CIRRHOSIS AND PORTAL HYPERTENSION
Cirrhosis and Portal Hypertension Dr. Aldo Torre Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”.
NATURAL HISTORY OF CHRONIC LIVER DISEASE
Natural History of Chronic Liver Disease
Chronic liver disease
Compensated cirrhosis
Decompensated cirrhosis
Development of complications:
Variceal hemorrhage Ascites Encephalopathy Jaundice
Death
NATURAL HISTORY OF CIRRHOSIS
Development of Complications in Compensated Cirrhosis 100 80
Ascites Jaundice Encephalopathy GI hemorrhage
Probability of 60 developing event 40 20 0 0
20
40
60
80
100
Months Gines et. al., Hepatology 1987; 7:122
120
140
160
SURVIVAL TIMES IN CIRRHOSIS
Decompensation Shortens Survival 100
80
Median survival ~ 9 years
All patients with cirrhosis
60
Probability of survival
40
20
Decompensated cirrhosis
Median survival ~ 1.6 years
0 0
20
40
60
80
100
Months Gines et. al., Hepatology 1987;7:122
120
140
160
180
VARICES INCREASE IN DIAMETER PROGRESSIVELY
Varices Increase in Diameter Progressively
No varices
Small varices 7-8%/year
Merli et al. J Hepatol 2003;38:266
Large varices 7-8%/year
PREVENTION OF VARICEAL DEVELOPMENT
Treatment of Varices / Variceal Hemorrhage No varices
Varices No hemorrhage
Variceal hemorrhage Recurrent hemorrhage
Prevention of variceal development
NON-SELECTIVE BETA BLOCKERS DO NOT PREVENT DEVELOPMENT OF VARICES
Pre-Primary Prophylaxis Multicenter, randomized, placebo-controlled trial of timolol (non-selective beta-blocker) vs. placebo in patients
Beta-blockers did not prevent the development of varices and were associated with a higher rate of serious adverse events Hepatic venous pressure gradient was the strongest predictor of the development of varices
Groszmann, et al., Hepatology 2003;38 (suppl 1):206A
MANAGEMENT OF PATIENTS WITHOUT VARICES
Treatment of Varices / Variceal Hemorrhage No varices
No specific therapy Repeat endoscopy in 2-3 yrs*
Varices No hemorrhage
Variceal hemorrhage Recurrent hemorrhage * Sooner with cirrhosis decompensation
PREVENTION OF FIRST VARICEAL HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage No varices
Varices No hemorrhage
Variceal hemorrhage Recurrent hemorrhage
Prevention of first variceal hemorrhage
MANAGEMENT OF PATIENTS WITH VARICES WHO HAVE NEVER BLED
Treatment of Varices / Variceal Hemorrhage No varices
Varices No hemorrhage
Variceal hemorrhage Recurrent hemorrhage
Management depends on the size of varices
MANAGEMENT OF PATIENTS WITH MEDIUM/LARGE VARICES WITHOUT PRIOR HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage No varices Small varices No hemorrhage
Medium/ large varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage
1) -blockers (propranolol, nadolol) indefinitely 2) Endoscopic variceal ligation in patients intolerant to -blockers
MANAGEMENT OF PATIENTS WITH SMALL VARICES WITHOUT PRIOR HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage No varices Small varices No hemorrhage
Medium/ large varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage
? Prevention of variceal growth
NADOLOL MAY PREVENT THE GROWTH OF SMALL VARICES
Nadolol May Prevent the Growth of Small Varices 100
Nadolol 80
Placebo
% Probability of variceal growth
p<0.001
60
40
20 0
10
36 Time (months)
24
Merkel et al., Gastroenterology 2004; 127:476
48
60
MANAGEMENT OF PATIENTS WITH SMALL VARICES WITHOUT PRIOR HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage No varices Small varices No hemorrhage
Repeat endoscopy in 1-2 years* Beta-blockers?
Medium/ large varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage * Sooner with cirrhosis decompensation
CASE MB - QUESTION
Case MB
What is the appropriate management of this patientâ&#x20AC;&#x2122;s varices?
CASE MB – TREATMENT
Case MB
Treatment of Varices Treatment with propranolol was initiated at a dose of 40 mg p.o. BID Heart rate decreased to 58 bpm; the patient remained asymptomatic
Treatment should be continued indefinitely
CONTROL OF ACUTE VARICEAL HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage No varices Small varices No hemorrhage
Medium/ large varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage
Control of hemorrhage
IN ACUTE VARICEAL HEMORRHAGE, HEPATIC VENOUS PRESSURE GRADIENT (HVPG) >20 mmHg PREDICTS POOR OUTCOME
In Acute Variceal Hemorrhage, HVPG > 20 mmHg Predicts a Poor Outcome 40
32
HVPG (mmHg)
83% 28%
24
20 16 8
0
Early rebleeding Failure to control bleeding
Uneventful outcome
Moitinho et al., Gastroenterology 1999; 117:626
Poor outcome
TREATMENT OF ACUTE VARICEAL HEMORRHAGE
Treatment of Acute Variceal Hemorrhage General Management: IV access and fluid resuscitation Do not overtransfuse (hemoglobin ~ 8 g/dL) Antibiotic prophylaxis
Specific therapy: Pharmacological therapy: terlipressin, somatostatin and analogues, vasopressin + nitroglycerin Endoscopic therapy: ligation, sclerotherapy Shunt therapy: TIPS, surgical shunt
EARLY TIPS IN PATIENTS WITH ACUTE VARICEAL HEMORRHAGE AND HVPG > 20 mmHg MAY IMPROVE SURVIVAL
Early TIPS In Patients With Acute Variceal Hemorrhage and HVPG > 20 mmHg (High Risk) May Improve Survival 1 HVPG <20
0.8 HVPG >20 - TIPS
0.6
Probability of survival
0.4
HVPG >20 â&#x20AC;&#x201C; No TIPS 0.2 0 0
3
6
Months Monescillo et al., Hepatology 2004; 40:793
9
12
MANAGEMENT OF PATIENTS WITH ACUTE VARICEAL HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage No varices Small varices No hemorrhage
Medium/ large varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage
1) Safe vasoactive drug + endoscopic therapy + antibiotic prophylaxis 2) TIPS / Shunt (rescue therapy)
PREVENTION OF RECURRENT VARICEAL HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage No varices Small varices No hemorrhage Small varices Medium/ large varices No hemorrhage Variceal hemorrhage Recurrent hemorrhage
Preventing recurrent hemorrhage
COVERED STENTS ARE MORE LIKELY TO REMAIN FUNCTIONAL THAN UNCOVERED STENTS
Covered Stents Are More Likely to Remain Functional Than Uncovered Stents 100
Covered
80
%
60
free of shunt disfunction
40
p=0.0005
Uncovered 20
0 0
6
12
Months Bureau et al. Gastroenterology 2004; 126:469
18
24
COVERED TIPS STENTS ARE ASSOCIATED TO LESS ENCEPHALOPATHY WITH EQUIVALENT SURVIVAL
Covered TIPS Stents Lead to Less Encephalopathy with Equivalent Survival Encephalopathy
Death
100
Covered
80
%
Covered
p = 0.0586
60
Free of event 40
Uncovered
Uncovered
p = 0.17
20
0 0
6
12
18
Months Bureau et al. Gastroenterology 2004; 126:469
24 0
6
12
Months
18
24
PREVENTION OF RECURRENT VARICEAL HEMORRHAGE
Treatment of Varices / Variceal Hemorrhage No varices
Varices No hemorrhage
Variceal hemorrhage 1) -blockers + ISMN or EVL
Recurrent hemorrhage
2) -blockers + EVL may be preferable 3) TIPS / shunt surgery
SUMMARY OF MANAGEMENT OF VARICES AND VARICEAL HEMORRHAGE
Evolution of Varices
Level of Intervention
Cirrhosis with no varices Pre-primary prophylaxis
Management Recommendations Repeat endoscopy in 2-3 years No specific therapy
SUMMARY OF MANAGEMENT OF VARICES AND VARICEAL HEMORRHAGE
Evolution of Varices
Level of Intervention
Cirrhosis with no varices Small varices No hemorrhage
Medium / large varices No hemorrhage
Pre-primary prophylaxis
Management Recommendations Repeat endoscopy in 2-3 years No specific therapy Small varices Repeat endoscopy in 1-2 years No specific therapy ? beta-blocker to prevent enlargement
Primary prophylaxis
Medium/Large varices Non-selective beta-blockers EVL in those who are intolerant to drugs
SUMMARY OF MANAGEMENT OF VARICES AND VARICEAL HEMORRHAGE
Evolution of Varices
Level of Intervention
Cirrhosis with no varices Small varices No hemorrhage
Medium / large varices No hemorrhage
Variceal hemorrhage
Pre-primary prophylaxis
Management Recommendations Repeat endoscopy in 2-3 years No specific therapy Small varices Repeat endoscopy in 1-2 years No specific therapy ? beta-blocker to prevent enlargement
Primary prophylaxis
Medium/Large varices Non-selective beta-blockers EVL in those who are intolerant to drugs Endoscopic/pharmacologic therapy Antibiotics in all patients TIPS or shunt surgery as rescue therapy
SUMMARY OF MANAGEMENT OF VARICES AND VARICEAL HEMORRHAGE
Evolution of Varices
Level of Intervention
Cirrhosis with no varices Small varices No hemorrhage
Medium / large varices No hemorrhage
Pre-primary prophylaxis
Repeat endoscopy in 2-3 years No specific therapy Small varices Repeat endoscopy in 1-2 years No specific therapy ? beta-blocker to prevent enlargement
Primary prophylaxis
Medium/Large varices Non-selective beta-blockers EVL in those intolerant to drugs Endoscopic/pharmacologic therapy Antibiotics in all patients TIPS or shunt surgery as rescue therapy
Variceal hemorrhage
Secondary prophylaxis Recurrent variceal hemorrhage
Management Recommendations
Beta-blockers + nitrates or EVL Beta-blockers + EVL ? TIPS or shunt surgery as rescue therapy
AVANCES EN EL TRATAMIENTO DE LA ASCITIS Y SINDROME HEPATORENAL Dr. Aldo Torre Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”
JUNIO 2015
ASCITIS • 60% de los cirróticos compensados desarrollan ascitis a 10 años de iniciada la enfermedad. • Supervivencia posterior a la aparición de la ascitis a 1 y 5 años del 50 y 20%. • Ascitis refractaria en el 5 a 10% de los casos. • SV promedio 6 meses. • Indicación de trasplante.
Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Supervivencia del paciente con ascitis
Arroyo V et al. Semin Liver Dis 1986; 6: 353-369.
PATIENTS WITH REFRACTORY ASCITES HAVE A WORSE SURVIVAL THAN PATIENTS WITH DIURETIC-RESPONSIVE ASCITES
SV ascitis refractaria vs. ascitis que responde a diuréticos 1.0 .8
Non refractory ascites Survival probability
.6 .4
p<0.001
.2
Refractory ascites 0 0
12
24
36
48
60
72
84
Months Salerno et al., Am J Gastroenterol 1993; 88:514
NATURAL HISTORY OF ASCITES
Historia Natural de la Ascitis HTP sin ascitis
HVPG <10 mmHg Vasodilatación leve
Ascitis no complicada
HVPG >10 mmHg VD moderada
Ascitis refractaria
HVPG >10 mmHg VD severa
Síndrome Hepato-renal
HVPG >10 mmHg VD extrema
Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
NATURAL HISTORY OF ASCITES
Historia Natural de la Ascitis HTP sin ascitis
No tx. Restricción de sal
Ascitis no complicada
Ascitis refractaria
Síndrome Hepato-renal Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
NATURAL HISTORY OF ASCITES
Historia Natural de la Ascitis HTP sin ascitis
Ascitis no complicada
Restricción de sal Diuréticos
Ascitis refractaria
Síndrome Hepato-renal Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
MANAGEMENT OF UNCOMPLICATED ASCITES
Ascitis no complicada Definición: Ascitis que responde a diuréticos sin efectos adversos. Restricción de sodio
Efectivo en el 10 a 20%. Predictores de respuesta: Ascitis leve a moderada, Nau > 50 mEq/día
Diuréticos Basados en espironolactona Esquema ascendente, solo ó combinado con furosemide. Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
MANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTION
Manejo de la ascitis no complicada Restricción de sodio 2 g de sal al día; 90 mEq La restricción de líquidos es necesaria solo si el sodio esta por debajo de <125 mmol/L. Obtener balance negativo de sodio. Efectos colaterales: Afección nutricional. Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Manejo de la ascitis no complicada Terapia con diuréticos MANAGEMENT OF UNCOMPLICATED ASCITES: DIURETIC THERAPY
Dosis Espironolactona 100-400 mg/día Furosemida (40-160 mg/d) Incrementar diurético si la pérdida de peso es <1 kg en la primera semana y < 2 kg/sem en la semana posterior. Disminuír diurético si la pérdida de peso es >0.5 kg/día en pacientes sin edema >1 kg/día en pacientes con edema.
Efectos colaterales Insuficiencia renal, hiponatremia, hiperkalemia, encefalopatía ginecomastia
TRATAMIENTO DE LA ASCITIS MODERADA (GRADO 2) Pautas de tratamiento diurético Edemas periféricos Pérdida de peso ideal 1000g/día Escasa retención de sodio
Esp
Fur
Intensa retención de sodio
Esp
No Edemas periféricos Pérdida de peso ideal 500g/día Escasa retención de sodio
Fur
Esp
100
40
200
40
100
200
80
300
80
300
120
400
120
200 200
160
400
160
400
300 400 400
Intensa retención de sodio
Fur
Esp
Fur
-----
200 200 300 400 400
---
40 80 120 160
40 80 120 160
NATURAL HISTORY OF ASCITES
Historia Natural de la Ascitis HTP sin ascitis
Ascitis no complicada
Ascitis refractaria
Paracentesis evacuadora TIPS CCPV
Síndrome Hepato-renal Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
PARACENTESIS
ASCITIS REFRACTARIA Ventajas - Procedimiento fácil y disponible
- No encefalopatía - Pocos efectos colaterales Desventajas - Alta recurrencia de la ascitis
- Requiere uso de albúmina - Ingresos frecuentes al hospital Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
CORTO-CIRCUITO HEPATICO TRANSYUGULAR (TIPS)
ASCITIS REFRACTARIA Ventajas - Disminuye la actividad de los sistemas antinatriuréticos - Mejora la respuesta al diurético - Mejora la función renal en el SHR
Desventajas - Obstrucción frecuente - Equipo de hemodinámica hepática - Alta incidencia de encefalopatía - Mortalidad elevada en los pacientes Child C - Costo elevado Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Colocación de TIPS • -
Contraindicaciones absolutas. ICC. Quistes hepáticos múltiples. Sepsis descontrolada. Obstrucción biliar no resuelta. Hipertensión pulmonar severa.
Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Colocación de TIPS • • • • • • •
Contraindicaciones relativas. HCC, mayormente central. Trombosis venosa portal. Coagulopatía severa (INR >5). Plaquetas < 20,000. Hipertensión pulmonar moderada. Bioquímicos: Child > 11, Bilirrubinas > 3 mg/dL, Cr > 1.9 mg /dL Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
TRASPLANTE • • • -
Supervivencia de 70-80% a 5 años. Sin trasplante 20%. Factores pronósticos al trasplante: Disminución en la excreción renal de agua. Hiponatremia dilucional. PAM < 80 mmHg. FG disminuido. Na urinario < 10 mEq/día Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Magnitud del problema • • • • • •
Hacia el 2020 habrá 1,498,096 cirróticos. Hacia el 2050 serán 1,866,613 cirróticos. La prevalencia de EH es del 30 al 45%. Riesgo anual de desarrollo del 20%. Prevalencia estimada de EHM del 60 al 84%. 2020 pacientes con EH 444,209, hacia el 2050 565,984. • EHM 2020: 888,576, y hacia el 2050 1,258,400. Lizardi J et al Annals of Hepatol 2007 Bajaj JS Aliment Pharmacol Ther 2010
Glutamina
GLN
NH3 GLU ↑GABA
Cortocircuito
Astrocito
INFLAMACIÓN
NH3
Urea
Dieta
Flora colónica Glutaminasa
Urea Semin Liver Dis 2008;28:70-80. Gutt 2008;571156-1165.
Glutamina
GLN
NH 3 crecimiento. Hormona de GLU ↑GABA
Factor de crecimiento semejante a la insulina. Antagonistas de miostatina. Testosterona. Cortocircuito Astrocito Aminoácidos de cadena ramificada. Ejercicio. Dietas hiperproteícas.
INFLAMACIÓN
NH3
Urea
Dieta
Flora colónica Glutaminasa
Urea Semin Liver Dis 2008;28:70-80. Gutt 2008;571156-1165.