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Neopterin as an indicator of inflammation in chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma

Year 2018, Volume: 17 Issue: 3, 142 - 147, 29.12.2018
https://doi.org/10.17941/agd.502317

Abstract

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.

References

  • 1. Reibnegger G, Auhuber I, Fuchs D, et al. Urinary neopterin levels in acute viral hepatitis. Hepatology 1988;8:771-4.
  • 2. Eisenhut M. Neopterin in diagnosis and monitoring of infectious diseases. J Biomark 2013;2013:196432.
  • 3. Berdowska A, Zwirska-Korczala K. Neopterin measurement in clinical diagnosis. J Clin Pharm Ther 2001;26:319-29.
  • 4. 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.
  • 5. 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.
  • 6. Oettl K, Reibnegger G. Pteridines as inhibitors of xanthine oxidase: structural requirements. Biochim Biophys Acta 1999;1430:387-95.
  • 7. Weiss G, Widner B, Zoller H, et al. Immune response and iron metabolism. Br J Anaesth 1998;81(Suppl 1):6-9.
  • 8. 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.
  • 9. Müller MM, Curtius HC, Herold M, Huber CH. Neopterin in clinical practice. Clin Chim Acta 1991;201:1-16.
  • 10. 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.
  • 11. 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.
  • 12. 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.
  • 13. Melichar B, Spisarová M, Bartoušková M, et al. Neopterin as a biomarker of immune response in cancer patients. Ann Transl Med 2017;5:280.
  • 14. 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.
  • 15. Demirturk N, Demirdal T, Aktepe OC, et al. Serum neopterin levels in patients with HBV infection at various stages. Hepatogastroenterology 2007;54:903-5.
  • 16. 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.

Kronik viral hepatitler, karaciğer sirozu ve hepatosellüler karsinomada inflamasyon göstergesi olarak neopterin

Year 2018, Volume: 17 Issue: 3, 142 - 147, 29.12.2018
https://doi.org/10.17941/agd.502317

Abstract

Giriş 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<0,05 istatistiksel olarak anlamlı kabul edildi. Bulgular: Cinsiyet
ve neopterin düzeyleri arasında istatistiksel olarak ilişki saptanmadı.
Hastalıklar değerlendirildiğinde, neopterin seviyeleri siroz, hepatosellüler
kanser, kronik hepatit grubundaki hastalarda sağlıklı taşıyıcı ve sağlıklı
kontrol grubundaki hastalara göre istatistiksel olarak anlamlı düzeyde
yüksekti. Neopterin düzeyleri, bu hasta gruplarında aktivite göstergeleri olan aspartat
aminotransferaz, alanin aminotransferaz, hepatit B virüs deoksiribonükleik asit,
hepatit C virüs ribonükleik asit, sedimentasyon ve C-reaktif protein değerleri
ile arasında pozitif korelasyon vardı ve yüksek olarak saptandı. İnterferon
tedavisi sonrası değerlendirilen 14 hastada ise tedaviye cevap alınmasına
rağmen, neopterin düzeyleri ile aktivite belirteçleri arasında anlamlı ilişki
saptanmadı. Sonuç: Sonuç olarak neopterin seviyeleri inflamasyonu olan
hastalarda sağlıklı kontrol ve inflamasyon aktivitesi beklenmeyen hepatit B
taşıyıcılarına göre anlamlı olarak daha yüksekti. İnterferon tedavisi verilen
ve tedaviden fayda gören hastalarda hepatit B virüs deoksiribonükleik asit ve hepatit
C virüs ribonükleik asit düzeyleri ile neopterin arasında bir korelasyon
saptanmadı. Neopterin seviyesi kronik hepatit, karaciğer sirozu ve
hepatosellüler kanserli olgularda inflamasyon aktivitesini gösterirken bunun
klinik pratikteki yararı konusunda ilave çalışmalara gerek olduğu açıktır.

References

  • 1. Reibnegger G, Auhuber I, Fuchs D, et al. Urinary neopterin levels in acute viral hepatitis. Hepatology 1988;8:771-4.
  • 2. Eisenhut M. Neopterin in diagnosis and monitoring of infectious diseases. J Biomark 2013;2013:196432.
  • 3. Berdowska A, Zwirska-Korczala K. Neopterin measurement in clinical diagnosis. J Clin Pharm Ther 2001;26:319-29.
  • 4. 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.
  • 5. 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.
  • 6. Oettl K, Reibnegger G. Pteridines as inhibitors of xanthine oxidase: structural requirements. Biochim Biophys Acta 1999;1430:387-95.
  • 7. Weiss G, Widner B, Zoller H, et al. Immune response and iron metabolism. Br J Anaesth 1998;81(Suppl 1):6-9.
  • 8. 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.
  • 9. Müller MM, Curtius HC, Herold M, Huber CH. Neopterin in clinical practice. Clin Chim Acta 1991;201:1-16.
  • 10. 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.
  • 11. 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.
  • 12. 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.
  • 13. Melichar B, Spisarová M, Bartoušková M, et al. Neopterin as a biomarker of immune response in cancer patients. Ann Transl Med 2017;5:280.
  • 14. 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.
  • 15. Demirturk N, Demirdal T, Aktepe OC, et al. Serum neopterin levels in patients with HBV infection at various stages. Hepatogastroenterology 2007;54:903-5.
  • 16. 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.
There are 16 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Muhammed Fatih Aydın This is me 0000-0001-6056-9360

Şule Namlı Koç This is me 0000-0001-5376-3739

Sabiye Akbulut 0000-0002-8338-8674

Dilek Oğuz

Publication Date December 29, 2018
Published in Issue Year 2018 Volume: 17 Issue: 3

Cite

APA Aydın, M. F., Namlı Koç, Ş., Akbulut, S., Oğuz, D. (2018). Neopterin as an indicator of inflammation in chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. Akademik Gastroenteroloji Dergisi, 17(3), 142-147. https://doi.org/10.17941/agd.502317

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