31

Pharmacotherapy in patients with cirrhosis and complications

alcohol

spontaneous bacterial peritonitis
hepatic encephalopathy
(esophageal varices)

1.

2.
3.

4.

1.
2.
3.

1.
2.
3.

32

Pharmacotherapy in patients with cirrhosis and complications

(cirrhosis) chronic inflammatory

(hepatocyte necrosis) nodular fibrous tissue cirrhosis
(Greek) kirrhos -

portal hypertension portal hypertension

varices (ascites)

hepatic encephalopathy coagulopathy

alcohol
viral hepatitis B C
1 (liver
transplantation) alcohol hepatitis C 2
1

Alcohol, methotrexate, isoniazid, methyldopa, organic hydrocarbons

Viral hepatitis ( B C), (schistosomiasis)

Immune-mediated

Primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis

Metabolic

Hemochromatosis, porphyria, 1-antitrypsin deficiency, Wilsons disease

Biliary obstruction

Cystic fibrosis, atresia, stricture, gallstones

Cardiovascular

Chronic right heart failure, Budd-Chiari syndrome, veno-occlusive disease

Cryptogenic

Unknown

Other

Nonalcoholic steatohepatitis, sarcoidosis, gastric bypass

(Epidemiology)
3.6 1,000
26,000 (chronic liver

33

disease) 4 45 54
malignancy
2

Alcohol
Hepatitis C
Cryptogenic
Primary biliary cirrhosis
Primary sclerosing cholangitis
Acute hepatitis failure
Autoimmune hepatitis
Hepatitis B (chronic)
Hepatocellular cancer
Hemochromatosis
Hepatitis B (acute)
Budd-Chiari syndrome
Other

23
22.4
11
9.4
8.3
6
5.8
3.2
2.9
1.1
0.9
0.7
5.3

acute variceal bleeding,

spontaneous peritonitis hepatic encephalopathy 50
2
(Liver anatomy)
1.5
2
diaphragmatic surface visceral surface
4 (peritoneum)
falciform ligament right lobe left lobe visceral surface
(porta hepatic)
1. Hepatic artery oxygen
2. Hepatic portal vein
3. Bile duct
(Pathophysiology)


portal vein hepatic artery 1 portal triad

34

hepatic liver lobule

central vein 2
fibrosis 3
portal vein portal hypertension (PHT)
portal venous 5-10 mmHg PHT
portal venous 10 mmHg
PHT (mediators)
hepatic sinusoidal nitric oxide (nitric
oxide ) vasoconstrictor endothelin
nitric oxide portal vein

1 (Sease et al, 2008)

35

2 (Sease et al, 2008)

3 fibrosis
(Lisman et al, 2002)

36

(Clinical feature)

(complication)
1. Systemic symptoms


2. Jaundice
serum bilirubin conjugated form uncongugated
bilirubin form hemolysis
conjugated bilirubin bilirubin
3.
(Spider nevi) (palmar erythema)
4. Coagulation abnormality
purpura
ecchymosis (factor)
vitamin K dependent factor (factor II, VII, IX X) platelet
(hypersplenonism)
5. Ascites ascites

6. Hepatic encephalopathy

7. Fetal hepaticus methyl
mercaptan

1. Serum amylase 20-100 U/L (SI = 0.33-1.66 kat/L)

2
isoenzymes P-type S-type
isoenzyme amylase acute pancreatitis
serum amylase pancreatitis pancreatic duct
acute alcoholic intoxication acute cholecystitis
pethidine, thiazide, pentazocine morphine
advance chronic hepatitis acute and subacute liver necrosis alcoholism toxic
hepatitis severe burn severe thyrotoxicosis
2. Lipase 115-285 U/L (SI = 1.92-4.75 kat/L)

37

amylase amylase 3
lipase 14 acute pancreatitis
lipase acute/chronic pancreatitis, acute
cholecystitis pancreatic duct
codeine, morphine, pethidine steroids
3. Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase
(SGOT) 0-65 U/L (SI = 0-1.08 kat/L)
hepatocellular injury
myocardial injury myocardial infarction 96-98
infarction 4-6 ( 24-36
) 4-5 AST hepatitis
AST
alanine aminotransferase (ALT) upper limit
3-5
4. Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT)
0-65 U/L (SI = 0-1.08 kat/L) AST
ALT (specificity) AST
ALT hepatitis, cirrhosis
5. Alkaline phosphatase (AP)
1-12
75-375 U/L
75-450 U/L
13-17
50-325 U/L
150-225 U/L
18 35-130 U/L
AP isoenzyme

intrahepatic/extrahepatic bilirubin obstruction AP bone
disease, jaundice, hepatocellular cirrhosis, hepatitis, hyperthyroidism
intravenous albumin, erythromycin, cloxacillin, lincomycin isoniazid
hypothyroidism, malnutrition, hypophosphatemia, pernicious anemia
propranolol AP
6. Ammonia (NH3) 0-40 mol/L (SI = 0-40 mol/L) ammonia by
product metabolism ammonia
portal circulation urea
plasma ammonia
plasma ammonia hepatic failure (ammonia )
congestive heart failure acidosis

38

ammonia renal failure, essential hypertension

neomycin, MAOIs ammonia
7. Bilirubin 2 total bilirubin 0-1.4 mg/dL (SI =
< 23.9 mol/L) direct 0-0.3 mg/dL (SI = < 5.1 mol/L) bilirubin
hemoglobin direct
indirect direct diglucoronide indirect bilirubin
glucoronidation direct indirect
bilirubin total bilirubin total bilirubin
direct indirect bilirubin bilirubin
obstructive jaundice (direct bilirubin) hepatitis ( direct indirect bilirubin)
amphotericin B, erythromycin, MTX clindamycin
8. Gamma glutamyl transferase (GGT) 0-85 U/L (SI = 0-1.42 kat/L)
0-40 U/L (SI = 0-0.67 kat/L) GGT
peptide
(sensitivity)
(specificity) AST
ALT alcohol GGT 12-24
2-3 alcohol liver cirrhosis,
cholecystitis, cholelithiasis, biliary obstruction phenytoin warfarin GGT

9. Lactate dehydrogenase (LD) 90-200 U/L (SI = 1.50-3.33 kat/L) LD

glycolytic enzyme Krebs cycle 5 isoenzyme
LD1 LD2 (myocardium)
LD3
LD4
LD5
LD 5 isoenzyme

2 compensated
decompensated (ascites)
portal hypertension
decompensated compensate cirrhosis 10
58 decompensated cirrhosis

39

(median time to death) 9 1.6

Child-Pugh classification 3 Child-Pugh class B C
decompensated cirrhosis

(ascites), portal hypertension (PHT), esophageal varices, hepatic encephalopathy
(HE) coagulation disorder hepatorenal
syndrome, hepatopulmonary syndrome endocrine dysfunction
Ascites () spontaneous bacterial peritonitis (SBP)
Ascites Askos
ascites peritoneal cavity
50 ascites 10
ascites PHT nitric oxide
vasodilation baroreceptors rennin-angiotensin system
sodium 1
Child-Pugh classification
The newer Mayo End-Stage Liver Disease (MELD) scoring system Mayo score
the United Network for Organ
Sharing (UNOS) MELD score
serum creatinine, bilirubin international normalized ratio (INR)
MELD score = 0.957 x Loge (creatinine mg/dL) + 0.378 x Loge (bilirubin mg/dL) +
1.120 x Loge (INR) + 0.643
10
1 1 serum creatinine 4 4
MELD score
varices TIPS (Tranjugular intrahepatic portosystemic shunt)
UNOS

6 40
40 20 4

40

4 MELD (Heidelbaugh et al, 2006)

3 Child-Pugh classification
Parameters
Serum albumin (g/dL)
Serum bilirubin (mg/dL)
Prolong bilirubin time
(seconds)
or INR
Ascites
Encepalopathy

1
> 3.5
< 2.0
1-4
< 1.7

2
2.8-3.5
2.0-3.0
4-6
1.7-2.3

3
< 2.8
> 3.0
>6
> 2.3

I-II

III-IV

41

1 ascites (Sease et al, 2008)

aldosterone metabolized
aldosterone ascites fluid (leak) peritoneal cavity
intravascular volume (renal perfusion)
rennin angiotensin aldosterone system aldosterone albumin
albumin free active aldosterone
albumin
aldosterone (aldosterone antagonist) spironolactone

ascites
(poor prognostic sign)
AASLD sodium
2,000 mg/day serum sodium < 120 mEq/L

tense ascites, hyponatremia ( serum sodium < 125 mEq/L)

sodium tense ascites serum sodium < 125 mEq/L
1-1.5 tense ascites, hyponatremia serum sodium
125 mEq/L sodium 15
75 bed rest
metabolite portal venous blood flow renal perfusion

42

spironolactone 100-400 mg/day

3-5 furosemide 40-100 mg/day
spironolactone furosemide 100 : 40 mg
potassium (normokalemia) spironolactone
hyperkalemia
0.5 kg/day
orthostatic hypotension

4 ascites
spiderman () sallow ()
(www. imannooor.wordpress.com. 2012)
Spontaneous bacterial peritonitis (SBP)

25

(ascites) SBP 10
1 /

SBP gram-negative Enterobacteriaceae, Escherichia coli

, leuko-cytosis, , hypoactive rebound tendernase
absolute polymorphonuclear (PMN) 250 cell/mm3

43

SBP
1. 1
2. polymorphonuclear (PMN) 250 /3
50
monomicrobial non-neutrocytic bacterascites (MNB)
PMN < 250 /3 1
MNB

Culture-negative neutrocytic ascites (CNNA) PMN > 250 /3

SBP
SBP
Polymicrobial bacterascites PMN < 250 /3
1

Secondary bacterial peritonitis

PMN > 250 /3 1
(Etiology)
SBP bacterial translocation
endotoxin bacterial deoxynucleic acid (DNA)
(mesenteric lymph nodes)
bacterial
translocation
1. Intestinal bacterial overgrowth bacterial
translocation

SBP

(delayed intestinal transit)

nitric oxide sympathetic

2. Increased intestinal permeability

(portal hypertension)
(translocation)
(intercellular spaces) portal
hypertension (intestinal mucosal oxidative
damage)
3. Alterations in immune defense in cirrhosis

44

- (mucins)

- immnunoglobulins IgA lamina propria

toxin
- endotoxins

- (gut associated lymphoid tissue, GALT)

Peyers patches lymphocytes mesenteric
portal
hypertension shunt Kupffer cells

SBP
1. 70 SBP
Child Pugh score class C bilirubin > 2.5 ./.
2. ( 1 /)
3.
4. SBP
5. ( 20 SBP
30-40 SBP )

mild tenderness, GI bleeding

ascites
ascites
1. Complication Spontaneous bacterial peritonitis
2.

3.
SBP broad-spectrum antibiotics therapy
Escherichia coli, klebsiella pneumonia streptococcus pneumoniae

45

bacterascites stage ( PMN count ascites fluid

) PMN
drug of choice (DOC) cefotaxime third-generation
cephalosporin aztreonam ampicillin tobramycin
fluoroquinolone oral bioavailability ascites fluid
ofloxacin 400 12 ascites fluid PMN count
250/mm3 ofloxacin cefotaxime IV cefotaxime
IV gastrointestinal hemorrhage
oral bioavailability
aminoglycosides SBP
SBP
IV 5-8
SBP (switched therapy) ciprofloxacin IV 2
IV
switched therapy switched therapy
PMN 25 48
SBP high risk
SBP low protein ascites (< 1 )
norfloxacin 400 IV OD 400 12
norfloxacin 400 OD recurrent SBP
70 20 1 ofloxacin 400 IV OD
ciprofloxacin amoxicillin-clavulanic acid
4 Treatment regimen SBP
1. Cefotaxime 2 IV 8 5-7
2. 3rd generation cephalosporin cefoniacid, ceftriaxone (2 ), ceftizoxime
ceftazidime 5-7
3. Amoxicillin 1 clavulanic acid 250 IV 3 5
500 /125 3 3
4. Ciprofloxacin 200 IV 12 7
5. Ciprofloxacin 200 IV 12 2 500
12 5
6. Ofloxacin 400 2 8

46

SBP
1. Prokinetics cisapride beta-adrenegic blockers propranolol
intestinal transit time bacterial translocation

2. Probiotics Lactobacillus
bacterial translocation
bacterial translocation

3. Bile acids bacteriostatic

bile acids bacterial
translocation

ascites
1.

portal hypertension
2. serum sodium 120
mmol/L
3.
4.


Portal hypertension (PHT) varices
PHT
esophageal varices (
) portal venous 12 mmHg
vena cava variceal bleeding
bleeding varices 25-40
bleeding 5-50 (rebleeding)
60-70 1
portal hypertension
portal
1. (hepatic resistance)
2. portal (portal blood flow)
splanchnic (splanchnic vasodilatation)

47

portal hypertension endogenous vasodilator

nitric oxide splanchnic vasodilatation splanchnic vasodilatation
cardiac output hypervolemia
hyperkinetic circulatory syndrome portal hypertension
(fibrosis)
myofibroblast,
stellate cell portal
hypertension vasoconstrictor
varices 3
1. acute variceal bleeding
2. bleeding PHT bleeding
3. rebleeding bleeding
(pre-primary prophylaxis)
Groszmann
timolol non-selective beta-blockers
213
2 timolol 4
2 beta-blockers
beta-blockers

2-3 Endoscopy banding

acute variceal bleeding

(melana) active variceal bleeding alcohol,
NSAIDs Aspirin rebleeding
PHT
The Child-Pugh scoring system 3 bleeding
(coagulation system)
colloidal packed red blood cells, fresh
frozen plasma (FFP) platelets concentration vasoactive drug therapy
(somatostatin, octreotide terlipressin) bleeding
ascites variceal
bleeding 2
Somatostatin Octrotide
Somatostatin 14-amino acid peptide
octrotide octapeptide vascular tone

48

vasodilatory peptide portal variceal pressure meta-analysis

somatostatin octreotide vasopressin terilpressin
4 bleeding octreotide somatostatin
bleeding Somatostatin 50-250 mcg bolus, 250-500 mcg/hr IV infusion
octreotide50-100 mcg bolus, 25-50 mcg/hr IV infusion
50 mcg/hr hypoglecemia hyperglycemia

Vasopressin (Antidiuretic hormone)
non selective vasoconstrictor acute variceal bleeding
portal pressure splanchnic vasoconstriction ( splenic blood flow)
vasoconstriction vasopressin
vasoconstriction
coronary ischemic, myocardial infarction metaanalysis 15 RCTs vasopressin variceal bleeding
50 bleeding

2 Portal HTN esophageal bleeding (Sease et al, 2008)

49

Teripressin (Glypressin)
triglycyl-lysin teripressin
(prodrug) vasopressin unblined clinical trials teripressin
variceal bleeding vasopressin vasopressin
nitroglycerine teripressin glycl residues
terlipressin vasopressin teriplressin (long half-life)
intermittent infusion 4
(primary prophylaxis)
portal hypertension
Endoscopy banding
stent portal hypertension
vasoconstrictor vasodilator
propranolol, nadolol, carvedilol, isosorbide-5-mononitrate (ISMN) nonselective beta-blocker (propranolol, nadolol, carvedilol) portal
cardiac output beta 1-blockade splanchnic
circulation portal system beta 2-blockade
splanchnic circulation non-selective
beta-blocker
non-selective beta-blocker
30 14
meta-analysis Khuroo ..2005 Tripathi
..2007 non-selective beta-blocker Endoscopy banding
Endoscopy
banding 37-43
.. 2009 Tripathi
Endoscopy banding carvedilol non-selective beta-blocker vasodilator
alpha-1 blocker carvedilol 10
Endoscopy banding 23
carvedilol Endoscopy
banding meta-analysis
Cales ..1999 propranolol

..2004 nadolol

nadolol

50

Child-Pugh C non-selective
beta-blocker
1-2
rebleeding (secondary prophylaxis)
80 rebleeding variceal
bleeding rebleeding
-adrenergic blocker bleeding
endoscopic band ligation (EBL) endoscopic injection sclerotherapy (EIS)
EBL EIS bleeding esophageal varices
EBL octreotide
rebleeding
meta-analysis RCTs 11 (10 RCTs propranolol 1
RCT nadolol) rebleeding -adrenergic blocker
rebleeding 21
shunting endoscopy TIPs
(transjugular intrahepatic portosystemic shunt) shunting
well-compensated hepatic function child-Pugh grade A B
rebleeding (secondary prophylaxis) propranolol 20
mg 2-3 nadolol 20-40 2 carvedilol 6.25 2
50-60
(HR) 25 baseline -adrenergic blocker
nitrates spironolactone portal
12 (bronchospasm)
glucose intolerance
5 portal hypertension

Propranolol
Nadolol
Carvedilol
Isosorbide-5-mononitrate

20 2-3
40 2
6.25 2
10-20 2

Primary, secondary prophylaxis

Primary, secondary prophylaxis
Primary, secondary prophylaxis
Primary, secondary prophylaxis ( beta-blocker
)

51

esophageal bleeding
1. Balloon tamponade 2
5
45
24 pressure necrosis

5 Sengstagen Blakemore tube 2

(Medical image. 2012)
2. Sclerotherapy ballon tamponade
sclerosing agent ethoxysclerol sodium morrhuate
(varices) intravariceal injection
paravariceal injection fibrosis
submucosa

6 Sclerotherapy (Medical image. 2012)

3. Endoscopy banding sclerotherapy
varices
sclerotherapy

52

7 Endoscopy banding (Medical image. 2012)

4. Surgical shunt portal system
portal
5. Transjugular intrahepatic portosystemic shunt (TIPS)
jugular vein portal system portal pressure
bleeding

8 TIPS (Sease et al, 2008)

6. sodium
2
7. (restrict fluids)
serum sodium 130 mEq/L
8. large volume paracentesis
large ascites albumin circulatory dysfunction
large volume paracentesis albumin 5-6

53

g/L ascites fluids albumin fluids 5

creatinine BUN peripheral edema
Antibiotics prophylaxis variceal bleeding
variceal hemorrhage bacterial infection
rebleeding
norfloxacin 400 mg
2 7

9 variceal bleeding (Sharara et al, 2001)

54

Hepatic encephalopathy (HE)

HE

HE

HE

(circulatory bypass of the liver) HE
(neurotoxic substances)

HE 50-80
electroencephalopathy
HE 5

(Flapping tremor)
5 HE West Haven criteria
Grade
0
Subclinical
1

Level of Consciousness
Normal
Normal
Inverted sleep patterns/
Restless

Lethargic, slow responses

Somnolent but
rousable, confused

Coma/unrousable

Personality /
Intellect
Normal
Normal
Forgetful, mild
confusion,
agitation, irritable
Disorientation for
time, amnesia,
decreased
inhibitions,
inappropriate
behavior
Disorientation for
place,
Aggressive
None

Neurologic
Abnormalities
None
Psychological only
Tremor, apraxia,
incoordination,
impaired
handwriting
Asterixis, dysarthria,
ataxia, hypoactive
reflexes

EEG Abnormalities
None
None
Triphasic waves (5
cycles/s)

Triphasic waves (5
cycles/s)

Asterixis, hyperactive Triphasic waves (5

reflexes, Babinskis
cycles/s)
sign,
muscle rigidity
Decerebrate
Delta activity, (23
cycles/s)

55

HE
functional change

1. ammonia (hyperammonemia)
urease
( 40
60 metabolism )
(hepatic urea synthesis)
portal
systemic shunt
(astrocytes)
Alzheimer type II astrocytes
(neurotransmission) blood-brain barrier
peripheral-type benzodiazepine receptors (PTBR)
neurosteroids gamma-aminobutyric acid (GABA)/benzodiazepine
receptor complex GABA (inhibitory neurotransmitter)

GABA PTBR GABA/benzodiazepine
receptor complex Alzheimer type II astrocytes
HE tryptophan
tyrosine BBB tryptophan tyrosine serotonin
dopamine false neurotransmitter
(motor disturbance) (psychiatric disturbance) 10

porto-systemic shunt

Alzheimer type II astrocytes PTBR

2. False neurotransmitter portal
octapamine false neurotransmitter
neurotransmitter nor-epinephrine dopamine false neurotransmitter
branch chain amino acids (BCAA)
valine, leucine isoleucine aromatic amino acid (AAA) phenylalanine, tyrosine
tryptophane BCAA:AAA 4.6 : 1 AAA
BCAA BCAA metabolism
blood brain barrier (BBB) permeability

56

AAA aromatic compound metabolize octapamine

3. neurotransmitters (Gamma-aminobutyric acid, GABA)

(receptor) GABA (-aminobutyric acid)
benzodiazepine false neurotransmitters neurotransmitters
dopamine false neurotransmitters neurotransmitters

10
(chemistry.gravitywaves.com. 2012)
1. amine amine
oxidase ammonia
2. urease
portal vein

HE

57

6 HE
Factors
Variceal
Nonvariceal
Infection/sepsis
Electrolyte abnormalities
Sedative ingestion
Dietary excesses
Constipation
Renal insufficiency

Therapy alternatives
Band ligation/sclerotherapy
Octreotide
Endoscopic therapy
Proton pump inhibitors
Antibiotics
Paracentesis
Discontinue diuretics
Fluid and electrolyte replacement
Discontinue sedatives/transquilizers
Consider reversal (flumazenil/naloxone)
Limit daily protein
Lactulose
Cathartics
Bowel cleansing/enema
Discontinue NSAIDs, nephritic antibiotics
Fluid resuscitation

Hepatic encephalopathy
HE HE
hyperammonemia

1.
1,500

10-20 1-1.5 //
2. Nondigestable disaccharide first-line therapy Lactulose syrup
lacitol metabolize (short chain
fatty acid) lactic acid ammonia ammonium ion

lactulose 30-45 1-2 90-

58

150 nasogastric tube

(retension enema) lactulose lactulose 300
sterile water NSS 700 rectal balloon catheter
30-60 4-6 Lactitol 0.5-0.7
3 ( sachet)
3. (antibiotics) second-line therapy
lactulose lactulose
metronidazole neomycin
Metronidazole 500-750 2-3
Neomycin 2-4 6
neomycin 1 renal toxicity
metronidazole neomycin vancomycin
1 2 rifaximine
4. L-Ornithine-L-Aspartate (Amp 5 /10 )
(5 /sachet) 20-40 (4-8 amp/)
D5W NSS IV infusion 1 amp/
6 amp/500 1-2 sachet 3

5. Branched-chain amino acid (BCAA)

hepatic encephalopathy AAA BCAA
AAA BCAA
aminoleban infusion aminoleban oral
6. Flumazenil injection (0.5 /5 ) 0.2-0.4
IV 1-2 15-30 HE unlabel use flumazenil
HE Gamma-Aminobutyric
acid (GABA) GABA blood brain
barrier (BBB) GABA receptor GABA receptor receptor receptor
benzodiazepine (BZD) GABA- benzodiazepine receptor 7
flumazenil BZD antagonist N-desmethyl diazepam
HE HE
7. Bromocriptine L-dopa HE extrapyramidal
symptom
dopamine neurotransmitter
dopamine HE dopamine false neurotransmitter

59

octapamine dopamine dopamine agonist

dopamine
8. Zinc () supplement
hepatic encephalopathy zinc zinc
cofactor enzyme urea cycle zinc supplement
chronic HE zinc 220 2
elemental zinc 100 3

Hepatic Encephalopathy

Identify and eliminate precipitants

Lactulose

lactulose

Neomycin

Vegetable diet

BCAA

Flumazenil

Neomycin

Metronidazole

Liver transplantation

3 Hepatic encephalopathy

60

1. Hepatorenal syndrome (HRS)
HRS intrinsic renal disease (BUN/SCr ratio = 20)
sodium
retention oligulia ( 400 24 ) HRS
40 5
HRS 2 type 1 HRS
serum creatinine 2.5 2
renal failure
2 type 1 HRS SBP, alcoholic hepatitis large volume
paracentesis albumin infusion type 2 HRS
type 1 serum creatinine 2.5
4-6 11 type 1 HRS
splanchic arterial vasodilatation systemic vasoconstrictors plasma
expanders albumin infusion
Intravenous teripressin
Midodrin (alpha-adrenergic agonist) octreotide (glucagons inhibitor)
Noradrenaline
type 2 HRS repeated
paracentesis albumin infusion large ascites vasoconstrictors
type 2 HRS

11 HRS Type-1 HRS

2 type-2 HRS 4-6
(Salerno et al, 2008)

61

(nephrotoxic)
nonsteroidal anti-inflammatory drugs (NSAIDs) aminoglycosides
low dose-dopamine (3-5 g/kg/min) IV dopamine norepinephrine

2. Hepatorenal syndrome 20-40

(ascites) pleural effusion
gas
supplement oxygen
3. Coaggulation disorder chronic liver disease
bleeding coagulation factor
factor I, II, V, VII, IX X prothrombin time
fresh frozen plasma (FFP)

62

7 Cirrhosis

Recommendations
alcohol folic acid (1 ), thiamine (100

) HE protein 35-50
Bleeding disorders
vitamin K 10 OD SC IV 2-3 infusion rate
1-2 SC
IV
Ascites ()
Na 10-20 mEq spironolactone 50
-
400 potassium, BUN electrolyte
HCTZ 25-50
0.3-1 furosemide 20-40
spironolactone
Esophageal varices
IV fluids/blood replacement BP, Propranolol 20-80
6
portal BP pulse rate, nadolol
40 160 isosorbide mononitrate
nadolol 10 2 20
2 BP ( )
Somatostatin 50-250 bolus, 250-500
IV infusion octreotide50-100 bolus,
25-50 IV infusion, Terlipressin 2
IV bolus 6
Vasopressin 20 IV bolus 0.2-0.4 (
0.9 )
Hepatic encephalopathy 30
Lactulose syrup (10 g/15 ) 30-45
3
Neomycin 2-4 ( 1 ),
metronidazole 500-750 2-3
Flumazenil 0.2-0.4 IV 1-2
15-30
Hepatorenal syndrome
Dopamine 0.5-1 IV infusion

63

(varices)
(variceal hemorrhage) nonselective -adrenergic
blockers (rebleeding)
55 60
octreotide endoscopic band ligation
(ascites)
aldosterone spironolactone hyperkalemia
furosemide hepatic
encephalopathy lactulose
lactulose neomycin metronidazole

course neomycin

(X) (/)
...............1. portal nitric oxide
.......................................................................................................................................................................................
...............2. Jaundice conjugated bilirubin unconjugated bilirubin
form
.......................................................................................................................................................................................
...............3. Spider nevi
.......................................................................................................................................................................................
...............4. factor factor II, VII, IX X
.......................................................................................................................................................................................
...............5. Fetal hepaticus Ammonia

.......................................................................................................................................................................................
..............6. Serum amylase
.......................................................................................................................................................................................
...............7. lipase
.......................................................................................................................................................................................

64

...............8. SGOT SGPT

.......................................................................................................................................................................................
...............9. Ascites aldosterone
.......................................................................................................................................................................................
...............10.
.......................................................................................................................................................................................
...............11. SBP Escherichia coli
.......................................................................................................................................................................................
12. first line ascites furosemide
.......................................................................................................................................................................................
13. SBP aminoglycoside
.......................................................................................................................................................................................
14. Somatostatin
prodrug

.......................................................................................................................................................................................
...............15. metronidazole neomycin hepatic
encephalopathy
.......................................................................................................................................................................................

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RL, Yee GC, Matzke GR, Well BG, Posey LM, editors. Pharmacotherapy: a pathophysiologic
approach. 7th ed. Appleton&Lange: Stamford; 2008.
2. Desmet VJ, Roskams T. Cirrhosis reversal: a duel between dogma and myth. Journal of
Hepatology 2004; 40: 860867.
3. Sharara AI, Rockey DC. Gastrointestinal variceal hemorrhage. N Engl J Med. 2001. 345 (9) :
669-681.
4. Lisman T, Frank W.G., Philip G. Haemostatic abnormalities in patients with liver disease.
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