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Effect of seasonal variation on the clinical course of chronic hepatitis B

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Abstract

Background

Seasonal variation in immunity has been found in healthy individuals and in association with some diseases. It is still unknown whether seasonal variation affects the clinical course of chronic hepatitis B. Our aim in this study was to explore the effect of seasonal variation on the clinical course of chronic hepatitis B.

Methods

The flare and remission time of chronic hepatitis B were observed in patients with hepatitis B virus (HBV) infection. All patients enrolled were followed up at least every 3 months for a mean follow-up time of 24.0 (range, 12–60) months. Seasonal decomposition was employed to analyze the relationship between seasonal variation and flares, remission, and hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B patients during follow-up.

Results

A total of 2238 patients were observed in our study. Flare and HBeAg seroconversion were seldom seen in 1076 patients (48.08%) with alanine aminotransferase (ALT) levels of less than 2.0 × upper limit of normal (ULN) during follow-up (mean, 36 months). The remaining 1162 patients (51.92%) (766, HBeAg positive; 387 anti-HBeAg positive; 9 negative for both HBeAg and anti-HBeAg) with ALT levels ≥2.0 × ULN were followed longitudinally for 12 months to judge flare, remission, and HBeAg seroconversion. Flare, remission, and HBeAg seroconversion in patients with ALT levels ≥2.0 × ULN showed clear seasonal patterns (P < 0.001), with high peaks during spring, summer, and summer, respectively. An autocorrelation correlogram showed that flares, remission, and HBeAg seroconversion occurred with distinct periodicity in winter, spring, summer, and autumn.

Conclusions

Seasonal variation might affect the clinical course of chronic hepatitis B. The role of seasonal triggering factors should be further investigated.

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References

  1. JH Kao DS Chen (2002) ArticleTitleGlobal control of hepatitis B virus infection Lancet Infect Dis 2 395–403 Occurrence Handle10.1016/S1473-3099(02)00315-8 Occurrence Handle12127351

    Article  PubMed  Google Scholar 

  2. Y Nakamoto S Kaneko (2003) ArticleTitleMechanisms of viral hepatitis induced liver injury Curr Mol Med 3 537–44 Occurrence Handle10.2174/1566524033479591 Occurrence Handle1:CAS:528:DC%2BD3sXnslyru7w%3D Occurrence Handle14527085

    Article  CAS  PubMed  Google Scholar 

  3. RN Chien YF Liaw (2004) ArticleTitleThymalfasin for the treatment of chronic hepatitis B Expert Rev Anti Infect Ther 2 9–16 Occurrence Handle10.1586/14787210.2.1.9 Occurrence Handle1:CAS:528:DC%2BD2cXisFCqsL8%3D Occurrence Handle15482167

    Article  CAS  PubMed  Google Scholar 

  4. EJ Crighton R Moineddin RE Upshur M Mamdani (2003) ArticleTitleThe seasonality of total hospitalizations in Ontario by age and gender: a time series analysis Can J Public Health 94 453–7 Occurrence Handle14700246

    PubMed  Google Scholar 

  5. M Hashimoto T Fukuda T Shimizu S Watanabe S Watanuki Y Eto M Urashima (2004) ArticleTitleInfluence of climate factors on emergency visits for childhood asthma attack Pediatr Int 46 48–52 Occurrence Handle10.1111/j.1442-200X.2004.01835.x Occurrence Handle15043664

    Article  PubMed  Google Scholar 

  6. LA Akslen RB Sothern (1998) ArticleTitleSeasonal variations in the presentation and growth of thyroid cancer Br J Cancer 77 1174–9 Occurrence Handle1:STN:280:DyaK1c3ivVSisQ%3D%3D Occurrence Handle9569058

    CAS  PubMed  Google Scholar 

  7. F Boulay F Berthier MDC Dahan A Tran (2001) ArticleTitleSeasonal variations in variceal bleeding mortality and hospitalization in France Am J Gastroenterol 96 1881–7 Occurrence Handle10.1111/j.1572-0241.2001.03889.x Occurrence Handle1:STN:280:DC%2BD3MzlvFWjsA%3D%3D Occurrence Handle11419844

    Article  CAS  PubMed  Google Scholar 

  8. N Singh MM Wagener T Gayowski (2001) ArticleTitleSeasonal pattern of early mortality and infectious complications in liver transplant recipients Liver Transpl 7 884–9 Occurrence Handle10.1053/jlts.2001.27864 Occurrence Handle1:STN:280:DC%2BD3MrntVGhtw%3D%3D Occurrence Handle11679987

    Article  CAS  PubMed  Google Scholar 

  9. MF Yuen CL Lai (2001) ArticleTitleTreatment of chronic hepatitis B Lancet Infect Dis 1 232–41 Occurrence Handle10.1016/S1473-3099(01)00118-9 Occurrence Handle1:CAS:528:DC%2BD3MXptFajtb8%3D Occurrence Handle11871510

    Article  CAS  PubMed  Google Scholar 

  10. S Locarnini C Birch (1999) ArticleTitleAntiviral chemotherapy for chronic hepatitis B infection: lessons learned from treating HIV-infected patients J Hepatol 30 536–50 Occurrence Handle10.1016/S0168-8278(99)80118-4 Occurrence Handle1:STN:280:DyaK1M3gsFSitQ%3D%3D Occurrence Handle10190742

    Article  CAS  PubMed  Google Scholar 

  11. RP Perrillo (2001) ArticleTitleAcute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease Gastroenterology 120 1009–22 Occurrence Handle10.1016/S0016-5085(01)82819-5 Occurrence Handle1:CAS:528:DC%2BD3MXitlertLk%3D Occurrence Handle11231956

    Article  CAS  PubMed  Google Scholar 

  12. D Ganem AM Prince (2004) ArticleTitleHepatitis B infection—natural history and clinical consequences J N Engl Med 350 1118–29 Occurrence Handle10.1056/NEJMra031087 Occurrence Handle1:CAS:528:DC%2BD2cXitV2qurs%3D

    Article  CAS  Google Scholar 

  13. YF Liaw (2002) ArticleTitleManagement of patients with chronic hepatitis B J Gastroenterol Hepatol 17 406–8 Occurrence Handle10.1046/j.1440-1746.2002.02736.x Occurrence Handle11982720

    Article  PubMed  Google Scholar 

  14. GE Demas (2004) ArticleTitleThe energetics of immunity: a neuroendocrine link between energy balance and immune function Horm Behav 45 173–80 Occurrence Handle10.1016/j.yhbeh.2003.11.002 Occurrence Handle1:CAS:528:DC%2BD2cXisVSms7w%3D Occurrence Handle15047012

    Article  CAS  PubMed  Google Scholar 

  15. M Maes F De Meyer D Peeters H Meltzer P Cosyns C Schotte (1992) ArticleTitleSeasonal variation and meteotropism in various self-rated psychological and physiological features of a normal couple Int J Biometeorol 36 195–200 Occurrence Handle1:STN:280:ByyD2M3osVE%3D Occurrence Handle1428221

    CAS  PubMed  Google Scholar 

  16. RJ Nelson (2004) ArticleTitleSeasonal immune function and sickness responses Trends Immunol 25 187–92 Occurrence Handle10.1016/j.it.2004.02.001 Occurrence Handle1:CAS:528:DC%2BD2cXisVarsrs%3D Occurrence Handle15039045

    Article  CAS  PubMed  Google Scholar 

  17. L Sher (2001) ArticleTitleEffects of seasonal mood changes on seasonal variations in coronary heart disease: role of immune system, infection, and inflammation Med Hypotheses 56 104–6 Occurrence Handle10.1054/mehy.2000.1122 Occurrence Handle1:STN:280:DC%2BD3M7jtlalsQ%3D%3D Occurrence Handle11133264

    Article  CAS  PubMed  Google Scholar 

  18. P Myrianthefs S Karatzas K Venetsanou E Grouzi P Evagelopoulou E Boutzouka et al. (2003) ArticleTitleSeasonal variation in whole blood cytokine production after LPS stimulation in normal individuals Cytokine 24 286–92 Occurrence Handle10.1016/j.cyto.2003.08.005 Occurrence Handle1:CAS:528:DC%2BD3sXovVeiurY%3D Occurrence Handle14609570

    Article  CAS  PubMed  Google Scholar 

  19. TJ Nelson GE Demas SL Klein LJ Kriegsfeld (1995) ArticleTitleThe influence of season, photoperiod and pineal melatonin on immune function J Perineal Res 19 149–65 Occurrence Handle1:CAS:528:DyaK28XltFahsA%3D%3D

    CAS  Google Scholar 

  20. FN Boctor RA Charmy EL Cooper (1989) ArticleTitleSeasonal differences in the rhythmicity of human male and female lymphocyte blastogenic responses Immunol Invest 18 775–84 Occurrence Handle1:STN:280:BiaA2MfhvVc%3D Occurrence Handle2767738

    CAS  PubMed  Google Scholar 

  21. HJ Kruse I Wieczorek H Hecker A Creutzig SM Schellong (2002) ArticleTitleSeasonal variation of endothelin-1, angiotensin II, and plasma catecholamines and their relation to outside temperature J Lab Clin Med 140 236–41 Occurrence Handle10.1067/mlc.2002.127169 Occurrence Handle1:CAS:528:DC%2BD38Xoslegtrk%3D Occurrence Handle12389021

    Article  CAS  PubMed  Google Scholar 

  22. CL Carty U Gehring J Cyrys W Bischof J Heinrich (2003) ArticleTitleSeasonal variability of endotoxin in ambient fine particulate matter J Environ Monit 5 953–8 Occurrence Handle10.1039/b308488d Occurrence Handle1:CAS:528:DC%2BD3sXpt1GmtLs%3D Occurrence Handle14710938

    Article  CAS  PubMed  Google Scholar 

  23. JH Park DL Spiegelman HA Burge DR Gold GL Chew DK Milton (2000) ArticleTitleLongitudinal study of dust and airborne endotoxin in the home Environ Health Perspect 108 1023–8 Occurrence Handle1:STN:280:DC%2BD3M7htVWhuw%3D%3D Occurrence Handle11102291

    CAS  PubMed  Google Scholar 

  24. BP Leaderer L Naeher T Jankun K Balenger TR Holford C Toth et al. (1999) ArticleTitleIndoor, outdoor, and regional summer and winter concentrations of PM10, PM2.5, SO4 2−, H+, NH4 +, NO3−, NH3, and nitrous acid in homes with and without kerosene space heaters Environ Health Perspect 107 223–31 Occurrence Handle1:CAS:528:DyaK1MXislKgur0%3D Occurrence Handle10064553

    CAS  PubMed  Google Scholar 

  25. RJ Nelson DL Drazen (1999) ArticleTitleMelatonin mediates seasonal adjustments in immune function Reprod Nutr Dev 39 383–98 Occurrence Handle1:CAS:528:DyaK1MXksVaqtLc%3D Occurrence Handle10420440

    CAS  PubMed  Google Scholar 

  26. G Matarese A La Cava (2004) ArticleTitleThe intricate interface between immune system and metabolism Trends Immunol 25 193–200 Occurrence Handle10.1016/j.it.2004.02.009 Occurrence Handle1:CAS:528:DC%2BD2cXisVarsrg%3D Occurrence Handle15039046

    Article  CAS  PubMed  Google Scholar 

  27. B Plytycz R Seljelid (1997) ArticleTitleRhythms of immunity Arch Immunol Ther Exp (Warsz) 45 157–62 Occurrence Handle1:CAS:528:DyaK2sXmt1Wrs7c%3D

    CAS  Google Scholar 

  28. KZ Long N Nanthakumar (2004) ArticleTitleEnergetic and nutritional regulation of the adaptive immune response and trade-offs in ecological immunology Am J Hum Biol 16 499–507 Occurrence Handle10.1002/ajhb.20064 Occurrence Handle15368598

    Article  PubMed  Google Scholar 

  29. S Fiorucci A Mencarelli E Distrutti M Baldoni P del Soldato A Morelli (2004) ArticleTitleNitric oxide regulates immune cell bioenergetics: a mechanism to understand immunomodulatory functions of nitric oxide-releasing anti-inflammatory drugs J Immunol 173 874–82 Occurrence Handle1:CAS:528:DC%2BD2cXlsVGhtbw%3D Occurrence Handle15240674

    CAS  PubMed  Google Scholar 

  30. GE Demas V Chefer MI Talan RJ Nelson (1997) ArticleTitleMetabolic cost of mounting an antigen-stimulated immune response in adult and aged C57Bl/6J mice Am J Physiol 273 R1631–7 Occurrence Handle1:CAS:528:DyaK2sXnsVCksLY%3D Occurrence Handle9374803

    CAS  PubMed  Google Scholar 

  31. C Bonneaud J Mauc G Gonzalez C Haussey O Chastel B Faire et al. (2003) ArticleTitleAssessing the cost of mounting an immune response Am Nat 161 367–79 Occurrence Handle10.1086/346134 Occurrence Handle12703483

    Article  PubMed  Google Scholar 

  32. W Waelput P Brouckaert D Broekaert J Tavernier (2002) ArticleTitleA role for leptin in the systemic inflammatory response syndrome (SIRS) and in immune response Curr Drug Targets Inflamm Allergy 1 277–89 Occurrence Handle10.2174/1568010023344634 Occurrence Handle1:CAS:528:DC%2BD38XmtF2rsL0%3D Occurrence Handle14561193

    Article  CAS  PubMed  Google Scholar 

  33. M Shifrine A Garad LS Rosenblatt (1982) ArticleTitleSeasonal variation in immunity in humans J Interdiscipl Cycle Res 12 157–65

    Google Scholar 

  34. BJ Prendergast SD Bilbo FS Dhabhar RJ Nelson (2004) ArticleTitleEffects of photoperiod history on immune responses to intermediate day lengths in Siberian hamsters (Phodopus sungorus) J Neuroimmunol 149 31–9 Occurrence Handle10.1016/j.jneuroim.2003.12.006 Occurrence Handle1:CAS:528:DC%2BD2cXitFCht7k%3D Occurrence Handle15020062

    Article  CAS  PubMed  Google Scholar 

  35. M Maes F De Meyer (2000) ArticleTitleRelationships of climatic data to immune and hematologic variables in normal human Neuroendocrinol Lett 21 127–36 Occurrence Handle11455342

    PubMed  Google Scholar 

  36. M Maes W Stevens S Scharpe E Bosmans F De Meyer P D'Hondt et al. (1994) ArticleTitleSeasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukin-2 and -6 receptor concentrations in normal volunteers Experientia 50 821–9 Occurrence Handle10.1007/BF01956463 Occurrence Handle1:CAS:528:DyaK2cXmslymt7w%3D Occurrence Handle7523180

    Article  CAS  PubMed  Google Scholar 

  37. J Killestein MH Rep JF Meilof HJ Ader BM Uitdehaag F Barkhof et al. (2002) ArticleTitleSeasonal variation in immune measurements and MRI markers of disease activity in MS Neurology 58 1077–80 Occurrence Handle1:STN:280:DC%2BD383itlymtw%3D%3D Occurrence Handle11940696

    CAS  PubMed  Google Scholar 

  38. KE Balashov MJ Olek DR Smith SJ Khoury HL Weiner (1998) ArticleTitleSeasonal variation of interferon-gamma production in progressive multiple sclerosis Ann Neurol 44 824–8 Occurrence Handle10.1002/ana.410440519 Occurrence Handle1:CAS:528:DyaK1cXnsFChtrw%3D Occurrence Handle9818941

    Article  CAS  PubMed  Google Scholar 

  39. RJ Shephard PN Shek (1998) ArticleTitleCold exposure and immune function Can J Physiol Pharmacol 76 828–36 Occurrence Handle10.1139/cjpp-76-9-828 Occurrence Handle1:CAS:528:DyaK1MXhsFWjsLw%3D Occurrence Handle10066131

    Article  CAS  PubMed  Google Scholar 

  40. ZW Tian DY Duan (2001) ArticleTitleEffects of cold exposure on the activities of NK and LAK cell in mouse J Xinxiang Med Coll 18 100–5

    Google Scholar 

  41. BK Pedersen JA Woods DC Nieman (2001) ArticleTitleExercise-induced immune changes—an influence on metabolism? Trends Immunol 22 473–5 Occurrence Handle10.1016/S1471-4906(01)02013-0 Occurrence Handle1:CAS:528:DC%2BD3MXms1Ciurw%3D

    Article  CAS  Google Scholar 

  42. M Biermer R Puro RI Schneider (2003) ArticleTitleTumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid integrity through activation of NF-kappaB J Virol 77 4033–42 Occurrence Handle10.1128/JVI.77.7.4033-4042.2003 Occurrence Handle1:CAS:528:DC%2BD3sXisVKku7g%3D Occurrence Handle12634363

    Article  CAS  PubMed  Google Scholar 

  43. LG Guidotti FV Chisari (2001) ArticleTitleNoncytolytic control of viral infections by the innate and adaptive immune response Annu Rev Immunol 19 65–91 Occurrence Handle10.1146/annurev.immunol.19.1.65 Occurrence Handle1:CAS:528:DC%2BD3MXivFKgtb0%3D Occurrence Handle11244031

    Article  CAS  PubMed  Google Scholar 

  44. V Pasquetto SF Wieland SL Uprichard M Tripodi FV Chisari (2002) ArticleTitleCytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte cultures J Virol 76 5646–53 Occurrence Handle10.1128/JVI.76.11.5646-5653.2002 Occurrence Handle1:CAS:528:DC%2BD38XjslGnurs%3D Occurrence Handle11991993

    Article  CAS  PubMed  Google Scholar 

  45. BE Wang (2000) ArticleTitleManagement of chronic hepatitis B: treatment of chronic liver diseases with traditional Chinese medicine J Gastroenterol Hepatol 15 IssueIDSuppl E67–70 Occurrence Handle10.1046/j.1440-1746.2000.02100.x Occurrence Handle1:CAS:528:DC%2BD3cXltFOjsbc%3D Occurrence Handle10921385

    Article  CAS  PubMed  Google Scholar 

  46. GB Yao (2000) ArticleTitleManagement of chronic hepatitis B: treatment of chronic hepatitis B in China J Gastroenterol Hepatol 15 IssueIDSuppl E61–6 Occurrence Handle10.1046/j.1440-1746.2000.02106.x Occurrence Handle1:CAS:528:DC%2BD3cXltFOjsbY%3D Occurrence Handle10921384

    Article  CAS  PubMed  Google Scholar 

  47. S Zhang Z Chen S Lao B Huang (2004) ArticleTitleEffect of Hejie decoction on T cellular immune state of chronic hepatitis B patients World J Gastroenterol 10 1436–9 Occurrence Handle15133849

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China

    Shi-Jun Zhang, Ze-Xiong Chen & Cui-Yi Zhang

  2. Department of Gastroenterology, Traditional Chinese Medicine Hospital of FuShan, FuShan, China

    Kai-Ping Jiang

  3. Institute of Integrated Traditional Chinese and Western Medicine, Sun Yat-Sen University, Guangdong, China

    Wei-Kang Wu

  4. Department of General Surgery, University of Essen, Essen, Germany

    Yan-Li Gu

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  1. Shi-Jun Zhang
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Zhang, SJ., Chen, ZX., Jiang, KP. et al. Effect of seasonal variation on the clinical course of chronic hepatitis B. J Gastroenterol 41, 1107–1115 (2006). https://doi.org/10.1007/s00535-006-1903-1

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