Download Liver Cirrhosis

Faculty of Pharmacy- Clinical Pharmacy Program level 5 - Spring 2016
Gastroenterology
Third Lecture: Cirrhosis & Portal Hypertension
Prof.Dr. Hasan El-Asklany
Professor of internal medicine, Gastroenterology & Hepatology
Faculty of medicine Mansoura University
Liver Cirrhosis

Definition: It is diffuse irreversible chronic liver disease results from necrosis of
hepatocytes followed by fibrous tissue deposition and formation of regenerating nodules
with loss of hepatic architecture.

Pathologically:
o A chronic liver disease characterized by:
1- Degeneration of liver cells.
2- Excessive fibrosis.
3- Formation of regenerating nodules( micronodular /
macronodular ).
4- Distortion of the hepatic architecture.
o Cirrhosis pathophysiology: Long standing injury to the liver lead to inflammation,
necrosis and eventually fibrosis (initiated by activation of stellate cells).
o These liver injuries e.g. (virus, alcohol, .... ) stimulate kupffer cells to release
cytokines, stimulate ito (stellate) cells , excessive release and deposition of collagen
fibers loss of hepatic architecture (cirrhosis).
Causes of Liver Cirrhosis:
I. Bilharzial (Mixed Cirrhosis)

II. Portal: The main pathological changes are in the portal tract:
12345-
Idiopathic “Cryptogenic”.
Alcoholic.
Auto-immune hepatitis.
Post-hepatitis.
Metabolic: Hemochromatosis & Wilson's disease.
III.Cardiac (Liver congestion due to cardiac causes):
1. R.S.H.F.
2. Pericardial diseases
3. Tricuspid diseases.
4. I.V.C. thrombosis.
5. Budd-Chiari syndrome.
6. Veno-occlusive disease
IV. Biliary:
A. Primary: Due to intrahepatic biliary obstruction of unknown cause. Which is
supposed to be due to an autoimmune disorder. It usually affects middle aged
females.
B. Secondary:
Other causes of cholestasis (intra or extra hepatic).

Clinical Presentation:
A. Compensated cirrhosis:
• No symptoms OR Nonspecific symptoms: vague right upper quadrant
pain, fever, nausea, vomiting, diarrhea, anorexia & malaise.
• The case is discovered accidentally on physical examination.
B. Decompensated cirrhosis: may present with one of the following:
• Liver cell failure& hepatic encephalopathy.
• Portal hypertension.
• Combination of them.
Clinically: Cirrhotic liver = sharp edge & firm in consistency.

Investigations:

1- Liver function tests: show pattern of cirrhosis in cases of liver cell-failure.
2- Investigations for portal hypertension: To assess the presence & degree of portal
hypertension.
3- Liver biopsy: It shows the aetiology.
4- Special investigations to detect the cause.
A. Lab findings:
The following findings are typical in cirrhosis:
o Aminotransferases - AST and ALT: are moderately elevated, with AST > ALT.
However, normal aminotransferases do not preclude cirrhosis.
o Alkaline phosphatase: slightly elevated but less than 2-3 times the upper limit of
normal.
o Bilirubin: Levels normal when compensated but may elevate as cirrhosis
progresses.
o Albumin levels fall as the synthetic function of the liver declines with
worsening cirrhosis since albumin is exclusively synthesized in the liver
o Leukopenia and Thrombocytopenia - due to splenomegaly with splenic
margination.
o Coagulation defects - the liver produces most of the coagulation factors and thus
coagulopathy correlates with worsening liver disease. Prothrombin
time increases since the liver synthesizes clotting factors.
o Other laboratory studies performed for diagnosis the cause of cirrhosis include:
• Serology for hepatitis viruses & autoantibodies
• Immunoglobulin levels (IgG, IgM, IgA) - these immunoglobins are nonspecific but may help in distinguishing various causes
• Ferritin and transferrin saturation: markers of iron overload as in
hemochromatosis,
• copper and ceruloplasmin: markers of copper overload as in Wilson's disease
• Alpha 1-antitrypsin
B. Imaging
o Ultrasound is routinely used in the evaluation of cirrhosis. It may show:
• a small and nodular liver in advanced cirrhosis .
• An enlarged spleen (splenomegaly) is suggestive of cirrhosis with portal
hypertension .
• screen for hepatocellular carcinoma,
• portal hypertension
• Budd-Chiari syndrome (by assessing flow in the hepatic vein).
o CT of the abdomen
o Endoscopy
Gastroscopy (endoscopic examination of the esophagus, stomach,
and duodenum) is performed in patients with established cirrhosis to exclude
the possibility of esophageal varices. If these are found, prophylactic local
therapy may be applied (sclerotherapy or banding) and beta blocker treatment
may be commenced.
C. Biopsy:
This may be necessary to confirm the severity and type of liver disease.

Management:
o Generally, liver damage from cirrhosis cannot be reversed, but treatment could stop or
delay further progression and reduce complications. A healthy diet is encouraged, as
cirrhosis may be an energy-consuming process.
o Treatment of the underlying cause:
• Alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from
alcohol.
•
Treatment for hepatitis-related cirrhosis involves medications used to treat the
different types of hepatitis, such as interferon for viral hepatitis and
corticosteroids for autoimmune hepatitis.
• Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is
treated with chelation therapy (for example, penicillamine) to remove the copper.
o Preventing further liver damage
• Regardless of underlying cause of cirrhosis, alcohol and paracetamol, as well as
other potentially damaging substances, are discouraged. Vaccination of
susceptible patients should be considered for Hepatitis A and Hepatitis B.
•
Transplantation: If complications cannot be controlled or when the liver ceases
functioning, liver transplantation is necessary. Survival from liver transplantation
has been improving over the 1990s, and the five-year survival rate is now around
80%.
Portal Hypertension

Definition:
o High blood pressure in the hepatic portal system, which is composed of the
portal vein and its branches and tributaries.
o Portal hypertension is defined as elevation of portal venous pressure above 7
mmHg

Pathophysiology of portal hypertension
o Factors induce liver damage and inflammation (often via activation of local and
recruited macrophages) leads to activation of hepatic stellate cells and
proliferation of myofibroblasts.
o Their fibrogenetic and contractile properties are the main causes of increases in
intrahepatic resistance and portal venous congestion inducing portal hypertension.
o Patients with cirrhosis have a hyperdynamic circulation due to the release of nitric
oxide and glucagon, which leads to peripheral and splanchnic vasodilatation.

Causes:
Portal hypertension can be classified according to the site of obstruction:
I. Prehepatic :
o Portal Vein thrombosis
o Splenic Vein Thrombosis
II. Hepatic :
o Presinusoidal:
• Schistosomiasis
o Sinusoidal
• Cirrhosis
o Postsinusoidal:
• Veno-occlusive Disease
III. Posthepatic :
o Budd Chiari syndrome
o Inferior vena caval webs
o Cardiac Causes :
• Restrictive Cardiomyopathy
• Constrictive Pericarditis

Clinical feature of Portal Hypertension:
o variceal haemorrhage
o ascites
o Splenomegaly & hypersplenism

Investigations for portal hypertension:
o Duplex Doppler ultrasonography of the liver and upper abdomen
o Computed tomography (CT) scanning and/or magnetic resonance imaging (MRI):
Can be used when ultrasonographic findings are inconclusive
o Bleeding scan or angiography: Used when bleeding is obscure and the source is
unclear
o Procedures:
• Liver biopsy and histologic examination
• Hemodynamic measurement of the hepatic venous pressure gradient
(HVPG): A criterion standard for assessment of portal hypertension
• Upper GI endoscopy: standard for assessment of portal hypertension

Management of portal hypertension:
Treatment is directed at the cause of portal hypertension and its complications
especially gastroesophageal variceal hemorrhage
Gastroesophageal variceal hemorrhage
o Gastroesophageal variceal hemorrhage is the most dramatic and lethal complication of
portal hypertension often presents with hematemesis and/or melena. Patients may also
present with complications, including chest pain, syncope and shock
o Treatment strategies of gastroesophageal variceal hemorrhage:
• Resuscitation, supportive therapy, balloon tamponade
• Pharmacologic therapy
• Endoscopic therapy
• Decompressive therapy (surgical)
• Liver transplantation
1. Resuscitation, supportive therapy:
o
o
o
o
o
o
o
Airway, breathing, and circulation evaluation
Nasogastric tube placement with hemodynamically significant upper GI bleeding
Nothing by mouth; establish 2 large-bore venous accesses
Volume resuscitation, with or without blood product transfusion
ICU monitoring
Sengstaken-Blakemore tube
Prevention of complications (eg, prophylactic antibiotics)
2. Pharmacologic therapy of gastroesophageal variceal hemorrhage
o
Administration of vasoconstrictors [octreotide & vasopressin] to decreases the
rate of bleeding+ Enhances the endoscopic ability to visualize the site of
bleeding
 Somatostatin = Octreotide: Initial drug of choice for acute variceal
bleeding: decrease splanchnic blood flow indirectly; fewer side effects.
Dose: intravenous infusion at 250 μg/hr.
 Vasopressin (Terlipressin): potent splanchnic vasoconstrictor; decreases
portal venous blood flow and pressure. Dose of terlipressin: 2mg every 4
hrly for 2-5 days .
3. Endoscopic therapy of gastroesophageal variceal hemorrhage:
o
o
Endoscopic Sclerotherapy: complications occur in 10-30% and include fever,
retrosternal chest pain, dysphagia, perforation
Endoscopic variceal ligation: becoming the initial intervention of choice;
success rates range from 80-100%
4. Balloon-tube tamponade:
o
o
The Sengstaken-Blakemore tube stops hemorrhage in approximately 80% of
patients bleeding from esophageal varices.
A trial of balloon tamponade should be considered, however, in an
exsanguinating patient with probable variceal bleeding in whom endoscopy is
not immediately available and vasopressin has not slowed the hemorrhage.
5. Transjugular intrahepatic portosystemic shunt (TIPS)
o Secondary prophylaxis for gastroesophageal variceal hemorrhage:




Nonselective beta-blockers
Endoscopic therapy (EVL, treatment of choice; endoscopic sclerotherapy)
Combination EVL and pharmacotherapy
Surgery has no role in primary prophylaxis. Consider procedures, such as the
following, for the prevention of rebleeding when pharmacologic and/or
endoscopic therapy have failed:
1. Portosystemic shunts& TIPS
2. Devascularization procedures
3. Orthotopic liver transplantation: Treatment of choice for advanced liver disease