Non-invasive liver fibrosis markers: use of serum levels of cytokines IL 1α and TGF ß1 in  management of chronic liver diseases.
OBJECTIVE
To analyze the usefulness of specified immunological parameters, proinflammatory IL-1α and profibrogenic, antiinflammatory TGF-β1, along with routinely used laboratory tests, in the differential - diagnostic procedure of chronic hepatitis of infectious and noninfectious etiology.


METHODS
A total of 150 subjects were divided into two groups, depending on the infectious or noninfectious etiology of liver damage, and the control group. Apart from standard laboratory tests, the analysis included serum levels of cytokines: IL-1α and TGF-β1.


RESULTS
A high degree of correlation of serum level of IL-1α with viral hepatitis has been found, especially with active replication of genetic material ( HBV-DNA or HCV-RNA-PCR positive), p less 0.01. The highest mean concentration of TGF-β1 was noted in the group of malignant and toxic hepatitis, p less 0.0001. A negative correlation between the concentration of IL-1α and TGF-β1 has been found (-0.18). For IL-1 α significant predictive parameters included a previous infection of hepatitis B, lower serum level of TGFβ, age, use of alcohol, lower MELD and Chilld-Pugh scores. For TGF-β1 significant predictive parameters were age, lower MELD and Child-Pugh scores, history of receiving transfusions, lower serum level of IL-1α, higher serum level of fibrinogen. A predictive model has been delivered MELD = (TGF-β1) x 0,001- (IL-1 α) x 0,085 + CTP x 1,771-2,052; ( ± 2.04, R2=0,61; p less 0,001).


CONCLUSIONS
Inflammatory and immune parameters, analyzed together could significantly contribute to the understanding of chronic liver damage and thus differential diagnostic procedure. IL-1α and TGF-β1 are important parameters of inflammatory activity and fibrosis evaluation in chronic liver damage.
1 Department of Gastroenterology and Hepatology, Referral Centre for Gastrointestinal Endoscopy, Clinical Centre, University  of  Sarajevo,  2 Department of Pathophysiology, School of Pharmacy, University of Sarajevo; Sarajevo,  3  General Hospital Tešanj, Tešanj,  4 Institute of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Sarajevo, Sarajevo;  Bosnia and  Herzegovina,  5 Cantonal Hospital Zenica, Department of Internal Medicine.
Amila
A
Mehmedović
Rusmir
R
Mesihović
Besim
B
Prnjavorac
Nenad
N
Vanis
Zora
Z
Vukobrat-Bijedić
Nađa
N
Borovac
Nađa
N
Zubčević
Aida
A
Pilav
Srđan
S
Gornjaković
Aida
A
Kulo-Ćesić
Ekrema
E
Mujarić
Aida
A
Saray
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D006521:Hepatitis, Chronic / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy; D006801:Humans; D053582:Interleukin-1alpha / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000097:blood*
D015415:Biomarkers; D053582:Interleukin-1alpha; D053773:Transforming Growth Factor beta1