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Università di Perugia
Scuola di Medicina CLMMC -Patologia sistematica V
Gastroenterologia
Prof. Stefano Fiorucci
Portal hypertension and gastrointestinal bleeding
ADE 28/11/2017 Aula 7
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Liver cirrhosis Cirrhosis could be classified clinically in
compensated cirrhosis and decompensated cirrhosis.
Patients who have developed complications of their liver disease and have become decompensated should be considered for liver
transplantation.
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Source: D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217-31.
Prognosis of patients with deconpensated cirrhosis is dismail
and has not changed in the last 30 years
Liver cirrhosis
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Liver cirrhosis
Compensated Decompensated liver cirrhosis liver cirrhosis
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Chronic liver disease
Portal hypertension
Cirrhosis could be classified clinically in
compensated cirrhosis and decompensated cirrhosis.
Portal hypertension
Portal hypertension is defined as the elevation of the hepatic venous pressure gradient (HVPG) to >5 mmHg.
Portal hypertension is caused by a combination of two simultaneously occurring
hemodynamic processes: (1) increased intrahepatic resistance to the passage of blood flow through the
liver due to fibrosis and regenerative nodules, and (2) increased splanchnic blood flow secondary to vasodilatation within the
splanchnic vascular bed.
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Portal hypertension
In liver cirrhosis, portal hypertension is caused primarily by increased intrahepatic resistance caused
by liver fibrosis at the perisinusoidal level
Portal hypertension
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Portal hypertension porto-caval anastomosis: 3 common sites
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Portal hypertension: diagnosis
• In patients with cirrhosis who are being followed chronically, the development of portal hypertension is usually revealed by the presence of:
1. splenomegaly
2. Hypersplenism (thrombocytopenia, GR, WBC);
3. development of ascites, encephalopathy and/or esophageal varices with or without bleeding.
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Portal hypertension
Diagnosis - Indirect measurement of portal pressure (HVPG)
- Imaging of liver and spleen and portal system and collateral circulation
Sonography
CT/angiography
- Detecting and grading varices in the GI tract
Endoscopy
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Portal hypertension Hepatic Venous Pressure Gradient
(HVPG)
Is the difference between the wedged (WHVP) and the free
hepatic venous pressures (FHVP).
HVPG represents the gradient between pressures in the portal
vein and the intra-abdominal portion of inferior vena cava.
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Portal hypertension
The normal HVPG value is between 1 to 5 mmHg.
Pressure higher than this defines the presence of portal hypertension, regardless of clinical evidence.
HVPG >or= 10 mmHg
(clinically significant portal hypertension)
is predictive of the development of complications of cirrhosis.
HVPG above 12 mmHg
is the threshold pressure for variceal rupture
HVPG above 20 mmHg
High risk of death
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Portal hypertension: diagnosis
• Abdominal imaging, either by sonography, CT or MRI can be helpful in demonstrating a nodular liver and in finding changes of portal hypertension with intraabdominal collateral circulation. These technique could give information on the main hemodynamic changes occurring in a individual patient butb have no prognostic implication
• Esophageal and rectal varices should be identified by endoscopy
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Portal hypertension Imaging identification of porto-caval
anastomosis
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Portal hypertension Imaging identification of porto-caval
anastomosis
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Portal hypertension Imaging identification of porto-caval
anastomosis
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Portal hypertension: diagnosis
Esophageal, gastric and rectal varices should be identified by
endoscopy
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Portal hypertension: porto-caval anastomosis rectal
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Portal hypertension: esophageal varices
F0 F1 F2 F3
F0 F1 F2 F3
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Endoscopy grading
F0 F1 F2 F3
Portal hypertension: gastric varices: ecoendoscopy
Portal hypertensive gastropathy
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Large varices are likely to bleed
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Esophageal varices evolves from small to large and correlates with the
Severity of cirrhosis (CHILD score)
Prophylaxis and treatment of variceal bleeding
Emmanuel A Tsochatzis, Jaime Bosch, Andrew K Burroughs. Liver cirrhosis. Lancet 2014; 383: 1749 26
Variceal Hemorrhage: Profilaxis of first bleeding- primary prophylaxis
• Primary prophylaxis requires routine screening by endoscopy of all patients with cirrhosis.
• Once varices that are at increased risk for bleeding are identified, then primary prophylaxis can be achieved either through:
• 1. nonselective beta blockers
• 2. endoscopic variceal band ligation (EVL).
• Numerous placebo-controlled clinical trials of either propranolol or nadolol have been reported in the literature. Carvediol has been used more recently
• Propanol dosing: up to maximal tolerated dose (systolic PA > 90 mmHg, heart rate > 50 bpm)
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Catecholamine receptors and mesenteric circulation
ISA= intrinsic sympaticometic activty (partial agonist)- vasodilation
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Β-blockers for primary prophylaxis
Variceal Hemorrhage: prophylaxis of first bleeding
Endoscopic variceal ligation (EVL or EBL) in patients with cirrhosis who are screened for portal hypertension and are
found to have large varices, it is recommended that they receive either beta blockade or primary prophylaxis with EVL.
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Primary prophylaxis of variceal bleeding in cirrhotic patients
Alimentary Pharmacology & Therapeutics pages 178-186, 28 JUN 2008 DOI: 10.1111/j.1365-2036.2008.03729.x
Variceal Hemorrhage: prophylaxis of first bleeding
• Patients treated with beta blockers have a lower risk of variceal hemorrhage than those treated with placebo over 1 and 2 years of follow-up.
• There is also a decrease in mortality related to variceal hemorrhage.
• Unfortunately, overall survival is not improved versus the endoscopy treatment
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Primary prophylaxis
EVL vs βBlockers
Current evidence suggests that either nonselective β-blockers or EVL are effective in the primary prophylaxis of variceal hemorrhage in patients with medium or large varices. The decision on which treatment to use should be based on local resources, expertise, and patient preference. EVL should be considered in patients who have contraindications to β-blockers or are intolerant of them due to side effects.
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Β-blockers for primary prophylaxis
Primary prophylaxis
Portal hypertension
Emmanuel A Tsochatzis, Jaime Bosch, Andrew K Burroughs. Liver cirrhosis. Lancet 2014; 383: 1749 36
Esophageal bleeding : why esophageal varices bleed
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Explosion hypothesis, that suggests that the main factor leading to rupture of the varices is the increased
hydrostatic pressure inside the varix and its ensuing consequences, increasing variceal size and decreasing the
thickness of its wall.
Esophageal bleeding : mortality
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Acute varicael bleeding
Acute variceal bleeding (Treatment 1b)
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Patients with suspected acute variceal bleeding require admission to an intensive care unit for resuscitation and
management.
Resuscitation is centered on the basic medical principles of establishing airway, breathing, and circulation.
Patients with active hematemesis or altered mental status due to hepatic encephalopathy should be intubated for airway protection to decrease the risk of aspiration, which is a significant cause of morbidity and mortality in patients.
Acute variceal bleeding (Treatment 1c)
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Patients with suspected acute variceal bleeding require admission to
an intensive care unit for resuscitation and management.
Volume resuscitation should be performed promptly to achieve hemodynamic stability and protect the function of vital organs such as the kidneys. The ideal fluid of choice for resuscitation is blood, but crystalloids may be used for immediate resuscitation until blood product becomes available. Blood transfusion should be performed conservatively to achieve a target hemoglobin level of 7–8 g/dL, (excessive blood volume restitution increases portal pressure And mortality).
Similarly, aggressive resuscitation with crystalloids should be avoided.
The target hemoglobin may be higher in patients with ischemic heart disease or rapid ongoing hemorrhage with hemodynamic instability.
Acute variceal bleeding: blood transfusion
N Engl J Med 2013; 368:11-21
Acute variceal bleeding (Treatment 1d)
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Transfusion of fresh frozen plasma or platelets can be considered in patients with significant coagulopathy or thrombocytopenia, but no formal studies have assessed this.
The recombinant factor VIIa in patients with advanced cirrhosis and active variceal bleeding did not show any differences in the rates of failure to control 24-h bleeding or failure to prevent rebleeding or death at day 5 compared to placebo .
Acute variceal bleeding (Treatment 1e)
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Antibiotic prophylaxis
Cirrhotic patients with upper gastrointestinal hemorrhage have
been shown to have a high prevalence of bacterial infections
including spontaneous bacterial peritonitis (SBP), bacteremia,
pneumonia, and urinary tract infections.
Studies have demonstrated that the presence of bacterial infection is an independent prognostic factor of the failure to control bleeding as well as early rebleeding in acute variceal hemorrhage.
The antibiotic of choice is norfloxacin 400 mg twice daily for 7 days
Acute variceal bleeding (Treatment 2)
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SST-R VPR1
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Acute variceal bleeding
Acute varicael bleeding (Treatment 3) Endoscopy
Endoscopic intervention is employed as first-line treatment to control bleeding acutely. Some endoscopists will use variceal injection therapy (sclerotherapy) as initial therapy, particularly when bleeding is vigorous. Variceal band ligation is used to control acute bleeding in over 90% of cases and should be repeated until obliteration of all varices is accomplished. 47
Acute variceal bleeding (Treatment 3) Endoscopy
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Acute variceal bleeding (Treatment 5) Balloon tamponade
• Balloon tamponade (Sengstaken-Blakemore tube or Minnesota tube) can be used in patients who cannot get endoscopic therapy immediately or who need stabilization prior to endoscopic therapy.
• Control of bleeding can be achieved in the vast majority of cases; however, bleeding recurs in the majority of patients if definitive endoscopic therapy has not been instituted.
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Acute variceal bleeding (Treatment 5) Balloon tamponade
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Acute variceal bleeding (Treatment 6) TIPS
• When esophageal varices extend into the proximal stomach, band ligation is less successful. In these situations, when bleeding continues from gastric varices, consideration for transjugular intrahepatic portosystemic shunt (TIPS) should be made.
• This technique creates a portosystemic shunt by a percutaneous approach using an expandable metal stent, to create a direct portocaval shunt.
• This offers an alternative to surgery for acute decompression of portal hypertension.
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TIPS
TIPS transjugular porto-hepatic shunt 53
Acute variceal bleeding (Treatment 6) TIPS
• Encephalopathy can occur in as many as 20% of patients after TIPS and is particularly problematic in elderly patients and in those patients with preexisting encephalopathy.
• TIPS should be reserved for those individuals who fail endoscopic or medical management or who are poor surgical risks.
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Surgical intervention is now rarely performed as salvage therapy for the control of acute variceal bleeding. Its use should be reserved for patients with Child–Pugh class A cirrhosis or patients with an anatomical preclusion to TIPS such as complete portal vein thrombosis. The options for surgical shunts include nonselective surgical shunts (portocaval (a and b) or mesocaval shunts (d) ) or the selective distal splenorenal shunt (c and f ). The distal splenorenal shunt is associated with lower rates of hepatic encephalopathy but requires more operating time which makes it less suitable as an emergency surgery [143].
Acute variceal bleeding (Treatment 7) Surgery
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Acute variceal bleeding (Treatment 8) Gastric varices
The data on the management of gastric variceal bleeding are much more limited than that for esophageal varices, due to the lack of large RCTs and the heterogeneity of studies which include patients with various types of gastric varices. Thus, the optimal strategy for management remains to be determined. Endoscopic variceal obturation (EVO) with tissue adhesives such as N-butyl-2-cyanoacrylate (Histoacryl) has emerged as the treatment of choice for acute gastric variceal bleeding. N-butyl-2-cyanoacrylate is a monomer in liquid form that polymerizes upon contact with blood, solidifying within the varix instantly and leading to hemostasis. In the majority of cases, the glue cast will extrude into the stomach lumen within weeks to months after injection . A large number of case series have established that N-butyl-2-cyanoacrylate is effective in achieving hemostasis in greater than 90% of patients with bleeding from gastric varices
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Acute variceal bleeding (Treatment 8) Summary
Portal hypertension
Emmanuel A Tsochatzis, Jaime Bosch, Andrew K Burroughs. Liver cirrhosis. Lancet 2014; 383: 1749 58
Secondary prophylaxis
Secondary prophylaxis • Once patients have had an acute bleed and have been managed successfully,
attention should be paid to preventing recurrent bleeding.
• This usually requires repeated variceal band ligation until varices are obliterated.
• Beta blockade may be of adjunctive benefit in patients who are having recurrent variceal band ligation; however, once varices have been obliterated, the need for beta blockade is lessened.
• Nonselective beta blockade may be helpful to prevent further bleeding from portal hypertensive gastropathy once varices have been obliterated.
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Secondary prophylaxis
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Gastric varices
Portal hypertensive gastropathy
Portal hypertensive gastropathy
Portal hypertension
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