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COHORTE DE PACIENTES CON CIRROSIS HEPÁTICA . Dr. José R Arribas Unidad VIH Servicio de Medicina Interna. Morbidity and mortality in HIV infected patients with compensated and decompensated cirrhosis: prospective cohort of 373 patients.

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cohorte de pacientes con cirrosis hep tica
COHORTE DE PACIENTES CON CIRROSIS HEPÁTICA

Dr. José R Arribas

Unidad VIH

Servicio de Medicina Interna

slide2

Morbidity and mortality in HIV infected patients with compensated and decompensated cirrhosis: prospective cohort of 373 patients

M López-Diéguez, JF Pascual, M Montes, C Quereda, MA Von Wichmann, J Berenguer, C Tural, JM Miró, F Pulido, E Ortega, A Arranz, J González-García, JR Arribas and the GESIDA 37/03-FIPSE 364665/03 Study Group.

Oral Presentation at EACS2007 PS8/4

objective
OBJECTIVE

To evaluate morbidity/mortality in HIV-infected patients with compensated vs decompensated liver cirrhosis.

study design 1
STUDY DESIGN (1)
  • Multicenter national prospective cohort.
    • País Vasco
      • H. Virgen de Aranzazu.
    • Valencia
      • H. General Universitario Valencia.
    • Barcelona
      • H. Clinic y Provincial.
      • H. Germans Trias i Pujol.
    • Madrid
      • H. Príncipe de Asturias.
      • H. Gregorio Marañón.
      • H. Ramón y Cajal.
      • H. Doce de Octubre.
      • H. La Paz.
study design 2
STUDY DESIGN (2)

Cirrhosis Diagnosis

Biopsy: (Cirrhosis or advanced bridging fibrosis).

Decompensation

Gastrointestinal bleeding, ascites, hepatic encephalopathy.

Bonacini Score > 8 (Am J Gastroenterol 1997;92:1302).

bonacini score for cirrhosis diagnosis
BONACINI SCORE FOR CIRRHOSIS DIAGNOSIS

Three-parameter cirrhosis discriminant score:

Platelets – ALT/AST ratio – PT

Cutoff for cirrhosis diagnosis = 8

Sensibility 46%

Specifycity 98%

Bonacini M, et al. Am J Gastroenterol 1997;92:1302.

study design 3
STUDY DESIGN (3)

Total planned follow-up 48 months.

Visits: baseline and then every 6 months.

Each visit:

Personal interview.

Hematology, Biochemistry, Inmmunology, Virology, alfa-fetoprotein.

Abdominal US.

Each year:

Endoscopy to detect esophageal varices (according to Schepis criteria*).

Schepis et al. Hepatology 2001; 33:471-2.

study design 4
STUDY DESIGN (4)

SURVIVAL: time from the date of entry until the first endpoint occurred.

ENDPOINT: death, hepatocarcinoma or liver transplant.

STATISTICAL ANALISYS: Kaplan-Meyer analysis, log rank test (comparison of survival between different groups).

slide10

BASELINE CHARACTERISITICS (2)

*Below limit of quantification (50-200) c/ml.

survival
SURVIVAL

0.82

Cumulative probability of survival

Months

N 332 302 264 169

survival compensated vs decompensated
SURVIVALCompensated vs Decompensated

0.92

Cumulative probability of survival

0.53

p<0,0001 (log-rank)

Months

Compensated 253 241 218 141

Decompensated 78 60 45 27

survival child pugh score
SURVIVAL Child Pugh Score

A

0.96

B

0.53

Cumulative probability of survival

C

0.27

p<0,0001 (log-rank)

Months

CP-A 219 213 196 128

CP-B 57 46 34 17

CP-C 21 12 7 5

probability of first decompensation
PROBABILITY OF FIRST DECOMPENSATION

Percent wiithout decompensation

Months

N 253 237 210 147

conclusions
CONCLUSIONS

HIV-infected patients with compensated liver cirrhosis had a relatively high survival with a low per year probability of first decompensation.

HIV-infected patients with decompensated cirrhosis have a very poor prognosis. One third of our patients with decompensated liver cirrhosis died during the first year of follow-up.

Child Pugh score apears as a good prognostic score for HIV-infected patients with liver cirrhosis.

These results emphasize the critical importance of avoiding the development of end-stage liver disease in HIV-infected patients.

Analysis of factors associated to survival will be available soon

slide20

FACTORS ASSOCIATED WITH SURVIVAL AND FIRST HEPATIC DECOMPENSATION IN A LARGE PROSPECTIVE COHORT OF HIV-HCV CO-INFECTED PATIENTS WITH LIVER CIRRHOSIS.

M López-Diéguez, JF Pascual, M Montes, C Quereda, MA Von Wichmann, J Berenguer, C Tural, JM Miró, F Pulido, E Ortega, A Arranz, J González-García, JR Arribas and the GESIDA 37/03-FIPSE 364665/03 Study Group.

Poster Presentation at CROI2008 [1057]

methods
METHODS
  • Prospective multicenter cohort of 331 HIV-HCV coinfected patients with cirrhosis. Median follow-up time: 18 months.
  • Cirrhosis diagnosis (n,%): biopsy (209, 63%), prior decompensation (86, 26%), Bonacini Score ≥ 8 (36, 11%).
  • Endpoints: death, hepatocarcinoma or liver transplant.
  • Survival defined as the time from entering in the cohort until first endpoint occurred.
  • The association of survival with different factors was explored in univariate and multivariate Cox proportional hazard models. Variables included: age, sex, time since cirrhosis/HIV diagnosis, alcohol intake, CD4 count (nadir, baseline and <100 at baseline), HIV viremia, suppressed HIV replication, history of anti-HCV therapy, HCV genotype, sustained viral response to anti-HCV therapy, concomitant chronic HBV, history of cirrhosis decompensation, Child Pugh score and HAART (at baseline, continuous/interrupted during follow-up).
  • For patients with no history of prior liver decompensation at baseline we explored variables associated with the development of first decompensation.
endpoints
ENDPOINTS
  • Endpoints: 62 (54 deaths, 9 hepatocarcinomas, and 1 liver transplant).
  • Compensated cirrhosis at baseline: 19 (16 deaths, 3 Hepatocarcinomas)
  • Decompensated cirrhosis at baseline: 43 (38 deaths, 6 Hepatocarcinomas, 1 Liver Transplant)
multivariate analysis hazard ratio of factors associated with decreased survival hr ci p
Multivariate analysis: Hazard ratio of factors associated with decreased survival [HR, (CI), p]
survival according to child pugh score
Survival according to Child Pugh Score

Child Pugh A

Child Pugh B

Child Pugh C

(N) CP-A 220 213 205 184 74

CP-B 58 48 38 30 7

CP-C 22 14 8 6 1

probability of first decompensation according to child pugh score
Probability of first decompensation according to Child Pugh Score

Child Pugh A

Child Pugh B

(N) CP-A 206 198 187 167 65

CP-B 25 19 11 8 3

conclusions29
CONCLUSIONS
  • Child-Pugh scores B and C are significantly associated with decreased survival in HIV-HCV coinfected patients with cirrhosis.
  • Maintaining HIV viral suppression and receiving continuous HAART are associated with prolonged survival. Our study supports the continuous use of HAART in this population.
  • Child-Pugh B is significantly associated with the short-term risk of first hepatic decompensation. HIV-HCV coinfected patients with compensated cirrhosis and a Child-Pugh B score should be followed closely for the development of decompensation.
resumen
RESUMEN
  • El estudio GESIDA 37/03 es una de las cohortes más grandes de pacientes infectados por VIH con cirrosis hepática.
  • Hasta el momento esta cohorte nos ha permitido caracterizar mejor la historia natural de la cirrosis hepática en esta población
  • Además hemos podido analizar los factores relacionados con la supervivencia y la primera descompensación.
  • Continuamos el seguimiento activo de esta cohorte (Dra. Marisa Montes)
agradecimientos
AGRADECIMIENTOS
  • M López-Diéguez, JF Pascual, M Montes, C Quereda, MA Von Wichmann, J Berenguer, C Tural, JM Miró, F Pulido, E Ortega, A Arranz, J González-García, Rosario Madero, Herminia Esteban