V. Petrenkiene*, D. Petrauskas L. Kupcinskas, Lithuanian University of Health sciences

Clinic of Gastroenterology Kaunas

Utility of non-invasive markers for prediction of significant hepatic

fibrosis in chronic hepatitis C patients

• 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.

BACKGROUNDBACKGROUND

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)

• 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.

Inclusion criteria

Biopsy: Menghini 14-gauge needle;Histology: Knodell–Ishak fibrosis staging system on a scale F0-F6 (Masson trichrome stain).

1. Fibrosis of some portal areas. 3. Fibrosis with occasional (P-P) bridging.

4. Fibrosis with P-P and P-C bridging.5. Incomplete cirrhosis. 6. Cirrhosis, probable or definite.

2. Fibrosis expansion of most portal areas.

Staging was performed blinded to clinical data by one expert pathologist.

METHODS (2)METHODS (2)

METHODS (3)

1. AAR - AST/ALT.

2. Platelet count.

3. APRI - AST/platelet count (×109/l)×100.

4. GUCI (the Göteborg University Cirrhosis Index):AST×prothrombin(INR)×100/platelet count (×109/l).

5. Platelet count/spleen diameter ratio index.

Indirect non-invasive testsof liver fibrosis used

METHODS (4)

402 CHC PATIENTS REGISTERED FROM January 2000 UNTIL November 2005

323 CHC PATIENTSINCLUDED

43 patients with insufficient liver sample

31 patients with incomplete data

5 patients withactive alcohol abuse

F 0-2N=148

F 3-6N=175

F 5-6N=67

Flow diagram of the potential candidatesfor participation in the study

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)

• 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.

Statistical analysis

Results (2)

VariablesPrediction of significant fibrosis

(F3-F6)AUC (95%CI)

Prediction of cirrhosis(F5-F6)

AUC (95%CI)

Platelet count 0.69 (0.49-0.71) 0.85 (0.72-0.89)

AAR 0.65 (0.59-0.72) 0.76 (0.69-0.83)

APRI 0.73 (0.68-0.79) 0.89 (0.84-0.94)

GUCI 0.74 (0.69-0.79) 0.89 (0.85-0.95)

Platelet/spleendiameter

0.71 (0.65-0.77) 0.88 (0.88-0.93)

Variables for predictingsignificant fibrosis and cirrhosis

RESULTS (3)

VariablesSignificant fibrosis

(F3-F6) Cirrhosis(F5-F6)

Presence Absence

APRI ≥1.5 <2.0

Platelet/spleen diameter <1.5 >1.5

AAR ≥ 1 <1

GUCI >1.5 <2.0

Platelet count <150 x10(9)/L ≥ 150 x10(9)/L

Cut-off points to predict the absence or presence of significant fibrosis and cirrhosis

RESULTS (4)

Variables Sensitivity %

Specificity %

PPV % NPV % Accuracy %

Platelet count 42.5 87.8 80.4 56.5 63.4

AAR 46.8 89.2 83.7 58.7 66.3

APRI 81,4 61.7 79.5 70.7 72.1

GUCI 58.0 81.5 58.0 38.0 68.8

Platelet/spleen diameter

56.1 79.5 76.4 60.4 60.2

Sensitivity, specificity, positive (PPV), and negative (NPV) predictive value of evaluated parameters in detecting significant (F 3-6) fibrosis

RESULTS (5)

Variables Sensitivity %

Specificity %

PPV % NPV % Accuracy %

Platelet count 73.1 83.1 52.3 92.2 81.1

AAR 80.1 81.6 50.0 92.9 80.5

APRI 83.6 85.5 60.2 95.2 85.1

GUCI 83.6 82.6 56.0 95.0 82.8

Platelet/spleen diameter

87.8 72.7 45.7 95.8 75.9

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 ratio are 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 routine laboratory tests can reduce, but not completely eliminate, the need for liver biopsy. 

• Therefore,, liver biopsy still remain a ‘gold standard’ foriver biopsy still remain a ‘gold standard’ for assessment assessment ofof liver liver fibrosis in tertiary hospital setting.fibrosis in tertiary hospital setting.

Kaunas, Lithuania