Natural Killer Cell Characteristics in Patients with Chronic Hepatitis B Virus (HBV) Infection Are Associated with HBV Surface Antigen Clearance after Combination Treatment with Pegylated Interferon Alfa-2a and Adefovir

Journal of Infectious Diseases

Volumn 212, Issue 7, 2015, Pages 1042-1051

  Stelma, Femke ^a   De Niet, Annikki ^a   Tempelmans Plat Sinnige, Marjan J ^a   Jansen, Louis ^a   Takkenberg, R Bart ^a   Reesink, Hendrik W ^a   Kootstra, Neeltje A ^a   Van Leeuwen, Ester M M ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

combination therapy; Hepatitis B; innate immunity; interferon alfa; NK cells; TRAIL.

Indexed keywords

ADEFOVIR; CD56 ANTIGEN; CHEMOKINE RECEPTOR CX3CR1; GAMMA INTERFERON; HEPATITIS B SURFACE ANTIGEN; HEPATITIS B(E) ANTIGEN; NATURAL KILLER CELL RECEPTOR NKG2A; PEGINTERFERON ALPHA2A; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; VIRUS DNA; ADENINE; ALPHA INTERFERON; ANTIVIRUS AGENT; MACROGOL DERIVATIVE; MEMBRANE ANTIGEN; PHOSPHONIC ACID DERIVATIVE; RECOMBINANT PROTEIN;

ADULT; AGED; ARTICLE; CELL COUNT; CELL FUNCTION; CHRONIC HEPATITIS B; CLINICAL ARTICLE; CLINICAL TRIAL (TOPIC); CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG RESPONSE; FEMALE; HEPATITIS B VIRUS; HUMAN; HUMAN CELL; MALE; MIDDLE AGED; NATURAL KILLER CELL; PHENOTYPE; PRIORITY JOURNAL; SEROCONVERSION; VIRAL CLEARANCE; VIRUS LOAD; ANALOGS AND DERIVATIVES; DRUG COMBINATION; HEPATITIS B, CHRONIC; IMMUNOLOGY; TREATMENT OUTCOME; YOUNG ADULT;

ADENINE; ADULT; AGED; ANTIGENS, SURFACE; ANTIVIRAL AGENTS; DNA, VIRAL; DRUG THERAPY, COMBINATION; FEMALE; HEPATITIS B E ANTIGENS; HEPATITIS B SURFACE ANTIGENS; HEPATITIS B VIRUS; HEPATITIS B, CHRONIC; HUMANS; INTERFERON-ALPHA; KILLER CELLS, NATURAL; MALE; MIDDLE AGED; ORGANOPHOSPHONATES; POLYETHYLENE GLYCOLS; RECOMBINANT PROTEINS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84943383941     PISSN: 00221899     EISSN: 15376613     Source Type: Journal    
DOI: 10.1093/infdis/jiv180     Document Type: Article

References (34)

1. Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012; 30:2212-9.
2. Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 1988; 61:1942-56.
3. Micco L, Peppa D, Loggi E, et al. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol 2013; 58:225-33.
4. Binder D, Fehr J, Hengartner H, Zinkernagel RM. Virus-induced transient bone marrow aplasia: major role of interferon-alpha/beta during acute infection with the noncytopathic lymphocytic choriomeningitis virus. J Exp Med 1997; 185:517-30.
5. Marshall HD, Urban SL, Welsh RM. Virus-induced transient immune suppression and the inhibition of T cell proliferation by type I interferon. J Virol 2011; 85:5929-39.
6. Rehermann B, Lau D, Hoofnagle JH, Chisari FV. Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest 1996; 97:1655-65.
7. Tan AT, Hoang LT, Chin D, et al. Reduction of HBV replication prolongs the early immunological response to IFN therapy. J Hepatol 2014; 60:54-61.
8. Penna A, Laccabue D, Libri I, et al. Peginterferon-does not improve early peripheral blood HBV-specific T-cell responses in HBeAg-negative chronic hepatitis. J Hepatol 2012; 56:1239-46.
9. Peppa D, Micco L, Javaid A, et al. Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection. PLoS Pathog 2010; 6:e1001227.
10. Tjwa ETTL, van Oord GW, Hegmans JP, Janssen HL, Woltman AM. Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B. J Hepatol 2011; 54:209-18.
11. Boni C, Laccabue D, Lampertico P, et al. Restored function of HBVspecific T cells after long-term effective therapy with nucleos(t)ide analogues. Gastroenterology 2012; 143:963-73.
12. Thimme R, Dandri M. Dissecting the divergent effects of interferonalpha on immune cells: time to rethink combination therapy in chronic hepatitis B? J Hepatol 2013; 58:205-9.
13. Janssen HL, van Zonneveld M, Senturk H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet 2005; 365:123-9.
14. Takkenberg RB, Jansen L, de Niet A, et al. Baseline hepatitis B surface antigen (HBsAg) as predictor of sustained HBsAg loss in chronic hepatitis B patients treated with peginterferon alfa-2a and adefovir. Antivir Ther 2013; 18:895-904.
15. Lutgehetmann M, Volzt T, Quaas A, et al. Sequential combination therapy leads to biochemical and histological improvement despite low ongoing intrahepatic hepatitis B virus replication. Antivir Ther 2008; 13:57-66.
16. Wursthorn K, Lutgehetmann M, Dandri M, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology 2006; 44:675-84.
17. Kittner JM, Sprinzl MF, Grambihler A, et al. Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B. J Clin Virol 2012; 54:93-5.
18. Ouzan D, Pénaranda G, Joly H, Khiri H, Pironti A, Halfon P. Add-on peg-interferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs. J Clin Virol 2013; 58:713-7.
19. de Niet A, Tempelmans Plat-Sinnige MJ, Takkenberg RB, Reesink HW, van Lier RAW, van Leeuwen EMM. 278 Augmented hepatitis B specific T cell response after clearance of chronic hepatitis B. J Hepatol 2011; 54:S114.
20. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012; 57:167-85.
21. Li F, Wei H, Wei H, et al. Blocking the natural killer cell inhibitory receptor NKG2A increases activity of human natural killer cells and clears hepatitis B virus infection in mice. Gastroenterology 2013; 144:392-401.
22. Bellora F, Castriconi R, Dondero A, et al. Human NK cells and NK receptors. Immunol Lett 2014; 161:168-73.
23. Oo YH, Shetty S, Adams DH. The role of chemokines in the recruitment of lymphocytes to the liver. Dig Dis 2010; 28:31-44.
24. Becknell B, Caligiuri M. Interleukin-2, interleukin-15, and their roles in human natural killer cells. Adv Immunol 2005; 86:209-39.
25. Bjorkstrom NK, Riese P, Heuts F, et al. Expression patterns of NKG2A, KIR, and CD57 define a process of CD56 dim NK-cell differentiation uncoupled from NK-cell education. Blood. 2010; 116:3853-64.
26. Lopez-verges S, Milush JM, Pandey S, et al. CD57 defines a functionally distinct population of mature NK cells in the human CD56dim CD16+ NK-cell subset. Blood 2010; 116:3865-74.
27. Yu J, Mao HC,WeiM, et al. CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets. Blood 2010; 115:274-81.
28. Markova A, Mihm U, Schlaphoff V, et al. PEG-IFN alpha but not ribavirin alters NK cell phenotype and function in patients with chronic Hepatitis C. PLoS One 2014; 9:e94512.
29. Lunemann S, Malone DFG, Grabowski J, et al. Effects of HDV infection and pegylated interferon treatment on the natural killer cell compartment in chronically infected individuals. Gut 2015; 64:469-82.
30. Riley CH, Hansen M, Brimnes MK, et al. Expansion of circulating CD56 (bright) natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon. Eur J Haematol 2015; 94:227-34.
31. Stegmann K, Björkström NK, Veber H, et al. Interferon-alpha-induced TRAIL on natural killer cells is associated with control of hepatitis C virus infection. Gastroenterology 2010; 138:1885-97.
32. Peppa D, Gill U, Reynolds G. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion. J Exp Med 2013; 210:99-114.
33. Dunn C, Brunetto M. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med 2007; 204:667-80.
34. Golden Mason L, Bambha K. Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with chronic hepatitis C. Hepatology 2011; 54: 1559-69.