Vascular Endothelial Growth Factor Levels in Chronic
Hepatitis and Liver Cirrhosis Associated with Hepatitis C

Okcu, Nihat; Keskin, Havva; cadirci, kenan

doi:10.5505/kjms.2019.33340

Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C

kenan cadirci, (Department of Internal Medicine, University of Health Sciences, Erzurum Regional Training and Research Hospital, Erzurum, Türkiye)

Havva KESKİN, (Department of Internal Medicine, İstanbul Medeniyet University Göztepe Training and Research Hospital, İstanbul, Türkiye)

Nihat OKÇU (Department of Gastroenterology, Erzurum Atatürk University Faculty of Medicine, Erzurum, Turkey)

Kafkas Tıp Bilimleri Dergisi

1 0

Yıl: 2019 Cilt: 9 Sayı: 2 Sayfa Aralığı: 74 - 78 Metin Dili: İngilizce DOI: 10.5505/kjms.2019.33340 İndeks Tarihi: 13-06-2022

Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C

Öz:

Aim: The hepatitis C virus is a significant public health problem across the world. The purpose of this study is to investigate whether serum Vascular Endothelial Growth Factor (VEGF) can be used as a non-invasive marker of liver damage in patients with hepatitis C virus infection-related chronic hepatitis (Chronic Hepatitis C- CHC) and liver cirrhosis (LC). Material and Method: A total of newly diagnosed 44 patients (34 with CHC and 10 with LC) and 28 healthy subjects were recruited into the study. All the patients had not yet received any treatment for the disease. Detailed medical histories and systemic examination were recorded for all study participants. Also, biochemical and hematological parameters, viral markers, VEGF levels, and upper abdominal ultrasounds were evaluated for all study participants. All subjects in the patient group also underwent biopsy of the liver. Serum VEGF levels were determined by ELISA method. Results: Mean CHC, LC and healthy control group VEGF levels were 255±237 pg/ml, 198±130 pg/ml, and 78±27 pg/ml, respectively. VEGF values in CHC group were significantly higher as compared to the controls (p1<0.001), but the elevation in the LC group was not statistically significant (p2=0.06). VEGF levels of the CHC group decreased as degrees of fibrosis, based on Ishak Fibrosis Scores increased. Similarly, VEGF levels of the LC group decreased as Child-Turcotte-Pugh (CTP) scores increased at subgroup analysis based on the CTP classification system. Additionally, a VEGF level above 115 pg/ml was determined to predict development of chronic hepatitis with 67% specificity and 79% sensitivity, but any VEGF level was unable to predict the development of LC. Conclusion: Serum VEGF levels may be used as a non-invasive marker of progressive damage and regeneration occurring in the liver, but the current findings need to be supported with randomized controlled trials involving wider patient groups.

Anahtar Kelime:

Hepatit C’ye Bağlı Kronik Hepatit ve Karaciğer Sirozu Hastalarında Vasküler Endotelyal Büyüme Faktör Düzeyleri

Öz:

Amaç: Hepatit C virüsü, dünya genelinde önemli bir halk sağlığı sorunudur. Bu çalışmamızın amacı, hepatit C virüs enfeksiyonu ilişkili kronik hepatit (Kronik Hepatit C- KHC) ve karaciğer sirozu (KCS) olan hastalarda serum Vasküler Endotelyal Büyüme Faktörü (VEGF)’ nün, karaciğer hasarının noninvazif bir belirteci olarak kullanılıp kullanılmayacağını araştırmaktı. Materyal ve Metot: Çalışmaya yeni tanı konulmuş 44 hasta (34’ü KHC ve 10’u KCS) ve 28 sağlıklı kişi alındı. Hastalardan hiçbiri karaciğer hastalığı için henüz herhangi bir tedavi almamıştı. Tüm çalışma katılımcıları için ayrıntılı tıbbi öyküler ve sistemik muayene kaydedildi. Ayrıca tüm katılımcıların biyokimyasal ve hematolojik parametreleri, viral belirteçleri, VEGF düzeyleri ve üst abdominal ultrasonografik değerlendirilmeleri yapıldı. Hasta grubunda yer alan tüm hastalara karaciğer biyopsisi uygulandı. Serum VEGF düzeyleri ELİSA yöntemi ile çalışıldı. Bulgular: KHC, KCS ve sağlıklı kontrol grubunun ortalama VEGF değerleri sırasıyla: 255±237 pg/ml, 198±130 pg/ml ve 78±27 pg/ ml olarak tespit edildi. Kontrol grubuna göre KHC grubunun VEGF değeri anlamlı derecede yüksek (p1<0.001) iken, KCS grubunun VEGF değer yüksekliği ise anlamlı değildi (p2=0.06). KHC grubunun Ishak skoru göz önüne alınarak yapılan fibrozis evrelemesine göre, fibrozis derecesi arttıkça VEGF düzeylerinin azaldığı gözlendi. Benzer şekilde KCS grubunda da Child-Turcotte-Pugh (CTP) evreleme sistemine göre yapılan alt grup analizlerinde CTP skoru ilerledikçe VEGF düzeylerinin azaldığı tespit edildi. Ayrıca, VEGF’in 115 pg/ml üzerinde tespit edilmesi kronik hepatit gelişmesini %67 spesifite ve %79 sensitivite ile predikte edebileceği, ancak KCS gelişmesini predikte edebilme özelliğinin olmadığı gösterildi. Sonuç: Serum VEGF düzeylerinin karaciğerde meydana gelen progressif bir harabiyetin ve rejenerasyonun noninvazif bir göstergesi olarak kullanılabileceği, ancak mevcut verilerin daha geniş hasta gruplarında çalışmalar ile desteklenmesi gerektiği sonucuna varıldı.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. http://www.who.int/news-room/fact-sheets/detail/hepatitis-c (Accessed 10.02.2019)
2. Aguilera V, Berenguer M. Hepatitis C and fibrosis. Rev EspEnfern Dig 2004;96(6):402–14.
3. Medina J, Arroyo AG, Sanchez-Madrid F, Moreno-Otero R. Angiogenesis in chronic inflammatory liver disease. Hepatology 2004;39;1185–95.
4. Chaparro M, Sanz-Cameno P, Trapero-Marugán M, GarcíaBuey L, Moreno-Otero R. Mechanisms of angiogenesis in chronic inflammatory liver disease. Annals of Hepatology 2007;6(4):208–13.
5. Soria JC, Fayette J, Armand JP. Molecular targeting: targeting angiogenesis in solid tumors. Annals of Oncology 2004;15(4): iv223-iv7.
6. Veikkola T, Alitalo K. VEGF’s, receptors and angiogenesis. Seminars in Cancer Biology 1999;9:211–20.
7. Vincenti V, Cassano C, Rocchi M, Persico G. Assignment of the vascular endothelial growth factor gene to human chromosome 6p21 3. Circulation 1996;15(93):1493–5.
8. Huang YH, Chen MH, Guo QL, Chen YX, Zhang LJ, Chen ZX et al. Interleukin-10 promotes primary rat hepatic stellate cell senescence by upregulating the expression levels of p53 and p21. Mol Med Rep 2018;17(4):5700–7.
9. Aydın MM, Akçalı KC. Liver fibrosis. Turk J Gastroenterol 2018:29:14–21.
10. Ankoma-Sey V, Wang Y, Daı Z. Hypoxic Stimulation of Vascular Endothelial Growth Factor expression in activated rat hepatic Stellate cells. Hepatology 2000;31(1):141–8.
11. Ishak K, Baptista A, Bianchi L, Callea F, Groote JD, Gudat F. Histolgical grading and staging of chronic hepatitis. Journal of Hepatology 1995;22:696–9.
12. Child CG, Turcotte JG. Surgery and portal hypertension. Philadelphia. Major Probl Clin Surg 1:1–85.
13. Pugh RN, Murray-Lyon IM, Dawson JI, Pietroni Mc, Williams R. Transection of the oesophagus for bleeding oesophageal varics. Br J Surg 1973;60(8):646–9.
14. Pohl A, Behling C, Oliver D, Kilani M, Monson P, Hassanein T. Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection. Am J Gastroenterol 2001;3142–6.
15. Sheth SG, Flamm SL, Gordon FD, Chopra S. AST/ ALT ratio predicts cirrhosis in patient with chronic hepatitis C virus infection. Am J Gastroenterol 1998;93:44–8.
16. Akıyoshi F, Sata M, Suzuki H, Uchimura Y, Mitsuyama K, Matsuo K et al. Serum vascular endothelial growth factor levels in varius liver diseases. Dig Dis Sci 1998;1:41–5.
17. Desideri G, Ferri C. Circulating vascular endothelial growth factor levels are decreased in patients with chronic hepatitis and liver cirrhosis depending on the degree of hepatic damage. Clin Sci 2000;99:159–60.
18. Amarapurkar AD, Amarakurpar DN, Vibhav S, Patel ND. Angiogenesis in chronic liver disease. Ann Hepatol 2007;6:170–3.
19. Salcedo XM, Medina J, Sanz-CamenoP, García-Buey L, MartínVilchez S, Borque MJ, et al. The potential of angiogenesis soluble markers in chronic hepatitis C. Hepatology 2005;42:696–701.
20. Rosmorduc O, Wendum D, Corpechot C, Galy B, Sebbagh N, Raleigh J, et al. Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis. Am J Pathol 1999;155(4):1065–73.
21. Corpechot C, Barbu V, Wendum D, Kinnman N, Rey C, Poupon R, et al. Hypoxia-induced VEGF and collagen I expression are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology 2002;35:1010–21.

APA	cadirci k, Keskin H, Okcu N (2019). Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. , 74 - 78. 10.5505/kjms.2019.33340
Chicago	cadirci kenan,Keskin Havva,Okcu Nihat Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. (2019): 74 - 78. 10.5505/kjms.2019.33340
MLA	cadirci kenan,Keskin Havva,Okcu Nihat Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. , 2019, ss.74 - 78. 10.5505/kjms.2019.33340
AMA	cadirci k,Keskin H,Okcu N Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. . 2019; 74 - 78. 10.5505/kjms.2019.33340
Vancouver	cadirci k,Keskin H,Okcu N Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. . 2019; 74 - 78. 10.5505/kjms.2019.33340
IEEE	cadirci k,Keskin H,Okcu N "Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C." , ss.74 - 78, 2019. 10.5505/kjms.2019.33340
ISNAD	cadirci, kenan vd. "Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C". (2019), 74-78. https://doi.org/10.5505/kjms.2019.33340

APA	cadirci k, Keskin H, Okcu N (2019). Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. Kafkas Tıp Bilimleri Dergisi, 9(2), 74 - 78. 10.5505/kjms.2019.33340
Chicago	cadirci kenan,Keskin Havva,Okcu Nihat Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. Kafkas Tıp Bilimleri Dergisi 9, no.2 (2019): 74 - 78. 10.5505/kjms.2019.33340
MLA	cadirci kenan,Keskin Havva,Okcu Nihat Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. Kafkas Tıp Bilimleri Dergisi, vol.9, no.2, 2019, ss.74 - 78. 10.5505/kjms.2019.33340
AMA	cadirci k,Keskin H,Okcu N Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. Kafkas Tıp Bilimleri Dergisi. 2019; 9(2): 74 - 78. 10.5505/kjms.2019.33340
Vancouver	cadirci k,Keskin H,Okcu N Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C. Kafkas Tıp Bilimleri Dergisi. 2019; 9(2): 74 - 78. 10.5505/kjms.2019.33340
IEEE	cadirci k,Keskin H,Okcu N "Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C." Kafkas Tıp Bilimleri Dergisi, 9, ss.74 - 78, 2019. 10.5505/kjms.2019.33340
ISNAD	cadirci, kenan vd. "Vascular Endothelial Growth Factor Levels in Chronic Hepatitis and Liver Cirrhosis Associated with Hepatitis C". Kafkas Tıp Bilimleri Dergisi 9/2 (2019), 74-78. https://doi.org/10.5505/kjms.2019.33340