cohorte de pacientes con cirrosis hepÁtica dr. josé r arribas unidad vih servicio de medicina...
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COHORTE DE PACIENTES CON CIRROSIS HEPÁTICA
Dr. José R Arribas
Unidad VIHServicio de Medicina Interna
Morbidity and mortality in HIV infected patients with Morbidity and mortality in HIV infected patients with compensated and decompensated cirrhosis: compensated and decompensated cirrhosis:
prospective cohort of 373 patientsprospective 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
To evaluate morbidity/mortality in HIV-infected patients with compensated vs decompensated liver cirrhosis.
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)
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
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)
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)
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).
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 >8 (%)- 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
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
BASELINE CHARACTERISITICS (2)
*Below limit of quantification (50-200) c/ml.
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)
RESULTS
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)
SURVIVAL
N 332 302 264 169
Cum
ulative probability of survival
Months
0.82
SURVIVALCompensated vs Decompensated
Compensated 253 241 218 141Decompensated 78 60 45 27
p<0,0001 (log-rank)
Cum
ulative probability of survival
Months
0.92
0.53
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
_
SURVIVAL Child Pugh Score
A
B
C
CP-A 219 213 196 128CP-B 57 46 34 17 CP-C 21 12 7 5
p<0,0001 (log-rank)
Cum
ulative probability of survival
Months
0.96
0.53
0.27
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
_
_
SURVIVAL (months)
N 253 237 210 147
PROBABILITY OF FIRST DECOMPENSATION
Percent wiithout decom
pensation
Months
Probability of decompensation
One year
Two years
Three years
0.04 (IC95% 0.01 – 0.07)
0.07
0.09
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
FACTORS ASSOCIATED WITH SURVIVAL AND FIRST HEPATIC FACTORS ASSOCIATED WITH SURVIVAL AND FIRST HEPATIC DECOMPENSATION IN A LARGE PROSPECTIVE COHORT OF DECOMPENSATION IN A LARGE PROSPECTIVE COHORT OF HIV-HCV CO-INFECTED PATIENTS WITH LIVER CIRRHOSIS.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 <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.
BASELINE CHARACTERISTICS
Male, N, (%) 258 (78)Age, median, (IQR) 44 (41–47)Months of follow-up, median, (IQR) 18 (12–20)Years since HIV diagnosis, median, (IQR) 16 (11–19)Years since cirrhosis diagnosis, median, (IQR) 3 (2–5)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)
BASELINE CHARACTERISTICS
CD4, median, (IQR)
at baseline
nadir
384
150
(232–589)
(71–258)HIV-RNA < 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)
Variables associated to survival. Univariate analysis
HR (CI 95%) p
Male gender 2.37 (1.078 – 5.21) 0.032Alcohol intake 0.506 (0.306 – 0.838) 0.008CD4 <100 at baseline 3.26 (1.48 – 7.19) 0.003Unsuppressed VL at baseline 2.16 (1.27 – 3.65) 0.004No HCV therapy received 3.01 (1.76 – 5.14) < 0.0001No response to HCV therapy 7.31 (1.01 – 52.81) 0.048Non-Continuous HAART during follow up
15.37 (6.15 – 38.46) < 0.0001
CD4 nadir 0.997 (0.995 – 0.999) 0.008Child Pugh score B
Child Pugh score C
14.46 (6.97 – 29.9)
39.45 (17.96 – 86.65)
< 0.0001
< 0.0001
Multivariate analysis: Hazard ratio of factors associated with decreased survival [HR, (CI), p]
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
(N) CP-A 206 198 187 167 65 CP-B 25 19 11 8 3
Child Pugh A
Child Pugh B
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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