Liver stiffness predicts liver related events and mortality in HIV/HCV coinfected patients

Transcription

1 Liver stiffness predicts liver related events and mortality in HIV/HCV coinfected patients José Vicente Fernández-Montero, Pablo Barreiro, Eugenia Vispo, Pablo Labarga, Francisco Blanco, Fernanda Rick, Vicente Soriano Department of Infectious Diseases, Hospital Carlos III, Madrid (Spain)

2 BACKGROUND

3 Mortality in HIV+ patients Global HIV/AIDS Response. WHO, 2011

4 Mortality in HIV+ patients Adapted from Weber R, et al. Arch Intern Med 2006

5 De Lédinghen et al. J Viral Hepat 2008

6 Fernández-Montero JV et al. ICVH Abstract Figure 2. Liver fibrosis progression rate (kpa/year) * p< p<0.0001

7 Transient elastometry Lengthy experience of use >500 papers in indexed journals since 2003 Validated HCV Ziol M. Hepatology 2005 HCV/HIV HBV De Lédinghen. JAIDS 2006 Foucher J. Gut 2006

8 Transient elastometry Accuracy similar to liver biopsy Stebbing J. J Clin Gastroenterol 2010 Good interobserver concordance Neukam K. Eur J Gastroenterol Hepatol 2010 Cost-effective García-Jurado L. Enferm Infecc Microbiol Clin 2011 Suitable for different patients Pediatric Nobili V. Hepatology 2008 Obesity De Lédinghen. Liver Int 2010

9 OBJECTIVES

10 Assessment of the reliability of TE as predictive tool of liver-related morbidity and all-cause mortality in HIV/HCV coinfected patients Determination of factors related with liver morbidity and mortality in this population

11 METHODS

12 Follow-up Event TE 1 TE 2 18 months N= Jan 2012 Data collection: -Demographics -Laboratory -HIV-related -HCV-related Data collection: -Demographics -Laboratory -HIV-related -HCV-related

13 Methods METAVIR estimates F0-F1: <7.2 kpa F2: kpa F3: kpa F4: >12.5 kpa Castéra L. Hepatology 2005 Liver-related event Development of ascites, encephalopathy, oesophageal varices or HCC Liver fibrosis progression Increase from F0-F2 in TE1 to F3-F4 in TE2 or an increase of >30% in liver stiffness in those patients with F3-F4 in TE1

14 RESULTS

15 N=525 Mean ±SD Age (years) 41.5±5.3 Male sex (%) 71.5 IDU (%) 81 HBsAg+ (%) 4.2 HDV+ (%) 1.5 Alcohol >60 g/day (%) 8.4 BMI (kg/m 2 ) 23.3±3.9 CD4 cell count (cells/µl) 519±284 Glucose (mg/dl) 100±14 Total cholesterol (mg/dl) 166±37 ALT (IU/mL) 65±54 HIV viral load (log copies/ml) 2.24±1 HCV viral load (log copies/ml) 4.9±2.2 F3-F4 in TE1 (%) 33.2 Mean period between TE (mo) 53±16 Mean follow-up period (mo) 70.9±15.7

16 Table 2. HCV genotype distribution HCV genotype % Table 3. Patient distribution according to HCV therapy Antiviral therapy N Achieving SVR 138 (25.2%) Therapy failure 197 (36%) Naïve 192 (35.1%)

17 Clinical outcomes 12 patients (2.2%) died 4 liver-related 2 HCC 2 cirrhosis 3 Non-HIV malignancies 2 CVD 2 non-aids infectious complications 1 renal failure

18 Clinical outcomes 53 patients (10%) developed liver-related events 28 oesophageal varices 17 ascites 4 encephalopathy 4 HCC

19 Table 4. Factors associated with all-cause mortality Univariate (OR, CI 95%, p) Multivariate (OR, IC95%, p) Age 1.05 ( ), 0.4 Sex 4.02 ( ), 0.19 Baseline stiffness 1.04 (1-1.08), ( ), Liver fibrosis progression 5.42 ( ), HBV 0 (0-), 0.99 BMI 0.89 ( ), ( ), Alcohol abuse 0 (0-), 0.99 CD4 cell count 0.99 ( ), 0.25 Glucose 0.97 ( ), 0.36 Total cholesterol 0.99 ( ), 0.29 ALT 0.99 ( ), 0.93 Baseline METAVIR 1.63 ( ), Months between TE 0.96 ( ), 0.02 Baseline Log CV VIH 1.21 ( ), 0.46 Baseline Log CV VHC 1.13 ( ) ( ), 0.09 SVR after therapy 0.22 ( ), 0.15 Baseline Fib ( ), ( ), 0.08 Baseline APRI 1.21 ( ), 0.16

20 Figure 1. Survival curve according to baseline METAVIR stage F0-F2 F3-F4 Log Rank= 0.02 Cumulative survival Follow-up (mo.)

21 Table 5. Factors related with liver morbidity Univariate (OR, CI 95%, p) Multivariate (OR, CI 95%,p) Age 1.02 ( ), 0.39 Sex 1.56 ( ), 0.2 Baseline stiffness 1.1 ( ), < ( ), Liver fibrosis progression 8.35 ( ), < ( ), HBV 2.25 ( ), 0.16 BMI 1.01 ( ), ( ), 0.03 Alcohol abuse 1.8 ( ) CD4 cell count ( ), Glucose 1.02 (1-1.04), 0.04 Total cholesterol 0.99 ( ), 0.04 ALT 1 (1-1.01), ( ), 0.08 Baseline METAVIR 2.85 ( ) < ( ), Months between TE 0.99 ( ), 0.45 Baseline Log CV VIH 1.13 ( ), 0.36 Baseline Log CV VHC 0.95 ( ), 0.65 SVR after therapy 0.18 ( ), ( ), Baseline Fib ( ), < Baseline APRI 3 ( ) <0.0001

22 Figure 2. K-M curve for development of liver-related events F0-F2 F3-F4 Cumulative survival Log rank < Follow-up (mo.)

23 CONCLUSIONS

24 Baseline transient elastometry values are predictors of all-cause mortality and liverrelated morbidity in HIV/HCV-coinfected patients The achievement of SVR after antiviral therapy and higher BMI values protect against the development of liver-related morbidity

25 Acknowledgements Medical staff: Vicente Soriano, Pablo Barreiro, Eugenia Vispo, Francisco Blanco, Fernanda Rick Everyone at the Molecular Biology Laboratory of the ID Department, Hospital Carlos III