Review

Portal hypertensive bleeding www.cardiconcept.com

Primary prophylaxis

• Half of patients with liver cirrhosis have EV

– 90% of patient in life time (5%/year)

• Variceal bleeding mortality rate 7-15%

Every patient with newly diagnosed liver

cirrhosis should underwent upper endoscopy for screening of esophageal

and/or gastric varices

Risk factor of variceal bleeding

Diameter of varix > 5 mm Rx < 5mm F/U

Presence of red wale sign (Varices of Varix)

Impaired Liver function

Hepatic Venous Pressure Gradient

1 Year Mortality 10-15% (Stage A) , 25-30% (Stage B) , 70-80% (Stage C)

Child Turcotte Pugh (CTP)

Clinical and Lab Criteria Points*

1 2 3

Encephalopathy None Mild to moderate (grade 1 or 2)

Severe (grade 3-4)

Ascites None Mild to moderate Severe

Bilirubin (mg/dL) <2 2-3 >3

Albumin (g/dL) >3.5 2.8-3.5 <2.8

Prothrombin time Seconds prolonged INR

<4

<1.7

4-6

1.7-2.3

>6

>2.3

Child Turcotted Pugh Class obtained by adding score for each parameter (total points) Class A = 5 to 6 points (least severe liver disease) Class B = 7 to 9 points (moderately severe liver disease) Class C = 10 to 15 points (most severe liver disease)

Progression of disease

2014 WGO Practice Guideline Esophageal Varices

8%

8%

5-15%

EGD q 2-3 yr

EGD q 1-2 yr

Rx

Guideline for diagnosing esophageal varices

Primary Prophylaxis for EV bleed

• Non-selective betablocker w/wo ISMN :Propranolol ,Nadolol (Target HR 50-55/min)

– Beta2 inhibition (splanchnic vasoconstriction)

– Beta1 inhibition (decrease cardiac output)

• Slow Progression – From no EV to small EV Not effective

– From Small to large EV Slow progression

– Reduce risk of bleeding Effective ( RRR 50% )

• (size > 5 mm , Red wale sign)

– Reduce HVPG 20% from baseline or < 12 mmHg achieved

Predictor of EV bleeding Dose of betablocker

Up to 320 mg/day Up to 240 mg /day

Primary Prophylaxis for EV bleed Carvedilol

carvedilol caused a more pronounced decrease in HVPG than propranolol (A), a significantly greater proportion of patients exhibiting a good hemodynamic response (B)."

6.25-12.5 mg/day

Primary Prophylaxis for EV bleed Endoscopic Variceal Band Ligation

Efficacy Betablocker = EVL

(Batablocker easier)

Cochrane Database Syst Rev. 2012 Aug 15;(8)

Primary prevention

Non-selective Betablocker As 1st line

EVL As 2nd line (if can’t tolerate betablocker)

Sclerotherapy Not Recommend in primary prophylaxis

EV bleeding

EV bleeding

• 40% of patients die from exsanguinating bleeding.

• Most deaths are caused by complications of bleeding like liver failure, infections and hepatorenal syndrome

• Risk factors for an adverse course – the degree of liver dysfunction – Creatinine – hypovolemic shock – active bleeding on endoscopy – presence of hepatocellular carcinoma

Control of bleeding

• Band ligation

• Terlipressin – induces splanchnic vasoconstriction

– portal pressure mortality rate.

• Somatostatin – reduce the amount of blood transfused

• balloon tamponade – usually successful but balloons should not be inflated

for more than 12 hours (mucosal necrosis)

Terlipressin

A/E : Hyponatremia

Achieves control of bleeding in 75%-80% Dose

• 2 mg every 4 h for the first 48 h and continued for prevention of early rebleeding

• 1 mg every 4 h for up to 5 d(Bevano V guidelines)

Efficacy : Terlipressin > Vasopressin + Nitrate Liver Study Group of V. Cervello Hospital. J Hepatol. 1994;20:206–212.

Somatostatin

• initial bolus of 250 μg followed by a 250 to 500 μg/h continuous infusion

– until a bleed-free period of 24 h is achieved

Octreotide is a synthetic analogue of somatostatin with longer half-life

• initial bolus of 25 μg, followed by an infusion of 25 to 50 μg/h

Efficacy : Somatostatin = Vasopressin Octreotide no superiority of Terlipressin

A/E : Hypoglycemia , abdominal craps (Somatostatin & Octreotide)

Endoscopic therapy : Sclerosing agents

• 80%-90% of acute variceal bleeding episodes are successfully controlled by endoscopic therapy

• Sclerosing agents – Ethoxysklerol is injected next to - not into - the varix.

– cyanoacrylate is injected directly into the varix

(2nd line when EVL failed)

– ethoxysklerol or cyanoacrylate less common use.

causes local inflammation and scaring

causing immediate obliteration of the vessel.

Efficacy :Sclerosing agents = Balloon Tamponade

Endoscopic therapy : EVL

Complication : EVL < Sclerosing agent Mortality : EVL < Sclerosing agent Cost : EVL > Sclerosing agent

Balloon Temponade

Prefer in gastric varices

Deflating of the balloon after six hours

Self-expandable metal stents (SEMS)

• controls bleeding by compression of the bleeding varices.

• can be left in place for up to two weeks

• reserved for patients with bleeding refractory to medical and endoscopic treatment.

• safe bridging procedure (not definite Rx)

SX-Ella Danis Stent

Transjugular intrahepatic portosystemic stent shunts (TIPS)

(depend on local resources)

decompressing the portal circulation into the hepatic vein via a stent inserted percutaneously through the liver via the internal jugular vein.

[consider in 1) child B with bleeding 2) child C with child < 10-13 points Or 3) despite combine VBL and NSBB or monotherapy who intolerance to betablocker)]

The rate of recurrent bleeding after 1 year is

8%-18%

Rebleeding

Survival benefit

Hepatic encephalopathy

Complication of TIPS

• (a) volume overload as a result of portal shunting into the right atrium, which can induce heart failure

• (b) bypassing the portal circulation resulting in ischemic liver injury and, rarely, liver failure

• (c) worsening of encephalopathy grade (the most common complication)

The use of PTFE-covered prostheses improves TIPS patency decreases the number of clinical relapses and reinterventions without increasing the risk of encephalopathy.

Shunt dysfunction P = 0.005

Survival P= 0.17

อารมณ์เดียวกบั DES VS BMS ของ cardio เลย ลด restenosis ไมล่ด mortality

Portocarval surgery

• VS no active Rx or sclerotherapy – Better bleeding control – Increase hepatic encephalopathy – No survival benefit

• VS sclerotherapy – Better bleeding control – Improve survival

• VS bare TIPS

– similar bleeding control – Lower encephalopathy – Lower failure rate in surgery group – Improve survival rate

• VS PTFE-covered prostheses

– ???? Unknown

H-graft

Side to side

Coagulation abnormalities

• fresh frozen plasma (FFP)

– correct abnormal partial thromboplastin time (PTT)

– INR or aPTT >1.5X

– Fibrinogen < 1 g/L

• platelets targeted

– correct platelet count.

– Active bleeding and Platelet < 5 x 109

Antibiotic prophylaxis

• 35-60% of cirrhotic patients with bleeding varices have documented infection over the following 2 weeks. (1)

• Reduce the incidence of infection (1,2)

– It has been proposed that infection is the precipitant to an acute increase in portal pressure that may trigger bleeding. (3)

• Reduce short term mortality rate (1,2)

• Reduce rebleeding (4)

(1) A meta-analysis. Hepatology. 1999; 29( 6): 1655– 1661.

(2) Aliment Pharmacol Ther. 2011; 34( 5): 509– 518. (3) Lancet. 1999; 353( 9147): 139– 142.

(4) Hepatology. 2004;39:746–753.

Antibiotic prophylaxis

• Low risk

– Fluoroquinolone

• Higher risk

– Ceftriaxone

Ascites, Encephalopathy, Jaundice, Malnutrition or

previous therapy with quinolones

Transfusion of blood

Hb level 7-8 g/dl

(Higher increase portal pressure)

Failure to control active bleeding

Fresh haematemesis or NG aspiration of >/= 100 ml of fresh blood >/2 hr after specific drug Rx or therapeutic endoscopy

Hypovolemic shock

3 g/dl in hemoglobin within 24 hr any period

Balloon Temponade until endoscopic Rx TIPS or surgery depend on local resources and expertise

Mx

Secondary prophylaxis

• Betablocker : (Propranolol , Nadolol) w/wo nitrates

– Carvedilol As an alternative

• Endoscopic therapy

– VBL (prefer) > Sclerotherapy

VBL alone in patients with contraindications for beta-blocker therapy or in patients who suffer from side effects of beta-blocker therapy.

Patients who tolerate drug treatment well should be placed on a combination therapy.

Reduce rebleed No survival benefit

A/E : dizziness, headache

Summary Guideline for diagnosing esophageal varices

Patients with cirrhosis but no varices.

Patients with cirrhosis with small varices but no Hx of hemorrhage

Patients with cirrhosis with large varices but no Hx of hemorrhage

Summary

Summary Considerations in the diagnosis, prevention, and management

of esophageal varices and variceal hemorrhage

Summary Patients with cirrhosis and acute variceal hemorrhage

Summary Pharmacotherapy

Summary Patients with cirrhosis who have recovered

from acute variceal hemorrhage

Summary Recommendations for first-line management.

Summary Cascade for the treatment of acute esophageal

variceal hemorrhage.

GASTRIC VARICES AND HYPERTENSIVE GASTROPATHY

Sarin Classification

5-10% of portal hyprtensive bleeding Bleed from GV

4% recurrent bleeding in 1st year

9% in 3rd year

53% Recur in IGV-1

53% recur

Bleeding Rx as esophageal varices , EVL

Bleeding Rx Cyanoacylate

injection

Isolated gastric varices

• If only isolated gastric varices are present, the exclusion of portal or splenic vein thrombosis as the underlying cause is mandatory.

Splenectomy or Splenic artery embolization in all patients

with splenic vein thrombosis

Prophylaxis

• Primary prophylaxis

– Almost no data is available whether medical treatment for the primary prophylaxis of bleeding from gastric varices is effective.

• Secondary prophylaxis

– TIPS (more effective than cyanoacrylate)

– Cyanoacrylate

– Non-selective betablocker with nitrates (not effective)

Treatment of acute bleeding

• Therapy with terlipressin or somatostatin is recommend (Lacking of controlled studies)

• The endoscopic treatment of choice is injection with cyanoacrylate

• TIPS insertion is highly effective with control of bleeding

PORTAL HYPERTENSIVE GASTROPATHY

• Typical signs are mosaic, also called

“snakeskin”, pattern of erythema.

The incidence of portal hypertensive gastropathy is around 80% in patients with liver cirrhosis

incidence of less than 3% in three years.

Acute bleeding

• Terlipressin – effective in acute bleeding from portal hypertensive

gastropathy

• Propranolol – Lack of data (1 arm study no control group)

• TIPS or surgical shunt

Hosking SW, Kennedy HJ, Seddon I, Triger DR. The role of propranolol in congestive gastropathy of portal hypertension. Hepatology 1987; 7: 437-441

Zhou Y, Qiao L, Wu J, Hu H, Xu C. Comparison of the efficacy of octreotide, vasopressin, and omeprazole in the control of acute bleeding in patients with portal hypertensive gastropathy: a controlled study. J Gastroenterol Hepatol 2002; 17: 973-979

Secondary prophylaxis of bleeding from portal hypertensive gastropathy,

• Propranolol

Pérez-Ayuso RM, Piqué JM, Bosch J, Panés J, González A, Pérez R, Rigau J, Quintero E, Valderrama R, Viver J. Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis. Lancet 1991; 337: 1431-1434

Gastric antral vascular ectasia syndrome (GAVE)

4% of non-variceal upper GI-bleeding

Typical appearance of a “watermelon stomach” Or “honeycomb stomach”

The pathogenesis of GAVE is not well known. Hypothesis for the pathogenesis include mechanical stress , humoural and autoimmune factors.

Medical Treatment

• estrogen-progesterone to be highly effective in GAVE related bleeding (2 Small studies)

– increased risk for breast and endometrial cancer

• Octreotide

van Cutsem E, Rutgeerts P, Vantrappen G. Treatment of bleeding gastrointestinal vascular malformations with oestrogen-progesterone. Lancet 1990; 335: 953-955 Manning RJ. Estrogen/progesterone treatment of diffuse antral vascular ectasia. Am J Gastroenterol 1995; 90: 154-156

Nardone G, Rocco A, Balzano T, Budillon G. The efficacy of octreotide therapy in chronic bleeding due to vascular abnormalities of the gastrointestinal tract. Aliment Pharmacol Ther 1999; 13: 1429-1436

Endoscopic treatment

• Argon plasma coagulation therapy.

• Laser photoablation

• Endoscopic treatment using (Nd:YAG) laser

Disadvantages high costs and the need for a long training period

Efficacy 90-100%

TIPS and surgery

• TIPS

– not effective in chronic bleeding from GAVE

• Surgery (antrectomy)

– efficient in bleeding from GAVE

– but bears a significant morbidity and mortality

ECTOPIC VARICES

dilated porto-venous vessels of the gastrointestinal mucosa that are located outside of the esophagus or the stomach.

origin from preexisting small veins of the gastrointestinal mucosa that are portosystemic collaterals between the portal vein and the inferior vena cava.

Diagnosis

• 1%-5% of all gastrointestinal bleeding episodes in patients with portal hypertension

• Endoscopy and Colonoscopy

• nuclear magnetic resonance (NMR) with NMR-angiography

Therapy

• Sclerotherapy/injection therapy

– Sclerotherapy with ethoxysklerol as well as injection of the varix with cyanoacrylate are feasible

• Band ligation may be useful but Rebleed

• Surgery and TIPS

– Porta-caval shunts are effective therapy measures in recurrent bleeding from ectopic varices[

Reference