sign of portal hypertension, pruritus,
xanthomatous lesions.
•  Lab: ALP↑, HDL chol ↑, Bil ↑
 TREATMENT
•  Symptomatic, include
•  Cholestyramin 3x4g in water or juice for the pruritus or
ondansetron
•  Calcium supplementation
•  Ursodeoxycholic acid 10-15mg/kg/d to slow the progression, ↑
long term survival, ↓ the risk of oesophageal varices
•  MTX 15mg/wk ↑liver histology
•  Colchicine 2 x 0,6mg ↑ symptomp
•  Corticosteroid, AZT of no benefit
 ASCITES MANAGEMENT

•  Ascites terbentuk o/k produksi↑atau absorpsi↓ dari cairan

peritoneum. Hipertensi portal me ↑tekanan sinusoid
berakibat produksi kelenjar limfa ↑
•  Komplikasi: SBP, GERD, LBP, HRS, mbilical hernia.
•  Management: bed rest, restriksi Na dan air, stop alkohol,
loop diuretik 1 x 40mg PO, Spironolakton1x100mg
•  Monitoring: BB 0,5kg/hari tanpa oedema, 1kg/hari bila ada
oedema, elektrolit
•  Konseling: Diuretik diminum pagi hari, hindari NSAID
HEPATIC ENCEPHALOPATHY

•  DEF: Syndrome perubahan status mental berhubungan

dengan kegagalan hati dengan karakteristik impaired
cognitive skills, worsened motor abilities, somnolence, coma
•  Outcome: Pencegahan coma.
•  Pencetus: konstipasi, infeksi, Bleeding GI, hipokalemia,
dehidrasi, benzodiazepin, hipotensi
•  Treatment:
o  Intake BCAA L-Isoleucine, L-Leucine, dan L-Valine) ↑ than
AAA
HE (LANJUTAN)
•  Treatment (lanjutan)
o  Reduksi blood ammonia: laktulosa, Neomycin 4 x 500 mg
o  Benzodiazepin antagonis (Flumazenil) 0,2 –15 mg iv bila
terapi konvensional gagal.
•  Monitoring:
o  Kondisi pasien: status mental, kesadaran
o  Efek katartik: 3-4 kali
o  Elektrolit.
SPONTANEOUS BACTERIAL PERITONITIS
•  Common complications of ascites
•  Causa: intestinal bacterial overgrowth, ↑ permeability of intestinal mucosa,
↓ neutrophil activity, ↓ phagocytic activity of RES
•  High mortality rate (40%, Quan), high reinfection rate (70%)
SPONTANEOUS BACTERIAL PERITONITIS
l Predisposing factors: Hx of SBP, GI bleeding, UTI,
bladder/intravasc. cath.,repeated paracentesis
l Findings: Abdo pain, fever, elevated WBC, renal failure,
precipitation of HE
l Treatment: Cefotaxime 3x1-2 g for 5-10 days or
Ceftriaxone 1x1g for 5-10 days, albumin 1g/kg on day 0
and day 3
l Prophylaxis for reinfection: Cipro 1x750mg/week
HEPATORENAL SYNDROME
l Renal failure associated with liver disease
l Defined by oligouria in euvolemia or hypervolemia
l No structural damages in the kidneys
l Management:
l renal dose dopamine has not been proven to be
beneficial
l RRT
l Liver Transplant
 DRUG THERAPY MONITRING

§  Kondisi klinik: Oedema, ascites, BB,

§  Vital sign : BP, Nadi
§  Kimia Klinik: elektrolit, albumin
 IMPLIKASI FARMASI KLINIK
§  Assess kemungkinan Drug induced Hepatotoxicity pada
setiap Hepatitis
§  Sering diiringi gangguan GIT, shg perlu antasid, H2-Bloker
§  Waspada thd obat highly-protein bound, monitor efek
samping
§  Waspada intake Na terutama pd CH dg ascites/oedema
§  Awasi bila ada kelebihan cairan yg masuk
§  Kurangi dosis, perpanjang interval untuk obat highly
metabolised in the liver khususnya pada CH
§  Waspada thd obat yang dapat memicu/memperburuk
encephalopati
IMPLIKASI FARMASI KLINIK
•  Hindari obat yang dapat memperparah Liver
•  Stop Drug-induced hepatotoxicity
•  Monitor efek samping obat lebih ketat, karena peluang semakin besar.
DRUG-INDUCED HEPATOXICITY
l  Acute Hepatic Injury
§  Hepatocellular injury:Halothane, INH, Pamol, PZA
§  Cholestatic injury:Steroid anabolik, OC, erythromycin, CPZ
§  Mixed injury: Sulfonamida, rifampin, PAS
l  Chronic Hepatic Injury
§  Chronic Hepatitis: Metildopa, nitrofurantoin, Pamol,
Sulfonamida, INH
§  Chronic cholestatic: Fenothiazin, amitryptiline
§  Granulomatous hepatitis: Quinidin, Fenitoin, diltiazem
§  Cirrhosis: MTX
 CASE 1
•  Ny SH, 28 th, 53kg, 161cm
•  Mengeluh panas selama > 2 minggu, batuk selama > 1 bulan
•  TTV: temp 37, 8°C, BP 110/80 mmHg, lemah
•  Lab: Widal O 1/320; S 1/200, leuko (N), LED↑.
•  Tx: Thiamphenicol selama 10 hari kemudian cravit 4 hari.
•  Pada hari ke-14 ditemukan tanda KP dari hasil x-ray paru, shg
seketika tTx dirubah menjadi regimen TB. Setelah satu minggu
terlihat jaundice disertai mual. Apa rencana farmasis terhadap
kasus ini?
 CASE 2
•  Ny. SM, 58th, 55kg, 153cm
•  MRS dg keluhan perut membesar disertai mual, kembung, febris
38 °C, lemah, anoreksia, insomnia. Px mengaku tidak pernah
sakit. Pada pemeriksaan fisik dijumpai eritema palmaris, spider
naevy dan hsl lab menunjukkan hipoalbuminemia, prolongasi PT
1,8 x normal, SGOT 53 mg/dL, SGPT 49 mg/dL, leuko (N).
Didukung hasil USG, selanjutnya Px didiagnosa CH + susp SBP.
Bgmana rencana pelayanan farmasi?
CASE 3
•  Tn HM, 62 th, 58kg, 160cm
•  MRS dengan gelisah, marah-marah, tidak bisa diajak
komunikasi. Mengaku tidak pernah sakit berat/liver. Pada
pemeriksaan dijumpai jaundice, erytema palmaris. Hasil
lab menunjukkan : Albumin 2,7 mg/dL; Na 126 meq/L, K
3,1 meq/L, SGOT 75 mg/dL; SGPT 56 mg/dL.Px
didiagnosa CH dg HE.
•  Rekomendasi terapi apa yang dapat diberikan thd kasus
ini?