Homocysteine and selenium levels in hepatic diseases (cirrhosis or hepatitis)

Yıl 2006, Cilt: 5 Sayı: 1, 26 - 30, 01.04.2006

Naime Canoruç Fikri Canoruç Çetin Aslan Şerif Yılmaz Cengiz Turgut Mehmet Dursun Zeki Akkuş Ebru Kale

Öz

Background/aim: The liver has a crucial role in homocysteine synthesis and metabolism. Important changes in homocysteine metabolism occur when hepatic deficiency exists. Selenium levels have also been reported as being decreased in liver damage. Furthermore, many changes take place in the liver when selenium deficiency occurs, and the role in pathogenesis is being investigated. We aimed to search the changes in homocysteine and selenium levels in liver damage and determine the probable influencing factors. Materials and methods: Twenty-two chronic hepatitis (m:11, f:11, average age: 43.90±15.02), 28 cirrhotic patients (m:25, f:3, average age: 42.50±16.00) and 20 healthy subjects (m:12, f:8, average age: 36.65±8.29) were included in the study. Etiology was hepatitis B in 36, hepatitis C in 7, hepatitis B + D in 3 and Wilson disease in 1 patient. Three patients had cryptogenic cirrhosis. Homocysteine level was measured by fluorescent detector using high performance liquid chromatography (HPLC); selenium level in graphite mode by atomic absorption; AST, ALT, GGT and albumin by Abotte Aeroset autoanalyzer with photometric method; and vitamin B12 and folate levels by ELECYSIS E170 using chemiluminescence method; methylene tetrahydrofolate reductase (MTHFR) gene analysis in DNA of whole blood samples was done. Results: There was no significant difference between the three groups with respect to age. Both chronic hepatitis and cirrhotic groups had higher homocysteine levels than those of the control group (p=0.001). There was no difference in homocysteine levels between chronic hepatitis and cirrhotic groups. On the other hand, there was no difference between chronic hepatitis and control groups with respect to vitamin B12 levels. Vitamin B12 level was higher in the cirrhotic group than in controls and the difference was statistically significant. There was no difference between any of the groups in respect to folate levels. MTHFR gene mutation was similar in both patient and control groups. Selenium level was found to be lower in both patient groups than in the control group (p=0.001). Conclusion: Our results showed that hyperhomocysteinemia in chronic hepatitis and cirrhosis is not related to deficiency in folate and vitamin B12 and MTHFR gene mutation. It is seen that other enzymes involved in homocysteine metabolism might play a part in this process. It is noteworthy that selenium deficiency exists in both chronic hepatitis and liver cirrhosis.

Anahtar Kelimeler

Chronic hepatitis, cirrhosis, homocysteine, selenium

Karaciğer hastalıklarında (siroz veya hepatit) homosistein ve selenyum düzeyleri

Öz

Giriş ve amaç: Homosisteinin sentezinde ve metabolizmasında karaciğer önemli bir rol oynar. Karaciğer hasarı oluştuğunda homosisteinin metabolizmasında önemli değişiklikler meydana gelmektedir. Selenyum düzeyinin karaciğer hasarında düştüğü rapor edilmektedir. Yine selenyum eksikliğinde karaciğerde önemli değişikliklerin olduğu ifade edilmekte ve patogenezdeki rolü araştırılmaktadır. Çalışmamızda karaciğer hasarında homosistein ve selenyum düzeylerinde meydana gelen değişiklikleri ve bu değişikliklere etki edebilecek faktörleri incelemeyi amaçladı k. Gereç ve yöntem: Çalışmaya 22 kronik hepatitli (E: 12, K: 10; yaş ortalamaları: 43,90±15,02), 28 sirozlu (E: 25, K: 3; yaş ortalamaları: 42,50±16,00) hasta ile, 20 sağlıklı kontrol grubu (E: 12, K: 8; yaş ortalamaları: 36.65±8.29) dahil edildi. Etyolojik dağılım: 36'sı Hepatit B virusu, 7'si Hepatit C virusu, 3'ü Hepatit B virusu + Hepatit D virusu, 1'i Wilson hastasıydı. Üç olgu kriptojenik sirozluydu. High Performance Liquide Chromotography (HPLC) cihazında floresan dedektörle homosistein; atomik absorbsyon cihazında grafit modunda selenyum; Abotte Aeroset otoanalizor cihazında fotometrik yöntemle ALT, AST, GGT, albumin düzeyleri; Roche E170 modüler analitik sistem ile, kemiluminesans metodu kullanılarak B12 ve folat düzeyleri çalışıldı. Metilen tetrahidrofolat redüktaz (MTHFR) geni ise, hastalardan alınan tam kan örneklerinden elde edilen DNA'lar kullanılarak incelendi. Bulgular: Her 3 grubun yaşları arasında fark saptanmadı. Hem kronik hepatit hem de siroz grubundaki homosistein düzeylerinin kontrol grubundan istatistiksel olarak daha yüksek olduğu saptandı (p=0.001). Kronik hepatit grubu ile siroz grubunun homosistein düzeyleri arasında fark saptanmadı. Öte yandan, kronik hepatit ile kontrol grubu arasında vitamin B12 düzeyi açısından fark yoktu. Siroz grubunda vitamin B12 düzeyinin kontrol grubundan istatistiksel olarak daha yüksek olduğu izlendi. Folat düzeyi bakımından gruplar arasında fark saptanmadı. MTHFR gen mutasyonu bakımından da hasta ve kontrol grupları arasında fark saptanmadı. Her iki hastalık grubundaki selenyum düzeyinin kontrol grubundan daha düşük olduğu görüldü (p=0.001). Sonuç: Sonuçlarımız göstermektedir ki sirozlu ve kronik hepatitli hastalarda gözlenen hiperhomosisteinemi folat, vitamin B12 eksikliği ve MTHFR gen mutasyonu ile ilgili değildir. Homosistein metabolizmasında görev alan diğer enzimlerin rollerinin olabileceği anlaşı lmaktadır. Kronik hepatit ve sirozlularda belirgin selenyum eksikliğinin varlığı dikkat çekicidir

Anahtar Kelimeler

Kronik hepatit, siroz, homosistein, selenyum

Kaynakça

• Al-Bader A, Abul H, Hussain T et al. Selenium and liver cirrho- sis.Mol Cell Biochem 1998 Aug; 185(1-2): 1-6.
• Navarro-Alarcon M, Lopez-Ga de la Serrana H, Perez-Valero V et al. Selenium concentrations in serum of individuals with liver dise- ases (cirrhosis or hepatit): relationship with some nutritional and biochemical markers. Sci Total Environ 2002 May 27; 291(1-3): 135-41.
• Yu As, Keeffe EB. Liver transplantation. Hepatology. [edited by] David Zakim, Thomas D. Boyer. 4thedition. Elsevier Science, Saun- ders. 2003; Vol. II: 1617-56.
• Bablok W, et al. General regression procedure for method transfor- mation. J. Clin. Chem. Clin. Biochem. 1988; 26: 783-90.
• Dursun M, Ertem M, Özekinci T, et al. Hepatit B seroprevalence and risk factors in adult population of Southeast Anatolia: Commu- nity based study. 20. National Gastroenterology Week, Abstracts book. 2003: PB06/9.
• García-Tevijano ER, Berasain C, Rodríguez JA, et al. Hyperho- mocysteinemia in Liver Cirrhosis Mechanisms and Role in Vascular and Hepatic Fibrosis. Hypertension. 2001; 38: 1217.
• De la Vega MJ, Santolaria F, Gonzalez-Reimers E, et al. High pre- valence of hyperhomocysteinemia in chronic alcoholism: the impor- tance of the thermolabile form of the enzyme methylenetetrahydro- folate reductase (MTHFR). Alcohol 2001 Oct; 25(2): 59-67.
• Bosy-Westphal A, Petersen S, Hinrichsen H, et al. Increased plasma homocysteine in liver cirrhosis. Hepatol Res 2001 May 1; 20(1): 28- 38.
• Ventura P, Rosa MC, Abbati G, et al. Hyperhomocysteinaemia in chronic liver diseases: role of stage disease,vitamin status and methylenetetrahydrofolate reductase genetics. Liver International 2005: 25: 49-56.
• Ferre N, Gomez F, Camps J, et al. Plasma homocysteine concentra- tions in patients with liver cirrhosis. Clin Chem. 2002 Jan; 48(1): 183-5.
• Lambert D, Benhayoun S, Adjalla C, et al. Alcoholic cirrhosis and cobalamin metabolism. Digestion. 1997; 58(1): 64-71.
• Stabler SP, Lindenbaum J, Allen RH. The use of homocysteine and other metabolites in the specific diagnosis of vitamin B-12deficiency. J Nutr. 1996 Apr; 126(4 Suppl): 1266S-72S.
• Brattstrom L, Zhang Y, Hurtig M, et al. A common methylenetet- rahydrofolate reductase gene mutation and longevity. Atherosclero- sis. 1998 Dec; 141(2): 315-9.
• Czuczejko J, Halota W, Zachara BA et al. [Plasma selenium con- centration, glutathione peroxidase and glutathione S-transferase activities in patients with chronic liver diseases] Pol Merkuriusz Lek. 2002 Oct; 13(76): 312-5. (A)
• Ho AV, Kaplan J. Liver injury resulting from iron. Iron metabolism and pathophysiology. Cell Biology, Biochemistry, and Physiology of liver function. Hepatology. [edited by] David Zakim, Thomas D. Bo- yer. 4thedition. Elsevier Science, Saunders. 2003; Vol. I: 424-5.
• Wasser S, Lim GY, Ong CN et al. Anti-oxidant ebselen causes the re- solution of experimentally induced hepatic fibrosis in rats. J Gast- roenterol Hepatol. 2001 Nov; 16(11): 1244-53.
• Thuluvath PJ, Triger DR. Selenium in chronic liver disease. J He- patol. 1992 Mar; 14(2-3): 176-82.
• Burk RF, Early DS, Hill KE, et al. Plasma selenium in patients with cirrhosis. Hepatology. 1998 Mar; 27(3): 794-8.