{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:34:41Z","timestamp":1791326081339,"version":"4.3.1"},"reference-count":80,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T00:00:00Z","timestamp":1419206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Regione Emilia Romagna, Italy","award":["PRUa1RI-2012-006"],"award-info":[{"award-number":["PRUa1RI-2012-006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatitis B virus (\n                    <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\n                    ) infection acquired in adult life is generally self\u2010limited while chronic persistence of the virus is the prevalent outcome when infection is acquired perinatally. Both control of infection and liver cell injury are strictly dependent upon protective immune responses, because hepatocyte damage is the price that the host must pay to get rid of intracellular virus. Resolution of acute hepatitis B is associated with functionally efficient, multispecific antiviral T\u2010cell responses which are preceded by a poor induction of intracellular innate responses at the early stages of infection. Persistent control of infection is provided by long\u2010lasting protective memory, which is probably sustained by continuous stimulation of the immune system by trace amounts of virus which are never totally eliminated, persisting in an occult episomic form in the nucleus of liver cells even after recovery from acute infection. Chronic virus persistence is instead characterized by a lack of protective T\u2010cell memory maturation and by an exhaustion of\n                    <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\n                    \u2010specific T\u2010cell responses. Persistent exposure of T cells to high antigen loads is a key determinant of functional T\u2010cell impairment but also other mechanisms can contribute to T\u2010cell inhibition, including the tolerogenic effect of the liver environment. The degree of T\u2010cell impairment is variable and its severity is related to the level of virus replication and antigen load. The antiviral T\u2010cell function is more efficient in patients who can control infection either partially, such as inactive\n                    <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>\n                    sAg carriers with low levels of virus replication, or completely, such as patients who achieve\n                    <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>\n                    sAg loss either spontaneously or after antiviral therapy. Thus, understanding the features of the immune responses associated with control of infection is needed for the successful design of novel immune modulatory therapies based on the reconstitution of efficient antiviral responses in chronic\n                    <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\n                    patients.\n                  <\/jats:p>","DOI":"10.1111\/liv.12749","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T05:26:34Z","timestamp":1419225994000},"page":"121-128","source":"Crossref","is-referenced-by-count":175,"title":["<scp>HBV<\/scp>\n                    and the immune response"],"prefix":"10.1111","volume":"35","author":[{"given":"Carlo","family":"Ferrari","sequence":"first","affiliation":[{"name":"Unit of Infectious Disease and Hepatology Laboratory of Viral Immunopathology Azienda Ospedaliero\u2010Universitaria di Parma Parma 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