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Utility of non-invasive markers for prediction of significant hepatic fibrosis in chronic hepatitis C patients. V. Petrenkiene * , D. Petrauskas L. Kupcinskas, Lithuanian University of Health sciences Clinic of Gastroenterology Kaunas. BACKGROUND.
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Utility of non-invasive markers for prediction of significant hepatic fibrosis in chronic hepatitis C patients V. Petrenkiene*, D. Petrauskas L. Kupcinskas, Lithuanian University of Health sciences Clinic of Gastroenterology Kaunas
BACKGROUND • Over the past decade many studies have evaluated non-invasive tests of liver fibrosis to assess the presence and severity of fibrosis in chronic liver diseases. • Non-invasive markers and commercial tests of liver fibrosis have been proposed and assessed in the clinical setting as surrogates of liver biopsy. • However, their implementation in clinical practice is slow and still limited.
AIM To determine the utility of non-invasive markers using routine laboratory tests for the prediction of significant fibrosis and cirrhosis in a cohort of chronic hepatitis C (CHC) patients
METHODS (1) Inclusion criteria • Treatment naive 18-70 years old CHC patients with serum HCV-antibody and HCV RNA positivity. • Having liver biopsy between Jan 2000 and Nov 2005 with sufficient liver tissue for fibrosis staging (>7 intact portal tracts). • Having a blood sample drawn for the measurement of the liver panel and blood counts one day before the biopsy and abdominal ultrasound examinations with measurement of spleen diameter. • Patients without a history of alcohol intake (> 30 g/day for males and 20 g/day for females). • No evidence of other liver diseases.
METHODS (2) Biopsy: Menghini 14-gauge needle;Histology:Knodell–Ishak fibrosis staging system ona scale F0-F6 (Masson trichrome stain). 3. Fibrosis with occasional (P-P) bridging. 1. Fibrosis of some portal areas. 2. Fibrosis expansion of most portal areas. 6. Cirrhosis, probable or definite. 5. Incomplete cirrhosis. 4. Fibrosis with P-P and P-C bridging. Staging was performed blinded to clinical data by one expert pathologist.
METHODS (3) Indirect non-invasive tests of liverfibrosis used • AAR - AST/ALT. • Platelet count. • APRI - AST/platelet count (×109/l)×100. • GUCI (the Göteborg University Cirrhosis Index):AST×prothrombin(INR)×100/platelet count (×109/l). • Platelet count/spleen diameter ratio index.
METHODS (4) Flow diagram of the potential candidatesfor participation in the study 402 CHC PATIENTS REGISTERED FROM January 2000UNTIL November 2005 43 patients with insufficient liver sample 31 patients with incomplete data 5 patients with active alcohol abuse 323 CHC PATIENTS INCLUDED F 0-2 N=148 F 3-6 N=175 F 5-6 N=67
RESULTS (1) • 323 naive CHC patients • 194 (60.1%) male • 129 (39.9%) female • Mean age: 48.5 year • Histological staging • F0 6.5% (n= 21) • F1 13.9% (n= 45) • F2 25.4% (n= 82) • F3 23.5% (n= 76) • F4 9.9% (n= 32) • F5 3.7% (n= 12) • F6 17.0% (n= 55)
METHODS (5) Statistical analysis • Quantitative data were expressed as mean and standard error (SE). • The variation in the proportions were assessed using Chi-square test. • P values of 0.05 were considered significant. • The diagnostic value for each marker was assessed using the area under the receiver operating characteristics curves (AUROC). • Statistical analysis was carried out using the SPSS 12.0 software package.
Results (2) Variables for predicting significant fibrosis and cirrhosis
RESULTS (3) Cut-off points to predict the absence or presence of significant fibrosis and cirrhosis
RESULTS (4) Sensitivity, specificity, positive (PPV), and negative (NPV) predictive value of evaluated parameters in detecting significant (F 3-6) fibrosis
RESULTS (5) Sensitivity, specificity, positive (PPV), and negative (NPV) predictive value of evaluated parameters in detecting cirrhosis (F 5-6)
CONCLUSIONS (1) • Non-invasive tests of liver fibrosis based on a few standard laboratory tests: APRI, platelet count, AST/ALT ratio, GUCI, platelet count/spleen diameter ratioare useful to predict advanced fibrosis in HCV-infected patients and can bee used in clinical setting when liver biopsy is not available (outpatient care, regional hospitals). • Prediction of cirrhosis (F5-F6) by simple non-invasive tests is superior to prediction of significant fibrosis (F3-F6).
CONCLUSIONS (2) • Implementation of fibrosis markers using routinelaboratory testscan • reduce, but not completely eliminate, theneedforliver biopsy. • Therefore,liver biopsy still remain a ‘gold standard’ forassessment of • liver fibrosis in tertiary hospital setting.