Circulating CD56dim natural killer cells and CD56+ T cells that produce interferon-γ or interleukin-10 are expanded in asymptomatic, E antigen-negative patients with persistent hepatitis B virus infection.

Infection with hepatitis B virus (HBV) can result in spontaneous resolution or chronic infection, which can remain asymptomatic or can progress to cirrhosis and/or hepatocellular carcinoma. The host immune response is thought to be a major determinant of the outcome of HBV infection and virus-specific cytotoxic T lymphocytes (CTL) can mediate immunity against the virus and cause liver pathology. Antigen-nonspecific innate lymphocytes may also contribute to HBV infection and liver disease, therefore, we examined the frequencies, phenotypes, cytolytic activities and cytokine profiles of circulating natural killer (NK) cells, CD1d-restricted invariant natural killer T (iNKT) cells and CD56(+) T cells in 102 asymptomatic HBV-infected patients and compared them with those in 66 uninfected control subjects. NK cells expressing low levels of CD56 (CD56(dim)) and CD56(+) T cells were significantly expanded in the circulation of HBV-infected patients compared with control subjects. CD1d expression and iNKT cell frequencies were similar in both groups. Despite these expansions, we did not detect augmented natural or cytokine-induced cytotoxicity in the HBV-infected subjects. All lymphocyte populations studied produced interferon-γ (IFN-γ) significantly more frequently when taken from HBV-infected patients compared with when taken from healthy controls. Additionally, NK cells from the patients more frequently produced interleukin-10. As our HBV-infected cohort consisted of asymptomatic patients with low viral loads, we propose that CD56(dim) NK cells and CD56(+) T cells control HBV infection by noncytolytic mechanisms.

Review article: optimizing SVR and management of the haematological side effects of peginterferon/ribavirin antiviral therapy for HCV - the role of epoetin, G-CSF and novel agents.

BACKGROUND: Chronic hepatitis C is one of the leading causes for chronic liver disease globally. The past two decades have seen many advances in hepatitis C treatment. Despite these advances, side effects of treatment are common. Haematological complications of treatment can result in treatment cessation and suboptimal results. Recent data have suggested a role for epoetin/granulocyte colony stimulating factor (G-CSF) in optimizing sustained virological response (SVR). AIM: To investigate the nature, frequency and management of haematological side effects in the treatment of chronic hepatitis C infection. METHODS: The terms hepatitis C, hepatitis C virus (HCV), treatment, side effects, interferon, peginterferon, ribavirin, anaemia, haemoglobin, neutropenia, thrombocytopenia, haematological, growth factor, erythropoietin and G-CSF were searched on MEDLINE for the period 1991-2009. References from selected articles were also included. RESULTS: Haematological side effects such as anaemia, neutropenia and thrombocytopenia are frequent in anti-HCV treatment. The off-label use of haematological growth factors is common and effective. CONCLUSIONS: Erythropoietic agents are effective in treating anaemia, preventing ribavirin dose reduction, improving patients' quality of life, but the effect on SVR is not fully elucidated. G-CSF is effective in raising absolute neutrophil count; however, neutropenic HCV-infected patients on combination treatment may not experience increased bacterial infections. Eltrombopag, a new oral thrombopoietin mimetic, may allow combination treatment in patients with thrombocytopenia.