Decompensated Liver
Cirrhosis
By Dr. Doaa Kamal
Definition:
Cirrhosis is defined histologically as a
diffuse hepatic process characterized
by fibrosis and the conversion of
normal liver architecture into
structurally abnormal nodules.
Causes of liver cirrhosis:
1) Viral Hepatitis B, C.
2) Alcoholic liver disease.
3) Non-alcoholic fatty liver
disease (NAFLD).
4) Autoimmune hepatitis.
5) Primary biliary cirrhosis.
6) Secondary biliary cirrhosis
(associated with chronic
extrahepatic bile duct
obstruction).
7) Primary sclerosing
cholangitis.
8) Hemochromatosis
9) Wilson disease.
10) Alpha-1 antitrypsin
deficiency.
11) Granulomatous disease (eg,
sarcoidosis).
12) Type IV glycogen storage
disease.
13) Drug-induced liver disease
(eg, methotrexate, alpha
methyldopa, amiodarone).
14) Venous outflow obstruction
(eg, Budd-Chiari syndrome,
veno-occlusive disease).
15) Cardiac cirrhosis: chronic
right-sided heart failure,
tricuspid regurgitation.
Causes of hepatic decompensation:
 Alkalosis.
 Hypokalemia.
 GIT bleeding.
 Hypotension.
 Hepatotoxic drugs.
 Infection.
 Diuretic therapy.
 General anesthesia.
 Surgery and general anesthesia place the cirrhotic
liver at risk for decompensation. Why? Anesthesia
reduces cardiac output, induces splanchnic
vasodilation and causes a 30-50% in hepatic blood
flow.
Pathophysiology and clinical picture of
liver cell failure:
1) Liver:
 Hyper-bilirubinemia (d.t ↓ secretory function
of the liver).
 Hypo-albuminemia (d.t ↓ synthetic function)
→ tissue edema, ascites, pleural effusion.
 Elevated liver enzymes as a result of
hepatocellular damage.
2) GIT:
 Portal hypertension: defined as a pressure gradient
of > 10 mmHg between the portal vein and IVC. It
is a major contributory factor for ascites and
esophageal varices.
 Variceal Bleeding
 Ascites: as a result of portal HTN. It is a transudate in
nature with protein concentration less than 2.5
mg/dL.
 SBP: appears to be caused by the translocation of GI
tract bacteria across the gut wall and also by the
hematogenous spread of bacteria. The most common
causative organisms are Escherichia coli,
Streptococcus pneumoniae, Klebsiella, and other
gram-negative enteric organisms. C/P: abdominal
pain, fever, leukocytosis, and worsening hepatic
encephalopathy.
3) Renal: Hepato-renal Syndrome
 It is the occurrence of acute renal dysfunction in patients with
preexisitng liver failure in the absence of primary renal
disease.
 May be caused by an imbalance between renal
vasoconstrictors (eg. Angiontensin, ADH, NE) and
vasodilators (eg. PGE2, PGI2, ANF). Plasma levels of
vasoconstrictors are elevated resulting in decreased renal
perfusion. NSAIDS inhibit PG synthesis and hence potentiate
renal vasoconstriction with a resulting drop in glomerular
filtration. Thus the use of NSAIDS is contra indicated in
patients with decompensated cirrhosis.
 It is diagnosed by:
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Creatinine clearance < 40 ml/min
Serum creatinine > 1.5 mg/dL
Oliguria urine volume < 500 ml/day
Urine Na < 10 mlEq/L
4) Pulmonary:
(A) Hepato-pulmonary Syndrome (HPS)
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This is the presence of abnormal intrapulmonary vascular
dilatation that can cause profound hypoxemia and can be
very difficult to treat. It may be explained by decreased
hepatic clearance of endogenous vasodilators (eg. NO).
HPS is marked by the symptom of platypnea (shortness of
breath occurring more in the upright position) and
othrodeoxia (O2 desaturation occurring more in the upright
position).
It can be diagnosed by echocardiography. Pts are
diagnosed when their PaO2 is less than 70 mmHg. Some
cases may be corrected by liver transplantation and pts may
receive a speedy course to liver transplantation if their PaO2
is less than 60 mmHg.
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(B) Porto-pulmonary hypertension (PPHTN)
PPHTN is defined as the presence of a mean PAP
greater than 25 mmHg in the presence of normal
PCWP.
It results from excessive pulmonary
vasoconstriction and vascular remodelling that
eventually leads to right-heart failure.
It is also diagnosed by Doppler echocardiography.
Many liver transplantation programs rule out the
presence of PPHTN in pts on the transplant waiting
list. Pts who develop PPHTN require aggressive
medical therapy in effort to stabilize PAP and
decrease perioperative mortality
5) CNS changes: Hepatic encephalopathy
 Hepatic encephalopathy is a syndrome marked by personality
changes, intellectual impairment, and a depressed level of
consciousness occurring as a result of diversion of portal blood
into the systemic circulation (porto-systemic shunting).
 It is believed to be caused by the passage of neurotoxins which
bypass hepatic detoxification and reach the brain via portosystemic shunting. Neurotoxins include short-chain fatty acids,
mercaptans, false neurotransmitters (eg, tyramine,
octopamine), ammonia (NH3), and gamma-aminobutyric acid
(GABA). Patients may have altered brain energy metabolism
and increased permeability of the blood-brain barrier.
 Today it is believed that neurosteroids may play a key role in
hepatic encephalopathy. They are elevated in patients with
encephalopathy and are capable of binding to their receptor
within the neuronal GABA receptor complex and can increase
inhibitory neurotransmission.
 Acute encephalopathy occurs in fulminating hepatic failure.
There is cerebral edema and increased ICP.
Symptoms are graded on the following scale:
 Grade 0 - Subclinical; normal mental status, but minimal
changes in memory, concentration, intellectual function,
coordination.
 Grade 1 - Mild confusion, euphoria or depression, decreased
attention, slowing of ability to perform mental tasks,
irritability, disorders of sleep pattern (ie. inverted sleep cycle).
 Grade 2 - Drowsiness, lethargy, gross deficits in ability to
perform mental tasks, obvious personality changes,
inappropriate behaviour, intermittent disorientation (usually
for time). Diminished short term memory and concentration.
Asterixis on physical examination.
 Grade 3 - Somnolent but arousable, unable to perform mental
tasks, disorientation to time and place, marked confusion,
amnesia, occasional fits of rage, speech is present but
incomprehensible.
 Grade 4 - Coma, with or without response to painful stimuli.

Diagnosis of hepatic encephalopathy:
a)
b)
c)
Elevated free serum ammonia level.
EEG: shows non-specific high amplitude low frequency waves
and triphasic waves.
CT scan and MRI of the brain may be necessary in ruling out
intracranial lesions. In acute encephalopathy brain edema may
be seen.
Common precipitating factors:
Renal failure, GIT bleeding, infection, constipation, increased
dietary protein intake. Opiates, benzodiazepines, anti-depressants
and anti-psychotics may also worsen encephalopathy. Hypokalemia
and alkalosis (due to vomiting or excessive use of K-losing
diuretics) increase solubility of NH3 thus increase its passage
across the blood brain barrier.
Differential diagnosis of encephalopathy (other causes of
coma):

Intracranial lesions (intracranial hge, tumour, abcess), infections
(meningitis, encephalitis), metabolic encephalopathy
(hypoglycaemia, uremia, electrolyte imbalance), alcoholic
encephalopathy, post-seizure encephalopathy.
6) Blood:
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Anemia: may result from folic acid deficiency,
hemolysis, hypersplenism, or GIT bleeding.
Thrombocytopenia: usually is secondary to
hypersplenism and decreased levels of
thrombopoietin.
Coagulopathy: results from decreased hepatic
production of coagulation factors. Decreased
vitamin K absorption results in reduction of VitK-dependent factors: II, VII, IX, and X. Patients
with cirrhosis also may experience fibrinolysis
and DIC.
7) Metabolic changes:
 Fasting hypoglycemia: due to reduced glycogen stores.
 Electrolytes:
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Na and water retention: occurs 2ry to relative
hypovolemia and 2ry hyperaldosteronism.
Dilutional hyponatremia: occurs due to increased ADH,
2ry hyperaldosteronism, impaired renal handling of free
water and decreased dietary Na.
Hypokalemia: due to diuresis and 2ry hyperaldosteronism.
Hyperkalemia: may occure due to the use of K-sparing
diuretics, renal failure and metabolic acidosis.
Hypomagnesemia: due to poor dietary intake, intestinal
malabsorption hyperaldosteronism and diuretic therapy.
Acid base disorders:
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Respiratory alkalosis: due to hyperventilation 2ry to
ascites and hepatopulmonary $ (most common).
Metabolic alkalosis: due to K-losing diuretics,
hyperaldosteronism, or vomiting.
Metabolic acidosis: in renal failure.
8) CVS changes:
Hyperdynamic circulatory state due to:

Peripheral vasodilation by endogenous vasodilators that
bypass hepatic metabolism (NO and glucagon).

Portal and systemic shunts.
Child-Turcotte-Pugh classification:
Child-Turcotte-Pugh Scoring System for Cirrhosis (Child
Class A=5-6 points, Child Class B =7-9 points, Child Class
C=10-15 points).
Mo’emen Modified Classification of Liver Disease:
Scoring Points
Variables
1) Encephalopathy
2) Ascites
3) Serum bilirubin
(mg/dL)
4) Serum albumin
(g/L)
5) Prothrombin
Time prolonged
(seconds)
6) Serum Sodium
(mmol/L)
7) Serum creatinine
(mg/dL)
8) Leucocytic count
(103/mm3)
9) Alveolar/arterial
gradient
2 (Class B)
3 (Class C)
I, II
Mild
III, IV
Moderate, severe
< 4.0
4.0-5.0
> 5.0
> 3.5
3.5-2.8
< 2.8
0
1-4
>4
> 130
130-120
< 120
< 1.5
1.5-2.5
> 2.5
< 10
10-12
> 12
> 0.75
0.74-0.55
< 0.55
1 (Class A)
0
0
The surgical risk is classified according to the scoring points into:
mild (9-10 points), moderate (11-14 points) and severe (15-27 points).
Treatment
(1) ttt of GIT bleeding (variceal bleeding):
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Upper GIT endoscopy to exclude other causes of hematemesis
as peptic ulcer and gastritis.
Gastric lavage through a NG tube using cold saline.
Replacement of blood loss by IV fluids and blood products
(anti-shock measures).
Vasopressin infusion (or its analogue Terlispressin):
 IV infusion: 0.3-0.8 units/min
 Localised infusion into Superior mesenteric artery (identified
by selective arteriography): 0.15-0.2 untis/min
Balloon tamponade by Sengstaken-Blakemoore, Minnesota
tubes.
Emergency sclerotherapy.
IV nitroglycerin and propranolol can decrease portal pressure.
Octreotide:somatostatin analogue that acts as intestinal
vasocontrictor.
H2 Blockers: eg. Ranitidine
(2) ttt of Encephalopathy:
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Treatment of the precipitanting factors of hepatic
encephalopathy (eg. metabolic disturbances, GI bleeding,
infection, constipation).
Lactulose is a nonabsorbable disaccharide that stimulates
the passage of ammonia from tissues into the gut lumen
and inhibits intestinal ammonia production.
Other cathartics, including colonic lavage also may be
effective in patients with severe encephalopathy.
Neomycin and other antibiotics (eg. metronidazole, oral
vancomycin) serve as second-line agents. They work by
decreasing the colonic concentration of ammoniagenic
bacteria. Neomycin dosing is 250-1000 mg orally 2-4
times daily.
Rifaximin is a nonabsorbable antibiotic that can decrease
colonic levels of ammoniagenic bacteria, with resulting
improvement in symptoms of hepatic encephalopathy.
Flumazenil: a benzodiazepine receptor antagonist that
has been tried successfully in hepatic encephalopathy.
(3) ttt of Hepatorenal $:

Expansion of intravascular volume with albumin &
FFP. Proper hydration.
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Avoid nephrotoxic drugs as: aminoglycosides,
cyclosporine and contrast dyes.
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Mannitol to prevent renal failure.
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Hemodialysis.
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Liver transplantation: kidney function usually
recovers when patients with cirrhosis and
hepatorenal syndrome undergo liver transplantation.
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If end stage renal failure develops combined liverkidney transplantation is needed.
(4) Nutrition of hepatic patient:

Caloric requirements:
 25-30 Kcal/Kg/day of normovolemic BW.

Protein requirements:
 Ptn restriction is controversial but still routinely
implemented (esp. in pts with TIPSS).
 Amount: 40-60 g/day or 0.8g/kg/day (of normovolemic BW).
 Type: rich in branched chain (non-aromatic) amino
acids.
 Some studies support that parentral ptn carries less risk
of encephalopathy since not converted by colonic bacteria
into NH3.

Micronutrients: Thiamine, folic acid, Mg, Zn.
(5) Avoidance of heaptotoxic medications:
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Medications associated with drug-induced liver
disease include:
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NSAIDs
Isoniazide
valproic acid
Erythromycin
amoxicillin-clavulanate
Ketoconazole
chlorpromazine
Aminoglycosides are considered obligate
nephrotoxins in patients with cirrhosis and should
be avoided.
(6) Analgesia in patients with hepatic failure:
 Although high-dose acetaminophen is a well-known
hepatotoxin, most hepatologists permit the use of
acetaminophen in patients with cirrhosis at doses up
to 2 g/d.
 NSAID use may predispose patients with cirrhosis to
develop GI bleeding. Patients with decompensated
cirrhosis are at risk for NSAID-induced renal
insufficiency, because of prostaglandin inhibition and
worsening of renal blood flow.
 Opiate analgesics are not contraindicated but must
be used with caution in patients with preexisting
hepatic encephalopathy.