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)
BACKGROUND
Mortality in HIV+ patients Global HIV/AIDS Response. WHO, 2011
Mortality in HIV+ patients Adapted from Weber R, et al. Arch Intern Med 2006
De Lédinghen et al. J Viral Hepat 2008
Fernández-Montero JV et al. ICVH 2012. Abstract 78766 Figure 2. Liver fibrosis progression rate (kpa/year) * p<0.0001 p<0.0001
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
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
OBJECTIVES
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
METHODS
Follow-up Event TE 1 TE 2 18 months N=525 2004 Jan 2012 Data collection: -Demographics -Laboratory -HIV-related -HCV-related Data collection: -Demographics -Laboratory -HIV-related -HCV-related
Methods METAVIR estimates F0-F1: <7.2 kpa F2: 7.2-9.4 kpa F3: 9.5-12.4 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
RESULTS
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
Table 2. HCV genotype distribution HCV genotype % 1 63.4 2 1.1 3 20.7 4 14.8 Table 3. Patient distribution according to HCV therapy Antiviral therapy N Achieving SVR 138 (25.2%) Therapy failure 197 (36%) Naïve 192 (35.1%)
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
Clinical outcomes 53 patients (10%) developed liver-related events 28 oesophageal varices 17 ascites 4 encephalopathy 4 HCC
Table 4. Factors associated with all-cause mortality Univariate (OR, CI 95%, p) Multivariate (OR, IC95%, p) Age 1.05 (0.94-1.17), 0.4 Sex 4.02 (0.51-31.65), 0.19 Baseline stiffness 1.04 (1-1.08), 0.03 1.35 (1.04-1.74), 0.026 Liver fibrosis progression 5.42 (1.62-18.14), 0.006 HBV 0 (0-), 0.99 BMI 0.89 (0.76-1.05), 0.17 0.54 (0.29-1.01), 0.051 Alcohol abuse 0 (0-), 0.99 CD4 cell count 0.99 (0.99-1.001), 0.25 Glucose 0.97 (0.92-1.03), 0.36 Total cholesterol 0.99 (0.97-1.01), 0.29 ALT 0.99 (0.98-1.01), 0.93 Baseline METAVIR 1.63 (0.99-2.67), 0.051 Months between TE 0.96 (0.93-0.99), 0.02 Baseline Log CV VIH 1.21 (0.72-2.05), 0.46 Baseline Log CV VHC 1.13 (0.65-1.96) 0.66 3.07 (0.85-11), 0.09 SVR after therapy 0.22 (0.03-1.71), 0.15 Baseline Fib4 1.04 (0.97-1.12), 0.28 0.056 (0.002-1.42), 0.08 Baseline APRI 1.21 (0.93-1.58), 0.16
Figure 1. Survival curve according to baseline METAVIR stage F0-F2 F3-F4 Log Rank= 0.02 Cumulative survival Follow-up (mo.)
Table 5. Factors related with liver morbidity Univariate (OR, CI 95%, p) Multivariate (OR, CI 95%,p) Age 1.02 (0.97-1.08), 0.39 Sex 1.56 (0.78-3.13), 0.2 Baseline stiffness 1.1 (1.08-1.14), <0.0001 1.22 (1.06-1.41), 0.007 Liver fibrosis progression 8.35 (4.56-15.27), <0.0001 214.1 (7.3-6285), 0.002 HBV 2.25 (0.72-7.04), 0.16 BMI 1.01 (0.94-1.1), 0.68 0.8 (0.65-0.98), 0.03 Alcohol abuse 1.8 (0.75-4.31) CD4 cell count 0.998 (0.997-0.999), 0.003 Glucose 1.02 (1-1.04), 0.04 Total cholesterol 0.99 (0.98-0.99), 0.04 ALT 1 (1-1.01), 0.053 1.02 (0.99-1.04), 0.08 Baseline METAVIR 2.85 (2.12-3.84) <0.0001 4.42 (0.97-20.4), 0.056 Months between TE 0.99 (0.97-1.01), 0.45 Baseline Log CV VIH 1.13 (0.87-1.48), 0.36 Baseline Log CV VHC 0.95 (0.77-1.18), 0.65 SVR after therapy 0.18 (0.06-0.51), 0.001 0.04 (0.003-0.66), 0.002 Baseline Fib4 1.48 (1.28-1.7), <0.0001 Baseline APRI 3 (1.9-4.74) <0.0001
Figure 2. K-M curve for development of liver-related events F0-F2 F3-F4 Cumulative survival Log rank <0.0001 Follow-up (mo.)
CONCLUSIONS
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
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