Upload
stewart-mcdaniel
View
248
Download
3
Embed Size (px)
Citation preview
IV CURSO PARA RESIDENTES DE LA AEEHDIAGNÓSTICO Y TRATAMIENTO DE LAS
ENFERMEDADES HEPÁTICAS
Barcelona, 18-19 de Octubre de 2013
ASCITIS Y SINDROME ASCITIS Y SINDROME HEPATORRENALHEPATORRENAL
Pere Ginès
Servei d’HepatologiaHospital Clínic
Universitat de Barcelona
SINDROME HEPATORRENAL
TIPS
Aldosteroneantagonists
Large-volumeparacentesis + albumin
CIRRHOSIS
Portal hypertension
Splanchnic arterial vasodilation
Reduced effective arterial blood volume
Activation of vasoconstrictor/antinatriuretic systems
Renin-aldosteronesystem
Sodium retention
ASCITES/EDEMA
Sympathetic nervoussystem
Other diuretics
ASCITES Pathogenesis and established therapies
1. Treat the first episode of ascites with low doses of spironolactone. Don’t push weight loss above 0.5 Kg/day (1Kg/day in patients with leg edema)
2. Full antagonism of aldosterone by spironolactone takes approx 5 days. Don’t expect immediate natriuresis
3. Visit or call patients weekly when ascites is decreasing or the dose of diuretics has been increased. Educate patients on the effects of diuretics
4. Monitor the effect of diuretics with body weight. Measure urine sodium in patients with poor or no response
DIURETICS IN THE MANAGEMENT OF ASCITESTips for clinical use
5. Use spironolactone with caution in patients with increased serum creatinine levels because of risk of hyperkalemia
6. Old patients or patients with chronic kidney disease have an impaired response to diuretics
7. Patients with pleural effusion respond poorly to diuretics and frequently develop side effects. Doses should be adjusted very carefully
8. USE DIURETICS WISELY. IMPORTANT SIDE EFFECTS CAUSED BY DIURETICS ARE VERY COMMON
DIURETICS IN THE MANAGEMENT OF ASCITESTips for clinical use
HYPOVOLEMIC HYPONATREMIA IN A PATIENT WITH CIRRHOSIS AND ASCITES DUE TO OVERDIURESIS
132
124
122
128
BW (kg) 74 72 70.5 68.3 67.2 64.8 61.5 59.2 59.5 60.3 61.1
1
130
126
3 7 8 115 64
1.50
1.00
1.25
0.50
Furosemide (40 mg/day) + Spironolactone (200 mg/day)
Ser
um s
odiu
m (
mE
q/L)
(
)
Serum
creatinine (mg/dL) ( )
Hepaticencephalopathy
9 10
0.75
2Days
Bernardi et al, Hepatology 2012
Odds Ratio (CI)
ALBUMIN IN LARGE-VOLUME PARACENTESIS Comparison albumin vs other expanders
Effects on survival
TIPS
Aldosteroneantagonists
Large-volumeparacentesis + albumin
CIRRHOSIS
Portal hypertension
Intense splanchnic arterial vasodilation
Severely reduced effective arterial blood volume
Marked activation of vasoconstrictor/antinatriuretic systems
Renin-aldosteronesystem
Intense sodium retention
REFRACTORY ASCITES
Sympathetic nervoussystem
Other diuretics
REFRACTORY ASCITES Pathogenesis and established therapies
Cost
-
-
-
-
Greaterwith TIPS
Hepatorenalsyndrome
-
-
-
Less frequentwith TIPS
Less frequentwith TIPS
Rossle et al.,N Engl J Med 2000
Ginès et al.,Gastroenterology 2002
Sanyal et al.,Gastroenterology 2003
Salerno et al.,Hepatology 2005
Lebrec et al.,J Hepatol 1997
Controlof ascites
Better withTIPS
Better withTIPS
Better withTIPS
Better withTIPS
Better withTIPS
Hepatic encephalopathy
No difference
Worsewith TIPS
Worsewith TIPS
Worsewith TIPS
No difference
Survival
Better withTIPS?
No difference
No difference
Better withTIPS
Worsewith TIPS
TIPS vs. PARACENTESIS FOR REFRACTORY ASCITES
Summary of studies
- Repeated large volume paracentesis plus albumin (8 g/L of ascites removed) is the first line of treatment for refractory ascites
- The use of TIPS should be considered in patients with very frequent requirement of paracentesis or in those in whom paracentesis is ineffective (e.g. due to the presence of loculated ascites)
EASL Guidelines on Ascites, J Hepatol 2010
EASL GUIDELINES ON ASCITES IN CIRRHOSIS 2010Management of Refractory Ascites
Epstein et al., Am J Med 1970
HEPATORENAL SYNDROME
Type 1- Rapidly progressive renal failure: doubling of the initial serum creatinine concentration to a level greater than 2.5 mg/dL in less than 2 weeks- Clinical presentation::acute renal failure- Median survival: 2 weeks, if untreated
Type 2- Stable renal failure - Clinical presentation: refractory ascites- Median survival: 6 months
International Ascites Club, Hepatology 1996
HEPATORENAL SYNDROMEClinical types
1. Consider liver transplantation; give priority to candidates
2. Terlipressin and albumin is the first-line treatment
3. Alternative therapies include norepinephrine and midodrine and octreotide plus albumin but information is limited
4. Consider TIPS if no response to vasoconstrictors in patients without contraindications (low applicability)
5. Use renal replacement therapy if no response to vasoconstrictors
6. Liver transplantation alone. No combined liver-kidney tx except for patients requiring prolonged renal support
TYPE 1 HEPATORENAL SYNDROMEEASL Guidelines 2010
HEPATORENAL SYNDROME
CIRRHOSIS
Splanchnic arterial vasodilation
Decreased effective arterial blood volume
Cerebralvasoconstriction
Maintenance of effectivearterial blood volume
Renalvasoconstriction
Brachial/femoralvasoconstriction
Vasoconstrictor systems
Portal hypertension
Terlipressin
Albumin
CIRCULATORY AND KIDNEY FUNCTION IN HEPATORENAL SYNDROME AND EFFECTS OF
TERLIPRESSIN AND ALBUMIN
IMPROVED KIDNEY FUNCTION
CIRRHOSIS
Splanchnic arterial vasoconstriction
Increase in effective arterial blood volume
CerebralVasodilation??
Maintenance of effectivearterial blood volume
Kidneyvasodilation
Brachial/femoralVasodilation??
Suppressed vasoconstrictor systems
Portal hypertension
CIRCULATORY AND KIDNEY FUNCTION IN HEPATORENAL SYNDROME AND EFFECTS OF
TERLIPRESSIN AND ALBUMIN
Uriz et al., J Hepatol 2000
Serum creatinine (mg/dL)
Serum sodium (mEq/L)
Mean arterial pressure (mmHg)
Plasma renin activity (ng/mL.h)
Plasma aldosterone (ng/dL)
Plasma norepinephrine (pg/mL)
342±73
Pretreatment
3.9±0.7
122±1
68±2
23±12
1,549±373
89±29
End of treatment
1.5±0.2
131±2
80±4
3±2
373±98
<0.01
p
<0.001
<0.01
<0.05
<0.01
<0.01
HEPATORENAL SYNDROMEEffects of terlipressin and albumin on circulatory
and kidney function
Boyer T et al. JHepatol 2011
PHARMACOLOGICAL TREATMENT OF TYPE-1 HEPATORENAL SYNDROME
Changes in arterial pressure in respondersand non-responders
• Differential diagnosis between type-1 HRS and other causes of kidney failure
• Evaluation and management of type-1 HRS associated with infections
• Treatment of patients with type-2 HRS
SPECIFIC ISSUES IN THE MANAGEMENTOF PATIENTS WITH HEPATORENAL SYNDROME
• Differential diagnosis between type-1 HRS and other causes of kidney failure
• Evaluation and management of type-1 HRS associated with infections
• Treatment of patients with type-2 HRS
SPECIFIC ISSUES IN THE MANAGEMENTOF PATIENTS WITH HEPATORENAL SYNDROME
Barreto et al., unpublished
0
10
20
30
40
50
HEPATORENALSYNDROME
PRE-RENALAKI
INTRINSICAKI*
OTHER
36%
25%
15%
24%
%
PRE-RENAL AKI: KIDNEY FAILURE DUE TO HYPOVOLEMIAINTRINSIC AKI: KIDNEY FAILURE DUE TO ACUTE TUBULAR NECROSISAKI, ACUTE KIDNEY INJURY
CAUSES OF KIDNEY FAILURE IN CIRRHOSIS Prospective series of 265 hospitalized patients
Inducible biomarkers
NGAL
• Neutrophil gelatinase-associated lipocalin (NGAL)• Kidney injury molecule-1 (KIM-1)• Monocyte chemoattractant protein-1 (MCP-1)
NGAL
KIM-1MCP-1
• β2-microglobuline
Low molecularweight proteins
β2-microglobuline
• N-acetylglucoseaminidase (NAG)• α-glutation-S-transferase (α-GST)• π-glutation-S-transferase (π-GST)
Constituent biomarkers
π-GST
NAGα-GST
NGAL
• Neutrophil gelatinase-associated lipocalin (NGAL)
NGAL
BIOMARKERS FOR THE DIAGNOSIS OF ACUTE KIDNEY INJURY
Barreto et al, unpublished
p<0.001
* p<0.001** p<0.05∞ Miscellaneous: Chronic Kidney Disease, Nephrotoxicity …
Median 32 33 67 98 417
327 SENS 0.67SPECIF 0.86
∞
URINE NGAL AND CAUSE OF KIDNEYFAILURE IN HOSPITALIZED CIRRHOTICS
• Differential diagnosis between type-1 HRS and other causes of kidney failure
• Evaluation and management of type-1 HRS associated with infections
• Treatment of patients with type-2 HRS
SPECIFIC ISSUES IN THE MANAGEMENTOF PATIENTS WITH HEPATORENAL SYNDROME
TYPE-1 HEPATORENAL SYNDROME ASSOCIATED WITH SEPSIS
Lack of reversibility with antibiotic therapy
Barreto et al. Hepatology 2013
No Nosocomial infection Nosocomial infection
0%
64%60%
100%
0
25
50
75
100
Bilirubin <8mg/dL Bilirubin ≥8mg/dL
86%
67%
100%
80%
0
25
50
75
100
Bilirubin <8mg/dL Bilirubin ≥8mg/dL
Age < 60 years Age ≥ 60 years
No Reversibility
%
TYPE-1 HEPATORENAL SYNDROME ASSOCIATED WITH SEPSIS
Effects of terlipressin and albumin
a0
Responders
Non Responders
Responders
Efficacy 65%
Rodriguez E et al. unpublished
• Differential diagnosis between type-1 HRS and other causes of kidney failure
• Evaluation and management of type-1 HRS associated with infections
• Treatment of patients with type-2 HRS
SPECIFIC ISSUES IN THE MANAGEMENTOF PATIENTS WITH HEPATORENAL SYNDROME
• Information on treatment of type-2 HRS is limited
• Terlipressin and albumin is effective in improving kidney function in approximately 60% of patients, but recurrence after treatment withdrawal is almost constant
• The effect of pharmacological treatment on survival has not been evaluated in large studies
• TIPS may improve renal function but an improvement in survival has not been demonstrated
TREATMENT OF TYPE-2 HEPATORENAL SYNDROME
• The use of kidney biomarkers, such as NGAL, may be useful in the differential diagnosis of HRS from other causes of acute kidney dysfunction, but more studies are needed before the use of biomarkers can be applied to clinical practice.
• Terlipressin and albumin is the treatment of choice for type-1 HRS. Response to treatment is dependent on improvement of systemic hemodynamics. Early treatment may improve the response rate.
• Type-1 HRS associated with sepsis is seldom reversible only with antibiotic treatment. Terlipressin and albumin appears effective in these patients
CONCLUSIONS
BARCELONA LIVER CIRRHOSIS STUDY GROUP