Liver dysfunction
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Transcript of Liver dysfunction
Liver dysfunction in AHF syndromes: clinical and prognostic
implications
J. ParissisHeart Failure Clinic
Attikon University Hospital,Athens, Greece
Disclosures:
Research grants from Abbott USA and Orion Pharma Finland as
ALARM investigator, and Novartis international.
• Ten liver function tests were evaluated in a study of 135 cases of chronic protracted congestive heart failure of which 54 came to autopsy.
• Seventy-four per cent of the patients had at least one abnormal determination although only 30 per cent of the tests performed were out of the normal range.
• There is definite impairment of liver function in congestive heart failure. The exact basis for this change remains unknown.
Circulation. 1950;2:286-297
The Splanchnic Vasculature: Capacitance Function and Cardiac Pre-load
Verbrugge et al. J Am Coll Cardiol 2013;62:485–95
Hepatorenal Reflex
Verbrugge et al. JACC 2013
Pathophysiology in HFCan ischemic hepatitis be attributed only to hypotension?
Samski et al. JACC 2013
Transaminases in Ischemic Hepatitis
Sharp rise and fallALT/LDH<1.5
Cardio Hepatic Interactions•FORWARD HF/CARDIOGENIC SHOCK HYPOXIC HEPATITIS
• BACKWARD HF/CHRONIC CONGESTIONCIRRHOTIC LIVER
• LIVER CIRRHOSIS CIRRHOTIC CARDIOMYOPATHY
Distribution of abnormal liver enzymes in HF
Auer J. Eur Heart J 2013;34:711–714
CHF: prevalence & clinical significance of liver dysfunction
Association with• NYHA• JV distention, edema• EF• RVSP• TR
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18.3
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0Bilirubin γGT ALP ALT/AST Αlbumin
Poelzl (2014)
CHARM (2009)
Allen et al. Eur J HF 2009Poelzl et al. Eur J Clin Invest 2012
GGT, T-Bil, GGT, T-Bil, and ALPALP are related to disease severity
p <0.0001 p <0.0001p <0.0001
Poelzl G, et al. EJCI, 2012, 42:153
AST, AST, and ALTALT are not related to disease severity
p=0.168 p=0.495
Poelzl G, et al. EJCI, 2012, 42:153
CHF: prevalence & clinical significance of liver dysfunction
Allen et al. Eur J HF 2009
Prevalence and Prognostic Significance of Elevated g-Glutamyltransferase in Chronic HF
Poelzl et al. Circ Heart Fail. 2009;2:294-302
Prevalence of elevated GGT was 42.9% in men (GGT >65 U/L) and 50.2% in women(GGT> 38 U/L) with CHF.
Synergistic effect of hepatic and renal dysfunction on outcomes in CHF patients
Poelzl et al. Eur J Inter Med 2013;24:177–182
MELD score=11.2x(ln INR)+0.378x(ln bil)+0.957x(ln creat)+0.643
MELD-XI score=5.11x(ln bil)+11.76x(ln creat)+9.44
Cardiohepatic syndrome in CHF: general concepts
TheThe cardio-hepatic syndrome cardio-hepatic syndrome in chronic in chronic heart failure is :heart failure is :
- frequentfrequent
- characterized by a predominantly predominantly cholestatic cholestatic enzyme pattern
-- associated with disease severity associated with disease severity
- related to prognosisrelated to prognosis
AHF: prevalence & clinical significance of LFTs
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SURVIVE
ESCAPE
EVEREST
Abnormal LFTs:
Nikolaou et al. Eur Heart J 2013Ambrosy et al. Eur J Heart Fail 2012Scholfild et al. J Cardiac Fail 2014
Prevalence of elevated ALT and aspartate AST at admission by ejection fraction and clinical profile at presentation
European Heart Journal: Acute Cardiovascular Care 2013 2: 99
Additive values of abnormal transaminases and abnormal alkaline phosphatase on a short- andlong-term outcome
Nikolaou M, Parissis J, …, Mebazaa A. EHJ 2013;34:742-749
Assessment of Acute Heart Failure Syndromes: the role of hepatic dysfunction
Modified from Nohria et al. Am J Cardiol 2005;96[suppl]:32G–40G
High Transaminases plus ALP
High Transaminases
High ALP Normal
GGT levels in ADHF: prognostic value and relationship with renal function
Serum creatinine
Parissis et al. Int J Cardiol 2014
eGFReGFR and GGTGGT are related to CVPCVP
p = 0.007 p = 0.001
Poelzl G, courtesy
eGFR GGT
Standardized regression
coefficient beta
P-value Standardized regression
coefficient beta
P-value
Male gender 0.207 0.011 0.182 0.023
Age 65a -0.096 0.224 -0.022 0.776
Ischemic aetiology -0.160 0.054 0.192 0.020
Diabetes -0.049 0.550 0.210 0.117
Hypertension -0.211 0.008 -0.87 0.261
Alcohol consumption -0.041 0.601 -0.087 0.266
LV-EF 35% -0.164 0.047 0.006 0.945
NYHA III/IV -0.065 0.459 0.118 0.178
CVP -0.225 0.008 0.337 <0.001
CI 0.060 0.470 0.017 0.835
Determinants of worsening renal and hepatic function (n = 205)
Poelzl G, courtesy
Levosimendan, compared to dobutamine, reduces enzymatic markers associated with liver congestion: A SURVIVE subanalysis
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*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
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Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
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*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
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Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
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*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
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Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
Favo
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Levo
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*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
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Diff
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Cha
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Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
Favo
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utam
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Levo
sim
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*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
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Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
Favo
rsDob
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Levo
sim
enda
n
*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
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-25
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0
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Diff
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ce (L
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dan
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obut
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Cha
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From
Bas
elin
e, IU
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Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
Favo
rsDob
utam
ine
Levo
sim
enda
n
*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
-35
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-25
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0
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Diff
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ce (L
evos
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dan
–D
obut
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e) in
Cha
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From
Bas
elin
e, IU
/L†
Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
Favo
rsDob
utam
ine
Levo
sim
enda
n
*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
-35
-30
-25
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0
5
10
Diff
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ce (L
evos
imen
dan
–D
obut
amin
e) in
Cha
nge
From
Bas
elin
e, IU
/L†
Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
Favo
rsDob
utam
ine
Levo
sim
enda
n
*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
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-25
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Diff
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ce (L
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dan
–D
obut
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e) in
Cha
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From
Bas
elin
e, IU
/L†
Day 1 Day 3 Day 5Day 1 Day 3 Day 5
AST APALT
Favo
rsDob
utam
ine
Levo
sim
enda
n
*P-value from repeated measures ANCOVA model for treatment effect, model also included effects for time (all were p<0.05) and treatment -by-time interaction (all were p=NS). †Point estimates from ANCOVA model with baseline as covariate. Error ba rs are standard errors.
80 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
80 75 11180 75 111Baseline, μ, IU/L
0.008 0.002 <0.001P-value*
Nikolaou M, Parissis J, …, Mebazaa A. EHJ 2013
Impact of Liver Injury on Drug Metabolism
CRSCHS
HRS
Take Home Messages• Abnormal liver biochemistry is highly prevalent in chronic and
acute heart failure.• Elevated hepatic enzymes may have important prognostic
implications in chronic and acutely decompensated chronic heart failure (ADHF).
• Increased central venous pressure may be related with cholestasis in ADHF, while reduced cardiac output may additionally affect hepatic function by causing liver injury and transaminase release.
• Hepatic dysfunction is closely related with renal dysfunction in ADHF. These conditions may have synergistic prognostic implications.
• Drugs that protect liver function may improve outcomes in ADHF patients.
• More prospective trials targeting to liver function protection are needed in ADHF patients.