Liver cirrhosis.2018

Clinical Case
Clinical
55 years old Abdullah presents in ER with, sever
hemetemesis. His skin and eye are mildly
yellow colored. Has history of sever jaundice 8
years back. Since then he has increased
tiredness, decrease appetite, weak health. O/E,
he has jaundice, BP 100/70, pulse 100/min, mild
edema feet, red palms, flapping hand
movements on arm extension, abdominal vein
swollen, liver is smaller and rough surface on
palpation, m
Wednesday, February 28, 2018 Dr Afzal Haq Asif 1

ClinicalCase
Lab
sodium 135 mEq/L; chloride 95 mEq/L; potassium 3.8 mEq/L;
bicarbonate 25 mEq/L;
blood urea nitrogen (BUN) 15 mg/dL; serum creatinine (SrCr)
1.4 mg/dL;
Fasting glucose 136 mg/dL;
Hemoglobin 8.2 g/dL; hematocrits
AST 512 IU (normal, 0–35 IU); alkaline phosphatase 154 IU
(normal, 30–120 IU);
PT 16.5 seconds with a control of 12 seconds (Calculate INR)
total/direct bilirubin 5.8/3.7 mg/dL (normal, 1.0/<0.5 mg/dL);
albumin 2.3 g/dL (normal, 3.5–4.0)

Pre-Test
Enumerate functions of Liver
Enumerate Liver Function Tests
Write down normal values of liver function tests with
their diagnostic significance
LIVER FUNCTION TESTS.doc

Dr. Afzal
Ref:
1.ACCP updates 2017
2.Pharmacotherapy: Principles and Practice.2016 4th
ed

ILO’s
After completion of module, the student will be able to:
Define and identify a case of Cirrhosis of liver
Know and Interpret LFT’s
Know causes of Cirrhosis and educate patient of liver disease
regarding prophylaxis of cirrhosis
Know and able to educate regarding complications of
Cirrhosis
Design Therapeutic objectives for Therapeutic plan for
Cirrhotic patient/complication of cirrhosis
Identify monitoring parameters/follow up evaluation for
patient of cirrhosis/complications, (for
 Monitoring Therapy: Intervention
 Patients’ education

LIVER
The largest solid organ in the body : 3 pounds.
Functions, :
Manufacturing blood proteins that aid in clotting, oxygen
transport and immune system function.
Storing excess nutrients and returning some of the
nutrients to the bloodstream.
Manufacturing bile, a substance needed to help digest
food.
Helping the body store sugar (glucose) in the form of
glycogen.
Ridding the body of harmful substances in the
bloodstream, including drugs and alcohol.
Breaking down saturated fat and producing cholesterol.

LFT’s

Laboratory Investigations
Alkaline phosphatase : obstructive
Bilirubin …………………..Direct, Indirect
Aspartate transaminase (AST): hepatocellular injury
Alanine transaminase (ALT): hepatocellular injury
Gamma -glutamyl transpeptidase (GGT): obstructive
Additional markers for hepatocyte functioning
Albumin
Prothrombin time.
Thrombocytopenia: a relatively common feature in
chronic liver disease found in 30% to 64% of cirrhotic
patients.
Liver BiopsyWednesday, February 28, 2018 Dr Afzal Haq Asif 9

Questions
Enlist patient’s problem
Interpret clinical and lab data in terms of diagnosis
Therapeutic objectives for this patient
Therapeutic plan for patient
Prophylaxis of other complications
Possible complications
Patient education
Regarding disease
Therapy
Prevention/prophylaxis
Write SOAP Notes for this case for presentation

CIRRHOSIS
Cirrhosis is a slowly progressing disease in which
healthy liver tissue is replaced with scar tissue,
May be reversible if cause is removed
preventing the liver from functioning properly.
The scar tissue blocks the flow of blood through
the liver
Slows the metabolism of nutrients, hormones, drugs
and naturally produced toxins
Portal hypertension


FIBROSIS and a conversion of the normal hepatic
architecture into structurally ABNORMAL NODULES
Destruction of hepatocytes and their replacement by
fibrous tissue

Criteria and Scoring for the Child-Pugh Grading of Chronic Liver Disease
Bilirubin
<2 mg/dL (<34 µmol/L) +1
2-3 mg/dL (34-50 µmol/L) +2
>3 mg/dL (>50 µmol/L) +3
Albumin:
>3.5 g/dL (>35 g/L) +1
2.8-3.5 g/dL (28-35 g/L) +2
<2.8 g/dL (<28 g/L) +3
INR:
<1.7 +1
1.7-2.2 +2
>2.2 +3
Ascites
No Ascites +1
Ascites, Medically Controlled
+2
Ascites, Poorly Controlled +3
Encephlopathy:
No Encephalopathy +1
Encephalopathy, Medically
Controlled +2
Encephalopathy, Poorly
Controlled +3
 Grade A, 1–6 points; grade B, 7–9 points;
 Grade C, 10–15 points
 Pugh RNH, Murray-Lyon IM, Dawson JL et al. Transection of the oesophagus for bleeding oesophageal varices. Br J
Surg 1973;60:649-9.
 http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality

Child-Pugh Classification of severity of Cirrhosis

The Model of End Stage Liver Disease (MELD)
MELD score:
0.957 x log(serum creatinin mg/dL) +0.378 x log(bil
mg/dL) + 1.12 x log (INR) + 0.643
Lab value less than 1 is rounded to 1
The formula score is multiplied by 10 and rounded to
the nearest whole number

Causes of Cirrhosis
Most common
Chronic viral hepatitis (types B and C) most common
causes.
Excessive alcohol intake
Other: see next

Causes of Cirrhosis
Category Example
Drugs and
toxins
Alcohol, methotrexate, isoniazid, methyldopa,
organic hydrocarbons,
Infections Viral hepatitis (types B and C), schistosomiasis, Bud-
chiari syndrome
Immune-
mediated
Primary biliary cirrhosis, autoimmune hepatitis,
Metabolic Hemochromatosis, porphyria, alpha1-antitrypsin
deficiency, Wilson's disease
Biliary
obstruction
Cystic fibrosis, atresia, strictures, gallstones
Cardiovascula
r
Chronic right heart failure, , veno-occlusive disease
Other Nonalcoholic steatohepatitis, sarcoidosis, gastric
bypass
. Wednesday, February 28, 2018 Dr Afzal Haq Asif 21

Clinical findings
No symptom for long
time
Weakness fatigue
Disturbed sleep
Muscle cramps
Anorexia
Weight loss
Abdominal pain
Menstrual abnormalities
Loss of libido, impotence,
Sterility
Gynecomastia
Jaundice: May or may not
be
Hemetemesis: presenting
complaint in 15-25% of patients

Spider nevi
Palmer erythema
Dupuytren's contracture

Glossitis
Flapping tremors in severe cases
 https://www.youtube.com/watch?v=3fU-BbHdESY
 https://www.youtube.com/watch?v=sEnp2ss8VoA
Caput Medusae
distended and engorged umbilical veins which are seen
radiating from the umbilicus across the abdomen to
join systemic veins

Pathophysiologic outcomes of Cirrhosis
Portal hypertension
Ascites, edema
Pleural effusion
Esophageal varices,
Hepatic encephalopathy,
Coagulation disorders

Portal Hypertension
Elevated pressure gradient between the portal and central venous
pressure more than 5 mm Hg
Characterized by:
 Hypovolemia
 Increased cardiac index
 Hypotension
 Decreased systemic vascular resistance
Results in:
 Development of varices
 Variceal bleeding: can be predicted by:
 Child-pugh score
 Size of varices
 Presence of red wale marking on varices
 First variceal hemmorhage occurus at rate of 15% with 7-15% mortality


Treatment objectives
Clinical improvement or resolution of acute
complications,
variceal bleeding,
resolution of hemodynamic instability for an episode of
acute variceal hemorrhage.
Prevention of complications,
adequate lowering of portal pressure with medical
therapy using beta-adrenergic blocker therapy,
supporting abstinence from alcohol.

Gastroenterol Rep (Oxf). 2017 May; 5(2): 138–147.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421503/

Hepatic Encephalopathy
A metabolically induced functional disturbance of brain
Reversible impairment of neuropsychiatric function
(consciousness and behavior) associated with impaired hepatic
function
Pathophysiologic Mechanism:
Accumulation of gut derived nitrogenous substances in the systemic
circulation because of shunting through portosystemic collaterals
Enter into brain
Altering neurotransmission
Altered ammonia, glutamate, BZD receptors agonists, aromatic AA, and
manganese
Types:
A: caused byacute liver failure
B: Portal-systemic bypass without intrinsic liver disease
C: caused by cirrhosisWednesday, February 28, 2018 Dr Afzal Haq Asif 31

Hepatic encephlopathy (HE)
Severity
Acute HE : altered sensorium lasting less than 4 weeks, followed by
complete recovery to baseline mental status.
Chronic encephalopathy: a cognitive or neuropsychiatric abnormality
that persists for at least 4 weeks.
Subclinical encephalopathy: alterations in neuropsychiatric function
that are not clinically apparent
Duration
Episodic
Recurrent (occurs within a time frame of 6 months or less)
Persistent: Denotes a pattern of behavioral alteration that is always present
and interspersed with relapses of overt hepatic encephalopathy (HE)
Presence or absence of precipitating factors
 i. Precipitated
 ii. Nonprecipitated

Precipitating Factor for HE Therapy Options
Gastrointestinal bleeding
Variceal Band ligation/sclerotherapy
Octreotide
Nonvariceal Endoscopic therapy
Proton pump inhibitors
Infection/sepsis Antibiotics Paracentesis
Electrolyte abnormalities Discontinue diuretics
Fluid and electrolyte replacement
Sedative ingestion Discontinue sedatives/tranquilizers
Consider reversal (flumazenil/naloxone)
Dietary excesses Limit daily protein, Lactulose
Constipation Cathartics
Bowel cleansing/enema
Renal insufficiency Discontinue diuretics
Discontinue NSAIDs, nephrotoxic
antibiotics
Fluid resuscitation

Principles of Treatment of Hepatic Encaphlopathy
Acute HE Chronic HE
• Control precipitating factor • Reverse encephalopathy
• Reverse encephalopathy • Avoid recurrence
• Hospital/inpatient therapy
Grade II, III, IV
• Home/outpatient therapy
• Maintain fluid and
hemodynamic support
• Manage persistent
neuropsychiatric
abnormalities
Manage chronic liver disease
• Expect normal mentation
after recovery
• High prevalence of abnormal
mentation after recovery

Treatment
General:
Hospitalization
Appropriate nutritional support,
Treat hypokalemia
Avoid dehydration and electrolyte
abnormalities,
Agitation:
 Haloperidol safer than BZD: 0.5 mg followed by a
continuous infusion of 0.1 mg/hour for 12 hours

Treatment of episodic HE
Treat episodic overt HE and then use secondary
prophylaxis
Lactulose is rst-line treatment for overt HE
Rifaximin can be used as add-on therapy with lactulose to
prevent recurrence after the second episode of overt HE
Oral BCAA or IV LOLA can be used as alternative or
additional therapy in patients unresponsive to traditional
therapies
Neomycin or metronidazole can be used as alternative
treatment

Hepatic Encephlopathy
Reduction of blood ammonia
Dietary restrictions limit protein intake to 10 to 20 g/day
Enhancing its removal : Lactulose
 30 to 45 mL [20 to 30 g] given two to four times per day)
 or 45 mL every hour (or 300 mL lactulose syrup with 700 mL water given
as a retention enema should be titrated to achieve two to three soft stools
per day
 Powder formulation (KRISTALOSE) is available in 10- and 20-g packets
that may be dissolved in 4 oz water (10 g = 15 mL traditional lactulose).
This formulation is more palatable than the traditional syrup.
 May be continued over the long term to prevent recurrent
encephalopathy
 Flatulence, diarrhea, and abdominal cramping are common adverse
effects.
Intravenous l-ornithine l-aspartate (LOLA) can be added. It
stimulates the metabolism of ammonia, is an alterative for
the treatment of hepatic encephalopathy

Decreased synthesis of Ammonia: Antibiotics:
If no improvement with lactulose in 48 hours: rifaximin 400
mg orally three times daily or 550 mg orally two times daily
Targeted at reducing the number of intraluminal urease-
producing bacteria that may lead to excess NH3 production
Neomycin: as effective as lactulose: (3–6 g/day in three or
four divided doses × 1–2 weeks, then 1–2 g/day maintenance)
or
Metronidazole (250 mg orally twice daily) may be used;
Flumazenil, if benzodiazepine over dose is suspected
Bromocriptine 30 mg twice daily in chronic HE,
unresponsive to other treatment
Nutritional interventions include 35–40 kcal/kg/day based
on IBW and 1.2–1.5 g/kg/day protein intake

HE:BCAA
Oral branched chain amino acids
aliphatic side-chains with a branch: leucine, isoleucine
and valine
For patients who do not respond to lactulose, or
rifaximin
who are severely protein-intolerant
stimulate the building of protein in muscle and possibly
reduce muscle breakdown
Need further evidence

More options
Metabolic ammonia scavengers: Ornithine phenylacetate and
glyceryl phenylbutyrate remove ammonia from the circulation by
binding with its substrates; effective in reducing ammonia
concentrations and improving cognitive function. More clinical trial
data are necessary before any recommendations regarding therapy.
Polyethylene glycol -electrolyte solution (PEG) resulted in faster
HE resolution than rifaxamin in patients with cirrhosis who were
hospitalized for acute HE.
 PEG dose was 4 L for 4 hours orally or through nasogastric tube (JAMA
Intern Med 2014:174:1727-33).
Probiotics and microbiologic dietary supplements may reduce the
necessary substrates of pathogenic bacteria and supply fermentation
products for beneficial bacteria. Preliminary data are positive for
minimal HE, but further studies are needed.
Zinc deficiency is common; essential element that acts as a cofactor
in urea cycle. Thus, zinc supplementation may reduce ammonia
concentration.

Other Treatment options
L-Carnitine: metabolite in the degradation pathway of the
essential amino acid lysine: protective against ammonia
neurotoxicity
Glutamatergic antagonists: NMDA receptor antagonist
memantine
Opioid antagonists – Plasma levels of Met-enkephalin
and beta-endorphin are elevated in patients and in
experimental animals suffering from liver failure.
Naltrexone, but not (+)-naloxone is found effective

Commonly used drugs in HE
Drug Dose (Acute) Dose (Chronic) Side Effects
Lactulose
Oral 45 mL PO q1-2hr 15-45 mL PO q6-
12hr
Diarrhea,
flatulence, cramps
Enema 300 mL in 1 L of
water q4-6hr
Not used
chronically
Diarrhea,
flatulence, cramps
Antibiotics
Metronidazole 250 mg PO q8-
12hr
250 mg PO q8-
12hr
Peripheral
neuropathy
Rifaximin 400 mg PO q8hr 400 mg PO q8hr Rare flatulence,
constipation
Neomycin 1000 mg PO q4-
8hr
500 mg PO q6-
12hr
Rare nephro- and
ototoxicity

Summary of Management
Treatment
Approach
Monitoring
Parameter
Outcome
Assessment
1. Ammonia
reduction
(lactulose, ),
2. Elimination of
drugs causing
CNS depression,
3. Limit excess
protein in diet
1. Grade of
encephalopathy,
2. EEG,
3. psychological
testing,
4. mental status
changes,
5. concurrent drug
therapy
1. Maintain
functional
capacity,
2. Prevent
hospitalization
for
encephalopathy,
3. Decrease
ammonia levels,
4. Adequate

AscitesAccumulation of fluid in the peritoneal cavity.
A common clinical finding, with various extra-peritoneal and
peritoneal causes
Most often results from liver cirrhosis.
Secondary to increased resistence within the liver forces the
lymphatics to drain in the peritoneal cavity
The development of ascites in a cirrhotic patient indicates
deterioration in clinical status and a poor prognosis
Symptoms:
Progressive abdominal heaviness, fullness, pressure, and pain;
shortness of breath
Tense ascites: Clinical symptoms usually increased and more
significant
Refractory ascites: Fluid overload unresponsive to dietary
sodium restriction and diuretic therapyWednesday, February 28, 2018 Dr Afzal Haq Asif 46

AscitesPhysical examination:
Abdominal distension, shifting dullness, bulging flanks, and
fluid wave
Abdominal ultrasonography
 Detects ascites, especially in obese patients, when a physical
examination may be problematic
Classification
Grade 1: Mild, visible only on ultrasonography
Grade 2: Detected on physical examination, with flank
bulging and shifting dullness
Grade 3: Directly visible, confirmed with fluid wave

Who should be treated
Once a patient with cirrhosis develops clinically
apparent ascites, it is unlikely to resolve without
specific treatment
Following can be prevented by treating the specific
cause
Patients with alcoholic cirrhosis who have a huge dietary sodium
intake and a large reversible component of liver disease:…
 Stop alcohol, decrease Na and water intake
Patients who develop ascites for the first time during
resuscitation for upper gastrointestinal bleeding……stop IV fluid
administration
Patients with decompensated hepatitis B cirrhosis…treat HBs
infect

Ascites & Edema
Measure a serum-ascites albumin gradient (SAAG). If SAG is greater than 1.1,
portal hypertension. SAG= S.Alb—Fluid Alb.
Treatment:
Stop alcohol,
Fluid restriction less than 1.5 Liters/day, if serum sodium is less than 120-
125 mEq/L
Discontinue NSAIDs or drugs interfere with sodium and water retention.
Avoid ACEI and ARB’s to prevent renal failure
Sodium restriction, 2g/day
Diurectics.
 Goal is increase Na excretion more than 78 mEq/day
 Single morning doses of spironolactone, 100 mg, and furosemide, 40 mg, Usual
maximal doses are spironolactone 400 mg/day and furosemide 160 mg/day.
 Maximal weight-loss goal is 0.5 kg/day in patients without edema; no maximum
in patients with significant edema
For tense Ascites:
 4- to 6-L paracentesis prior to institution of diuretic therapy and salt restriction

Ascites & Edema
Stop diuretics in
 encephalopathy, severe hyponatremia renal insufficiency
Liver transplantation in patients with refractory ascites
Spironolactone
If Gynecomastia occur with spironolactone change to
other, such as
 Amiloride (10– 40 mg/day); the efficacy is less.
 Other options
 Metolazone, Eplerenone, Hydrochlorothiazide, and Triamterene.
 Data on the efficacy with these agents are unavailable

Paracentesis
Reserved for acute management and for patients with tense and/or
refractory ascites
Large-volume paracentesis (4–6 L) is performed to relieve pain and
pressure related to symptoms of ascites.
Colloid replacement after large-volume paracentesis remains
controversial;
Albumin replacement if more than 5 L is removed.
Dose: 6–8 g/L of ascitic fluid removed.
Continue with diuretics

Refrectory Ascites
 Fluid overload unresponsive to sodium diet restrictions, medical management
with diuretics, or recurring quickly posttherapeutic paracentesis
 Options:
 β-Blocker therapy: Assess risk-benefit; use may shorten survival in this patient
population.
 Midodrine (7.5 mg by mouth three times daily): Consider adding to diuretic therapy
to increase blood pressure by increasing urine volume, urine sodium, and
mean arterial pressure. A randomized trial reports increased survival when
used in this population of patients.
 Serial therapeutic paracentesis: Clinical trial data show this approach to be safe and
effective. Procedure is typically performed once diuretics have been
discontinued, about every 2 weeks.
 Liver transplants should be considered once ascites develops; 21% of people with
ascites die within 6 months of condition becoming refractory to routine medical
therapy.
 TIPS procedure, which is a side-to-side portacaval shunt.
 Four large-scale, multicenter, randomized controlled trials comparing TIPS with large-volume paracentesis
were performed; all reported better control of refractory ascites with TIPS.
 Peritoneovenous shunt:
 Not routinely performed.
 Considered in patients who are not candidates for serial paracentesis, TIPS, or liver transplantation

Role of the pharmacist
i. Patients with ascites are often nonadherent to sodium
restriction and diuretic therapy because of adverse effects.
In addition, drug therapies eventually become less
effective over time.
ii. Pharmacists should continually assess therapies to
treat/prevent ascites and target their recommendations
according to the patient’s adherence, adverse effects, and
lack of effectiveness of regimens. The pharmacist may
consider switching agents to improve patient adherence.
iii. Continual monitoring for electrolyte imbalances and
renal function, and communicate with the treatment team

Runyon B. Management of adult patients with ascites due to cirrhosis: Update of 2012. AASLD Practice
Guideline (February, 2013).

Summary
Treatment
Approach
Monitoring
Parameter
Outcome
Assessment
Diet, diuretics,
paracentesis,
TIPS
transjugular intrahepatic
portosystemic shunt
Daily
assessment of
weight
Prevent or
eliminate ascites
and its
secondary
complications

Management of al EsophagVarices
Abnormal enlarged veins in lower esophagus
Primary prophylaxis to prevent bleeding
Treatment of variceal hemorrhage
Secondary prophylaxis to prevent rebleeding in
patients who have already bled

Primary Prophylaxis
All patients of cirrhosis: endoscopic examination
With large varices should receive Beta blockers to Decrease
Blood Flow to mesenteric Vessels
Propranolol: 10 mg 8hrly daily
Nadolol: 20 mg once daily
Carvedilol: 6.25 mg daily
Heart rate decrease upto 20-25% of resting is recommended (55-
60/min)
Continue life time: abrupt discontinuation may cause severe bleeding
Nitrates if intolerance to beta blockers
Combination therapy, (Nitrates+beta blockers) if single drug is not
sufficient

Acute vericeal Hemmorrage
IV Fluids resuscitation:
Colloidal sollutions (containing dextran, albumen etc: Plasma expanders
Ringer lactate
Whole blood or Blood products
Vasoactive Therapy: Decrease portal Blood flow
Somatostatin: growth hormone
Octereotide: growth hormone analogue: preffered
 50-100 mcg stat, 25 mcg-50 mcg/hour. Monitor patient for hyper or
hypoglycemia
Terilipessin: vasopressin analogue
Endoscopic Band Ligation (EBL)
Balloon tamponade (with a Sengstaken-Blakemore tube)
Transjugular intrahepatic portosystemic shunt (TIPS),
Antibiotic Therapy: if signs of infection (see SBP)
Endoscopic Injection Sclerotherapy(EIS)
 ethanolamine, sodium tetradecyl sulfate, polidocanol, and sodium morrhuate.

Balloon tamponade with a Sengstaken-Blakemore tube

Transjugular Intrahepatic Portosystemic Shunt
(Tips)
The transjugular intrahepatic portosystemic shunt (TIPS) is a
radiologic procedure in which a stent (a tubular device) is placed in
the middle of the liver to reroute the blood flow.

Secondary Prophylaxix
Beta Blocker
Decrease in hepatic venous pressure gradient to <12 mm Hg
or a reduction of more than 20% from baseline are
considered therapeutic targets.
http://www.youtube.com/watch?v=9cEOpr-MRL4
Nodolol: 20 to 40 mg once daily
Propranolol: 20 mg three times daily
Carvedilol 6.25 mg daily
 Titrated weekly to achieve a goal of heart rate 55 to 60 beats/min or a heart rate
that is 25% lower than the baseline heart rate.
 Patients should be monitored for evidence of heart failure, bronchospasm,
or glucose intolerance.
Bata blockers +isosorbide mono-nitrate
EIS or EBL

Summary of Management Plan for Bleeding

Summary: Management of Bleeding
Treatment
Approach
Monitoring
Parameter
Outcome
Assessment
Pharmacologic
prophylaxis
1. Child-Pugh score,
endoscopy,
2. CBC
1. Reduction in heart
rate
2. Reduction in portal
pressure
Endoscopy, vasoactive
drug therapy
(octreotide),
sclerotherapy, volume
resuscitation,
pharmacologic
prophylaxis
1. CBC,
2. Evidence of overt
bleeding
1. Acute: control acute
bleed
2. Chronic: variceal
obliteration, reduce
portal pressures

SBI SBP
Bacterial infection of preexisting ascitic fluid without evidence of an
intra-abdominal source
Occurs in 15%–26% of hospitalized patients with liver disease
complicated by ascites
Pathophysiology
 Source of ascitic bacterial inoculation is unclear, but because enteric
organisms are usually isolated, the GI tract is often suggested as the
source of bacterial contamination.
The likely mechanism is increased gut permeability, which occurs
secondary to portal hypertension, allowing gut pathogens to enter
the bloodstream.
 Pathogens may be aerobic gram negative or positive, but 75% of the time,
SBP infections are caused by gram-negative organisms, including
Escherichia coli, Klebsiella pneumoniae, and pneumococci, with E.
coli being the most common species identified.

SBI /SBP Clinical presentation:
Highly variable
May be asymptomatic in the outpatient population.
May have one or more of the following:
 Local symptoms and/or signs of peritonitis (e.g., abdominal tenderness or pain,
vomiting, diarrhea)
 Signs and symptoms of systemic disease (e.g., hyperthermia or hypothermia,
chills, abnormal white blood cell count, tachycardia and/or tachypnea)
 Worsening of liver function test findings
 Worsening encephalopathy findings
 Shock
 Renal failure
 GI bleed
Diagnosis:
 increased number of PMN cells in ascetic fluid . The presence of more than 250 PMN
cells/mm3 is diagnostic for SBP.
 Ascitic fluid cultures are positive in 67% of cases; they are not necessary for the
 diagnosis of SBP but are important to guide antibiotic therapy.
 Blood cultures should be performed for all patients thought to have SBP before
antibiotictherapy is initiated.Wednesday, February 28, 2018 Dr Afzal Haq Asif 68

SBI /SBP Treatment: Empiric Antibacterial
Empiric antibiotic therapy for enteric gram-negative organisms if PMN 250
cells/mm3 or greater until susceptibility testing is available.
Patients with PMN less than 250 cells/mm3 and signs or symptoms of
infection should also receive empiric therapy while culture results are
pending
Empiric:
 Third-generation cephalosporins are preferred.
 Cefotaxime (2 g every 8–12 hours).
 May consider oral ofloxacin (400 mg twice daily) as a substitute in those
without prior quinolone exposure, vomiting, shock, grade 2 or higher
encephalopathy, or SCr greater than 3 mg/dL
 Ceftriaxone (2 g/day)
 Fluoroquinolones such as ciprofloxacin or levofloxacin may be used and are
often limited to use in patients with severe penicillin allergies owing to
resistance.
 Trimethoprim/sulfamethoxazole is another option.
Data show that 5 days of therapy are as effective as 10 days;
therefore, recommendations are to treat for 5 days

SBI /SBP Treatment: Albumin
Albumin administration if patient meets criteria described
below
Patients with ascites and SBP are intravascularly depleted with
decreased organ perfusion, resulting in renal
hypoperfusion and the potential of hepatorenal
syndrome (HRS).
Albumin administration is believed to help restore intravascular
volume and potentially avoid further complications.
Current guidelines recommend administering albumin (1.5 g/kg on
admission and then 1 g/kg on day 3), together with
antibiotics, in patients meeting the following criteria:
 SCr greater than 1 mg/dL,
 blood urea nitrogen (BUN) greater than 30 mg/dL, or
 Total bilirubin greater than 4 mg/dL.

SBP: Prevention
 Up to 70% of patients have a recurrent episode after the first episode of SBP;
thus, antibiotic prophylaxis is recommended.
 Risk factors for recurrence
 (a) Ascitic fluid protein concentration less than 1.0 g/dL
 (b) Variceal bleed
 (c) Previous episode of SBP
 (d) PPI use: Therapy with these agents has been associated with SBP; however,
clinical significance remains to be determined. Restricting PPI use to approved
indications may help reduce the incidence of SBP.
 Primary prophylaxis:
 Initiate in the following patient populations:
 (1) Cirrhosis and ascites with active GI bleed (typically hospitalized)
 (2) Cirrhosis and ascites without GI bleed with low ascitic protein concentration
(less than 1.5 g/dL) and at least one of the following criteria:
 (A) SCr greater than 1.2 mg/dL
 (B) BUN of 25 mg/dL or greater
 (C) Serum sodium concentration of 130 mmol/L or less
 (D) Child-Pugh score of 9 points or greater with bilirubin concentration of
 3 mg/dL or greater

SBP: Prevention
Primary:
Antibiotic therapies
 For an acute GI bleed:
 Administer a 7-day course of ceftriaxone or norfloxacin (400 mg twice daily)
while patient is hospitalized.
 A randomized trial showed that a 7-day course of eftriaxone was superior to
norfloxacin.
 Other options: ciprofloxacin (750 mg once weekly) or trimethoprim/ sulfamethoxazole
(one double-strength tablet five times weekly);
 Due to development of bacterial resistance, intermittent dosing inferior to daily dosing.
 Continue for 7 days in these patient populations.
Secondary prophylaxis
 (a) Any patient with a history of an SBP episode should receive antibiotic
prophylaxis indefinitely.
 (1) Norfloxacin 400 mg orally daily
 (2) Trimethoprim/sulfamethoxazole one double-strength tablet daily
 (3) Ciprofloxacin 500 mg orally daily.
 Guidelines recommend against intermittent (i.e., once weekly) dosing because of concerns
regarding increased resistance; further studies are warranted.

SBI: Summary of Therapeutic
management
Treatment
Approach
Monitoring
Parameter
Outcome
Assessment
Antibiotic therapy,
prophylaxis if
undergoing
paracentesis
1. abdominal pain,
2. fever,
3. anorexia,
4. malaise,
5. fatigue
Prevent/treat
infections to
decrease mortality

HRS
Characterized by
Very low renal perfusion and glomerular filtration rate,
Severe reduction in the ability to excrete sodium and
free water.
Diagnosed by exclusion of other known causes of
kidney disease in the absence of parenchymal disease.

A progressive rise in serum creatinine
An often normal urine sediment
No or minimal proteinuria (less than 500 mg per day)
A very low rate of sodium excretion (ie, urine sodium
concentration less than 10 meq/L)
Oliguria

HRS: Diagnostic FeaturesCirrhotic patients with ascites
Serum creatinine >133 µmol/L (1.5 mg/dL)
No improvement of serum creatinine ( to a level of ≤133 µmol/L)↓
after at least two days along with
Diuretic withdrawal and
Volume expansion with albumin (1 g/kg of body weight per day up
to a maximum of 100 g/day)
The absence of shock
No current or recent treatment with nephrotoxic drugs
The absence of parenchymal kidney disease indicated by following
parameters:
Proteinuria >500 mg/day,
Microhematuria (>50 red blood cells per high power field),
And/or abnormal renal ultrasonography

Treatment
Initial treatment with norepinephrine in combination
with albumin (Grade 2B).
Intravenously as a continuous infusion (0.5 to 3 mg/hr)
with the goal of raising the mean arterial pressure by 10
mmHg,
Albumin is given for at least two days as an intravenous
bolus (1 g/kg per day [100 g maximum]).
Intravenous vasopressin may also be effective, starting
at 0.01 units/min.

Treatment: Alternative
 Combination of midodrine, octreotide
nd albumin (Grade 2C).
Midodrine orally (7.5 to 15 mg by mouth three times
daily), o
Octreotide is either given as a continuous
intravenous infusion (50 mcg/hr) or subcutaneously
(100 to 200 mcg three times daily),
Albumin is given for two days as an intravenous bolus
(1 g/kg per day [100 g maximum]), followed by 25 to
50 grams per day until midodrine and octreotide
therapy is discontinued

Hepato-renal syndrome/shut down
Treatment Approach Monitoring
Parameter
Outcome Assessment
1. Eliminate
concurrent
nephrotoxins
(NSAIDs),
2. Decrease or
discontinue
diuretics,
3. volume
resuscitation,
4. liver
transplantation
1. Serum and urine
electrolytes,
2. Monitor
Concurrent drug
therapy
1. Prevent progressive
renal injury
a. preventing
dehydration
b. avoid
nephrotoxins
2. Liver
transplantation for
refractory
hepatorenal
syndromeWednesday, February 28, 2018 Dr Afzal Haq Asif 80
• Fatal complication of cirrhosis

Coagulation defects
Causes:
Reduction in the synthesis of coagulation factors
Portal hypertension is accompanied by a qualitative and
quantitative reduction in platelets
Treatment objectives/parameter for assessment:
Normalize PT time, maintain/improve hemostasis
Monitoring parameters:
CBC, prothrombin time, platelet count
Treatment:
Blood products (PPF, platelets), vitamin K


Coagulation
Defects:Management:Summary
Treatment
Approach
Monitoring
Parameter
Outcome
Assessment
1. Blood
products
(PPF,
platelets),
vitamin K
1. CBC,
2. prothrombi
n time,
platelet
count
1. Normalize
PT time,
2. Maintain/I
mprove
hemostasis

Inter-continental Hotel: Murree, Pakistan

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you
very
much

Liver cirrhosis.2018

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