Rapid decline of anti-hepatitis C virus (HCV) antibodies following early treatment of incident HCV infections in HIV-infected men who have sex with men.

OBJECTIVES: Following clearance of incident hepatitis C virus (HCV) infections, HCV antibody levels may decline, resulting in seroreversion. It is unclear to what extent HCV antibody level trajectories differ between patients with treatment-induced sustained virological response (SVR), those with spontaneous clearance and those with untreated replicating HCV infection. We investigated HCV antibody level dynamics in HIV-infected MSM with different clinical outcomes. METHODS: We investigated anti-HCV antibody level dynamics following an incident HCV infection in 67 HIV-infected men who have sex with men (MSM) with different clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated replicating infection (n = 22). Antibody levels were measured at the time of HCV diagnosis, and at yearly intervals for 3 years thereafter. RESULTS: At baseline, median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5 sample to cut-off (S/CO) for SVR, spontaneous clearance and untreated infection, respectively. Over 3 years of follow-up, SVR was associated with a more pronounced decrease in anti-HCV levels compared with spontaneous clearance and untreated infection [median decline 71% [interquartile range (IQR: 43-87%), 38% (IQR: 29-60%) and 12% (IQR: 9-22%), respectively; P < 0.001]. Seroreversions occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with spontaneous clearance. A shorter delay between time of infection and treatment start correlated with higher rates of decline in antibody levels. Seven patients experienced a reinfection. CONCLUSIONS: Treatment-induced HCV clearance was associated with a more pronounced decline in anti-HCV antibody levels and with higher rates of seroreversion compared with spontaneous clearance or untreated replicating HCV infection among HIV-infected MSM with incident HCV infections. Rapid clearance of HCV RNA following early HCV treatment might impair the development of persistent antibody titres.

Treatment of acute hepatitis C virus infection in HIV-infected MSM: the effect of treatment duration.

We evaluated hepatitis C virus (HCV) treatment and the effect of treatment duration (24 versus 48 weeks) on treatment outcome among 50 HIV-infected men who have sex with men with acute HCV infection in Amsterdam. Overall sustained virological response (SVR) rate was 76%. Treatment duration was not significantly associated with SVR (adjusted odds ratio = 2.32; 95% confidence interval 0.39-13.97), suggesting that 24-week treatment may be sufficient for acute HCV infection in HIV-coinfected patients.

[HCV: immune response and its modifiers in clinical development]. / Mechanizmy immunologiczne zakazen HCV--kierunek poszukiwan terapeutycznych.

Host immunological response is one of the major factors determining natural history of HCV infection. Disturbances of cellular immune response, especially dynamic Th1/Th2 balance and Th2 response domination seems to be the reason of HCV persistence. Recent therapeutic strategies based on immunomodulatory agents like interferon and ribavirin. Interferon action is regulated by many factors including immunological. In the work the results of experimental and clinical trials evaluating safety, tolerance and efficacy of interferon others as alpha were described. While the mechanism of immune modifiers is not clearly understood, various immunomodulatory agents are being studied for HCV-infected patients.

Predictive factors for sustained response to interferon treatment in patients with chronic hepatitis C: a randomized, open, and multi-center controlled trial.

BACKGROUND: This study was undertaken to investigate the predictive factors of sustained viral response in roferon-A or pegasys treated chronic hepatitis C patients after logistic regression analysis of the factors that might be associated with the therapeutic effects of interferon (IFN). METHODS: All patients enrolled into this randomized, open and multi-center controlled trial were divided into two groups randomly and treated with pegasys and roferon-A for 24 weeks, then followed up for another 24 weeks. Before treatment, hepatitis C virus (HCV) genotype was determined, and HCV-RNA in serum was detected before and at the end of treatment and follow-up. HCV-RNA turning negative was considered the major index for evaluating the therapeutic effect. The clinical characteristics including gender, age, infection route of HCV, treatment with IFN, platelet count, AST/ALT ratio and treatment drugs were analyzed by logistic regression. RESULTS: Intention to treat (ITT) and per-protocol (PP) population groups have 208 and 197 patients respectively. In the PP group, after treatment for 24 weeks, the response rates of female patients aged less than 50 years, infected through non-transfusion, relapsed after IFN treatment, and presented with a AST/ALT ratio/=1, virus load equal or more than 8 x 10(5) IU/ml, and genotype 1 infection, and treated finally with roferon-A. But, at the end of follow-up, the patients with a AST/ALT ratio>/=1 and virus load more than 8 x 10(5) IU/ml had a higher rate of sustained response than did those with a AST/ALT ratio

The effect of erythropoietin therapy and hemoglobin levels on the immune response to Engerix-B vaccination in chronic kidney disease.

BACKGROUND: Patients undergoing chronic hemodialysis have an increased risk of acquiring hepatitis B infection. Only 43-66% of dialysis patients develop effective anti-HBs titers after vaccination. AIM: To evaluate the effect of recombinant erythropoietin (rEPO) therapy and basal hemoglobin levels on the outcome of the immune response to four doses of IM 40 microg Engerix-B vaccination in hemodialysis and chronic kidney disease (CKD) patients before starting replacement therapy. SUBJECTS AND METHODS: One hundred and three patients were included in the study: 34 hemodialysis patients treated with rEPO (Group A), 36 predialytic patients who did not treated with rEPO (Group B) and 33 predialytic patients treated with rEPO (Group C). Plasma creatinine in predialytic patients was 2-7 mg/dL. All patients' HBsAg and anti-HBs antibodies were negative. Patients were immunized with IM 40 microg Engerix-B at 0, 1, 3, and 6 months. Anti-HBs titers were measured at 7th month. RESULTS: Eighty seven point one percent of patients from group C developed protective anti-HBs titers compared with 69.4% from group B and 44.1% from group A (p = 0.001). Patients from all groups with baseline hemoglobin levels above 11 gr/dL developed protective anti-HBs titers significantly more than patients with baseline hemoglobin levels below 11 gr/dL (p < 0.05). CONCLUSION: Predialytic patients treated with rEPO and with hemoglobin levels higher than 11 gr/dL had significantly better immune response outcomes to Engerix-B vaccination. Immunization against hepatitis B infection should be considered at early stages of CKD prior to the deterioration in kidney functions and the development of renal anemia.

Additives and protein-DNA combinations modulate the humoral immune response elicited by a hepatitis C virus core-encoding plasmid in mice.

Humoral and cellular immune responses are currently induced against hepatitis C virus (HCV) core following vaccination with core-encoding plasmids. However, the anti-core antibody response is frequently weak or transient. In this paper, we evaluated the effect of different additives and DNA-protein combinations on the anti-core antibody response. BALB/c mice were intramuscularly injected with an expression plasmid (pIDKCo), encoding a C-terminal truncated variant of the HCV core protein, alone or combined with CaCl2, PEG 6000, Freund's adjuvant, sonicated calf thymus DNA and a recombinant core protein (Co. 120). Mixture of pIDKCo with PEG 6000 and Freund's adjuvant accelerated the development of the anti-core Ab response. Combination with PEG 6000 also induced a bias to IgG2a subclass predominance among anti-core antibodies. The kinetics, IgG2a/IgG1 ratio and epitope specificity of the anti-core antibody response elicited by Co. 120 alone or combined with pIDKCo was different regarding that induced by the pIDKCo alone. Our data indicate that the antibody response induced following DNA immunization can be modified by formulation strategies.

Neutralization of transforming growth factor beta 1 augments hepatitis C virus-specific cytotoxic T lymphocyte induction in vitro.

In hepatitis C virus (HCV) infection, TGF-beta 1 is upregulated in the liver and may be involved in the pathogenesis of chronic liver disease. TGF-beta 1 is also produced by activated T cells and acts as a potent immunosuppressor. The aim of this study was to investigate the roles of TGF-beta 1 in HCV-specific cytotoxic T lymphocyte (CTL) induction and enhance their killer activity by TGF-beta 1 modulation. We generated anti-HCV CTL from peripheral blood mononuclear cells from HLA-A2 patients under stimulation with the HCV-core peptide having the HLA-A2.1 binding motif. The lytic activities of CTL or precursor frequency (CTLpf) generated with or without anti-TGF-beta antibody were compared. To optimize the IL-2 dose for CTL induction, low (50 U/ml) and high (500 U/ml) doses were tested and the lytic activities were compared. TGF-beta 1 amounts in the supernatants were assessed by enzyme-linked immunosorbent assay and by their growth inhibitory effect on mink lung epithelial cells. CTL activity was enhanced by anti-TGF-beta antibody in a dose-dependent manner but CTLpf did not significantly change. A high dose of IL-2 reduced the activity to 45% of that observed with a low dose, whereas TGF-beta 1 increased as the dose of IL-2 increased. Exogenous IL-10 reversed the inhibitory effect of a high dose of IL-2 on the killing activity by reducing TGF-beta 1 mRNA expression in T cells and its production. These results demonstrated that endogenous TGF-beta 1 is an autocrine suppressor in CTL induction in vitro. Therefore, the blockade of endogenous TGF-beta 1 could enhance the killing potential of anti-HCV CTL.