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 noninvasive 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 on a scale F0-F6 (Masson trichrome stain).
1. Fibrosis of some portal areas.
4. Fibrosis with P-P and P-C bridging.
2. Fibrosis expansion of most portal areas.
5. Incomplete cirrhosis.
3. Fibrosis with occasional (P-P) bridging.
6. Cirrhosis, probable or definite.
Staging was performed blinded to clinical data by one expert pathologist.
METHODS (3)
Indirect non-invasive tests
of liver fibrosis used
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.
METHODS (4)
Flow diagram of the potential candidates
for participation in the study
402 CHC PATIENTS REGISTERED FROM
January 2000 UNTIL November 2005
43 patients with
insufficient liver sample
31 patients with
incomplete data
323 CHC PATIENTS
INCLUDED
F 0-2
N=148
F 3-6
N=175
5 patients with
active alcohol abuse
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
Prediction 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/spleen
diameter
0.71 (0.65-0.77)
0.88 (0.88-0.93)
Variables
RESULTS (3)
Cut-off points to predict the
absence or presence of significant fibrosis and cirrhosis
Significant 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
<150 x10(9)/L
≥ 150 x10(9)/L
Variables
Platelet count
RESULTS (4)
Sensitivity, specificity, positive (PPV), and negative (NPV) predictive
value of evaluated parameters in detecting significant (F 3-6) fibrosis
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
RESULTS (5)
Sensitivity, specificity, positive (PPV), and negative (NPV) predictive
value of evaluated parameters in detecting cirrhosis (F 5-6)
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
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’ for assessment of
liver fibrosis in tertiary hospital setting.
Kaunas, Lithuania