Neopterin as an indicator of inflammation in chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma
Background and Aims: Neopterin is a proinflammatory indicator that plays a role in cell-mediated immunity, and elevated concentrations of neopterin indicate the presence of interferon-γ in body fluids. In this study, neopterin concentrations were determined in patients with a virus-induced chronic liver disease (chronic hepatitis, liver cirrhosis, and hepatocellular cancer), inactive hepatitis B virus carriers, and in a healthy control group to assess whether neopterin can be used as a disease marker in patients with virus-induced chronic liver disease. Materials and Methods: A total of 110 subjects (42 females and 68 males, with an average age of 44±8.90 years) were included in this study. Of these patients, 33 had chronic hepatitis; 22, liver cirrhosis; 22, hepatoma; 18, inactive hepatitis B virus carriers; and 15 were included in the healthy control group. Neopterin levels were measured before and after interferon treatment in patients with chronic hepatitis. Data collected among the groups were analyzed statistically using the Mann-Whitney test, considering p < 0.05 as statistically significant. Results: Neopterin concentrations and gender showed no statistically significant correlation. Patients with cirrhosis, hepatocellular cancer, and chronic hepatitis had statistically significantly higher neopterin levels than the healthy control and healthy carrier groups. A positive correlation was observed between neopterin levels and other disease activity indicators such as aspartate transaminase, alanine transaminase, hepatitis B virus deoxyribonucleic acid, hepatitis C virus ribonucleic acid, erythrocyte sedimentation rate, and C-reactive protein levels, and their levels were also high. Although 14 patients, who were also evaluated after interferon treatment, showed good response to the treatment, no statistically significant correlation was observed between their neopterin levels and disease activity indicator levels. Conclusion: Neopterin concentrations were found to be significantly higher in patients with inflammation than in inactive hepatitis B virus carriers who had no ongoing inflammatory activity and in the healthy control group. No correlation was detected between neopterin levels and hepatitis B virus deoxyribonucleic acid and hepatitis C virus ribonucleic acid levels in patients who received interferon treatment and benefitted from it. Although neopterin levels indicate inflammatory activity in cases of chronic hepatitis, liver cirrhosis, and hepatocellular cancer, additional studies are necessary to determine its usefulness in clinical practice.
Kronik viral hepatitler, karaciğer sirozu ve hepatosellüler karsinomada inflamasyon göstergesi olarak neopterin
iriş ve Amaç: Neopterin hücre aracılı immünitede rol oynayan proinflamatuvar bir belirleyicidir ve konsantrasyonu vücut sıvılarındaki γ interferonun varlığını gösterir. Viral etiyolojili karaciğer hastalığı olan kronik hepatit, karaciğer sirozu, hepatosellüler kanserli olgularda, inaktif hepatit B virüsü taşıyıcısı olanlarda neopterin seviyesini saptamak ve kontrol grubu ile karşılaştırarak; viral etiyolojili kronik karaciğer hastalıklarında yeri olabilecek bir belirteç olabileceğini ispatlamak amacıyla bu çalışma planlandı. Gereç ve Yöntem: Çalışmaya toplam 110 kişi (42 kadın, 68 erkek, yaş ortalaması 44±8.90) alındı. Bunlardan 33 hasta kronik hepatit, 22’si karaciğer sirozu, 22’si hepatoma, 18’i inaktif hepatit B taşıyıcısı ve 15’i sağlıklı kontrol grubu olarak belirlendi. Neopterin düzeyleri kronik hepatitli hastalarda interferon tedavisinden önce ve sonra ölçüldü. Gruplar arasındaki ölçümler istatistiksel olarak Mann-Whitney testiyle araştırıldı. p
Reibnegger G, Auhuber I, Fuchs D, et al. Urinary neopterin levels in acute viral hepatitis. Hepatology 1988;8:771-4.
Eisenhut M. Neopterin in diagnosis and monitoring of infectious diseases. J Biomark 2013;2013:196432.
Berdowska A, Zwirska-Korczala K. Neopterin measurement in clinical diagnosis. J Clin Pharm Ther 2001;26:319-29.
Huber C, Batchelor JR, Fuchs D, et al. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J Exp Med 1984;160:310-6.
Haavik J. [From butterflies to neurobiology and the diagnosis of AIDS. The 100th anniversary of the discovery of pteridines]. Tidsskr Nor Laegeforen 1989;109:1986-9. Norwegian.
Oettl K, Reibnegger G. Pteridines as inhibitors of xanthine oxidase: structural requirements. Biochim Biophys Acta 1999;1430:387-95.
Weiss G, Widner B, Zoller H, et al. Immune response and iron metabolism. Br J Anaesth 1998;81(Suppl 1):6-9.
Oda K, Arai T, Nagase M. Increased serum and urinary neopterin in nephrotic syndrome indicate cell-mediated immune dysfunction. Am J Kidney Dis 1999;34:611-7.
Müller MM, Curtius HC, Herold M, Huber CH. Neopterin in clinical practice. Clin Chim Acta 1991;201:1-16.
Schennach H, Schoenitzer D, Fuchs D. Association between chronic hepatitis C virus infection and increased neopterin concentrations in blood donations. Clin Chem 1998;44:2225-6.
Daito K, Suou T, Kawasaki H. Clinical significance of serum and urinary neopterin levels in patients with various liver diseases. Am J Gastroenterol 1992;87:471-6.
Kawasaki H, Watanabe H, Yamada S, et al. Prognostic significance of urinary neopterin levels in patients with hepatocellular carcinoma. Tohoku J Exp Med 1988;155:311-8.
Melichar B, Spisarová M, Bartousková M, et al. Neopterin as a biomarker of immune response in cancer patients. Ann Transl Med 2017;5:280.
Kaleli I, Demir M, Cevahir N, et al. Serum neopterin levels in patients with replicative and nonreplicative HBV carriers. BMC Infect Dis 2006;6:157.
Demirturk N, Demirdal T, Aktepe OC, et al. Serum neopterin levels in patients with HBV infection at various stages. Hepatogastroenterology 2007;54:903-5.
Gulcan EM, Tirit I, Anil A, et al. Serum neopterin levels in children with hepatitis-B-related chronic liver disease and its relationship to disease severity. World J Gastroenterol 2008;14:6840-3.