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LIVER FIBROSIS REGRESSES BETTER WITH PEGINTERFERON ALPHA AND URSODEOXYCHOLIC
ACID TREATMENT THAN SPONTANEOUS RECOVERY
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I. Tasci*, 1 M.R. Mas, 1 S.A. Vural, 2 N. Mas, 3 M. Serdar, 4 B. Comert, 1 G.
Alcigir, 2 I.H. Kocar, 1
*Presenting Author
1Internal Medicine, Gulhane Medical School, 2Pathology, Veterinarian Faculty
Of Ankara University, 3Anatomy, Hacettepe University, 4Biochemistry, Gulhane
Medical School, Ankara, Turkey
Fibrosis and cirrhosis are common complications of chronic liver diseases. An
imbalance between fibrogenesis and fibrolysis results in scarring of the
liver parenchyma. We aimed to investigate the possible antifibrotic
effectiveness of a newly modified interferon molecule peginterferon a2b
(PEG-IFN) which has better antiviral activity and ursodeoxycholic acid
(UDCA). Liver fibrosis was established on 60 male Sprague Dawley rats with
CCl4 in 12 weeks. After cessation of CCL4 Group I was left for spontaneous
recovery. Group II was treated with PEG-IFN 1.5mg/kg/week, Group III with
UDCA 25 mg/kg/day and Group IV with combination of both drugs. All rats were
killed at week 16. Histopathologic fibrosis scores, tissue hidroxyprolin,
TIMP-1 and MMP-13 levels were determined. Apoptosis was detected by TUNEL
staining. Fibrosis scores were lower in both Group II, III and IV than Group
I (p<0.05, p<0.05, p<0.007, respectively). Tissue hidroxyprolin levels were
significantly decreased in Group II, III and IV when compared to Group I
(p<0.05, p=0.00, p<0.001, respectively). Lower liver TIMP-1 and higher MMP-13
levels were measured in Group II, III, and Group IV than Group I (p=0.007,
p=0.05, p<0.001 for TIMP and p<0.001, p=0.02, p<0.001, for MMP,
respectively). Apoptosis was significantly increased in Group II, III and IV
when compared to Group I (p<0.001, p<0.05, p<0.05, respectively). There was
significantly higher apoptosis in Group II than III and IV (p<0.06, p<0.05,
respectively). In conclusion, treatment with both peginterferon a2b and
ursodeoxycholic acid improves CCL4 induced rat liver fibrosis. Significantly
higher effects can be obtained using these agents in combination.
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