COMPLICATIONS AND MANAGEMENT

OF CIRRHOSIS OF LIVER
 ASCITES
• Hepatic decompensation, defined by ascites,hepatic encephalopathy, and portal
hypertensive gastrointestinal bleeding, is an important landmark in the natural
history of cirrhosis.

• Hepatic decompensation, defined by ascites,hepatic encephalopathy, and portal

hypertensive gastrointestinal bleeding, is an important landmark in the natural
history of cirrhosis.

• The development of ascites is associated with a reduction in 5-year survival from

80% to 30%.

• patients with ascites being prone to additional complications,

such as bacterial infections, electrolyte abnormalities, HRS, and
nutritional imbalances, and, consequently, further clinicaldecline
• A diagnostic paracentesis should be performed in all patients
with new-onset ascites that is accessible for sampling.

• The initial laboratory investigation of ascitic fluid should

include ascitic fluid neutrophil count, ascitic fluid total
protein, ascitic fluid albumin, and serum albumin to calculate
the serum-ascites albumin gradient.
 TREATMENT
• Moderate dietary sodium restriction (2 gm) should be prescribed to
achieve a negative sodium balance and net fluid loss.
• Fluid restriction is not indicated unless hyponatremia is present.
• In most patients with cirrhosis presenting with ascites, dietary
sodium restriction alone is insufficient and diuretic therapy is
necessary.
• Daily monitoring of body weight, preferably at the same time of the
day, is essential in assessing the efficacy of diuretics and preventing
their adverse effects..
• Aldosterone antagonists (e.g., spironolactone) and loop diuretics
(e.g., furosemide, torsemide, bumetanide) are the mainstay of
diuretic treatment of cirrhotic ascites.

• The recommended initial dose of spironolactone is 100 mg/day,

which can be progressively increased up to 400 mg/day.

• The dose of furosemide (initially 40 mg/day) may be progressively

increased, according to the response and tolerability toward 160
mg/day
Adverse effects of diuretics

• Hypokalemia (loop diuretics)

• Hyperkalemia (potassium sparing)
• OTOTOXICITY
• For patients presenting with tense ascites, large-volume
paracentesis (LVP) combined with human albumin is the
initial treatment of choice, even in the presence of
hyponatremia.

• After LVP and a significant reduction in the intra-abdominal

pressure, diuretics can be instituted, which may eliminate
or reduce the frequency of paracentesis

 After ascites is adequately mobilized, attempts should be

made to taper the diuretics to the lowest dose necessary to
maintain minimal or no ascites to prevent the development
of adverse effects.

• In patients receiving diuretics, body weight and serum
creatinine and sodium should be regularly monitored to
assess response and to detect the development of adverse
effects.

• Nonsteroidal anti-inflammatory drugs, angiotensin-

converting enzyme inhibitors, and angiotensin receptor
blockers should be avoided in patients with cirrhosis and
ascites.
• • Aminoglycosides should be avoided whenever possible in
the treatment of bacterial infections.
 Refractory Ascites

• Refractory ascites, that is ascites which cannot be mobilized by low

sodium diet and maximal doses of diuretics (up to 400 mg spironolactone
and 160 mg furosemide per day)

• Refractory ascites (RA) has been defined by the International Club of

Ascites (ICA) as an ascites that recurs within 4 weeks after large volume
paracentesis (LVP) and cannot be prevented by medical therapy
 HEPATIC HYDROTHORAX
•Hepatic hydrothorax (HH) is a transudative pleural effusion that
occurs in portal hypertension.
•The prevalence of HH in cirrhosis is 4%-12% and is typically
unilateral.
•In HH, the pleural fluid originates in the peritoneal cavity and is
drawn through defects in the diaphragm by the negative intrathoracic
pressure at inspiration.
•A serum to pleural fluid albumin gradient of >1.1 g/dL is suggestive
of HH.
• Pleural fluid in HH may have higher protein content than
concurrent ascites, a finding attributed to the hydrostatic pressure
gradient.
• Patients with HH have a poor prognosis with a mortality risk
that exceeds that predicted by the MELD score and should be
considered for LT.

• Complications of HH include

• spontaneous bacterial empyema (SBE),

• progressive respiratory failure,

• trapped lung, and

• complications of thoracentesis such as pneumothorax and

bleeding.
 TREATMENT

•sodium restriction and diuretics.

• If ascites is present, LVP with IV
albumin may improve ventilatory
function, but thoracentesis is
generally also required.
•Thoracentesis can be performed
SPONTANEOUS BACTERIAL PERITONITIS

any cirrhosis patients with symptoms of

• abdominal pain,
• tenderness on palpation (with or without
rebound tenderness), and
• ileus.
• fever +/-

• “ALWAYS SUSPECT SBP”

• A diagnostic paracentesis should be performed as soon as a patient with
cirrhosis and ascites is hospitalized emergently for any reason, even in the
absence of symptoms
•
• Spontaneous bacteremia is established with positive blood cultures.

• The diagnosis of SBP or SBE is established with a fluid (ascites or pleural,

respectively) absolute neutrophil count greater than 250/mm3,

• Thus, ascitic fluid culture is essential in the evaluation of SBP and should be
performed before the administration of the first dose of antibiotics.
• Bedside inoculation of at least 10 mL of the ascitic sample into blood culture
bottles increases the sensitivity of the culture to >90% in the diagnosis of
SBP.
•
• Spontaneous infections are typically monobacterial, with
the most common (~60%) being gram-negative bacteria

• Specific microorganisms are mostly enteric (with the most

common being Escherichia coli,
• followed by Klebsiella pneumoniae,
Staphylococcus aureus,
Enterococcus faecalis, and
Enterococcus faecium).
 (1) Spontaneous infections (peritonitis, bacteremia, empyema)

Community acquired Nosocomial

•Third-generation cephalosporin •Piperacillin/tazobactam AND

•Daptomycin OR
•Meropenem if known to harbor
MDR gram-negative organisms
 SBP prophylaxis
• In a multicenter randomized controlled trial, the 1-year
probability of developing recurrent SBP was significantly
lower with norfloxacin (20%) compared with placebo (68%).

• single-center open-label randomized trial showed rifaximin

had a lower 6-month incidence of recurrent SBP compared
with norfloxacin (4% vs. 14%, respectively).
 HEPATO-RENAL SYNDROME
• Hepatorenal syndrome (HRS) has been defined as a purely
‘‘functional” type of renal failure that often occurs in patients with
cirrhosis in the setting of marked abnormalities in arterial
circulation, as well as overactivity of the endogenous vasoactive
systems.
• International Club of Ascites (ICA) classified HRS into types 1 and
2 (HRS-1 and HRS-2).
• Type-1 HRS: defined by an abrupt decline in kidney function,
(100% increase in creatinine to a value greater than 2.5 mg/dL),
and
• Type-2 HRS: moderate and stable or slowly progressive renal
dysfunction that often occurs without an obvious precipitant.
• HRS-1 :a rapid deterioration of renal function that often
occurs because of a precipitating event, while
• HRS-2 :is a moderate and stable or slowly progressive renal
dysfunction that often occurs without an obvious precipitant.

• “the diagnosis of HRS-AKI is made using the consensus

criteria after excluding hypovolemia, shock,
nephrotoxic agents, and structural kidney damage '
 Diagnosis of HRS-AKI
• Cirrhosis with ascites; acute liver failure; acute-on-chronic liver failure

• Increase in serum creatinine ≥0.3 mg/dl within 48 h or ≥50% from baseline value according
to ICA consensus document and/or urinary output ≤0.5ml/kg B.W. ≥6 h*

• No full or partial response, according to the ICA consensus document (20), after at least 2
days of diuretic withdrawal and volume expansion with albumin. The recommended dose of
albumin is 1 g/kg of body weight per day to a maximum of 100 g/day

• No current or recent treatment with nephrotoxic drugs

• Absence of shock

• Absence of parenchymal disease as indicated by proteinuria >500 mg/day, microhaematuria

(>50 red blood cells per high power field), urinary injury biomarkers (if available) and/or
abnormal renal ultrasonography**. Suggestion of renal vasoconstriction with FENa of <0.2%
(with levels <0.1% being highly predictive)
 Stages of AKI
Stage 1 Increase of creatinine ≥0.3 mg/dL up to 2-fold of
baseline

Stage 2 Increase in creatinine between 2-fold and 3-fold of

baseline
Stage 3 Increase in creatinine >3-fold of baseline or
creatinine >4 mg/dL (353.6 µmol/L) with an acute
increase ≥0.3 mg/dL (26.5 µmol/L) or initiation of
RRT
 Prevention of AKI

• The first principle in the prevention of AKI is the treatment or

prevention of possible precipitating factors, particularly GI bleeding
and bacterial infections, and avoiding LVP without albumin
administration.

• IV albumin, together with antibiotics, reduces the incidence of

HRS-AKI and improves survival in patients
• search for hypovolemia, drug-induced nephrotoxicity, or
urinary tract obstruction.
• Indwelling bladder catheterization should be avoided.

• Measurement of urine volume, is important because oliguria is

associated with poor prognosis.
• Diuretics should be stopped after the diagnosis of AKI.
• Several randomized controlled trials and meta-analyses
have shown that vasoconstrictors, either terlipressin or
norepinephrine, in combination with albumin are
effective in improving kidney function in patients with HRS-
AKI, with the response rate of 20%-80% (average ~50%).

• Vasoconstrictor drugs are maintained until creatinine

reached to normal value for 14 days

• In patients whose creatinine remains at or above the

pretreatment level over 4 days with the maximum tolerated
doses of the vasoconstrictor, therapy may be discontinued.
 Terlipressin
• The results of CONFIRM trial study confirm findings that
terlipressin, in combination with albumin, is associated with
higher likelihood of reversal of HRS and 10-day survival

• Side effects are abdominal pain or ischemia of fingers, skin,

intestines, heart,
• pulmonary edema from albumin infusion.
 Norepinephrine
• Norepinephrine appears to be equally effective to
terlipressin, although there are fewer data.
• Norepinephrine is given as continuous IV infusion, , starting at
0.5 mg/hour
• Goals: increase in mean arterial pressure of at least 10 mm Hg or

an increase in urine output of >200 mL/4 hours.

If at least one of these goals is not achieved, the dose of

norepinephrine is increased every 4 hours in increments of
0.5 mg/hour up to a maximum of 3 mg/hour.
 MIDODRINE + OCTREOTIDE

• Midodrine (an a1-agonist drug) combined with octreotide (a

somatostatin analogue), together with albumin infusion has
been shown to be effective in treating HRS-1.

• in a small, single center, RCT, the combination of

terlipressin + albumin was shown to be significantly more
effective than the combination of midodrine + octreotide
and albumin in the treatment of HRS (improvement of renal
function in 70 vs. 29%.
• Renal Replacement Therapy

• Initiation of RRT should be made on clinical grounds,

including worsening kidney function, electrolyte
disturbances such as severe acidosis, hyponatremia or
hyperkalemia not improving with medical management,
diuretic intolerance, or increasing volume overload.
• Continuous RRT is the modality preferred to intermittent
dialysis in patients who are hemodynamically unstable.
• Liver Transplantation and Simultaneous Liver-Kidney
Transplantation
• Restoring liver function by Liver Transplantation
is the ultimate therapy for HRS-AKI.
• However, recovery of kidney function after
LT is not always predictable for a number of
factors, such as preexisting comorbidities
 HEPATIC ENCEPHALOPATHY
• Hepatic encephalopathy (HE) is a reversible syndrome observed in
patients with liver disease.

• The syndrome is characterised by a spectrum of neuropsychiatric

abnormalities resulting from the accumulation of neurotoxic substances in
the bloodstream and ultimately in the brain
• In the early stages, patients may only report subtle symptoms, such as
disturbances in their sleep–wake cycles.

• As symptoms progress, patients may develop personality changes such as

apathy, irritability, and disinhibition.

• If left unrecognised, symptoms worsen and patients can present with

cognitive impairments such as disorientation, memory impairment, slurred
speech, confusion, and eventually coma.

• Along with neurologic and psychiatric symptoms, HE can also affect the
musculoskeletal system.
• Patients with minimal HE may show minor issues with coordination, such as
changes in their handwriting
• The most widely recognised
symptom of HE is asterixis.

• Asterixis presents as a flapping

tremor that occurs because of
negative myoclonus resulting in
loss of postural tone

• The severity of HE is generally

classified using the West Haven
Criteria (WHC)
 pathophysiology
• The liver is the major site of ammonia catabolism using
the urea cycle (Krebs–Henseleit cycle), which converts
ammonia into water-soluble urea.

• The generated urea is subsequently excreted via the

intestine and the urine.

• Due to the reduced capability of the liver to detoxify

ammonia, secondary to hepatocellular damage or
shunting, ammonia levels increase within the systemic
circulation
 Increase Nitrogen Load
• Constipation.
• Gastro intestinal bleeding.
• Excess dietary intake of protein & fatty acids.
• Azotemia.
• Infections & Trauma (Surgery)
• Electrolyte & Metabolic imbalance
• Hypokalemia.
• Alkalosis.
• Hypoxia.
• Hyponatremic
• Drugs- Diuretics, Narcotics, Tranquilizers, Sedatives
 TREATMENT
• Identify and remove the precipitating factors.
• Iv fluid dextrose ,saline.
• Stop Diuretic Therapy.
• Correct any electrolyte imbalance.
• Ryle tube feeding & bladder catheterization.
• Reduce the ammonia (NH3) Load.
• Diet – Restriction of protein diet.
• High glucose diet.
• Treat Constipation by Laxatives.
 LACTULOSE
• targeting the reduction of intestinal production and
absorption of ammonia
• is a non-absorbable synthetic disaccharide made of
galactose and fructose.
• The human small intestinal mucosa does not have the
enzymes to split lactulose, so lactulose reaches the large
bowel unchanged.

• Lactulose is metabolized in the colon by colonic bacteria

to monosaccharides and then to volatile fatty acids,
hydrogen, and methane.
Lactulose reduces intestinal ammonia production and absorption in 3 ways.
1. the colonic metabolism of sugars causes a laxative effect via increased
intraluminal gas formation

2. lactulose promotes increased ammonia uptake by colonic bacteria, which

utilize the trapped colonic ammonia as a nitrogen source for protein
synthesis.

3. lactulose also causes a reduction in intestinal production of ammonia. The

acidic pH destroys urease-producing bacteria involved in the production of
ammonia
• In patients with hepatic encephalopathy,
lactulose is typically given in syrup form at a
dose of 15 to 30 mL 2 to 4 times a day to aim
for 2 semisoft stools per day.

• For acute hepatic encephalopathy, a common

option is to administer a bolus of 45 mL (30 g)
and repeat the dose hourly until the first
bowel movement.
 Rifaximin
• Rifaximin is a minimally absorbed oral antibiotic that alters the gut flora,
leading to reduced ammonia production and absorption.

• It is concentrated in the gastrointestinal tract, and despite broad-spectrum

activity against gram-positive and gram-negative enteric bacteria, it has a
low risk of inducing bacterial resistance.

• treatment with rifaximin should be considered in patients with persistent

symptoms of encephalopathy despite lactulose or in lactulose-intolerant
patients, or in those who have had two or more episodes of over hepatic
encephalopathy in the previous 6 months.

• Rifaximin and lactulose in combination controls hepatic encephalopathy in

most patients.
 L-ornithine-aspartate
• it is a stable salt of the amino acids ornithine
and aspartic acid that is thought to lower
blood ammonia concentrations in patients
with cirrhosis by stimulating urea and
glutamine synthesis from hepatocytes and
skeletal muscle respectively.

• It can be administered orally or intravenously

• Supplementation with branched-chain amino acids is
another potential option.

• Levels of these amino acids are reduced in patients

with cirrhosis, which results in impaired conversion
of ammonia to glutamine in skeletal muscle and
reduces its detoxification.

• Oral supplementation is effective in treating overt

hepatic encephalopathy
 TIPS
• A transjugular intrahepatic portosystemic
shunt (TIPS) is a minimally invasive procedure
that creates a shunt between the portal vein
and hepatic vein in the liver to relieve
pressure from portal hypertension.
Possible risks with this procedure are:

• Damage to blood vessels

• Fever
• Hepatic encephalopathy (a disorder that affects
concentration, mental function, and memory, and may
lead to coma)
• Infection, bruising, or bleeding
• Reactions to medicines or the dye
• Stiffness, bruising, or soreness in the neck
• 88% of people with cirrhosis and variceal
bleeding who received TIPS survived for 2
years, and 61% survived for at least 5 years.
 coagulopathy
Patients with cirrhosis may have vitamin K
deficiency, due to the following:
• Malabsorption due to cholestatic liver disease
(bile salts are required to absorb dietary
vitamin K)
• Malnutrition
• Antibiotic use
• Prior use of vitamin K antagonists (e.g.,
warfarin)
diagnosis
• Both vitamin K deficiency and hepatic
dysfunction can cause prolongation of INR, PT
and aPTT.
• 10 mg IV vitamin K is infused over 30-60
minutes.
• Coagulation studies are obtained the following
day.