CIRRHOSIS/ESLD

NADA ZAKARIA
• CLD and Cirrhosis result in about 35,000 deaths /yea
r in US
 aetiology
VIRAL HEPATITIS
•Hepatitis B, which may be coincident with HDV
•Hepatitis C

•Alcoholic liver disease (21% in West)

•Cryptogenic causes (18%) (Many cases actually are du
e to nonalcoholic fatty liver disease.)

AUTOIMMUNE
• Autoimmune hepatitis/LUPUS Hepatitis
METABOLIC/GENETIC
• •Hemochromatosis
• •Wilson disease
• •Alpha-1 antitrypsin deficiency

MISCALLENOUS
• •Granulomatous disease (eg, sarcoidosis)
• •Type IV glycogen storage disease
• •Drug-induced liver disease (eg, methotrexate, alpha
methyldopa, amiodarone)
VASCULAR
• •Venous outflow obstruction (eg, Budd-Chiari
syndrome, veno-occlusive disease)

• •Chronic right-sided heart failure

• •Tricuspid regurgitation
LIVER ARCHITECTURE
Central veins coalesce into h
epatic veins, which leave th
e liver and empty into the v
ena cava.
A bile canaliculus is not a duct, but rather, the dilated intercellular space bet
ween adjacent hepatocytes.

Hepatocytes secrete bile into the canaliculi, and those

secretions flow parallel to the sinusoids, but in the opposite
direction that blood flows. At the ends of the canaliculi, bile
flows into bile ducts, which are true ducts lined with
epithelial cells. Bile ducts thus begin in very close
proximity to the terminal branches of the portal vein and
hepatic artery, and this group of structures is an easily
recognized and important landmark seen in histologic
sections of liver - the grouping of bile duct, hepatic
arteriole and portal venule is called a portal triad
 Architecture of the Hepatic Parenchyma
• The liver is covered with a connective tissue capsule t
hat branches and extends throughout the substance
of the liver as septae.
• This connective tissue tree provides a scaffolding of s
upport and the highway which along which afferent b
lood vessels, lymphatic vessels and bile ducts travers
e the liver.
• Additionally, the sheets of connective tissue divide t
he parenchyma of the liver into very small units calle
d lobules
• The hepatic lobule is the structural unit of the liver. It
consists of a roughly hexagonal arrangement of plate
s of hepatocytes radiating outward from a central vei
n in the center
LIVER LOBULE
 Diagnosis
• Liver biopsy
– Obtained by either a percutaneous, transjugular, l
aparoscopic, or radiographically-guided fine-needl
e approach

– Sensitivity of a liver biopsy for cirrhosis is in the ra

nge of 80 to 100 percent depending upon the met
hod used, and the size and number of specimens o
btained
 Diagnosis
– not necessary if the clinical, laboratory, and radiol
ogic data strongly suggest the presence of cirrhosi
s

– liver biopsy can reveal the underlying cause of cirr

hosis
Histopathology
Histopathology
Histopathology
Histopathology
 Morphologic Classification

• Micronodular cirrhosis
– Nodules less than 3 mm in diameter
– Believed to be caused by alcohol, hemochroma
tosis, cholestatic causes of cirrhosis, and hepati
c venous outflow obstruction
 Morphologic Classification
• Macronodular cirrhosi
s

– Nodules larger than 3

mm
– Believed to be seconda
ry to chronic viral hepa
titis
 Morphologic Classification
• Relatively nonspecific with regard to etiology
• The morphologic appearance of the liver may change as the li
ver disease progresses
– micronodular cirrhosis usually progresses to macronodular cirrhosis
• Serological markers available today are more specific than mo
rphological appearance of the liver for determining the etiolo
gy of cirrhosis
• Accurate assessment of liver morphology may only be achieve
d at surgery, laparoscopy, or autopsy
 Manifestations of Cirrhosis

• Variable signs and symptoms may vary depending on the und

erlying etiology of liver disease.

• As an example, patients with end-stage liver disease caused b

y hepatitis C might develop profound muscle wasting, marked
ascites, and severe hepatic encephalopathy, with only mild jau
ndice.

• In contrast, patients with end-stage primary biliary cirrhosis

might be deeply icteric, with no evidence of muscle wasting. T
hese patients may complain of extreme fatigue and pruritus a
nd have no complications of portal hypertension.
 common features
General
• fatigue
• anorexia
• weight loss
• muscle wasting

Cutaneous manifestations
• jaundice
• spider angiomata
• skin telangiectasias or "paper money skin"
• palmar erythema
• Dupuytren's contracture

Nail changes
• white nails or disappearance of lunulae
• finger clubbing, especially with HPS
Hormonal
increased conversion of androgenic steroids into estrogens in skin,
adipose tissue, muscle, and bone

• Males may develop gynecomastia and impotence

• Loss of axillary and pubic hair is noted in both men and women
• Hyperestrogenemia also may explain spider angiomata and palmar erythe
ma

Other features +/-

• Low grade fever
• Pigment gallstones
• Parotid gland enlargement
• Diabetes mellitus
Signs of ESLD
• Splenomegaly
• Ascites
• Caput medusae
• Cruveilhier-Baumgarten murmur
• Fetor hepaticus
• Jaundice
• Asterixis
 Hematologic manifestations

• Macrocytosis
• LEUCOPENIA/LEUCOCYTOSIS
• Anemia : folate deficiency
hemolysis
hypersplenism.
iron deficiency anaemia

• Thrombocytopenia
hypersplenism and/or decreased levels of thrombopoietin

Coagulopathy
• decreased hepatic production of coagulation factors
• In cholestasis is present, reduced bile flow into the small intestine lead
s
to decreased vitamin K absorption, with resulting reduction in hepatic
production of factors II, VII, IX, and X.
• Patients with cirrhosis also may experience fibrinolysis and DIC
 Hepatic Laboratory Values
Liver Function Tests (LFTs)
LFT Description Normal Values Comments
Aminotransferases Located in AST: 11-47 IU/L Degree of elevation
AST hepatocytes. ALT: 7-53 IU/L can help with
ALT Elevated with determining cause
hepatocellular of hepatic
injury dysfunction
Alkaline Elevations occur Alk Phos: 38-126 Not totally specific
Phosphatase from bile flow IU/L to hepatic function.
γ-Glutamyl obstruction GGT: 0-30 IU/L Elevations in both
Transpeptidase are indicative of
(GGT) liver disease
Bilirubin Breakdown product 0.3-1.1 mg/dL Multiple causes for
of Hgb derived form elevated levels
senescent RBCs
Albumin Most abundant 3.5-5 g/dL Low in liver disease,
plasma protein malnutrition, acute
illness
 Laboratory findings

• Aminotransferases -AST & ALT

• Alkaline phosphatase
• Gamma-glutamyl transpeptidase (GGT)
• Bilirubin
• Albumin
• Globulins
• Serum sodium /K+
• Urea
• Creat
Evaluation of Cirrhosis
 Scoring systems and prognostic indicators

• Patients with ESLD can be stratified into different categori

es of risk based on hepatic synthetic reserve.

Some of the predicting models used in ESLD are -

• Child's Pugh classification.

• The Maddrey index/score
• The model for end stage liver disease score (MELD score).
 Bilirubin in PBC or PSC (mg/dL) <4 4-10 10
Interpretation
A.Child Class A: 5 to 6 points
1.Life expectancy: 15 to 20 years
2.Abdominal surgery peri-operative mortality: 10%
B.Child Class B: 7 to 9 points
1.Indicated for liver transplantation evaluation
2.Abdominal surgery peri-operative mortality: 30%
C.Child Class C: 10 to 15 points
1.Life expectancy: 1 to 3 years
2.Abdominal surgery peri-operative mortality: 82%
 surgery and child pugh score

• On multivariate analysis, the Child-Pugh classification was th

e best predictor of surgical mortality and morbidity
• .
• Class A cirrhosis - 10% mortality for elective surgery. (no par
ticular restrictions)

• Class B cirrhosis - 30% mortality. (tolerate elective surgery; a

void major hepatic resections)

• Class C cirrhosis - 75% mortality. (with abdominal surgery).

 MELD SCORE
• preoperative MELD score of greater than 14 was a better predictor of pos
toperative death than Child Class C status

• the preoperative MELD scores and their associated 30-day postoperative

mortality rates were as follows:

• MELD score of < or equal to 7 5.7% mortality

• MELD score of 8-11 10.3% mortality
• MELD score of 12-15, 25.4% mortality
• MELD score of 16-20 44% mortality
• MELD score of 21-25 53.8% mortality
• MELD score of greater than 26 90% mortality

• The benefits and the risks of surgery should be carefully weighed before a
dvising the patient with cirrhosis to undergo surgery.
 Classification of Cirrhosis

• WHO divided cirrhosis into 3 categories based

on morphological characteristics of the hepati
c nodules
 Micronodular Alcohol, Metabolic, Haemachromatosis, Wilson's Disease
/biliary
 Macronodular Viruses, Toxins, Poisoning/wilson's
 Mixed
 Macronodular & Mixed Cirrhosis

• Nodules are >3 mm in diameter and vary

considerably in size
• Usually contain portal tracts and efferent
veins
• Liver is usually normal or reduced in size
• Mixed pattern if both type of nodules are
present in equal proportions
 Complications of ESLD

• Malnutrition • Pulmonary
• Encephalopathy Hypertension
• Coagulopathy {Hepatopulmonary
syndrome} and
• Portal Hypertension
portopulmonary
• Variceal Hemorrhage syndrome
• Hepatorenal
Syndrome {HRS}
• Spontaneous
Bacterial Peritonitis
{SBP}
• Hyponatremia
 fibrosis scores
• C:\Documents and Settings\radioshack\Deskto
p\grade_stage.pdf
• C:\Documents and Settings\radioshack\My Do
cuments\liver fibrosis scores.pdf
 treatment general considerations
• nutrition
• hepatotoxic drugs
• anti-pruritic agents
• disease specific treatment
• surveillance for oes varices
• hcc surveillance
• managing HE and complications of PHT
• Appropriate drug selection is important (INCL
UDING OTCs)
– Acetaminophen
• Patients with ETOH cirrhosis and/or malnourished: Use
lower doses than recommended
• Patients with cirrhosis due to other causes: Therapeutic
doses can be used, but for limited time periods
• Chronic therapy should be avoided in all cirrhotic patien
ts
– NSAIDS
• Should be avoided in all cirrhotic patients
10/05/2021
Cirrhosis: Concepts and Associat
ed Complications
 Cirrhosis: General Clinical Presentation
• Gastrointestinal
– Loss of appetite
– Nausea/Vomiting
– Loss of weight
– Pain in upper right quadrant
• Fatigue
• LE edema/edema in abdomen
• Jaundice
• Profuse itching
• Mental status changes
 Etiologies of Chronic Liver Disease
• Infections, esp. viral
• Toxins
• Genetic
• Drugs
• Autoimmune
• Vascular
• Biliary
 Mechanisms of Chronic Liver Injury
• Hepatocyte Injury
– Inflammation primary
– Injury primary – followed by inflammation
• Biliary Obstruction
• Hepatic venous obstruction
 Cystic Fibrosis Biliary
Genetic
Wilson’s Disease Obstruction

Hepatocellular Fibrosis
Necrosis and
Inflammation

INH
Drug Hepatic Venous
Estrogens Outflow Obstruction
 Target Cell (Activated Target) Fibrogenesis

Primary
Agent
Cytokines Altered Matrix + Matrix Peptides

Inflammation
 Etiologies of Chronic Hepatitis
• Hepatitis C
• Hepatitis B (w/wo Delta)
• Autoimmune Hepatitis
• Drugs
• Wilson’s Disease
Pathogenesis of Liver Injury with Chronic
Biliary Obstruction
Obstruction of bile flow

Bile acid, copper accumulation

Alterations in cannicular membrane and tight junction

s

Condensation of pericannicular microfilaments

Fibrosis (necrosis and inflammation)

Cirrhosis: Management Guidelines
• AASLD/ACG Practice Guidelines
Prevention and Management of Gastroesophageal
Varices and Variceal Hemorrhage in Cirrhosis
www.aasld.org
• Dept of VA Hepatitis C Resource Center Progr
am and the National Hepatitis C Program
Management and Treatment of Patients with Cirrh
osis and Portal Hypertension
Cirrhosis: General Clinical Presentation
• Gastrointestinal
– Loss of appetite
– Nausea/Vomiting
– Loss of weight
– Pain in upper right quadrant
• Fatigue
• LE edema/edema in abdomen
• Jaundice
• Profuse itching
• Mental status changes
10/05/2021
Complications of Cirrhosis
• Variceal Formation/Hemorrhage
• Ascities
• Spontaneous Bacterial Peritonitis
• Hepatic Encephalopathy
• Others
– Hepatorenal Syndrome
– Coagulation Disorders
– Hepatopulmonary Syndrome
– Hepatic Cardiomyopathy
– Hepatocellular Carcinoma
10/05/2021
 Cirrhosis: Variceal Formation

• Varix: An enlarged or dilated v

ein
– Esophageal
– Gastric (or IGVs)
– Gastroesphageal
• Varies result almost solely fro
m portal hypertension PHT

• Hyperdynamic circulation play

s a detrimental role

10/05/2021
Cirrhosis: Variceal Formation
• Portal Hypertension (PHT)
– Normal hepatic venous pressure gradient (HVP
G) 3-5 mm Hg
– Oes Variceal Formation
– Increased overall resistance
– Development of porto-systemic collateral circulati
on
– PHT persists for 2 primary reasons
• Splanchnic arteriolar vasodilatation occurring concomit
ant with the formation of collaterals
10/05/2021 • Insufficient portal decompression through collaterals
Cirrhosis: Variceal Formation
• Diagnostic Measures

– All patients need to undergo OGD

10/05/2021
 Cirrhosis: Variceal Formation
Characteristics of At-Risk Varices

Oesophageal Gastric

Medium and Large Size Medium (5-10 mm) and Large (>10 mm)

Elevated Child-Pugh Score (Child B/C) Elevated Child-Pugh Score (Child B/C)

Presence of red wales/cherry red spots Presence of red spots

10/05/2021
Cirrhosis: Variceal Formation
• Classification of patients

– Cirrhotic Patients with varices

– Cirrhotic Patients with actively bleeding varices
– Cirrhotic Patients that have survived a bleeding epi
sode

10/05/2021
Cirrhosis: Variceal Formation
• Primary Prevention Management
– Nonselective β-adrenergic antagonists
– Endoscopic Variceal Ligation
– Candidates for these therapies include:
• Any variceal size
• At-risk endoscopic findings
• Elevated Child-Pugh Score
– What about those patients who don’t have any var
ices present?? No medication

10/05/2021
Cirrhosis: Variceal Formation
(Primary Prevention)
• Nonselective β-adrenergic antagonists
– Propanolol
– Nadolol
• Mechanism of action makes them ideal agent
• RCTs have illustrated both:
– Reduction in first variceal hemorrhage
– Reduction in mortality
• Would any beta blocker work for these patient
s?
10/05/2021
Cirrhosis: Variceal Formation
(Primary Prevention)
• Nonselective β-adrenergic antagonists
– Propanolol 20 mg BID
– Nadolol 40 mg daily
• Titrate to maximally tolerated doses to HR 55-
60 BPM
• Assess for adverse effects
• Therapy is life-long

10/05/2021
Cirrhosis: Variceal Formation
(Primary Prevention)
• Endoscopic Variceal
Ligation (EVL)
– Local therapy that co
nsists of rubber band
s around the varices
until obliteration
– Works by capturing a
ll or part of a varix re
sulting in occlusion fr
om thrombosis
10/05/2021
Cirrhosis: Variceal Formation
(Primary Prevention)
• RCT data involving utilization of EVL indicates:
– Equally effective as non-selective BBs
• Ideal candidates for EVL therapy:
– Patients who have contraindications/cannot tolera
te non-selective BBs
• Frequency of procedure:
– Ligate q 1-2 wks until obliteration
• Which is better BBs or EVL?

10/05/2021
 Primary Prevention Recommendations of Varices

Variceal Characteristics Recommendation

Medium/large varices (at highest risk) Either BB’s or EVL

Medium/large varices (not at highest BB’s preferred , EVL may be considered

Small varices (at highest risk) BB’s recommended over EVL

Small varices (not a high risk) BB’s optional. If not given, OGD in 2 yea

Gastric varices (with or Oes Varices ) BB’s recommended over EVL

10/05/2021
 Why Do Varices Bleed?

Erosion Explosion

According to this theory Depends on size and

ulceration and acid pressure (tension in a
reflux are considered balloon = radius x
important, but this is not pressure)
supported by
histological
observations
Variceal Haemorrhage
 Oesophageal Varices
• PHT +/- Cirrhosis/Acute/Fulminant hepatitis

• Screening who and how often?

• Factors influencing bleeding

Size matters
V wall pressure
Wall thinnesss (red signs and weals)
HVWP 12mmHg
Child Pugh stage/ongoing liver injury
 Oesophageal Variceal Haemorrhage

Prevention and Primary Prophylaxis

• Propranolol
• Nadolol
• ? Nitrates

• Look for treatable cause

 Variceal Haemorrhage

• Identification of at risk groups

• Identify cause of bleeding

pre—OGD
 Variceal Haemorrhage
• ABC and Blood Products

• Airway Management esp Cirrhotics with Ence

phalopathy/spiration

• Terlipressin/Vasopressin

Antibiotics crucial 60-70% Sepsis esp. cirrhotics

 Endoscopy/local Management
Oesophageal Varices

 Oesophageal band ligation Gold standard

 Sclerotherapy
rescue therapy as more complication

 Sengestaken Balloon tamponade

Gastric Varices
 Gastric Varices
1.Oesopho-Gastric Varices
treat as oesophageal varices

2. Isolated Gastric Varices

Type 1 and 2

histoacryl\ injection not EVL

(bleeding/High risk stigmata)

3.Secondary Gastric Varices (within 2yrs after OV eradication) treat

according to location
Histoacryl for Type II/IGV
Gastric varices
Options for Control of Variceal Bleeding
• Medical
– Vasopressin (or glypressin) + NTG
– Somatostatin (or octreotide)
– Beta blockers
• Procedures
– SB, Minnesota, or Linton tube
– Endoscopic sclerotherapy or band ligation
– TIPS
• Surgical
– Shunts
– Variceal interruption
– Transplant
Cirrhosis: Variceal Hemorrhage
• Patients who fall under this category have the
following:
– Upper GIB (GI Bleed)
– Endoscopy reveals either one of the following:
• Active bleeding from varix
• “White nipple” overlying the varix
• Clots overlying the varix
• Varices present with no other bleeding sources

10/05/2021
Cirrhosis: Variceal Hemorrhage
• General Management Strategies
– Replace volume using crystalloids (preferred over
colloids)
– Blood transfusions (goal Hgb ~ 8g/dL)
– Endotracheal intubation
– Antibiotic prophylaxis
• Norfloxacin 400 mg PO BID
• Ciprofloxacin 500 mg PO BID or 400 mg IV BID
• Ceftriaxone 1 gm IV daily
– STAT EGD
10/05/2021
Cirrhosis: Variceal Hemorrhage
• Specific Treatment Strategies
– Splanchnic Vasoconstrictors
– EVL
– Endoscopic Variceal Sclerotherapy
– Salvage Therapies
• Transjugular Intrahepatic Portosystemic Shunt (TIPS)
• Surgical shunt

10/05/2021
Cirrhosis: Variceal Hemorrhage
• Splanchnic Vasoconstrictors
– Octreotide
• Mechanism of action is ideal due to localized effects
• Low rate of adverse effects
• RCT show benefit, but mortality data is lacking
• Dosing: Give initial bolus of 50 mcg, then start continu
ous infusion of 50 mcg/hr for at least 5 days

10/05/2021
Cirrhosis: Variceal Hemorrhage
• Splanchnic Vasoconstrictors
– Vasopressin
• Ideal MOA, however it is NOT selective
• Adverse effects include cardiac and peripheral ischemia
, arrhythmias, HTN, bowel ischemia
• Dosing: Continuous infusion of 0.2-0.4 units/min (max d
ose 0.8 units/min)
• Strategies to reduce adverse effects
– Run with nitroglycerin drip (40 mcg/min; max of 400 mcg/min
, adjusted to maintain SBP > 90 mm Hg)
– Run combination at highest effective doses for 24 hour limit

10/05/2021
Cirrhosis: Variceal Hemorrhage
• Endoscopic Variceal Sclerotherapy (EVS)
– Utilizes a sclerosant in the varix which ultimately s
tops bleeding
– Commonly used sclerosants include ethanolamine
and sodium tetradecyl sulfate
– Performed with the patient awake but sedated
– More adverse effects than with EVL
– Which is better EVL or EVS?

10/05/2021
Cirrhosis: Variceal Hemorrhage
• Combination endoscopic/pharmacological the
rapy represents the best approach to active bl
eeding
– EVL is preferred over EVS
– Pharmacotherapeutic choice should be started AS
AP
– Endoscopic procedure should be performed within
12 hrs of admission

10/05/2021
Cirrhosis: Variceal Hemorrhage
• Rescue Therapies
– Used in patients who fail combination therapy
– Patients with bleeding gastric fundal varies who ha
ve failed one endoscopic therapy
– Types include:
• Balloon Tamponade
• TIPS
• Shunt Therapy

10/05/2021
Cirrhosis: Variceal Hemorrhage
• Balloon Tamponade
– Highly effective meth
od of controlling blee
ds
– Balloon is inflated wit
hin the esophagus or
stomach to apply pre
ssure on the varices
– Temporary measure
ONLY
10/05/2021
 Cirrhosis: Variceal Hemorrhage
• TIPS
– Consists of the vascular plac
ement of an expandable met
al stent across a tract create
d between the portal vein an
d a major intrahepatic branc
h
– Complications include bleedi
ng ,infections, and Hepatic e
ncephalopathy (HE)
10/05/2021
Cirrhosis: Variceal Hemorrhage
• Surgical Shunts
– Last line procedure a
mongst the other sur
gical options
– Associated with high
morbidity and mortal
ity

10/05/2021
Cirrhosis: Preventing Variceal R
ebleeding
• Candidates who fall under this category includ
e:
– Recovery from an acute hemorrhage
• Why is prevention so important?
• Clinical predictors for recurrent events include
:
– Severity of initial hemorrhage
– Degree of decompensation
– Presence of HE or renal impairment
10/05/2021
Cirrhosis: Preventing Variceal R
ebleeding
• Combination endoscopic/pharmacological the
rapy represents the best approach to active bl
eeding
– EVL is preferred over EVS
– Β-blockade agents should start immediately after
splanchnic vasoconstrictors
– Endoscopic procedure should be performed within
12 hrs of admission

10/05/2021
Cirrhosis: Preventing Variceal R
ebleeding
• Combination pharmacological therapy
– Propanolol or nadalol plus isosorbide mononitrate
(IM)
– Produces synergistic portal pressure reduction
– RCT do support there use
• BB+IM+EVL reduced variceal rebleeding better than the
group treated with BB+IM without EVL (18% vs. 32%), b
ut with rates similar to those in a BB+EVL group
– Who would be an ideal candidate for BB+IM thera
py?
10/05/2021
•
Cirrhosis: Preventing Variceal R
ebleeding
• Second line options
– TIPS
– Surgical shunting

10/05/2021
Gastric Varices
 Gastric Varices
1.Oesopho-Gastric Varices
treat as oesophageal varices

2. Isolated Gastric Varices

Type 1 and 2

histoacryl\ injection not EVL

(bleeding/High risk stigmata)

3.Secondary Gastric Varices (within 2yrs after OV eradication) treat

according to location
Histoacryl for Type II/IGV
Gastric varices
 Newer options for Gastric Varices
• Transvenous obliteration

complex-type gastric varices treated by

balloon-occluded retrograde transvenous
obliteration (BRTO) EOA injection

Takaji R et al. AJR 2011;196:686-691

 PHT Gastropathy

• PPI and optimize beta-blockers/compliance

• Re-assess pathophysiology

• APC for Bleeding/Anaemia PHT gastropathy

 Challenging sites

• Colonic/Rectal varices

• SB varices

• Choledochal Varices
(malaena and obstructive jaundice)
 Other Options
• TIPSS
NB Child Pugh score and risk HE

• Surgical shunts no longer performed routinely

• Devascularisation

• Liver transplantation
 What is TIPS?

Put metal stent inside the flesh of liver

between the hepatic vein and portal branch
(side-to-side).
Technical Varieties:
A- Standard
B- Modified:
1- PHS: Porto-hepatic stent…standard
2- PCS: Porto-caval stent.
3- MHS: Meso-hepatic stent
 Portal veno
Catheter into HV + Pressure Portal vein wall cut
+ pressure

Cut the H V caudal Cut the Correct cut of the PV Dilating liver
wall Baseline PVP = 43
wall and biliary tree tissue track
liver tissue by the PSG = 21
and portal
TIPS Knife Needle
vein wall
 Which

S
t
e
n Trabiculated metal tube; got
0.13 rigid (cemented) once inside
t body.

s
 Challenging sites

• Colonic/Rectal varices

• SB varices

• Choledochal Varices
(malaena and obstructive jaundice)
 Subsequent management
Successful management of bleeding Mabrook and Masalam
a !!

End of story ?

Secondary prophylaxis

Establish cause PPF vs Cirrhosis vs other causes of PHT

US and Hepatitis Panel etc
HBV immunisation whatever the cause ?
 Ascites ascites
• ascites
• ascites
• ascites

10/05/2021
Cirrhosis: Ascities
• Fluid accumulation i
n the peritoneal cavit
y
• Most common compl
ication of cirrhosis
•

10/05/2021
 Peritoneal fluid
• It is a normal, lubricating fluid found in the pe
ritoneal cavity.
• The fluid is mostly water with electrolytes, anti
bodies, white blood cells, albumin, glucose an
d other biochemicals.
• Reduce the friction between the abdominal o
rgans as they move around during digestion.
 Setting the scene
• Occurs in 50% of patients over 10yrs

• Associated with 50% mortality over2 yrs

• Indicates the need to OLT

• Mortality from cirrhosis is 12.7/100,000

 Clinical features
Symptoms
 Abdominal Distension
 Diffuse Abdominal Pain
 Bloated Feeling of Abdomen

 Dyspnoea and Orthopnea (due to elevati

on of diaphragm)
 Indigestion and Heart burn (due to increa
sed intra abdominal pressure)
Abdominal examination
Inspection
 Abdominal Distension

 Fullness of Flanks

 Umbilicus Everted nd transverse slit

 Divarication of Recti Muscles

 Distended Abdominal Veins

 Skin is stretched and shiny

 Abdominal hernia or abdominal striae

Physical findings for aetiologic
al diagnosis
Virchow’s gland- GI malignancy
Skin changes of hepatocellular failure- usu
ally cirrhosis of liver
Engorged and pulsatile neck vein- CCF, P
ericardial effusion, constrictive pericarditis
Prominent abd. Vein- Portal Hypertension
Non pitting edema in feet- Myxoedema, fil
ariasis
Splenomegaly- mainly PHT(cirrhosis of liv
er), also in lymphoma, leukaemias, Budd-
Chiari

Hepatomegaly- firm liver indicates cirrhosi

s, hard and tender liver for malignancy, am
yloid/haemochromatosis

Tenderness- Peritonitis/malignancy/Budd/
abscess
 ∂∆
• Ascites • Obesity
• Ovarian cyst • The F’s
• Hydramnios
 Pathogensis

• Portal hypertension

• Sodium and water retention

 Role of portal hypertension
PHT occurs as a consequence of structural
changes within the liver in cirrhosis and inc
reased splanchnic blood flow

• Increased splanchnic flow because of vas

odilation due to release of NO and others
 y
• Progressive collagen deposition and nodule formatio
n alter vascular architecture and increases the resista
nce to portal flow

• Collagen is formed within the space of Disse and sinu

soids become less distensible

• PHT ↑ the hydrostatic pressure in hepatic sinusoids

and leads to transudation of fluid into the peritoneal c
avity
• Increased resistance in the hepatic sinusoid
• Portal hypertension
• Congestion of capillary in intestine
• Endotoxaemia
• NO release

• Arterial vasodilation in both systemic and splanchnic circulation- sys

temic ( tachycardia increased stroke volume) and splanchnic ( incre
ased portal flow- and more rise in portal pressure)

• Decrease in effective circulatory volume

• Activation of RAS system and sympathetic system- ( aldosterone inc

rease promoting Na retention and secondary fluid retention to restor
e blood volume)

• Renal vasoconstriction to increase glomerular pressure- ultimately a

ttempts at homeostasis fails- GFR starts to fall
• Increased resistance in the hepatic sinusoid
• Portal hypertension
• Congestion of capillary in intestine
• Endotoxaemia
• NO release
• Arterial vasodilation in both systemic and splanchnic circulation-
systemic ( tachycardia increased stroke volume) and splanchni
c ( increased portal flow- and more rise in portal pressure)
• Decrease in effective circulatory volume
• Activation of RAS system and sympathetic system- ( aldosteron
e increase promoting Na retention and secondary fluid retention
to restore blood volume)
• Renal vasoconstriction to increase glomerular pressure- ultimat
ely attempts at homeostasis fails- GFR starts to fall
• Presinusoidal portal hypertension does not
produce ascites ( portal vein thrombosis)

• Post sinusoidal portal hypertension does p

roduce back pressure and cause similar h
aemodynamic changes and causes ascite
s ( hepatic vein thrombosis)
Cirrhosis: Pathogenesis of Ascit
es

10/05/2021
 Differential aetiology of ascites

10/05/2021
Hypoalbuminemia

 Nephrotic syndrome
 Protein-losing enteropathy
 malnutrition
 Other causes of ascites
• Bacterial, fungal or parasitic disease
• Vasculitis
• Whipple's Disease
• Familial Mediterranean fever
• Endometriosis
• Starch peritonitis
• Budd-Chiari Syndrome
• Myxedema
• Ovarian disease (e.g. Meigs' Syndrome)
• Pancreatic disease
• Chylous Ascites
 Pathophysiology
1- Increased hydrostatic pressure
• Cirrhosis
• Hepatic vein occlusion (Budd-Chiari
Syndrome)
• Inverior vena caval obstruction
• Constrictive Pericarditis
• Congestive heart failure
 Pathophysiology
2. Decreased colloid osmotic pressure
• End-stage liver disease with poor protein syn
thesis
• Nephrotic syndrome
• Malnutrition
• Protein-losing enteropathy
3. Increase permeability of peritoneal capillari
es
• Tuberculous peritonitis
• Bacterial peritonitis
• Malignant disease of the peritoneum
 Pathophysiology
4. Leakage of fluid into the peritoneal cavity
• Bile ascites
• Pancreatic ascites
• Chylous ascites
• Urine ascites
5. Miscellaneous causes
• Myxedema
• Ovarian disease (Meig’s syndrome)
• Chronic hemodialysis
 Percentage by aetiology
• Cirrhosis/ppf 75%
• Malignancy 10%
• Heart failure 3%
• TB 2% in the west
• Pancreatitis 1%
differential/causes
 Morbidity and Mortality
• Ambulatory patients with an episode of cirr
hotic ascites have a 3-year mortality rate o
f 50%. The development of refractory asci
tes carries a poor prognosis, with a 1-year
survival rate of less than 50%.
 Grading of ascites

1. Grade I: Only detectable by US

2. Grade II: Moderate symmetrical distensio
n of the abdomen

3. Grade III: Marked abdominal distension

 Diagnosis
History
Pts should be questioned about:
• Liver diseases
• Risk factors for Hepatitis C ( needle shari
ng, tattoos, cocaine, heroin use and emig
ration from Egypt or Southeast Asia)
• Risk factors for Hepatitis B (needle shari
ng, tattoos, acupuncture, and emigration
from China, Korea, Taiwan, or Southeast
Asia).
• Pts with obesity, diabetes, hyperlipidemi
a and Nonalcoholic steatohepatitis ( NAS
H ) should be ruled out.
• Pts with ascites who lack risk factors for
cirrhosis should be questioned about
cancer, heart failure, TB, dialysis, and pa
ncreatitis.
• Operative injury to the ureter or bladder c
an lead to leakage of urine into peritonea
l cavity.
• HIV pts may have infections lead to as
cites.
 Diagnosis
2-Clinical Features
• A- Asymptomatic (fluid <100 - 400ml):
Mild ascites

• B- symptomatic (fluid >400ml):

Increased abdominal girth, presence of abd
ominal pain or discomfort,
early satiety, pedal edema, weight gain
and respiratory distress depending on the a
mount of fluid accumulated in the abdome
n.
Physical examination findings:
• Umbilicus Eversion (often with umbilical he
rniation)
• Tympany at the top of the abdomen
• Fluid wave
• Peripheral edema
• Shifting dullness (> 500ml fluid)
• Bulging flanks (>500ml fluid)
Shifting Dullness
Bulging Flanks and Umbilical Herni
a
 Diagnosis
3-paracentesis
• It is a diagnostic procedure to establish the
etiology of new-onset ascites or to rule out
spontaneous bacterial peritonitis in patient
s with preexisting ascites. Large volume p
aracentesis is performed in hemodynamic
ally stable patients with tense or refractory
ascites to alleviate discomfort or respirator
y compromise.
• For diagnostic purposes, a small amount
(20cc) may be enough for adequate testin
g.
 Abdominal paracentesis
• 15cm lateral to umbilicus
• Avoid enlarged spleen and liver
• Avoid sp and inf epigastric arteries
• No data to support use of FFP
• Most clinicians would give pooled platelets if <40
• Complication:
– Haematoma<1%
– Bowel perforation/haemoperitoneum <0.1%
• 10-20ml of fluid in a syringe with blue/green nee
dle
 Treatment Measures of Ascities
• OGD
• Abdominal Paracentesis
– Considered both diagnostic
– and therapeutic

10/05/2021
• video
• Blood tests- FBC/U&E/LFT/INR

• Ultrasound- liver/spleen/portal vein/LN

Ascitic fluid analysis
• Blood culture bottle- culture
• EDTA tube- cell type
• Yellow top tube- albumin/amylase
• Yellow top tube- serum albumin
• Sterile container cytology
• Others tb pcr/special stains et
c
 SAAG
• Previously transudate if >25g/L and exudate if >
25g/L of protein
• Up to 30% of cirrhosis will be exudate if we use
protein to categorize
• SAAG is far superior with 97% accuracy
• Eg Serum albumin 26 and ascitic albumin 11- so
SAAG is 15- so high SAAG- previously called tra
nsudate

SAAG>11g/L SAAG<11g/L
Cirrhosis Malignancy
Cardiac failure Pancreatitis
Nephrotic syndrome Tuberculosis
SBP
Ascitic fluid neutrophil count and cu
lture
• SBP is present in 15% patients admitted to hospi
tal
• Ascitic neutrophil count of >250cells/mm3 is diag
nostic of SBP in absence of perforated viscus or
inflammation of intraabdominal organs
• RBC count is usually <1000cells/mm3
• In 2% of cirrhotic bloody ascites >50,000
• In bloody ascites 50% no cause and 30% HCC
• The prevalence of occult ascitic fluid infection in
asymptomatic outpatients undergoing large volu
me paracentesis for resistant ascites is low
• As a result, the routine culture of fluid during par
acentesis in such patients is probably not warran
ted.
• Obtain a cell count and differential on all sample
s of ascitic fluid while obtaining cultures only in s
ymptomatic patients.
• Culture in sterile container will identify onl
Y 40% of cases of SBP
• Whereas culture in blood culture bottle will
identify 72-90 %
• Gram stain and AFFB stain inappropriate
• Fluid culture for mycobacteria 50% sensiti
vity superseded by TB PCR
 ascites cytology
• Cytology is 60-90% accurate in malignant ascites if seve
ral hundred ml of fluid is sent and concentration techniqu
e is used

• 96.7% sensitivty in peritoneal carcinomatosis is if 3 sa

mples are sent and processed promptly

• 50 mL of fresh warm ascitic fluid were hand-carried to t

he laboratory for immediate processing.
• 1st sample is positive in82.8%
• 1 0f 2 positive in 93.3%

• But it is not investigation of choice in HCC

 Differential Diagnosis
• cirrhotic
• non cirrhotic
• cardiac
• mixed
• multifactorial
 Treatment-bed rest
• No clinical data to back up the finding that
upright position is asscociated with reduce
d GFR and reduced Na excretion and redu
ced diuretic efficacy
• Bed rest promote muscle atrophy and othe
r complications and extends hospital stay
• So bed rest not recommended
 Treatment- salt restriction
• Suggestion is no added salt diet and avoid
ance of prepared food
• allow 90mmol/day ( 5.2gm)
• Lowers diuretic requirement, faster resoluti
on of ascites and shorter hospital stay
• Avoid high salt content of fluid and medicin
e except in HRS
 Treatment- water restriction
• No role in uncomplicated ascites
• Most hepatologists restrict fluid in ascites associated wit
h hyponatraemia- but is illogical
• The downside is water restriction causes increase in the
central effective hypovolaemia- more ADH- more water r
etention and further dilutional hyponatraemia
• So hepatologists including the authors of the BSG guideli
nes suggest further plasma expansion to inhibit ADH sec
retion
• Data emerging supporting use of specific vasopressin 2 r
eceptor antagonists
• To be effective the intake should be less than urine outpu
t rather than arbitrary 1.5L/day
• If the serum sodium concentration does not increase wit
hin the first 24 to 48 hours, the degree of fluid restriction
has been insufficient.
 Treatment- diuretic
• Spironolactone is drug of choice
• Aldosterone antagonist acting in distal tubule to i
ncrease natriuresis and conserve potassium
• Initial dose 100mg and increasing up to 400mg
• Lag of 3-5days
• Better natriuresis and diuresis than a loop diureti
c
• Antiandrogenic effect- gynaecomazia- tamoxifen
20mg bd
• Hyperkalaemia frequently limits the use
 Treatment- diuretic
• Stepped care approach
• If oedema is present no need to slow down the daily wei
ght loss
• Once oedema is resolved – daily weight loss should be l
ess than 0.5kg per day
• Over diuresis is associated with intravascular volume de
pletion, leading to renal impairment, hepatic encephalop
athy and hyponatraemia
• 10% will have refractory ascites
• Dietary history to exclude salt ingestion- 24hr urinary Na
excretion should be less than recommended intake
• Drug history - NSAID
 Problem with hyponatraemia
Na 126-135 and normal Continue diuretic
creatinine Do not water restrict

Na 121-125 and normal Continue/? discontinue

creatinine

Na 121-125 and high Stop diuretic and give

Creatinine volume expansion

Na <120 Stop diuretic

Controversy regarding normal salin
e
• Give only if renal function is worsening – c
reatinine >150 or 120 and rising
• Gelofusion/Haemaccel/ 4.5% albumin –all
have 153mmol of Na per L
• This will worsen salt retention but better to
have ascites than to develop HRS
 Therapeutic paracentesis
• Total paracentesis is associated with signif
icant haemodynamic changes
• Large volume paracentesis causes marke
d reduction of IAP and IVC pressure- decr
ease in right heart pressure and
• This changes are maximal at 3hrs
• Use Z technique- puncture site on the skin does
not overlie the puncture site on peritoneum
• Left flank is preferrable to right flank
• After drain is out patient lie on opposite site
• Colostomy bag if continuous leakage ( some use
purse string suture)
• As rapidly as possible- should not be left overnig
ht
• No upper limit of 8 litres or maximum time of 6 h
ours has been mentioned in the guidelines
• 10% of patients will have refractory ascites
and will need paracentesis
• Following paracentesis ascites will recur in
93% if diuretic is not reinstituted and only
18% if treated with spironolactone
• Reintroduction of diuretics after 1-2 days d
oes not appear to increase the risk of post
paracentesis circulatory dysfunction
Cirrhosis: Management of Unco
mplicated Ascities
• Which patients fall under this category?
• Specific Treatment Measures include:
– Sodium Restriction
– Nutrition Consult
– Oral Diuretics
– Large Volume Paracentesis (LVP)

10/05/2021
Cirrhosis: Management of Unco
mplicated Ascities
• Diuretic Therapy
– Spironolactone (starting dose: 50-100 mg q AM)
• Diuretic of choice
• Hyperkalemia is a concern
• Monotherapy recommended with minimal fluid overloa
d
– Spironolactone + furosemide (starting doses: Spironlacton
e 100 mg and furosemide 40 mg every morning)
• Titrate using a 100-mg : 40-mg ratio
• Hyponatremia is a definite concern
• Monitor renal function frequently
10/05/2021
Cirrhosis: Management of Unco
mplicated Ascities
• Large Volume Paracentesis (LVP)
– Only perform if tense ascities is present or unresp
onsive to diuretics
– Perform prior to starting diuretics/sodium restricti
ons
– Albumin administration
• Reasonable to give if extraction volume > 5L
• Choose albumin 25% solution
• Administer 6-8 gms/L of fluid removed

10/05/2021
Cirrhosis: Management of Unco
mplicated Ascities
• Monitoring Parameters
– Adjust diuretic dose every 4-7 days
– Instruct patient to weigh in weekly
– Order BMP every 1-2 weeks
– Add furosemide if weight loss not optimal or if ↑
K+ develops
– Monitor for adverse effects
• Hypovolemia
• Hyponatremia
• HE
10/05/2021
Cirrhosis: Management of Unco
mplicated Ascities
• Titration of diuretics
– Double dosage of diuretics
• Weight loss < 2 kg/wk AND SCr, BUN, electrolytes are st
able
– Halve or discontinue doses
• Weight loss ≥ 0.5 kg/day OR SCr, BUN, electrolytes are a
bnormal
– Maximum doses are spironolactone 400 mg daily
and furosemide 160 mg daily

10/05/2021
• Long-term antibiotic prophylaxis (norfloxacin 4
00 mg daily)
– NOT recommended in all patients
– High risk patients should be considered for prophy
laxis
• Ascities protein level < 1.5 g/dL
• Impaired renal fxn (SCr ≥ 1.2 mg/dL, BUN ≥ 25 mg/dL)
• Hyponatremia (Na ≤ 130 mEq/L)
• Advanced hepatic failure (CP score > 9 with bilirubin ≥ 3
mg/dL)

10/05/2021
Cirrhosis: Management of Refra
ctory Ascities
• Which patients fall under this category?
– Diuretic-Resistant Ascities
– Diuretic-Intractable Ascities

• Assess adherence patterns before to diagnosis

10/05/2021
 Refractory Ascites
• Refractory ascites: unresponsive to :-
• sodium-restricted diet

• high-dose diuretic treatment (400 mg/day spironolac

tone and 160 mg/day furosemide)

• or rapidly recurrs after LVP

• Prostaglandin inhibitors eg NSAIDS can reduce urinar

y sodium excretion in cirrhosis and can convert patie
nts from diuretic-sensitive to refractory .

10/05/2021
 Failure of diurtic therapy may be manifested b
y:-
A
• minimal to no weight loss
• inadequate ) urinary sodium excretion<78mm
0ls/day despite diuretics
or B )clinically significant complications of diure
tics,
1 HE
1.creatinine ≥ 2
2.NA +≤ 120
• K+ 6.0 mmol/L.
10/05/2021
Rx Refractory ascites
• serial therapeutic paracenteses
measure urine Na

• liver transplantation

• TIPSS

• peritoneovenous shunt

• experimental medical therapy

10/05/2021
 summary
• Recommendations:
• 7. Patients with ascites who are thought to have an
• alcohol component to their liver injury should abstain
• from alcohol consumption. (Class I, Level B)
• 8. First-line treatment of patients with cirrhosis
• and ascites consists of sodium restriction (88 mmol/
• day [2000 mg/day]) and diuretics (oral spironolactone
• with or without oral furosemide). (Class IIa, Level A)
• 9. Fluid restriction is not necessary unless serum
• sodium is less than 120-125 mmol/L. (Class III, Level
• C)
• 10. An initial therapeutic abdominal paracentesis
• should be performed in patients with tense ascites.
• Sodium restriction and oral diuretics should then be
• initiated. (Class IIa, Level C)

10/05/2021
 summary
• 14. Postparacentesis albumin i
nfusion may not benecessary f
or a single paracentesis of less
than 4-5 )
• For large-volume paracentese
s, an albumin infusion of 6-8 g/
L of fluid removed can be consi
dered.
10/05/2021
 SBP
DIAGNOSIS
• 12% admissions of cirrhotics with ascites
• absolute PMN count (i.e., ≥250 cells/mm
3 in absence of intra-abdominal, surgicall
y treatable source of infection hemorrha
gic ascites, peritoneal carcinomatosis, pa
ncreatitis, or peritoneal tuberculosis etc

10/05/2021
 SYMPTOMS
presence or absence
doesnt refute diagnosis

10/05/2021
 ANTIBIOTICS WHICH?
• 3 most common isolates: Escherichia coli, Kleb
siella pneumoniae,and pneumococci
• Cefotaxine 2 g tds
• ceftrioxone 1 g od
• iv ciprofloxacin in absence of resistance or prio
r quinolone prophyla;
• oral ofloxacin 400mg bd if no vomiting, shock,
grade≥ II HE or creatinine ≥3
10/05/2021
• Patients with ascitic fluid PMN counts <250
cells/mm3 ) and signs or symptoms of
infection (temperature >100°F or abdominal
pain or tenderness) should also receive
empiric antibiotic therapy

10/05/2021
 ALBUMIN IV IN SBP
• Patients with aSBP and :
1. serum creatinine >1 mg/dL,
2.or blood urea nitrogen >30 mg/dL
3.or total bilirubin >4

• should receive 1.5 g albumin/kg body weight

within 6 hours of detection and 1.0 g/kg on da
y3

10/05/2021
 SBP or SBP?

Secondary bacterial peritonitis, i.e., ascitic fluid infection

caused by a surgically treatable intra-abdominal
source
. Secondary peritonitis 2 subsets
1. free perforation of a viscus (e.g., duodenal ulcer
2. loculated abscesses in the absence of perforation (e.g., perin
ephric abscess)
Signs and symptoms do not help separate patients
• who need surgical intervention (both subsets of
• secondary peritonitis) from those who have SBP and need
• only antibiotic ttt

10/05/2021
 fluid analysis to differntiate
• this important distinction.33 The characteristic analysis in

1. Free Perforation
PMN count >250 cells/mm3 (usually 1000s ) multi
ple organisms (frequentlyincluding fungi and e
nterococcus) on Gram stain and culture
and at least 2 oftwo of the following criteria:
2.total protein ≤1 g/dL,
3.LDH >ULN for serum
4.Glucose >50 mg/dL.
10/05/2021
• An ascitic fluid CEA ≥5 ng/mL or
• ascitic fluid ALP ≥240 U/L accurate
• in detecting gut perforation into asci
tic fluid with a
• sensitivity of 92% and specificity of 8
8%

NB these criteria not useful in nonper

foration secondary peritonitis
10/05/2021
 PREVENTION
• 1. bleeders 7 days iv ceftrioxone or 400mg bd
norfloxacin

• after single episode of SBP all start longterm n

orfloxacin prohylaxis

10/05/2021