LA Portal HTN.ppt - American College of...

Fredric D. Gordon, MD

Complications of Portal Hypertension: Complications of Portal Hypertension: What to Do?What to Do?What to Do?What to Do?

Fredric D. Gordon, MDFredric D. Gordon, MD

Medical Director of Liver TransplantationMedical Director of Liver Transplantation

Director of HepatologyDirector of Hepatology

LaheyLahey Hospital and Medical CenterHospital and Medical CenterLaheyLahey Hospital and Medical CenterHospital and Medical Center

Associate Professor of MedicineAssociate Professor of Medicine

Tufts University School of MedicineTufts University School of Medicine

Agenda

• Pathophysiology of portal hypertension

• Portal hypertensive bleeding– Endoscopic

– Radiologic

– Surgical– Surgical

• Ascites– Radiologic

ACG Regional Postgraduate Course - Los Angeles, CA Copyright 2013 American College of Gastroenterology

1


PATHOGENESIS OF LIVER FIBROSIS

Alterations in Microvasculature in CirrhosisAlterations in Microvasculature in Cirrhosis

• Activation of stellate cells

• Collagen deposition in space of Disse

• Constriction of sinusoids

• Defenestration of sinusoids

• Activation of stellate cells

• Collagen deposition in space of Disse

• Constriction of sinusoids

• Defenestration of sinusoids


2


Poiseuille’s Law

R = 8nlr4R πr4

Q=constant

r =↓50%

r =↓75%

∆R = ↑16x

∆R = ↑256x

THE PERMEABILITY OF THE HEPATIC SINUSOID VARIES IN HEALTH AND DISEASETHE PERMEABILITY OF THE HEPATIC SINUSOID VARIES IN HEALTH AND DISEASE

Increased Resistance in Cirrhosis is Due to a Reduction in the Sinusoidal RadiusIncreased Resistance in Cirrhosis is Due to a Reduction in the Sinusoidal Radius

HepatocytesHepatocytes

NormalNormal SinusoidSinusoidNormalNormal

fibrous tissue depositionfibrous tissue deposition

CirrhosisCirrhosis SinusoidSinusoid


3


Mechanisms of Portal HypertensionMechanisms of Portal Hypertension

• Pressure (P) results from the interaction of resistance (R) and fl (Q)

• Pressure (P) results from the interaction of resistance (R) and fl (Q)

MECHANISMS OF PORTAL HYPERTENSIONMECHANISMS OF PORTAL HYPERTENSION

flow (Q):flow (Q):

P = Q x RP = Q x R

•Portal hypertension can result•Portal hypertension can result

Ohm’s Law

•Portal hypertension can result from:

• increase in resistance to portal flow and/or

• increase in portal venous inflow

•Portal hypertension can result from:

• increase in resistance to portal flow and/or

• increase in portal venous inflow

In Cirrhosis:In Cirrhosis:

MECHANISMS OF PORTAL HYPERTENSION IN CIRRHOSISMECHANISMS OF PORTAL HYPERTENSION IN CIRRHOSIS

Increased intrahepatic resistance

is the initial mechanism leading to portal hypertension


is the initial mechanism leading to portal hypertensionto portal hypertensionto portal hypertension


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NORMALLY, INCREASES IN PORTAL FLOW CAUSES NO INCREASE IN

PORTAL PRESSURE Fasting Post-prandialP=Q x R

Portal flow = 700 ml/min Portal flow = 1500 ml/min

IN CIRRHOSIS, SMALL INCREASES IN PORTAL FLOW PRODUCE LARGE

INCREASES IN PORTAL PRESSUREP=Q x RFasting Post-prandial

Portal flow = 700 ml/min Portal flow = 1500 ml/min


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Portal-Systemic Collaterals

In Cirrhosis:In Cirrhosis:

MECHANISMS OF PORTAL HYPERTENSION IN CIRRHOSISMECHANISMS OF PORTAL HYPERTENSION IN CIRRHOSIS


is the initial mechanism leading to portal hypertension


is the initial mechanism leading to portal hypertensionto portal hypertension

but is also influenced by increased portal inflow

to portal hypertension

but is also influenced by increased portal inflow


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Variceal Bleeding

Treatment of Acute Variceal Treatment of Acute Variceal BleedingBleeding

•• Pharmacologic therapyPharmacologic therapyG l R d ti f t lG l R d ti f t l–– Goal: Reduction of portal pressureGoal: Reduction of portal pressure

–– OctreotideOctreotide–– NonNon--specific betaspecific beta--blockersblockers

•• SengstakenSengstaken--Blakemore tubeBlakemore tube•• Endoscopic therapyEndoscopic therapy

–– Goal: Obstruction of blood flowGoal: Obstruction of blood flow–– Goal: Obstruction of blood flowGoal: Obstruction of blood flow–– SclerotherapySclerotherapy–– Band LigationBand Ligation

•• TIPSTIPS•• Goal: Reduction of portal pressureGoal: Reduction of portal pressure


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TIPS

Covered Stents Are More Likely to Remain Functional Than Uncovered StentsCovered Stents Are More Likely to Remain Functional Than Uncovered Stents

100100

CoveredCovered

COVERED STENTS ARE MORE LIKELY TO REMAIN FUNCTIONAL THAN UNCOVERED STENTS

8080

6060

4040

2020

CoveredCovered

UncoveredUncovered

p=0.0005p=0.0005%free of shunt disfunction

%free of shunt disfunction

Bureau et al. Gastroenterology 2004; 126:469Bureau et al. Gastroenterology 2004; 126:469

2020

0000 66 1212 1818 2424

MonthsMonths


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Band Ligation vs. Early TIPS

• 63 pts with acute variceal bleeding– CTP 7-13

– 82% had exclusion criteria

– Bleeding controlled with pharmacotherapy and endoscopy within 12 hours

• Randomized to:Randomized to: – Pharmacotherapy + EBL

– Covered TIPS within 72 hours

Garcia-Pagan et al, NEJM 2010;362:2370-79.

Band Ligation vs. Early TIPS

Freedom from Rebleeding Survival

Garcia-Pagan et al, NEJM 2010;362:2370-79.


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Primary ProphylaxisBanding vs. Beta-blockers (Mortality)

Banding (n/N) Beta-Blockers (n/N) Risk Ratio, M-H, Random, 95% CI Risk Ratio

De 1999 1/15 0/15 3.00

Drastich 2005 2/40 2/33 0.83

Jutahba 2005 0/31 4/31 0.11

Lay 2006 14/50 12/50 1.17

Lo 2004 12/50 11/50 1.09

Lui 2002 14/44 11/66 1.91

Norberto 2007 3/31 3/31 1.00

Perez 2010 20/39 12/36 1.54

v

Psilopoulos 2005 12/30 10/30 1.20

Sarin 1999 5/46 5/44 0.96

Schepke 2004 34/75 33/77 1.06

Thuluvath 2005 6/16 3/15 1.88

Tripathi 27/75 26/77 1.07

Subtotal 542 555 1.19Gluud, Krag, Cochran Collab, 2012

p=0.08

Primary ProphylaxisBanding vs. Beta-blockers (Bleeding)

Banding (n/N) Beta-Blockers (n/N) Risk Ratio, M-H, Random, 95% CI Risk Ratio

Jutahba 2005 0/31 4/31 0.11

Lo 2004 10/50 16/50 0.63v

Tripathi 17/75 8/77 2.18

Lui 2002 3/44 9/66 0.50

Schepke 2004 19/75 22/77 0.89

Perez 2010 5/39 9/36 0.51

Thuluvath 2005 2/16 1/15 1.88

Norberto 2007 5/31 4/31 1.25

v

Lay 2006 11/50 12/50 0.92

De 1999 2/15 2/15 1.00

Sarin 1999 4/46 12/44 0.32

Psilopoulos 2005 4/30 9/30 0.44

Drastich 2005 2/40 2/33 0.83

Subtotal 542 555 0.78Gluud, Krag, Cochran Collab, 2012

p=0.13


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“Nonselective” Shunts for Variceal Bleeding

End to Side Side to Side

Meso-caval Porto-renal

Distal Splenorenal Shunt


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Distal Splenorenal Shunt

• Advantages• preservation of portal flow (early)• decompression of gastric & esophageal varicesdecompression of gastric & esophageal varices• avoidance of hepatic hilum• relief of hypersplenism• refractory encephalopathy rare

• Disadvantages• late reduction in portal perfusion• technically demanding• aggravation of ascites• aggravation of ascites• potential for complications:

- portal vein thrombosis- pancreatic pseudocyst

The Role of the Distal Splenorenal Shunt (DSRS) In The Modern Era

of Liver Transplantation

• Determine the clinical outcome of cirrhotic patients after DSRS for recurrent variceal bleeding (failed medical therapy) or those with gastric varices or portal HTN gastropathy

41 Consecutive patients with well compensated cirrhosis• 41 Consecutive patients with well-compensated cirrhosis who underwent DSRS between 9/1999-12/2011 at the Lahey Clinic

Pomposelli J, Tongyoo A, Jenkins RL, et al.


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Pre-operative clinical features

Alcoholic liver disease 15 (36.6%)

Child-Turcotte-Pugh classification

- Class A 29 (70.7%)

- Class B 12 (29.3%)

A it ( di ll t ll d) 12 (29 3%)Ascites (medically-controlled) 12 (29.3%)

Encephalopathy grade I-II 7 (17.1%)

Thrombosed TIPS 6 (14.6%)

Post-operative complications after DSRS

Overall Morbidity 17 (41.5%)

- Progressive ascites 6 (14.6%)

- Wound complication (wound infection, dehiscence, incisional hernia) 6 (14.6%)

- Non surgical site infection 6 (14.6%)

- Hepatic encephalopathy 3 (7.3%)

- Intra-abdominal collection 1 (2.4%)

- Atelectasis 1 (2.4%)

-Recurrent variceal bleeding 1 (2.4%)

- Myocardial infarction 1 (2.4%)


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Multivariate logistic regression analysis: Overall mortality rate

Factors Odds ratio (95% CI) P-value

Age > 60 4.05 (0.32-51.15) 0.28

Male gender 8.28 (0.51-134.89) 0.14

Non-alcoholic, non-cholestatic disease† 0.38 (0.06-2.37) 0.30

Previously-performed TIPS 1.74 (0.15-20.36) 0.66

Ascites 13.09 (1.24-137.95) 0.03 *

Encephalopathy 2.44 (0.21-28.63) 0.48

Total bilirubin > 2 0.99 (0.09-11.23) 0.99

Albumin < 3 5 0 81 (0 12-5 52) 0 83Albumin < 3.5 0.81 (0.12 5.52) 0.83

INR > 1.2 9.11 (0.33-249.25) 0.19

Platelet < 100 0.37 (0.04-3.88) 0.41

Creatinine > 1 0.47 (0.05-4.45) 0.51

† cause of portal hypertension : “non-alcoholic, non-cholestatic disease” (viral hepatitis, NASH, PV thrombosis,cryptogenic) compared to reference group (alcoholic, cholestatic cause such as PBC, PSC)

Child’s A vs. B


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Endoscopic/Pharmacologic control

Acute Variceal Bleed

Endoscopic/Pharmacologic control

Child's A Child's B/C

if bleeding recurs

TIPS±

OLTxDSRS

Child s A Child s B/C

Portal Hypertensive Gastropathy

• Associated with portal HTN

MildMild SevereSevere

• Fundus most frequently affected

Carpinelli et al. Ital J Gastroenterol Hepatol 1997; 29:533Carpinelli et al. Ital J Gastroenterol Hepatol 1997; 29:533


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• Similar principles to esophageal variceal

Management of Acute Bleedingfrom Portal Hypertensive Gastropathy

Similar principles to esophageal variceal bleeding

• Portal pressure lowering drug (i.e. octreotide)

• Endoscopy

• Temporizing measuresp g– Focal coagulation

– Band ligation

Ripoll C, Garcia-Tsao G. Dig Liv Dis 2011;345-351

Management of Chronic Bleedingfrom Portal Hypertensive Gastropathy


Initial medical managementInitial medical management

TREATMENT ALGORITHM FOR BLEEDING FROM PORTAL HYPERTENSIVE GASTROPATHYTREATMENT ALGORITHM FOR BLEEDING FROM PORTAL HYPERTENSIVE GASTROPATHY

g(Non-Cardioselective beta-blockers and iron supplement)



16








Bleeding controlled?Bleeding controlled?

YES

Continue medical therapyContinue medical therapy








Transfusion dependent?Transfusion dependent?NOYES

NOContinue medical therapyContinue medical therapy


Blood transfusionas needed



17









Transfusion dependent?Transfusion dependent?NO

YES

YES


TIPSvs.

Surg shunt

TIPSvs.

Surg shunt

YESNO



• Historically, PHG does not respond to argon plasma coagulation (APC)

Management of Chronic Bleedingfrom Portal Hypertensive Gastropathy:

Is There a Role for Endoscopy?

plasma coagulation (APC)

• Herrera, et al. GI Endoscopy 2008;68:440-5.

– 11 pts with PHG acute and chronic bleeding

– Treatment: APC q2-4wks until obliteration

– Success = fewer transfusions, Hct ≥ 30% or Hct ≥ baseline + 10%

– Mean sessions per pt: 2.2±2.0

– 81% success


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• Endoscopic findings:R d t ith t b k d i tt

• Endoscopic findings:R d t ith t b k d i tt

Gastric Antral Vascular Ectasia(GAVE)

Gastric Antral Vascular Ectasia(GAVE)

GASTRIC ANTRAL VASCULAR ECTASIAGASTRIC ANTRAL VASCULAR ECTASIA

• Red spots without background mosaic pattern• Linear aggregates in antrum: “watermelon stomach”• Diffuse lesions in proximal and distal stomach

• Often occurs in absence of portal hypertension

M b diffi l diff i f l

• Red spots without background mosaic pattern• Linear aggregates in antrum: “watermelon stomach”• Diffuse lesions in proximal and distal stomach

• Often occurs in absence of portal hypertension

M b diffi l diff i f l• May be difficult to differentiate from portal hypertensive gastropathy (PHG)

• Ideal therapy not known

• May be difficult to differentiate from portal hypertensive gastropathy (PHG)

• Ideal therapy not known

Typical Gastric Antral Vascular Ectasia

ENDOSCOPIC IMAGE OF TYPICAL GASTRIC ANTRAL VASCULAR ECTASIAENDOSCOPIC IMAGE OF TYPICAL GASTRIC ANTRAL VASCULAR ECTASIA


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Severe Severe PHG May be Difficult to Distinguish from Diffuse GAVESevere Severe PHG May be Difficult to Distinguish from Diffuse GAVE

SEVERE PORTAL HYPERTENSIVE GASTROPATHY MAY BE DIFFICULT TO DISTINGUISH FROM DIFFUSE GAVESEVERE PORTAL HYPERTENSIVE GASTROPATHY MAY BE DIFFICULT TO DISTINGUISH FROM DIFFUSE GAVE

Diffuse GAVEDiffuse GAVESevere PHGSevere PHG

PHG GAVE

Distribution in stomach Proximal Distal

PHG GAVE


Endoscopy and Biopsy Distinguish Between Portal Hypertensive Gastropathy (PHG) and

Gastric Antral Vascular Ectasia (GAVE)

Endoscopy and Biopsy Distinguish Between Portal Hypertensive Gastropathy (PHG) and

Gastric Antral Vascular Ectasia (GAVE)

ENDOSCOPIC AND HISTOLOGICAL FEATURES DISTINGUISH BETWEEN PORTAL HYPERTENSIVE GASTROPATHY AND GAVEENDOSCOPIC AND HISTOLOGICAL FEATURES DISTINGUISH BETWEEN PORTAL HYPERTENSIVE GASTROPATHY AND GAVE


Mosaic pattern Present Absent

Red signs Present Present

Biopsy:

Thrombi - + + + Spindle cell


Mosaic pattern Present Absent

Red signs Present Present

Biopsy:

Thrombi - + + + Spindle cellSpindle cell

proliferation + ++

Fibrohyalinosis + + + +

Treatment: Beta blockers ? Transplant

TIPS

Spindle cell proliferation + ++

Fibrohyalinosis + + + +

Treatment: Beta blockers ? Transplant

TIPS


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• Primary treatment is endoscopic– APC

Management of Chronic Bleeding from GAVE:Is There a Role for Endoscopy?

• Lower risk of perforation

• Focal and “paint brush”

• Repeat q2-6 weeks

– Nd:YAG laser

• Higher risk of perforation

R id• Rapid response

• Repeat q2-4 weeks

• Surgery for treatment failure– Antrectomy

– Liver transplantation, if cirrhoticRipoll C, Garcia-Tsao G. Dig Liv Dis 2011;345-351

Ascites


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The Development of AscitesThe Development of AscitesThe Revised The Revised UnderfillUnderfill TheoryTheory

•• Peripheral vasodilation occurs as the Peripheral vasodilation occurs as the result of decreased hepatic clearance result of decreased hepatic clearance of vasodilators such as glucagon of vasodilators such as glucagon and NOand NO

•• The body compensates for the The body compensates for the perceived drop in circulating blood perceived drop in circulating blood volume in two ways:volume in two ways:volume in two ways:volume in two ways:–– increased cardiac output (Q)increased cardiac output (Q)

–– activation of the reninactivation of the renin--angiotensin angiotensin system resulting in increased renal system resulting in increased renal retention of sodium and free waterretention of sodium and free water

Initial Workup of AscitesDiagnostic ParacentesisInitial Workup of AscitesDiagnostic Paracentesis

Glucose, LDHGlucose, LDH

OptionalOptional

INITIAL WORKUP OF ASCITES: DIAGNOSIS PARACENTESISINITIAL WORKUP OF ASCITES: DIAGNOSIS PARACENTESIS

Glucose, LDHGlucose, LDH

CytologyCytologyPMN countCulturePMN countCulture

Protein/AlbuminProtein/AlbuminAmylaseAmylase

RoutineRoutine ? secondaryinfection

? secondaryinfection?

cirrhotic ascites

? cirrhotic ascites

? pancreatic ascites

? pancreatic ascites

? malignant ascites

? malignant ascites

? SBP? SBPascitesascites


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Serum Ascites Albumin GradientSAAG

Serum Ascites Albumin GradientSAAG

Best test for classifying ascites into Best test for classifying ascites into y gportal hypertensive (SAAG >1.1 g/dL) and non–portal hypertensive (SAAG <1.1 g/dL) causes.

y gportal hypertensive (SAAG >1.1 g/dL) and non–portal hypertensive (SAAG <1.1 g/dL) causes.

≥1.1 g/dL <1.1 g/dL

Cirrhosis Peritoneal carcinomatosis

Alcoholic hepatitis Peritoneal TB

CHF Pancreatitis

Vascular occlusion Serositis

Fatty liver of pregnancy Nephrotic syndrome

Massive hepatic mets Bowel perf/obstruct/infarct

Myxedema

The Management of AscitesThe Management of Ascites•• Dietary measuresDietary measures

–– SodiumSodium–– FluidFluid

•• DiureticsDiuretics–– SpironolactoneSpironolactone

•• Large volume Large volume paracentesisparacentesisTIPSTIPS•• TIPSTIPS

•• PeritoneovenousPeritoneovenousshuntshunt

•• Liver Liver transplantation transplantation


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TIPS for AscitesReaccumulation, 12 months

TIPS Paracentesis Odds Ratio, M-H, Random, 95% CI Odds ratio(n/N) (n/N)

Gines 2002 21/35 33/35 0.09

Lebrec 1996 10/13 11/12 0.30

Salerno 2004 7/33 19/33 0.20

Sanyal 2003 22/52 48/57 0.14

Total 133 137 0.15

101 1000.10.01

Saab et al., Cochran Collab, 2009

Favors TIPS Favors Paracentesis

p<0.00001

TIPS for AscitesHepatic Encephalopathy

TIPS Paracentesis Odds Ratio, M-H, Random, 95% CI Odds ratio(n/N) (n/N)

Gines 2002 27/35 23/35 1.76

Lebrec 1996 3/13 0/12 8.33

Rossle 2000 15/29 11/31 1.95

Salerno 2004 20/33 13/33 2.37

Sanyal 2003 22/52 13/57 2.48

Total 133 137 2 24Total 133 137 2.24

101 1000.10.01

Saab et al., Cochran Collab, 2009

Favors TIPS Favors Paracentesis

1000 p=0.00089


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Hepatic Hydrothorax

Reasonable options Ineffective options

• Diuretics

• Fluid management

• VATS– 48% success

– 40% 40-day mortality

• TIPS

• Thoracentesis

• Chest tube

• Pleurodesis

• Surgical repair of diaphragm

• Peritoneovenous shunt

– 70% success

– 20% 30-day mortality

Conclusion

• Portal hypertension is a result of increased i t h ti l i t d t lintrahepatic vascular resistance and portal inflow

• Management of upper GI bleeding related to portal hypertension

• Role of surgery• Role of surgery

• Management of ascites


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