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IV CURSO PARA RESIDENTES DE LA AEEH DIAGNÓSTICO Y TRATAMIENTO DE LAS ENFERMEDADES HEPÁTICAS Barcelona, 18-19 de Octubre de 2013 ASCITIS Y SINDROME HEPATORRENAL.

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Presentation on theme: "IV CURSO PARA RESIDENTES DE LA AEEH DIAGNÓSTICO Y TRATAMIENTO DE LAS ENFERMEDADES HEPÁTICAS Barcelona, 18-19 de Octubre de 2013 ASCITIS Y SINDROME HEPATORRENAL."— Presentation transcript:

1 IV CURSO PARA RESIDENTES DE LA AEEH DIAGNÓSTICO Y TRATAMIENTO DE LAS ENFERMEDADES HEPÁTICAS Barcelona, 18-19 de Octubre de 2013 ASCITIS Y SINDROME HEPATORRENAL Pere Ginès Servei d’Hepatologia Hospital Clínic Universitat de Barcelona SINDROME HEPATORRENAL

2 TIPS Aldosterone antagonists Large-volume paracentesis + albumin CIRRHOSIS Portal hypertension Splanchnic arterial vasodilation Reduced effective arterial blood volume Activation of vasoconstrictor /antinatriuretic systems Renin-aldosterone system Sodium retention ASCITES/EDEMA Sympathetic nervous system Other diuretics ASCITES Pathogenesis and established therapies

3 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 ASCITES Tips for clinical use

4 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 ASCITES Tips for clinical use

5 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 378115 6 4 1.50 1.00 1.25 0.50 Furosemide (40 mg/day) + Spironolactone (200 mg/day) Serum sodium (mEq/L) ( ) Serum creatinine (mg/dL) ( ) Hepatic encephalopathy 9 10 0.75 2 Days

6 Bernardi et al, Hepatology 2012 Odds Ratio (CI) ALBUMIN IN LARGE-VOLUME PARACENTESIS Comparison albumin vs other expanders Effects on survival

7 TIPS Aldosterone antagonists Large-volume paracentesis + albumin CIRRHOSIS Portal hypertension Intense splanchnic arterial vasodilation Severely reduced effective arterial blood volume Marked activation of vasoconstrictor /antinatriuretic systems Renin-aldosterone system Intense sodium retention REFRACTORY ASCITES Sympathetic nervous system Other diuretics REFRACTORY ASCITES Pathogenesis and established therapies

8 Cost - - - - Greater with TIPS Hepatorenal syndrome - - - Less frequent with TIPS Less frequent with 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 Control of ascites Better with TIPS Better with TIPS Better with TIPS Better with TIPS Better with TIPS Hepatic encephalopathy No difference Worse with TIPS Worse with TIPS Worse with TIPS No difference Survival Better with TIPS? No difference No difference Better with TIPS Worse with TIPS TIPS vs. PARACENTESIS FOR REFRACTORY ASCITES Summary of studies

9 - 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 2010 Management of Refractory Ascites

10 Epstein et al., Am J Med 1970 HEPATORENAL SYNDROME

11 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 SYNDROME Clinical types

12 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 SYNDROME EASL Guidelines 2010

13 HEPATORENAL SYNDROME CIRRHOSIS Splanchnic arterial vasodilation Decreased effective arterial blood volume Cerebral vasoconstriction Maintenance of effective arterial blood volume Renal vasoconstriction Brachial/femoral vasoconstriction Vasoconstrictor systems Portal hypertension Terlipressin Albumin CIRCULATORY AND KIDNEY FUNCTION IN HEPATORENAL SYNDROME AND EFFECTS OF TERLIPRESSIN AND ALBUMIN

14 IMPROVED KIDNEY FUNCTION CIRRHOSIS Splanchnic arterial vasoconstriction Increase in effective arterial blood volume Cerebral Vasodilation?? Maintenance of effective arterial blood volume Kidney vasodilation Brachial/femoral Vasodilation?? Suppressed vasoconstrictor systems Portal hypertension CIRCULATORY AND KIDNEY FUNCTION IN HEPATORENAL SYNDROME AND EFFECTS OF TERLIPRESSIN AND ALBUMIN

15 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 HEPATORENAL SYNDROME Effects of terlipressin and albumin on circulatory and kidney function

16 Boyer T et al. JHepatol 2011 PHARMACOLOGICAL TREATMENT OF TYPE-1 HEPATORENAL SYNDROME Changes in arterial pressure in responders and non-responders

17 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 MANAGEMENT OF PATIENTS WITH HEPATORENAL SYNDROME

18 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 MANAGEMENT OF PATIENTS WITH HEPATORENAL SYNDROME

19 Barreto et al., unpublished 0 10 20 30 40 50 HEPATORENAL SYNDROME PRE-RENAL AKI INTRINSIC AKI* OTHER 36% 25% 15% 24% % PRE-RENAL AKI: KIDNEY FAILURE DUE TO HYPOVOLEMIA INTRINSIC AKI: KIDNEY FAILURE DUE TO ACUTE TUBULAR NECROSIS AKI, ACUTE KIDNEY INJURY CAUSES OF KIDNEY FAILURE IN CIRRHOSIS Prospective series of 265 hospitalized patients

20 Inducible biomarkers NGAL Neutrophil gelatinase-associated lipocalin (NGAL) Kidney injury molecule-1 (KIM-1) Monocyte chemoattractant protein-1 (MCP-1) NGAL KIM-1 MCP-1 β 2 -microglobuline Low molecular weight proteins β 2 -microglobuline N-acetylglucoseaminidase (NAG) α-glutation-S-transferase (α-GST) π-glutation-S-transferase (π-GST) Constituent biomarkers π-GST NAG α-GST NGAL Neutrophil gelatinase-associated lipocalin (NGAL) NGAL BIOMARKERS FOR THE DIAGNOSIS OF ACUTE KIDNEY INJURY

21 Barreto et al, unpublished p<0.001 * p<0.001 ** p<0.05 ∞ Miscellaneous: Chronic Kidney Disease, Nephrotoxicity … Median32336798417 327SENS 0.67 SPECIF 0.86 ∞ URINE NGAL AND CAUSE OF KIDNEY FAILURE IN HOSPITALIZED CIRRHOTICS

22 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 MANAGEMENT OF PATIENTS WITH HEPATORENAL SYNDROME

23 TYPE-1 HEPATORENAL SYNDROME ASSOCIATED WITH SEPSIS Lack of reversibility with antibiotic therapy Barreto et al. Hepatology 2013 No Nosocomial infection Nosocomial infection Age < 60 yearsAge ≥ 60 years No Reversibility %

24 TYPE-1 HEPATORENAL SYNDROME ASSOCIATED WITH SEPSIS Effects of terlipressin and albumin a 0 Responders Non Responders Responders Efficacy 65% Rodriguez E et al. unpublished

25 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 MANAGEMENT OF PATIENTS WITH HEPATORENAL SYNDROME

26 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

27 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

28 BARCELONA LIVER CIRRHOSIS STUDY GROUP

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