Incidence of hospitalization for infection among patients with hepatitis B or C virus infection without cirrhosis in Taiwan: A cohort study

English version

Autoři: Yen-Chieh Lee ^aff001; Jiun-Ling Wang ^aff003; Yaa-Hui Dong ^aff005; Hsi-Chieh Chen ^aff007; Li-Chiu Wu ^aff007; Chia-Hsuin Chang ^aff007
Působiště autorů: Department of Family Medicine, Cathay General Hospital, Taipei, Taiwan ^aff001; Department of Medicine, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan ^aff002; Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan ^aff003; Department of Medicine, National Cheng Kung University Medical College, Tainan, Taiwan ^aff004; Faculty of Pharmacy, School of Pharmaceutical Science, National Yang-Ming University, Taipei, Taiwan ^aff005; Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan ^aff006; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan ^aff007; Department of Internal Medicine, National Taiwan University Hospital, Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan ^aff008; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan ^aff009
Vyšlo v časopise: Incidence of hospitalization for infection among patients with hepatitis B or C virus infection without cirrhosis in Taiwan: A cohort study. PLoS Med 16(9): e32767. doi:10.1371/journal.pmed.1002894
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1002894

Souhrn

Background

Infection is a major complication in liver cirrhosis and causes major morbidity and mortality. However, the incidence and mortality related to these conditions in patients infected with hepatitis C virus (HCV) are unclear, as is whether antiviral therapy could change their infection risk.

Methods and findings

In this community-based cohort study, a total of 115,336 adults (mean age 52.2 years; 35.6% men) without cirrhosis participating in the New Taipei City Health Screening in 2005–2008 were classified as having noncirrhotic HCV (NC-HCV) (n = 2,839), noncirrhotic hepatitis B virus (NC-HBV) (n = 8,316), or no HBV or HCV infection (NBNC) (n = 104,181). Participants were followed to their first hospitalization for infection or death after data linkage with the Taiwan National Health Insurance Research Database (NHIRD) and Death Registry. A Cox proportional hazard regression model, adjusted for age, sex, body mass index (BMI), smoking, alcohol consumption, education level, diabetes, renal function, systemic steroids, and history of hospitalization, was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and individual sites of infection and infection-related mortality. The reference group was NBNC participants with normal to mildly elevated alanine aminotransferase (ALT) (<1.5 times upper normal limit [UNL]) levels. To further address the impact of antiviral treatment on infection risk, we conducted analyses of data from the nationwide NHIRD and compared the risks for hospitalization because of infections and infection-related deaths between patients with HCV who received antiviral therapy (n = 20,264) and those who remained untreated (n = 104,360). During a median 8.2-year follow-up, the incidence of hospitalization for infection was substantially higher in NC-HCV patients. Compared to the reference group, NC-HCV was associated with a significantly higher risk for hospitalization because of overall infections (adjusted HR: 1.22; 95% CI: 1.12–1.33), but we observed no increased risk for patients in the NC-HBV (adjusted HR: 0.94; 95% CI: 0.88–1.01) or NBNC group with moderate to markedly elevated ALT levels (adjusted HR: 1.03; 95% CI: 0.93–1.14). For specific sites of infection, the NC-HCV group had increased risks for septicemia and lower respiratory tract, reproductive, and urinary tract infections. We noted no increased risk for infection-related death among patients with NC-HCV. Patients with HCV who received antiviral therapy had significantly reduced infection-related hospitalization and death risks (adjusted HR: 0.79; 95% CI: 0.73–0.84 for infection-related hospitalization and adjusted HR: 0.08; 95% CI: 0.04–0.16 for infection-related deaths). Study limitations include the exclusion of patients with cirrhosis from the cohort, the possibility of unmeasured confounding, and the lack of information on direct-acting antiviral agents (DAAs).

Conclusions

In this study, patients with NC-HCV were at increased risk for hospitalization for infection, while no increased risk was observed for NC-HBV-infected patients.

Klíčová slova:

Biology and life sciences – Organisms – Population biology – Medicine and health sciences – Microbiology – Medical microbiology – Microbial pathogens – Pathology and laboratory medicine – Pathogens – Population metrics – Death rates – Viral pathogens – Viruses – RNA viruses – Immunology – Flaviviruses – Hepacivirus – Hepatitis C virus – Hepatitis B virus – Vaccination and immunization – Pulmonology – Respiratory infections – Lower respiratory tract infections – Public and occupational health – Preventive medicine – Antiviral therapy – Gastroenterology and hepatology – Liver diseases – Cirrhosis – Urology – Urinary tract infections

Zdroje

1. Lee M-H, Yang H-I, Yuan Y, L’Italien G, Chen C-J. Epidemiology and natural history of hepatitis C virus infection. World J Gastroenterol. 2014;20(28):9270–80. 25071320

2. Mohamed AA, Elbedewy TA, El-Serafy M, El-Toukhy N, Ahmed W, Ali El Din Z. Hepatitis C virus: A global view. World J Hepatol. 2015;7(26):2676–80. doi: 10.4254/wjh.v7.i26.2676 26609344

3. Sievert W, Altraif I, Razavi Homie A, Abdo A, Ahmed Ezzat A, AlOmair A, et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver. 2011;31(s2):61–80.

4. Sun CA, Chen HC, Lu CF, You SL, Mau YC, Ho MS, et al. Transmission of hepatitis C virus in Taiwan: prevalence and risk factors based on a nationwide survey. J Med Virol. 1999;59(3):290–6. 10502258

5. Bonnel AR, Bunchorntavakul C, Reddy KR. Immune dysfunction and infections in patients with cirrhosis. Clin Gastroenterol Hepatol. 2011;9(9):727–38. doi: 10.1016/j.cgh.2011.02.031 21397731

6. Bunchorntavakul C, Chamroonkul N, Chavalitdhamrong D. Bacterial infections in cirrhosis: A critical review and practical guidance. World J Hepatol. 2016;8(6):307–21. doi: 10.4254/wjh.v8.i6.307 26962397

7. El-Serag HB, Anand B, Richardson P, Rabeneck L. Association between hepatitis C infection and other infectious diseases: a case for targeted screening? Am J Gastroenterol. 2003;98(1):167–74. 12526953

8. Jirillo E, Greco B, Caradonna L, Satalino R, Pugliese V, Cozzolongo R, et al. Evaluation of cellular immune responses and soluble mediators in patients with chronic hepatitis C virus (cHCV) infection. Immunopharmacol Immunotoxicol. 1995;17(2):347–64. doi: 10.3109/08923979509019756 7650295

9. King E, Trabue C, Yin D, Yao ZQ, Moorman JP. Hepatitis C: the complications of immune dysfunction. Expert Rev Clin Immunol. 2007;3(2):145–57. doi: 10.1586/1744666X.3.2.145 20477104

10. Della Bella S, Crosignani A, Riva A, Presicce P, Benetti A, Longhi R, et al. Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus-specific CD4(+) T-cell proliferation in patients with hepatitis C virus infection. Immunology. 2007;121(2):283–92. doi: 10.1111/j.1365-2567.2007.02577.x 17462079

11. Dolganiuc A, Garcia C, Kodys K, Szabo G. Distinct Toll-like receptor expression in monocytes and T cells in chronic HCV infection. World J Gastroenterol. 2006;12(8):1198–204. 16534871

12. Kim H, Meyer K, Di Bisceglie AM, Ray R. Hepatitis C virus suppresses C9 complement synthesis and impairs membrane attack complex function. J Virol. 2013;87(10):5858–67. doi: 10.1128/JVI.00174-13 23487461

13. Marrie TJ, Tyrrell GJ, Majumdar SR, Eurich DT. Concurrent Infection with Hepatitis C Virus and Streptococcus pneumoniae. Emerg Infect Dis. 2017;23(7):1118–23. doi: 10.3201/eid2307.161858 28628455

14. Wu PH, Lin YT, Hsieh KP, Chuang HY, Sheu CC. Hepatitis C Virus Infection Is Associated With an Increased Risk of Active Tuberculosis Disease: A Nationwide Population-Based Study. Medicine. 2015;94(33):e1328. doi: 10.1097/MD.0000000000001328 26287416

15. Laupland KB, Ross T, Gregson DB. Staphylococcus aureus Bloodstream Infections: Risk Factors, Outcomes, and the Influence of Methicillin Resistance in Calgary, Canada, 2000–2006. J Infect Dis. 2008;198(3):336–43. doi: 10.1086/589717 18522502

16. Awad SS, Elhabash SI, Lee L, Farrow B, Berger DH. Increasing incidence of methicillin-resistant Staphylococcus aureus skin and soft-tissue infections: reconsideration of empiric antimicrobial therapy. Am J Surg. 2007;194(5):606–10. doi: 10.1016/j.amjsurg.2007.07.016 17936421

17. Miller LG, Perdreau-Remington F, Rieg G, Mehdi S, Perlroth J, Bayer AS, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med. 2005;352(14):1445–53. doi: 10.1056/NEJMoa042683 15814880

18. Reddy S, Sullivan R, Zaiden R, De Mendoza VL, Naik N, Vega KJ, et al. Hepatitis C infection and the risk of bacteremia in hemodialysis patients with tunneled vascular access catheters. South Med J. 2009;102(4):374–7. doi: 10.1097/SMJ.0b013e31819bc34c 19279528

19. Nakasone H, Kurosawa S, Yakushijin K, Taniguchi S, Murata M, Ikegame K, et al. Impact of hepatitis C virus infection on clinical outcome in recipients after allogeneic hematopoietic cell transplantation. Am J Hematol. 2013;88(6):477–84. doi: 10.1002/ajh.23436 23483626

20. Mizrahi M, Roemi L, Shouval D, Adar T, Korem M, Moses A, et al. Bacteremia and "Endotipsitis" following transjugular intrahepatic portosystemic shunting. World J Hepatol. 2011;3(5):130–6. doi: 10.4254/wjh.v3.i5.130 21731907

21. Lopez-Medrano F, Fernandez-Ruiz M, Morales JM, San-Juan R, Cervera C, Carratala J, et al. Impact of hepatitis C virus infection on the risk of infectious complications after kidney transplantation: data from the RESITRA/REIPI cohort. Transplantation. 2011;92(5):543–9. doi: 10.1097/TP.0b013e318225dbae 21869745

22. Singh N, Gayowski T, Wagener MM, Marino IR. Increased infections in liver transplant recipients with recurrent hepatitis C virus hepatitis. Transplantation. 1996;61(3):402–6. doi: 10.1097/00007890-199602150-00014 8610350

23. Scher D, Kanlic E, Bader J, Ortiz M, Abdelgawad A. Hepatitis C viral infection as an associated risk factor for necrotizing fasciitis. Orthopedics. 2012;35(4):e510–3. doi: 10.3928/01477447-20120327-43 22495851

24. Lee PH, Fu H, Lai TC, Chiang CY, Chan CC, Lin HH. Glycemic Control and the Risk of Tuberculosis: A Cohort Study. PLoS Med. 2016;13(8):e1002072. doi: 10.1371/journal.pmed.1002072 27505150

25. National Health Insurance Administration Universal Health Coverage in Taiwan. Updated 2018 June 08. https://www.nhi.gov.tw/English/Content_List.aspx?n=8FC0974BBFEFA56D&topn=ED4A30E51A609E49. [cited 2018 Nov 20].

26. Kramer JR, Davila JA, Miller ED, Richardson P, Giordano TP, El-Serag HB. The validity of viral hepatitis and chronic liver disease diagnoses in Veterans Affairs administrative databases. Aliment Pharmacol Ther. 2007;27(3):274–82. doi: 10.1111/j.1365-2036.2007.03572.x 17996017

27. Schisterman EF, Cole SR, Platt RW. Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology. 2009;20(4):488–95. doi: 10.1097/EDE.0b013e3181a819a1 19525685

28. Bunchorntavakul C, Chavalitdhamrong D. Bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. World J Hepatol. 2012;4(5):158–68. doi: 10.4254/wjh.v4.i5.158 22662285

29. Schneeweiss S, Rassen JA, Glynn RJ, Avorn J, Mogun H, Brookhart MA. High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology. 2009;20(4):512–22. doi: 10.1097/EDE.0b013e3181a663cc 19487948

30. Melia MT, Bräu N, Poordad F, Lawitz EJ, Shiffman ML, McHutchison JG, et al. Infections During Peginterferon/Ribavirin Therapy Are Associated With the Magnitude of Decline in Absolute Lymphocyte Count: Results of the IDEAL Study. Clin Infect Dis. 2014;58(7):960–9. doi: 10.1093/cid/ciu009 24399086

31. Cooper CL, Al-Bedwawi S, Lee C, Garber G. Rate of Infectious Complications during Interferon-Based Therapy for Hepatitis C Is Not Related to Neutropenia. Clin Infect Dis. 2006;42(12):1674–8. doi: 10.1086/504386 16705570

32. Fried MW. Side effects of therapy of hepatitis C and their management. Hepatology. 2002;36(5 Suppl 1):S237–44. doi: 10.1053/jhep.2002.36810 12407599

33. Inoue T, Nakayama J, Moriya K, Kawaratani H, Momoda R, Ito K, et al. Gut Dysbiosis Associated With Hepatitis C Virus Infection. Clin Infect Dis. 2018;67(6):869–77. doi: 10.1093/cid/ciy205 29718124

34. Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60(6):1310–24. doi: 10.1016/j.jhep.2014.01.024 24530646

35. Preveden T, Scarpellini E, Milic N, Luzza F, Abenavoli L. Gut microbiota changes and chronic hepatitis C virus infection. Expert Rev Gastroenterol Hepatol. 2017;11(9):813–9. doi: 10.1080/17474124.2017.1343663 28621554

36. Dominitz JA, Boyko EJ, Koepsell TD, Heagerty PJ, Maynard C, Sporleder JL, et al. Elevated prevalence of hepatitis C infection in users of United States veterans medical centers. Hepatology. 2005;41(1):88–96. doi: 10.1002/hep.20502 15619249

37. Nseir W, Taha H, Khateeb J, Grosovski M, Assy N. Fatty Liver Is Associated with Recurrent Bacterial Infections Independent of Metabolic Syndrome. Dig Dis Sci. 2011;56(11):3328–34. doi: 10.1007/s10620-011-1736-5 21562784

38. Miura K, Seki E, Ohnishi H, Brenner DA. Role of toll-like receptors and their downstream molecules in the development of nonalcoholic Fatty liver disease. Gastroenterol Res Pract. 2010;2010:362847. doi: 10.1155/2010/362847 21274430

39. Ghetti FDF, Oliveira DG, Oliveira JMD, De Castro Ferreira Lincoln Eduardo Villela Vieira, Cesar DE, Moreira APB. Influence of gut microbiota on the development and progression of nonalcoholic steatohepatitis. Eur J Nutr. 2017;57(3):861–76. doi: 10.1007/s00394-017-1524-x 28875318

40. Pang J, Xu W, Zhang X, Wong GL-H, Chan AW-H, Chan H-Y, et al. Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017;46(2):175–82. doi: 10.1111/apt.14119 28464257

41. Nseir W, Artul S, Nasrallah N, Mahamid M. The association between primary bacteremia of presumed gastrointestinal origin and nonalcoholic fatty liver disease. Ital J Gastroenterol Hepatol. 2016;48(3):343–4.

42. Kaka AS, Filice GA, Kuskowski M, Musher DM. Does active hepatitis C virus infection increase the risk for infection due to Staphylococcus aureus? Eur J Clin Microbiol. 2017;36(7):1217–23.

43. Li W, Jin R, Chen P, Zhao G, Li N, Wu H. Clinical correlation between HBV infection and concomitant bacterial infections. Sci Rep. 2015;5:15413. doi: 10.1038/srep15413 26634436

44. Nahon P, Bourcier V, Layese R, Audureau E, Cagnot C, Marcellin P, et al. Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications. Gastroenterology. 2017;152(1):142–56.e2. doi: 10.1053/j.gastro.2016.09.009 27641509

45. Nahon P, Lescat M, Layese R, Bourcier V, Talmat N, Allam S, et al. Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort). Gut. 2017;66(2):330–41. doi: 10.1136/gutjnl-2015-310275 26511797

46. Eom C-S, Jeon CY, Lim J-W, Cho E-G, Park SM, Lee K-S. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183(3):310–9. doi: 10.1503/cmaj.092129 21173070

47. Romero-Corral A, Somers VK, Sierra-Johnson J, Thomas RJ, Collazo-Clavell ML, Korinek J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes. 2008;32(6):959–66.