LIVER CIRRHOSIS

ETIOLOGY
PATHOGENESIS
CLINICAL FEATURES
MANAGEMENT
PROGNOSIS
 DEFINITION

 Diffuse pathological process, characterized by fibrosis and conversion of

normal liver architecture to structurally abnormal nodules known as
regenerative nodules.

Laparoscopic view of cirrhotic liver

BMJ Best Practice
 ETIOLOGY
 Alcohol  Genetic
 Chronic viral hepatitis (B or C)  Haemochromatosis
 Non-alcoholic fatty liver disease  Wilsons’s disease
 Immune  α – antitrypsin deficiency
 Primary sclerosing cholangitis  Cryptogenic (unknown – 15%)
 Autoimmune liver disease  Chronic venous outflow
obstruction
 Biliary  Veno-occlusive disease
 Primary biliary  Budd-Chiari syndrome
cholangitis(PBC)
 Secondary biliary cirrhosis
 Cystic fibrosis

Davidson’s 21st ed
PATHOGENESIS

Davidson’s 21st ed
 CLINICAL FEATURES
 Constitutional symptoms such as fatigue, weakness, and weight loss.
 Hepatomegaly
 Jaundice
 Ascites
 Circulatory changes: spider naevi, palmar erythema
 Endocrine changes: loss of libido, hair loss
 men: gynaecomastia, testicular atrophy, impotence
 women: breast atrophy, irregular menses, amenorrhea
 Haemorrhagic tendencies: bruises, purpura, epistaxis
 Portal hypertension: splenomegaly, collateral vessels, variceal bleeding,
ascites
 Hepatic encephalopathy
 Other features: pigmentation, digital clubbing, Duypuytren's contracture
INVESTIGATIONS

INVESTIGATIONS RESULTS
Liver function test ↔ or ↑bilirubin, also increased in acute
↑AST, ↑ALT, ↑ALP inflammation
↓albumin
Full blood count ↓WCC & ↓platelet hypersplenism
Coagulation profile ↑PT/INR
Hepatitis serology HBV, HCV
Immunoglobulins ↑IgA (alcoholic liver disease)
↑IgG (autoimmune hepatitis)
↑IgM (PBC)
Autoantibodies ANA, AMA, SMA

α-fetoprotein ↑ in 50-80% of HCC

Iron studies ↑ferritin, ↑iron, ↓TIBC >1mg/L ferritin suggestive

of haemochromatosis
IMAGING
Abdomen USG + • small liver/hepatomegaly, splenomegaly
duplex • focal lesion, hepatic vein thrombus,
reverse flow of portal vein
• ascites

PATHOLOGY
Liver biopsy confirms the clinical diagnosis (not routinely
done)
Peritoneal tap Diagnosis & therapeutic
For culture & sensitivity (neutrophils >250/mm³
indicates SBP)
 MANAGEMENT

 Treatment of underlying chronic liver disease and

prevention of superimposed hepatic insult
 Monitor complications
 Portal hypertension causing ascites (further complicated
by spontaneous bacterial peritonitis)
 Gastro-oesophageal varices
 Hepatic encephalopathy
 Hepatorenal syndrome
 Hepatocellular carcinoma

BMJ Best Practice, Davidson’s 21st ed

 Hepatic encephalopathy

 Syndrome of altered consciousness and neuropsychiatric

disturbances in patient with severe liver failure.
 Pathophysiology:
 Portosystemic shunting and hepatocellular dysfunction causes build
up of ammonia which enters the circulation and passes the blood
brain barrier causing cerebral edema.
 Advanced neurological deficits: drowsiness and confusion,
which may be followed by unconsciousness or coma. Hyper-
reflexia, asterixis and clonus may be present.

BMJ Best Practice

 Treatment: identification and correction of reversible precipitating
factors and lactulose, alone or in combination with antibiotics such
as rifaximin.
 Avoid sedatives
 Lactulose: 30-50mL/8hrly with regular enemas to reduce the number
of nitrogen-forming gut bacteria; aim for 2-4 soft stools per day.
 Rifaximin: 400 mg orally 3 times daily; as addition or alternatives if
diarrhea.
 Chronic or refractory encephalopathy can consider for liver
transplant.
Hepatorenal syndrome

 Development of renal failure in patients with severe liver

disease (acute or chronic) in the absence of any other
identifiable cause of renal pathology.
 There are 2 types.
 Type 1: rapidly progressive deterioration in circulatory and renal
function, often triggered by other deteriorating pathologies.
Treatment with Terlipressin, haemodialysis may be needed.
 Type 2: more steady deterioration. TIPSS is the best option.
Sodium restriction and diuretic therapy
for ascites
 Diagnostic paracentesis: cell count with differential, albumin,
and total protein should be measured.
 The serum-ascites albumin gradient (SAAG) should be
calculated: a SAAG of ≥1.1 with low ascitic fluid total protein is
consistent with portal HTN secondary to cirrhosis.
 Dietary sodium restriction to <2 g/day
 Fluid restriction is not necessary unless the serum sodium is <125
mmol/L.
 Primary options: furosemide: 40 mg orally once daily, titrate as
needed every 3-5 days, maximum 160 mg/day and
spironolactone: 100 mg orally once daily, titrate as needed
every 3-5 days, maximum 400 mg/day
 Secondary options: furosemide: as above and amiloride: 10
mg orally once daily, titrate as needed every 3-5 days,
maximum 40 mg/day
 Liver transplantation
 Patients who develop complications of cirrhosis such as
hepatocellular carcinoma or signs of decompensation (ascites,
jaundice, variceal haemorrhage, portal systemic
encephalopathy, or hepatorenal syndrome) should be referred
for liver transplant evaluation without delay.
 A survival benefit from undergoing liver transplantation is seen
when the MELD score is ≥15.
PROGNOSIS
PORTAL HYPERTENSION
• ETIOLOGY
• PATHOGENESIS
• CLINICAL FEATURES
• COMPLICATIONS
• INVESTIGATIONS
• MANAGEMENT
Portal Hypertension

The normal hepatic venous pressure gradient is 5

to 6 mmHg.
The clinical significant portal hypertension is
present when the gradient exceeds 10 mmHg.
The risk of variceal bleeding increases beyond
the gradient of 12 mmHg.
At least 90% of the cases of portal hypertension
in adults is caused by cirrhosis.
Causes of Portal
Hypertension
PATHOPHYSIOLOGY

Increased portal vascular resistance.

 Gradual reduction in the flow of portal blood to the liver
 Development of collateral vessels
 Portal blood to bypass the liver and enter the systemic
circulation directly.
 Portosystemic shunting occurs
 Gastrointestinal tract (distal esophagus, stomach and rectum)
 Anterior abdominal wall
 Renal, lumbar, ovarian and testicular vasculature.
 Stomal varices (site of ileostomy)
Complications

 Variceal bleeding (esophageal and gastric)

 Congestive gastropathy
 Hypersplenism
 Ascites
 Iron deficiency anemia
 Renal failure
 Hepatic encephalopathy
Oesophageal Varices
Oesophageal varices

 Dilated collateral blood vessels that develop as a complication of

portal hypertension, usually in the setting of cirrhosis.
 Development of varices and their progression from small to large
each occur at a rate of approximately 7% per year.
The main factors associated with development of varices and
progression from small to large varices:
 hepatic vein pressure gradient (HVPG) >10 mmHg
 decompensated cirrhosis (Child-Pugh B/C)
 alcoholic cirrhosis
 Presence of red wale marks
 Symptoms and signs

 presence of risk factors • spider naevi

for variceal bleeding
• caput medusa
 cirrhosis
• jaundice
 more severe liver disease
 alcohol abuse • encephalopathy
 hepatitis B or C infection • haematemesis
 HIV co-infection
• melaena
 ascites
• Splenomegaly
IMAGING
Ultrasonography Features of portal hypertension
Endoscopy Presence of gastro-oesophageal
varices
CT & MRI angiography Extent of portal vein clot & to identify
hepatic vein patency
Management

Reducing the hepatic venous pressure gradient, or on

endoscopic ligation or sclerotherapy of varices. The
decision of the type of the therapy depends primarily on
risk stratification of patients.
PRIMARY PROPHYLAXIS (BEFORE
BLEEDING)
 Aimed at reducing portal pressure and consequently intravariceal
pressure
 A. Pharmacotherapy : drugs used are non selective B-blockers
(propranolol) alone or in combination with isosorbide
mononitrate
The dose of B-blocker is titrated to maintain heart rate around
55 beats/min or reducing by 25% from baseline rate.
 B. Endoscopic therapy : Endotherapy
Endoscopic band ligation of varices is better than
sclerotherapy.
Indicated in patients who do not tolerate B-blockers and
varices which are large and associated with red wale sign
 Screening endoscopy 1-2 years indicated for patients with small
varices on initial endoscopy.
MANAGEMENT OF ACUTE VARICEAL
BLEEDING
General resuscitation
• Hospitalisation preferably in an intensive care unit,
elevation of foot end of the bed to increase venous
return
• IV cannulation or a venous cut down and replacement
of fluid till blood is ready.
• Blood transfusion

Short term prophylactic antibiotics for 7 days to

prevent severe bacterial infections.
 Pharmacotherapy for variceal
bleeding
1. Vasopressin – causing vasoconstriction, it decreases the
blood flow to the varices and reduces bleeding in about
50% patients
2. Somatostatin – very effective and has no side effects.
However, it is costly
3. Terlipressin – has long half life. They act by producing
splanchnic vasoconstriction. They decrease the portal
pressure. Once started, they have to be continued for 2-5
days. Once bleeding stops, the varices are treated with
endotherapy to prevent rebleeding
4. Octreotide – lower portal pressure and prevent re-bleeding
5. Metochlopramide arrest bleeding by constricting gastro-
oesophageal spinchter
Endoscopic treatment
Endoscopic variceal ligation
Endoscopic injection sclerotherapy (polidocanol,
ethanolamine)
Balloon tamponade
esophageal variceal bleeding uncontrolled by
endoscopic/pharmacologic treatment.
eg; Minnesota tube, Sengstaken-Blakemore tube, Linton-
Nachlas tube)
employed only in patients with massive bleeding &
temporizing measure
Transjugular intrahepatic portosystemic shunt
indicated as rescue therapy
SECONDARY PROPHYLAXIS
(PREVENT RE-BLEEDING)

Pharmacological therapy
Non-selective Beta blocker recommended
Endoscopic therapy
endoscopic variceal ligation superceded
sclerotherapy
Combination Pharmacological and Endoscopic
Therapy
Surgical