Changes in serum levels of cytokeratin-18 fragments in patients with chronic hepatitis C under antiviral therapy

Year 2018, Volume: 17 Issue: 1, 28 - 32, 24.04.2018

Altay Kandemir , Mustafa Çelik , Belkis Ünsal

https://doi.org/10.17941/agd.428359

Abstract

Background and Aims: Cytokeratin-18 is the known substrate for caspases, which are encountered during hepatic and pancreatic acinar apoptosis. Studies performed in recent years have indicated that the cleavage level of serum cytokeratin-18 (M30 antigen) is correlated with hepatic fibrosis and disease severity in both chronic hepatitis C and non-alcoholic steatohepatitis. It was shown that antiviral therapy in chronic viral hepatitis C patients significantly reduced hepatocellular apoptosis and cytokeratin-18 is accepted as a reliable marker of hepatocyte apoptosis. Our aim was to determine the correlation between the cytokeratin-18 level and treatment response in patients with chronic viral hepatitis C. Materials and Methods: Sixty patients with chronic viral hepatitis C were included in the study. A 48-week course of peginterferon- ribavirin therapy was given to appropriate patients. Hepatitis C virus RNA was measured at 0, 12, and 24 weeks at the end of therapy and 72 weeks. In addition, cytokeratin-18 levels were measured at 0, 24, and 72 weeks. Results: The mean age of 60 patients was 52±10.9 years. While 31 (51.6%) of patients were in the sustained viral response group, 29 (8.4%) of patients were in the non-sustained viral response group. It was determined that while the cytokeratin-18 level at week 0 in the sustained viral response group was 243±21, the cytokeratin-18 level at week 24 was 115±12 U/L and the difference between the level of cytokeratin-18 at weeks 0 and 24 were 127±209 U/L (p: .014). While the cytokeratin-18 level at week 0 in the non- sustained viral response group was 270±14; at week 24, the cytokeratin-18 level was 136±19 U/L and the difference between cytokeratin-18 levels at weeks 0 and 24 was 136±156 U/L (p > .5). At week 72, the cytokeratin-18 level in the sustained viral response group was 109±38 and the difference between weeks 0 and 72 was 134±215 (p < .002). Conclusion: In chronic viral hepatitis C patients, there was a correlation between sustained viral response and cytokeratin-18, which is a marker of apoptosis. During treatment, it was found that there was a relationship between sustained viral response and the decrease in cytokeratin-18 levels. Thisfinding indicates that cytokeratin-18 level monitoring may be used as a predictive marker of sustained viral response.

Keywords

Chronic hepatitis C, cytokeratin-18, sustained viral response

Kronik hepatit C hastalarında antiviral tedavi ile serum sitokeratin-18 düzeylerinin değişimi

Abstract

Giriş ve Amaç: Sitokeratin-18, hepatik ve pankreatit asiner apopitozisi sırasında ortaya çıkan kaspazların bilinen substuratıdır. Son zamanlarda yapılan çalışmalarda; serum sitokeratin-18 (M30 antijen) düzeyi ile non-alkolik steatohepatit ve kronik hepatit C’nin şiddeti ve hepatik fibrozis ile korelasyonu belirtilmiştir. Kronik viral hepatit C hastalarında, başarılı antiviral tedavi ile hepatosellüler apopitozisin anlamlı olarak azaldığı, hepatosit apopitozisini göstermede sitokeratin-18’in güvenilir bir markır olduğu gösterilmiştir. Bizim amacımız kronik viral hepatit C’li hastalarda sitokeratin-18 düzeyi ve tedavi yanıtı arasındaki korelasyonu belirlemektir. Gereç ve Yöntem: Kronik viral hepatit C tanısı alan 60 hasta çalışmaya alındı. Tedavi için uygun hastalara 48 hafta peginterferon- ribavirin tedavisi verildi. Tedavinin 0-12-24. haftalarında, tedavinin sonunda ve 72. haftada hepatitis C virusu RNA miktarı ölçüldü. Ayrıca tedavinin 0-24 ve 72. haftasında sitokeratin-18 düzeyleri ölçüldü. Bulgular: Altmış hastanın ortalama yaşı 52±10.9 yıl idi. Hastaların 31’i (%51,6) kalıcı viral yanıt grubunda iken, 29’u (%48,4) kalıcı viral yanıt elde edilemeyen grupta idi. Kalıcı viral yanıt grubunda 0. haftada sitokeratin-18 düzeyi 243±21 U/L iken, 24. haftada sitokeratin-18 düzeyi 115±12 U/L saptanmış olup 0. hafta ile 24. hafta arasındaki değişim 127±209 U/L bulunmuştur (p: 0.014). Kalıcı viral yanıt elde edilemeyen grupta 0. haftada sitokeratin-18 düzeyi 270±14 U/L iken, 24. haftada sitokeratin-18 düzeyi 133±19 U/L saptanmış olup 0. hafta ile 24. hafta arasındaki değişim 136±156 U/L bulunmuştur (p>0,5). Kalıcı viral yanıt grubunda, 72. haftada sitokeratin-18 düzeyi 109±38 saptanmış olup 0. hafta ile 72. hafta arasındaki değişim 134±215 bulunmuştur (p<0.002). Sonuç: Apopitozisin göstergesi olan sitokeratin-18 ile kronik viral hepatit C hastalarında kalıcı viral yanıt arasında korelasyon tespit edildi ve tedavi seyrinde sitokeratin-18 düzeyinde azalma ile kalıcı viral yanıt arasında ilişki bulunduğu gösterildi. Bu da sitokeratin-18 düzeylerinde azalmanın kalıcı viral yanıtı ön görmede bir parametre olarak kullanılabileceğini göstermektedir.

Keywords

Kronik viral hepatit C, sitokeratin-18, kalıcı viral yanıt

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