COHORTE DE PACIENTES CON CIRROSIS HEP

1
COHORTE DE PACIENTES CON CIRROSIS HEPÁTICA
Dr. José R Arribas Unidad VIH Servicio de
Medicina Interna
2
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

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OBJECTIVE

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

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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.

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STUDY DESIGN (2)

• Cirrhosis Diagnosis
• Biopsy (Cirrhosis or advanced bridging
  fibrosis).
• Decompensation
• Gastrointestinal bleeding, ascites, hepatic
  encephalopathy.
• Bonacini Score gt 8 (Am J Gastroenterol
  1997921302).

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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
1997921302.
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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 33471-2.
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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).

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BASELINE CHARACTERISITICS (1)
All Compensated Decompensated
N 373 274 99
Mean age (years ) 44 44 43
Female () 80 (22) 61 (22,2) 19 (19,4)
Cirrhosis diagnosis Biopsy () Bonacini Score gt8 () Prior decompensation () 234 (63) 41 (11) 98 (26) 234 (85,1) 41 (14,9) _ _ _ 98 (100)
Cirrhosis causes Hepatitis C () Genotypes 2 or 3 () Hepatitis B () Prior alcohol abuse () 370 (99,2) 81 (21,7) 24 (6,4) 115 (31) 274 (99,7) 63 (22,9) 17 (6,2) 74 (26,9) 96 (97,9) 18 (18,4) 7 (7,1) 41 (41,8)
Median duration HIV infection (years) 15 15 15
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BASELINE CHARACTERISITICS (2)
All Compensated Decompensated
Median duration HVC infection (years) 23 23 23
HCV treatment received () 205 (55) 178 (64,7) 27 (27,6)
CDC stage C () 143 (39,3) 90 (32,8) 53 (54,1)
Receiving HAART at baseline () 322 (82,8) 244 (88,7) 78 (79,6)
HIV Transmission route - IVDU () 328 (88) 239 (86,9) 89 (90,8)
CD4 cell count (median, IQR) Baseline Nadir 373 (228 - 577) 145 (70 - 255) 434 (272 - 644) 175 (76 - 270) 239 (140 - 365) 104 (58 - 180)
HIV-RNA Baseline (median, IQR) HIV RNA BLQ 49 (49 - 398) 72,4 49 (49 - 200) 75,6 49 (49 - 1229) 65,2
Below limit of quantification (50-200) c/ml.
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RESULTS
All Compensated Descompensated
Lost to follow-up () 40 (10,7) 21 (7,6) 19 (19,4)
Follow-up (median, IQR) 18 (14-20) 18 (15,7-20,2) 16 (6-19)
Endpoints, n () Any Death Hepatocarcinoma Transplant 63 (18,9) 55 (16,5) 2 (0,6) 9 (2,7) 20 (7,9) 17 (6,7) _ 3 (1,2) 43 (54,4) 38 (48,1) 2 (2,5) 6 (7,6)
Deaths, n () Hepatic causes Other Unknown 33 (9,9) 14 (1,8) 6 (1,8) 6 (2,4) 6 (2,4) 5 (2) 27 (34,2) 8 (10,1) 1 (1,3)
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RESULTS
Baseline Initially compensated
Type of Decompensations n () Ascites GI bleeding Encephalopathy HRS SBP Unknown 99 (26,5) 51 (51,1) 12 (12,1) 10 (10,1) 15 (15,2) 4 (4) 7 (7,1) 17 (6,2) 6 (2,2) 2 (0,7) 7 (2,6) 2 (0,7)
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SURVIVAL
0.82
Cumulative probability of survival
Months
N 332 302
264 169
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SURVIVALCompensated vs Decompensated
0.92
Cumulative probability of survival
0.53
plt0,0001 (log-rank)
Months
Compensated 253
241 218
141 Decompensated
78 60
45 27
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SURVIVAL (months)
COMPENSATED DECOMPENSATED
Mean (IC95) Median (IC95) 1 year probability 2 years probability 3 years probability 66 (63-69) NA 0.95 0.90 0.90 19 (15-23) 18 (12-24) 0.63 0.32 _
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SURVIVAL Child Pugh Score
A
0.96
B
0.53
Cumulative probability of survival
C
0.27
plt0,0001 (log-rank)
Months
CP-A 219 213
196
128 CP-B 57
46
34 17
CP-C 21
12
7 5
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SURVIVAL (months)
CHILD-PUGH SCORE CHILD-PUGH SCORE CHILD-PUGH SCORE
A B C
Mean (IC95) Median (IC95) 1 year probability 2 years probability 3 years probability 68 (65-70) NA 0.98 0.92 0.92 22 (18-26) 19 (13-25) 0.65 0.49 _ 10 (6-13) 7 (5-9) 0.32 _ _
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PROBABILITY OF FIRST DECOMPENSATION
Probability of decompensation
One year Two years Three years 0.04 (IC95 0.01 0.07) 0.07 0.09
Percent wiithout decompensation
Months
N 253 237
210
147
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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

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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

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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 lt100 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.

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BASELINE CHARACTERISTICS
Male, N, () 258 (78)
Age, median, (IQR) 44 (4147)
Months of follow-up, median, (IQR) 18 (1220)
Years since HIV diagnosis, median, (IQR) 16 (1119)
Years since cirrhosis diagnosis, median, (IQR) 3 (25)
CDC C3, N, () 93 (28.1)
IVDU, N, () 292 (88.2)
HAART, N, () at baseline 287 (87)
non continuous HAART 166 (50)
Alcohol abuse, N, () 100 (30.2)
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BASELINE CHARACTERISTICS
CD4, median, (IQR) at baseline nadir 384 150 (232589) (71258)
HIV-RNA lt BLQ, N, () 236 (74)
HVB co-infection, N, () 20 (6)
HCV genotype 2 or 3, N, () 71 (27)
HCV therapy, N, () sustained viral response, N, () still non evaluable, N, () 191 37 52 (57.7) (11.2) (15.7)
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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)

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Variables associated to survival. Univariate
analysis
HR (CI 95) p
Male gender 2.37 (1.078 5.21) 0.032
Alcohol intake 0.506 (0.306 0.838) 0.008
CD4 lt100 at baseline 3.26 (1.48 7.19) 0.003
Unsuppressed VL at baseline 2.16 (1.27 3.65) 0.004
No HCV therapy received 3.01 (1.76 5.14) lt 0.0001
No response to HCV therapy 7.31 (1.01 52.81) 0.048
Non-Continuous HAART during follow up 15.37 (6.15 38.46) lt 0.0001
CD4 nadir 0.997 (0.995 0.999) 0.008
Child Pugh score B Child Pugh score C 14.46 (6.97 29.9) 39.45 (17.96 86.65) lt 0.0001 lt 0.0001
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Multivariate analysis Hazard ratio of factors
associated with decreased survival HR, (CI), p
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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
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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
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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.

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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)

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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