Infectious mononucleosis and hepatic function

Zhang,Li; Zhou,Pingping; Meng,Zhaowei; Pang,Chongjie; Gong,Lu; Zhang,Qing; Jia,Qiyu; Song,Kun

doi:10.3892/etm.2018.5736

Infectious mononucleosis and hepatic function

Authors:
- Li Zhang
- Pingping Zhou
- Zhaowei Meng
- Chongjie Pang
- Lu Gong
- Qing Zhang
- Qiyu Jia
- Kun Song
View Affiliations

Affiliations: Department of Infectious Diseases, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Health Management, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: January 10, 2018 https://doi.org/10.3892/etm.2018.5736
Pages: 2901-2909
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Abnormal hepatic function is common in infectious mononucleosis (IM). However, it remains unknown why increased transferase levels are more common than bilirubin abnormalities in IM. The current study aimed to investigate these associations in the Chinese population. A total of 95 patients with IM (47 males and 48 females) were enrolled in the current study, as well as 95 healthy controls. Patients were sorted by sex. A receiver operating characteristic (ROC) curve was used to determine cut‑off values for IM diagnosis and prediction. Crude and adjusted odds ratios (OR) for IM were analyzed using binary logistic regression. It was determined that alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ‑glutamyl transferase (GGT) levels were significantly higher in patients with IM compared with controls; however, total bilirubin (TB) levels were significantly lower in patients with IM. ROCs demonstrated that, if ALT, AST and GGT concentrations were higher than, or if TB was lower than, cut‑off values, they were predictive of IM. Binary logistic regression identified that the risk of IM in patients exhibiting high levels of transferases was significantly increased, particularly in males. Crude ORs in ALT quartile 4 were 21.667 and 10.111 for males and females, respectively and adjusted ORs were 38.054 and 9.882, respectively. A significant IM risk of IM was evident in patients with low bilirubin levels and females appeared to be particularly susceptible. For example, crude ORs in quartile 1 were 8.229 and 8.257 for males and females, respectively and adjusted ORs were 8.883 and 10.048, respectively. Therefore, the current study identified a positive association between transferase levels and IM and a negative association between TB and IM. Therefore, the results of the current study indicate that high transferases are suggestive of IM, particularly in males, whereas low TB is suggestive for IM, particularly in females.

View Figures

View References

1	Luzuriaga K and Sullivan JL: Infectious mononucleosis. N Engl J Med. 362:1993–2000. 2010. View Article : Google Scholar : PubMed/NCBI
2	Vouloumanou EK, Rafailidis PI and Falagas ME: Current diagnosis and management of infectious mononucleosis. Curr Opin Hematol. 19:14–20. 2012. View Article : Google Scholar : PubMed/NCBI
3	Wang Y, Li J, Ren YY and Zhao H: The levels of liver enzymes and atypical lymphocytes are higher in youth patients with infectious mononucleosis than in preschool children. Clin Mol Hepatol. 19:382–388. 2013. View Article : Google Scholar : PubMed/NCBI
4	Topp SK, Rosenfeldt V, Vestergaard H, Christiansen CB and Von Linstow ML: Clinical characteristics and laboratory findings in Danish children hospitalized with primary Epstein-Barr virus infection. Infect Dis (Lond). 47:908–914. 2015. View Article : Google Scholar : PubMed/NCBI
5	Cohn C and Lidman BI: Hepatitis without jaundice in infectious mononucleosis. J Clin Invest. 25:145–151. 1946. View Article : Google Scholar
6	Rosalki SB, Jones TG and Verney AF: Transaminase and liver-function studies in infectious mononucleosis. Br Med J. 1:929–932. 1960. View Article : Google Scholar : PubMed/NCBI
7	Horwitz CA, Burke MD, Grimes P and Tombers J: Hepatic function in mononucleosis induced by Epstein-Barr virus and cytomegalovirus. Clin Chem. 26:243–246. 1980.PubMed/NCBI
8	Yang SI, Geong JH and Kim JY: Clinical characteristics of primary Epstein Barr virus hepatitis with elevation of alkaline phosphatase and γ-glutamyltransferase in children. Yonsei Med J. 55:107–112. 2014. View Article : Google Scholar : PubMed/NCBI
9	Uluğ M, Celen MK, Ayaz C, Geyik MF and Hoşoğlu S: Acute hepatitis: A rare complication of Epstein-Barr virus (EBV) infection. J Infect Dev Ctries. 4:668–673. 2010. View Article : Google Scholar : PubMed/NCBI
10	Zenda T, Itoh Y, Takayama Y, Masunaga T, Asaka S, Oiwake H, Shinozaki K and Takeda R: Significant liver injury with dual positive IgM antibody to Epstein-Barr virus and cytomegalovirus as a puzzling initial manifestation of infectious mononucleosis. Intern Med. 43:340–343. 2004. View Article : Google Scholar : PubMed/NCBI
11	Baron DN, Bell JL and Dunnet WN: Biochemical studies on hepatic involvement in infectious mononucleosis. J Clin Pathol. 18:209–211. 1965. View Article : Google Scholar : PubMed/NCBI
12	Evans AS: Liver involvement in infectious mononucleosis. J Clin Invest. 27:106–110. 1948. View Article : Google Scholar : PubMed/NCBI
13	Straus SE, Cohen JI, Tosato G and Meier J: NIH conference. Epstein-Barr virus infections: Biology, pathogenesis, and management. Ann Intern Med. 118:45–58. 1993. View Article : Google Scholar : PubMed/NCBI
14	Hu L, Yang J, Cui T, Xing H and Cai P: Diagnosis of infectious mononucleosis by combined detection of atypical lymphocytes and transaminase. J Huazhong Univ Sci Technolog Med Sci. 26:384–385. 2006. View Article : Google Scholar : PubMed/NCBI
15	DeLong ER, DeLong DM and Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics. 44:837–845. 1988. View Article : Google Scholar : PubMed/NCBI
16	Ainley NJ: A fatal case of infectious mononucleosis with extensive zonal necrosis of the liver. Ulster Med J. 18:219–224. 1949.PubMed/NCBI
17	Harries JT and Ferguson AW: Fatal infectious mononucleosis with liver failure in two sisters. Arch Dis Child. 43:480–485. 1968. View Article : Google Scholar : PubMed/NCBI
18	McMahon JM, Elliott CW and Green RC: Infectious mononucleosis complicated by hepatic coma. Am J Gastroenterol. 51:200–207. 1969.PubMed/NCBI
19	Herbinger KH, Hanus I, Felbinger TW, Weber C, Beissner M, von Sonnenburg F, Löscher T, Bretzel G, Nothdurft HD, Hoelscher M and Alberer M: Elevated values of clinically relevant transferases induced by imported infectious diseases: A controlled cross-sectional study of 14,559 diseased german travelers returning from the tropics and subtropics. Am J Trop Med Hyg. 95:481–487. 2016. View Article : Google Scholar : PubMed/NCBI
20	Wadsworth RC and Keil PG: Biopsy of the liver in infectious mononucleosis. Am J Pathol. 28:1003–1025. 1952.PubMed/NCBI
21	Sullivan BH Jr, Irey NS, Pileggi VJ, Crone RI and Gibson JR: The liver in infectious mononucleosis. Am J Dig Dis. 2:210–223. 1957. View Article : Google Scholar : PubMed/NCBI
22	Maines MD: The heme oxygenase system: A regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 37:517–554. 1997. View Article : Google Scholar : PubMed/NCBI
23	Jangi S, Otterbein L and Robson S: The molecular basis for the immunomodulatory activities of unconjugated bilirubin. Int J Biochem Cell Biol. 45:2843–2851. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kapitulnik J: Bilirubin: An endogenous product of heme degradation with both cytotoxic and cytoprotective properties. Mol Pharmacol. 66:773–779. 2004. View Article : Google Scholar : PubMed/NCBI
25	Stocker R, Yamamoto Y, McDonagh AF, Glazer AN and Ames BN: Bilirubin is an antioxidant of possible physiological importance. Science. 235:1043–1046. 1987. View Article : Google Scholar : PubMed/NCBI
26	Wu TW, Fung KP and Yang CC: Unconjugated bilirubin inhibits the oxidation of human low density lipoprotein better than Trolox. Life Sci. 54:P477–P481. 1994. View Article : Google Scholar : PubMed/NCBI
27	Schwertner HA, Jackson WG and Tolan G: Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin Chem. 40:18–23. 1994.PubMed/NCBI
28	Akboga MK, Canpolat U, Sahinarslan A, Alsancak Y, Nurkoc S, Aras D, Aydogdu S and Abaci A: Association of serum total bilirubin level with severity of coronary atherosclerosis is linked to systemic inflammation. Atherosclerosis. 240:110–114. 2015. View Article : Google Scholar : PubMed/NCBI
29	Ghem C, Sarmento-Leite RE, de Quadros AS, Rossetto S and Gottschall CA: Serum bilirubin concentration in patients with an established coronary artery disease. Int Heart J. 51:86–91. 2010. View Article : Google Scholar : PubMed/NCBI
30	Wu BJ, Chen K, Barter PJ and Rye KA: Niacin inhibits vascular inflammation via the induction of heme oxygenase-1. Circulation. 125:150–158. 2012. View Article : Google Scholar : PubMed/NCBI
31	Basiglio CL, Arriaga SM, Pelusa HF, Almará AM, Roma MG and Mottino AD: Protective role of unconjugated bilirubin on complement-mediated hepatocytolysis. Biochim Biophys Acta. 1770:1003–1010. 2007. View Article : Google Scholar : PubMed/NCBI
32	Wu J, Ma J, Fan ST, Schlitt HJ and Tsui TY: Bilirubin derived from heme degradation suppresses MHC class II expression in endothelial cells. Biochem Biophys Res Commun. 338:890–896. 2005. View Article : Google Scholar : PubMed/NCBI
33	Hansen TW, Mathiesen SB and Walaas SI: Bilirubin has widespread inhibitory effects on protein phosphorylation. Pediatr Res. 39:1072–1077. 1996. View Article : Google Scholar : PubMed/NCBI
34	Peng F, Deng X, Yu Y, Chen X, Shen L, Zhong X, Qiu W, Jiang Y, Zhang J and Hu X: Serum bilirubin concentrations and multiple sclerosis. J Clin Neurosci. 18:1355–1359. 2011. View Article : Google Scholar : PubMed/NCBI
35	Liechti FD, Grandgirard D and Leib SL: Bacterial meningitis: Insights into pathogenesis and evaluation of new treatment options: A perspective from experimental studies. Future Microbiol. 10:1195–1213. 2015. View Article : Google Scholar : PubMed/NCBI
36	Vitek L, Muchová L, Jančová E, Pešičková S, Tegzová D, Peterová V, Pavelka K, Tesař V and Schwertner H: Association of systemic lupus erythematosus with low serum bilirubin levels. Scand J Rheumatol. 39:480–484. 2010. View Article : Google Scholar : PubMed/NCBI
37	Zuwała-Jagiełło J, Warwas M and Pazgan-Simon M: Ischemia-modified albumin (IMA) is increased in patients with chronic hepatitis C infection and related to markers of oxidative stress and inflammation. Acta Biochim Pol. 59:661–667. 2012.PubMed/NCBI
38	Komaravelli N and Casola A: Respiratory viral infections and subversion of cellular antioxidant defenses. J Pharmacogenomics Pharmacoproteomics. 5:pii: 10001412014.
39	Ngondi JL, Oben J, Forkah DM, Etame LH and Mbanya D: The effect of different combination therapies on oxidative stress markers in HIV infected patients in Cameroon. AIDS Res Ther. 3:192006. View Article : Google Scholar : PubMed/NCBI
40	Checconi P, Salzano S, Bowler L, Mullen L, Mengozzi M, Hanschmann EM, Lillig CH, Sgarbanti R, Panella S, Nencioni L, et al: Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress. PLoS One. 10:e01270862015. View Article : Google Scholar : PubMed/NCBI
41	Chakraborty SP, Das S, Chattopadhyay S, Tripathy S, Dash SK, Pramanik P and Roy S: Staphylococcus aureus infection induced redox signaling and DNA fragmentation in T-lymphocytes: Possible ameliorative role of nanoconjugated vancomycin. Toxicol Mech Methods. 22:193–204. 2012. View Article : Google Scholar : PubMed/NCBI
42	Aslan M, Nazligul Y, Horoz M, Bolukbas C, Bolukbas FF, Aksoy N, Celik H and Erel O: Serum prolidase activity and oxidative status in Helicobacter pylori infection. Clin Biochem. 40:37–40. 2007. View Article : Google Scholar : PubMed/NCBI
43	Kariya C, Chu HW, Huang J, Leitner H, Martin RJ and Day BJ: Mycoplasma pneumoniae infection and environmental tobacco smoke inhibit lung glutathione adaptive responses and increase oxidative stress. Infect Immun. 76:4455–4462. 2008. View Article : Google Scholar : PubMed/NCBI
44	Rosenthal P, Pincus M and Fink D: Sex- and age-related differences in bilirubin concentrations in serum. Clin Chem. 30:1380–1382. 1984.PubMed/NCBI
45	Pottel H, Vrydags N, Mahieu B, Vandewynckele E, Croes K and Martens F: Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods. Clin Chim Acta. 396:49–55. 2008. View Article : Google Scholar : PubMed/NCBI
46	Uemura O, Honda M, Matsuyama T, Ishikura K, Hataya H, Yata N, Nagai T, Ikezumi Y, Fujita N, Ito S, et al: Age, gender, and body length effects on reference serum creatinine levels determined by an enzymatic method in Japanese children: A multicenter study. Clin Exp Nephrol. 15:694–699. 2011. View Article : Google Scholar : PubMed/NCBI
47	O'Leary JG, Wong F, Reddy KR, Garcia-Tsao G, Kamath PS, Biggins SW, Fallon MB, Subramanian RM, Maliakkal B, Thacker L and Bajaj JS: Gender-specific differences in baseline, peak, and delta serum creatinine: The NACSELD experience. Dig Dis Sci. 62:768–776. 2017. View Article : Google Scholar : PubMed/NCBI
48	Meng Z, Liu M, Zhang Q, Liu L, Song K, Tan J, Jia Q, Zhang G, Wang R, He Y, et al: Gender and age impacts on the association between thyroid function and metabolic syndrome in Chinese. Medicine (Baltimore). 94:e21932015. View Article : Google Scholar : PubMed/NCBI
49	Meng Z, Liu M, Zhang Q, Liu L, Song K, Tan J, Jia Q, Zhang G, Wang R, He Y, et al: Gender and age impact on the association between thyroid-stimulating hormone and serum lipids. Medicine (Baltimore). 94:e21862015. View Article : Google Scholar : PubMed/NCBI
50	Ren X, Meng Z, Liu M, Zhu M, He Q, Zhang Q, Liu L, Song K, Jia Q, Jia Q, et al: No associations exist between mean platelet volume or platelet distribution width and thyroid function in Chinese. Medicine (Baltimore). 95:e45732016. View Article : Google Scholar : PubMed/NCBI
51	Zhou P, Meng Z, Liu M, Ren X, Zhu M, He Q, Zhang Q, Liu L, Song K, Jia Q, et al: The associations between leukocyte, erythrocyte or platelet, and metabolic syndrome in different genders of Chinese. Medicine (Baltimore). 95:e51892016. View Article : Google Scholar : PubMed/NCBI
52	Wang S, Zhang J, Zhu L, Song L, Meng Z, Jia Q, Li X, Liu N, Hu T, Zhou P, et al: Association between liver function and metabolic syndrome in Chinese men and women. Sci Rep. 7:448442017. View Article : Google Scholar : PubMed/NCBI
53	Zhang J, Meng Z, Zhang Q, Liu L, Song K, Tan J, Li X, Jia Q, Zhang G and He Y: Gender impact on the correlations between subclinical thyroid dysfunction and hyperuricemia in Chinese. Clin Rheumatol. 35:143–149. 2016. View Article : Google Scholar : PubMed/NCBI
54	Nowak J, Borkowska B and Pawlowski B: Leukocyte changes across menstruation, ovulation, and mid-luteal phase and association with sex hormone variation. Am J Hum Biol. 28:721–728. 2016. View Article : Google Scholar : PubMed/NCBI
55	Pérez-de-Heredia F, Gómez-Martínez S, Díaz LE, Veses AM, Nova E, Wärnberg J, Huybrechts I, Vyncke K, Androutsos O, Ferrari M, et al: Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents-the HELENA study. Eur J Pediatr. 174:999–1014. 2015. View Article : Google Scholar : PubMed/NCBI
56	Mandala WL, Gondwe EN, MacLennan JM, Molyneux ME and MacLennan CA: Age- and sex-related changes in hematological parameters in healthy Malawians. J Blood Med. 8:123–130. 2017. View Article : Google Scholar : PubMed/NCBI
57	Pratley RE, Wilson C and Bogardus C: Relation of the white blood cell count to obesity and insulin resistance: Effect of race and gender. Obes Res. 3:563–571. 1995. View Article : Google Scholar : PubMed/NCBI