Virus‐specific T‐cell responses associated with hepatitis C virus (HCV) persistence in the liver after apparent recovery from HCV infection

Abstract

Hepatitis C virus (HCV) RNA persistence in the liver has been described even after apparent resolution of HCV infection. Because T-cell reactivity plays a role in recovery from HCV infection, virus-specific T-cell responses were investigated in apparently recovered individuals in whom hepatic HCV RNA persistence was documented: 15 sustained virological responders to interferon (IFN)-treatment and 9 asymptomatic aviremic anti-HCV carriers. HCV-specific CD4(+) T-cell proliferative responses were detected significantly more often in apparently recovered individuals (sustained virological responders: 60%; asymptomatic anti-HCV carriers: 66%) compared with 50 chronic hepatitis C patients (28%; P < 0.05). However, T-cell frequencies and numbers tended to decline over time and the number of HCV proteins targeted by CD4(+) T-cell proliferative responses was limited. Interestingly, liver viral load correlated inversely with virus-specific immune responses. Thus, CD4(+) T-cell responders showed significantly lower hepatic HCV RNA levels (P < 0.05). HCV-specific IFN-gamma-secreting CD4(+) T-cells were not detected in all the apparently recovered patients although they were found significantly more often compared with chronic hepatitis C patients (P < 0.05). Also, HCV NS3-specific CD8(+) T-cells were detected in 11 HLA-A2-positive apparently recovered individuals (8 sustained virological responders and 3 asymptomatic anti-HCV carriers); T-cell frequencies tended to be greater in those patients who had lower hepatic viral levels. In conclusion, HCV-specific T-cells are detectable in apparently recovered individuals in whom HCV RNA can persist in the liver indicating that HCV replication may be prolonged in the face of an insufficient or inadequate virus-specific CD4(+) and CD8(+) T-cell response.

Occult hepatitis C: How convincing are the current data? #

“…Recent reports about "occult" persistence of HCV infection despite constantly negative serum HCV RNA [1][2][3][4][5][6][7][8][9][10][11][12][13][14] have led to uncertainty in patients and physicians. This review gives a summary of available data regarding "occult" HCV infection.…”

Occult Hepatitis C Virus Infection: Where are We Now?

“…The cellular immune response may be more efficient in patients with an occult HCV infection, but it is not strong enough to definitively eliminate the virus. The same team demonstrated that HCV-specific CD4+ and CD8+ proliferative responses were observed more frequently in patients who have spontaneously eliminated the virus than in those whose chronic infection was eliminated by treatment (Quiroga et al, 2006). The peripheral blood mononuclear cells like dendritic cells, monocytes, CD4+ and CD8+ T cells, and B cells of chronically infected patients can contain HCV virus particles.…”

“…The persistence of a T-specific immune response could be the result of low concentrations of HCV RNA that are undetectable by present techniques. One study compared the cellular immune responses of 50 patients with a cryptogenic occult HCV infection, 141 patients with a chronic HCV infection and 21 patients with cryptogenic liver pathology (Quiroga et al, 2004). Fifty-two per cent of the patients with a cryptogenic occult HCV infection had a specific proliferative CD4+ T cell response to HCV.…”

Hepatite B e C: diagnóstico e tratamento

“…Vários fatores externos incluindo o consumo de álcool, coinfecções HIV / HBV, resistência à insulina, obesidade, doenças hepáticas gordurosas não alcoólicas, entre outros, estão ligadas à progressão da fibrose acelerada e à cirrose. A gravidade da fibrose hepática está estreitamente correlacionada com o aumento do risco de carcinoma hepatocelular através da facilitação de aberrações genéticas e promoção de clones neoplásicos 31 . Semelhante ao HCV, o ciclo de vida do HBV começa com a ligação do vírus ao seu receptor na superfície do hepatócito.…”

“…Todos os pacientes devem ser avaliados para doença hepática e comorbidades. Estudos comprovam que pacientes com história de excesso de ingestão de álcool, excesso de peso ou obesidade, e de diabetes tipo 2 ou outra doença hepática aumenta significativamente a chance de um indivíduo ter fibrose avançada ou cirrose 31 . Exames complementares como, avaliação da função renal, glicose, outras infecções transmitidas pelo sangue, como HIV, hepatite B, enzimas hepáticas e contagem sanguínea total, devem ser solicitadas.…”