Immune Cell Subsets Evaluation as a Predictive Tool for Hepatitis B Infection Outcome and Treatment Responsiveness.

BACKGROUND: The patient's immune response is one of the major factors influencing HBV eradication or chronification, and it is thought to be responsible for the treatment success. AIM: Our study aimed to investigate whether cellular defense mechanisms are associated with the course of HBV infection (spontaneous recovery [SR] or chronification [CHB]) and with the therapeutic approach. PATIENTS AND METHODS: A total of 139 patients (118 with CHB, 21 SR) and 29 healthy individuals (HI) were immunophenotyped by flowcytometry. Fifty-six patients were treatment-naïve, 20 were treated with interferons and 42 with nucleoside/ nucleotide analogues. RESULTS: Deficiency of T lymphocytes, helper-inducer (CD3+CD4+), suppressorcytotoxic (CD8+CD3+) and cytotoxic (CD8+CD11b-, CD8+CD28+) subsets, activated T cells (CD3+HLA-DR+, CD8+CD38+) and increased CD57+CD8- cells, elevated percentages of B lymphocytes and NKT cells were observed in CHB patients compared with HI. In SR patients, elevated CD8+CD11b+, NKT and activated T cells were found in comparison with controls. The higher values of T cells and their subsets in SR patients than in CHB patients reflect a recovery of cellular immunity in resolved HBV infection individuals. In both groups of treated patients, reduced T lymphocytes, CD3+CD4+ and CD8+CD38+ subsets were found in comparison with HI. Higher proportions of cytotoxic subsets were observed in treated patients compared with treatment-naïve CHB patients, more pronounced in the group with interferon therapy. CONCLUSION: Our data demonstrate that cellular immune profiles may be of prognostic value in predicting the clinical course of HBV infection, and the determination of the therapeutic response.

Chronic hepatitis C virus infection: prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients.

AIM: To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia. METHODS: The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using chi2 and Fisher's exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis. RESULTS: Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation. Clinical manifestations included fatigue (59.6%), kidney impairment (25.0%), type 2 diabetes (22.8%), paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fibrosis (15.4%), thyroid dysfunction (14.7%), Raynaud's phenomenon (11.8%), B-cell lymphoma (8.8%), sicca syndrome (6.6%), and lichen planus (5.9%). The biological manifestations included cryoglobulin production (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome, and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were: age > or = 60 years, female gender, virus transmission by blood transfusions, longstanding infection (> or = 20 years), and extensive liver fibrosis. The most significant risks factors (multivariate analysis) were longstanding infection and extensive liver fibrosis. CONCLUSION: We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin production. Longstanding infection and extensive liver fibrosis were significant risk factors for the presence of extrahepatic manifestations in HCV patients.