These slides describe the pathophysiology and the management of patients with liver cirrhosis and portal hypertension. The slides are at the level of post-graduate students

1. 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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2. 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.
2
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.

3. Prognosis of patients with deconpensated
cirrhosis is dismail
and has not changed in the last 30 years

4. Liver cirrhosis
4

5. 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.

6. 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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7. Portal hypertension
In liver cirrhosis, portal hypertension is caused
primarily by increased intrahepatic resistance caused
by liver fibrosis at the perisinusoidal level

8. Portal hypertension
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9. Portal hypertension
porto-caval anastomosis: 3 common sites
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10. 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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11. 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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12. 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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13. 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
13

14. 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 14

15. Portal hypertension
Imaging identification of porto-caval
anastomosis
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16. Portal hypertension
Imaging identification of porto-caval
anastomosis
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17. Portal hypertension
Imaging identification of porto-caval
anastomosis
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18. Portal hypertension: diagnosis
Esophageal, gastric and rectal
varices should be identified by
endoscopy
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19. Portal hypertension:
porto-caval anastomosis rectal
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20. Portal hypertension:
esophageal varices
F0
F1
F2
F3
F0
F1
F2
F3
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Endoscopy grading
F0
F1
F2
F3

21. Gastric varices
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22. Portal hypertension:
gastric varices: ecoendoscopy

23. Portal hypertensive gastropathy
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24. 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)

26. Prophylaxis and treatment of
variceal bleeding
Emmanuel A Tsochatzis, Jaime Bosch, Andrew K Burroughs. Liver cirrhosis. Lancet 2014; 383: 1749
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27. 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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28. Catecholamine receptors and
mesenteric circulation
ISA= intrinsic sympaticometic activty (partial agonist)- vasodilation

29. 29
Β-blockers for primary prophylaxis

30. 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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31. 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

32. 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
32

33. 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.

34. 34
Β-blockers for primary prophylaxis

35. Primary prophylaxis

36. Portal hypertension
Emmanuel A Tsochatzis, Jaime Bosch, Andrew K Burroughs. Liver cirrhosis. Lancet 2014; 383: 1749
36

37. Esophageal bleeding : why
esophageal varices bleed
37
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.

38. Esophageal bleeding : mortality
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39. 39
Acute varicael bleeding

40. 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.

41. Acute variceal bleeding (Treatment 1c)
41
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.

42. Acute variceal bleeding:
blood transfusion
N Engl J Med 2013; 368:11-21

43. 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 .

44. 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

45. Acute variceal bleeding (Treatment 2)
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SST-R
VPR1

46. 46
Acute variceal bleeding

47. 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.
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48. Acute variceal bleeding (Treatment 3)
Endoscopy
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49. Treatment 4
Endoscopic band ligation
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50. 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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51. Acute variceal bleeding (Treatment 5)
Balloon tamponade
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52. 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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53. TIPS
TIPS transjugular porto-hepatic shunt 53

54. 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–Pughclass 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

58. Portal hypertension
Emmanuel A Tsochatzis, Jaime Bosch, Andrew K Burroughs. Liver cirrhosis. Lancet 2014; 383: 1749
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59. Secondary prophylaxis

60. 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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61. Secondary prophylaxis
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Gastric varices

63. Portal hypertensive gastropathy

64. Portal hypertensive gastropathy

66. Portal hypertension
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