Liver and Lung Treatment of hepatopulmonary diseases · Liver and Lung Treatment of hepatopulmonary...

Liver and LungTreatment of hepatopulmonary diseases

P. Schenk

Department of Internal Medicine 3Medical University Vienna

Hervé et al, Eur Respir J 1998

2-8,5%28%

PVR in patients with portal hypertension & healthy individuals

Definition:

PAPm > 25 mm Hg Rest> 30 mm Hg Exercise

PCP < 15 mm Hg

PVR > 240 dyn.sec.cm-5

Portopulmonary Hypertension

ERS Task Force, Eur Respir J 2004

• elevated portal pressure (> 10 mm Hg)

Staging:

Mild (Early) PAPm > 25 - 34 mm Hg

Moderate PAPm ≥ 35 - 44 mm Hg

Severe PAPm ≥ 45 mm Hg

Chemla et al, Eur Respir J 2002;20:1314Rodriguez-Roisin et al, ERS Task Force, Eur Respir J 2004;24:861


Prevalence in cirrhosis: 2-8,5% (catheter-based studies)

Haemodynamics & mortality: comparison with IPAH

Kawut el al,Liver Transpl 2005

Multivariatanalysis, adjusted for laboratory values, hemodynamics & treatment:

transplant-free survival

38%

HR = 2,8, 95% CI 1,04-7,4; P=0,04


21% 30-months survival, n=49; Robalino JACC 1991

28% 5-months survival without OLT, n=66; Swanson et al, Liver Transpl 2005

Treatment

β-blockers for bleeding prophylaxisin patients with esophageal varices

„….could contribute to deterioration of PPHTN“

Rodriguez-Roisin et al, ERS Task Force, Eur Respir J 2004;24:861


Treatment

Provencher et al, Gastroenterology 2006

prospective study, 10 patients with esophageal varicesβ-blockers for 38 ± 27 months



+79m +25% +37% +89%

Functional evaluation 2 ± 1 months after β-blocker discontinuation



+28% -19%


Hemodynamics 2 ± 1 months after β-blocker discontinuation

n treatment PAPm ↓ PVR ↓ Authortime

4 6-14 months 29-46% 22-71% Kuo et al, Transplant 19977 13 months 33% 68% McLaughlin et al, Ann Intern Med 19997 3 - 30 months 17% 47% Krowka et al, Hepatology 19991 4 months 24% 54% Plotkin et al, Transplant 19981 3 weeks 24% 67% Ramsay et al, Anesthesiology 19992 18 months -4% 52% Rafanan et al, Chest 20003 5 months 24% 40% Kähler et al, Wien Klin Wochenschr 20001 29 months 31% 43% Tan et al, Liver Transpl 20011 4 days 29% 15% Kett et al, Liver Transpl 20011 7 weeks 6% 57% Uchiyama et al, Liver Transpl 20068 6,5 months 23% 53% Sussman et al, Am J Transplant 200619 15 months 25% 55% Fix et al, Liver Transplant 2007

55 patients

Portopulmonary HypertensionTreatment i.v. prostacyclin

Treatment i.v. prostacyclin


AE: catheter infection, sepsis, gastrointest. bleeding

21% 9% 14% (1 died)McLaughlin et al, Ann Intern Med 1999

progressive splenomegaly with thrombocytopenia(from 149000 47000 G/L in 4 patients)

Findlay et al, Liver Transpl Surg 1999

5% (1 died) Fix et al, Liver Transplant 2007

Hoeper et al, Eur Respir J 2007

Case-series:n=13

8/13 patients died < 3 years

6: right heart failure1: variceal bleeding1: after liver+lung transplant

Change of treatment

5 → iv prostacyclin4 → bosentan

inhaled Iloprost


p.o. Bosentan

+78 m



Treatment

p.o. Bosentan



No aminotransferase ↑

Portopulmonary HypertensionBosentan vs. inhaled iloprost

Hoeper et al,Eur Respir J 2007

n=18 n=13retrospectivestudy:

Comparable baseline characteristics

Portopulmonary HypertensionBosentan vs. inhaled iloprost

Events:

deathtransplanttreatment change

Hoeper et al,Eur Respir J 2007



Multivariate analysis:

Portopulmonary Hypertensionp.o. Bosentan in Child C cirrhosis ?

Case-report:

Barth et al, Eur J Gastroenterol Hepatol 2006

41 y, HCV+alcohol

6 MWT:0 290m 400m

4 weeks 8 weeks

RVEF (MRT):7% 14%

Child C Child B

Treatment p.o. Sildenafil


Reichenberger et al, Eur Respir J 2006

n=14, NYHA III-IV, Sildenafil 3x 50 mg/day

Treatment p.o. Sildenafil


Reichenberger et al, Eur Respir J 2006

Sidenafil monotherapy

Sidenafil + inhaledProstanoids

Prognosis for OLT

● no increased periop. risk when PAPm ≤ 35 mm Hg

Castro et al, Mayo Clin Proc 1996;71:543Krowka et al, Liver Transpl 2000;6:443

● PAPm > 35 mm Hg & PVR >250 dyn.s.cm-5

↓periop. mortality > 50% Krowka et al, Liver Transpl 2000;6:443

40% Krowka et al, Liver Transpl 2004:10:174

OLT for Portopulmonary Hypertension

Why is OLT so dangerous for PH-patients ?

Acosta et al, Transpl Proc 2005

RV-preload ↑

OLT for Portopulmonary Hypertension


Ashfaq et al, Am J Transplant 2007

Prognosis of OLT under vasodilator therapy ?

16 patients, PAPm ≥ 35 mm Hg:

Recommendations of ERS Task Force:

Screening of OLT-candidates with echo

RVsyst > 40-50 mm Hg

Confirmation with catheter

Medical treatment (PAPm > 35 mm Hg = CI for OLT)

Rodriguez-Roisin et al, Eur Respir J 2004


Hepatopulmonary Syndrome

Definition

1) liver disease

2) abnormal arterial oxygenation

3) intrapulmonary vasodilatationKrowka, Hepatology 1990 Rodriguez-Roisin, Thorax 1992Rodriguez-Roisin, Eur Respir J 2004

Triad

Prevalence in Cirrhosis: 5-32%Schenk et al, Gut 2002

Potential mechanism and treatment in experimental HPS

Palma, FallonJ Hepatol 2006

Months

% c

umul

ativ

e su

rviv

al

0,0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1,0

0 6 12 18 24 30 36 42 48 54 60 66

without HPS, median 40.8 months

with HPS, median 10.6 months

p=0.018

111 patients with cirrhosis, 27 with HPS

without HPS, median 40,8 months

with HPS, median 10,6 months

Months

% c

umul

ativ

esu

rviv

al

Schenk et al, Gastroenterology 2003

Prognosis of patients with HPS ?

Months

% c

umul

ativ

e su

rviv

al

0,0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1,0

0 6 12 18 24 30 36 42 48 54 60 66

P = 0.00472

mit HPS, PaO2 > 60 mm Hg

mit HPS, PaO2 ≤ 60 mm Hg

Prognosis according to the severity of HPS

Parameter Regression-coefficient (β) P

BUN 0.021576 0.000222Age 0.041554 0.002103HPS 0.708367 0.014151Child-class -0.403450 0.039510 Schenk et al,

Gastroenterology 2003

O2-long-term therapy for HPS

→ recommended for patients with PaO2 < 60 mm Hg ERS Task ForceEur Respir J 2004

63-y ♀, HCV-cirrhosis Child C, PaO2 63 mm Hg

PT

Albumin

Child-Pugh score

after 1 year:

Child Ano ascites

Influence on liver function ?

Fukushima et al,J Gastroenterol 2007

Hypoxemia in patients with HPS is no CI for OLT

high risk: PaO2 < 50 mm Hg: 30% postop. mortality

high shunt (> 40%): 50% postop. mortality

Krowka et al, Mayo Clin Proc 1997Egawa et al, Transplantation 1999

OLT improves HPS in most patients: 86% Battaglia et al, Hepatology 1997

82% Krowka et al, Mayo Clin Proc 1997

OLT for HPS

Medical therapies for HPS

No established medical therapies ….

Sympathomimetic agentsSomatostatinAlmitrineIndomethacinPlasma exchangeAspirinGarlicMethylene blueL-NAME

Schenk et al, Ann Intern Med 2000

Medical therapies for HPS

Sympathomimetic agentsSomatostatinAlmitrineIndomethacinPlasma exchangeAspirinGarlicMethylene blueL-NAME

No established medical therapies ….

Liver and Lung Treatment of hepatopulmonary diseases · Liver and Lung Treatment of hepatopulmonary...

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