Paul Naylor

African Americans with genotype 1 treated with interferon for chronic hepatitis C have a lower end of treatment response than Caucasians

African Americans as a group have a higher incidence of chronic hepatitis C (CHC) than Caucasians but are often under‐represented in clinical trials used to define response rates to interferon therapy. The aim of this study was to compare African Americans with Caucasians with respect to end‐of‐treatment response to interferon. This retrospective study had 61 African Americans and 49 Caucasians with CHC. All patients were treated for at least 12 weeks with interferon‐α2b (Intron A) thrice weekly. End‐of‐treatment response was defined as three consecutive nondetectable HCV RNA measurements at least 1 month apart. Sustained response was defined as a negative serum HCV RNA 6 months after end of treatment. Of the 110 patients, 19 achieved an end‐of‐treatment response (17%) but only four achieved a sustained response (4/110=4%). Of the patients achieving a sustained response, one was genotype 1 (male Caucasian), three were genotype 2/3 with four patients having no follow‐up information. The end‐of‐treatment response was 7% for patients with genotype 1 and 71% for genotype non‐1 (P < 0.005 for genotype non‐1). The end‐of‐treatment response was significantly higher in Caucasians (14/49=31%) compared with African Americans (5/61=8%; P < 0.05). A lower response rate in African Americans with genotype 1 in contrast to Caucasians was the primary reason for the difference in end‐of‐treatment response (1/45=2% vs. 5/33=15%, P < 0.05). Hence, interferon treatment resulted in a poor sustained response rate in the group of patients representative of the urban populations with the highest prevalence of hepatitis C. A genotype other than type 1 was the strongest predictor of end‐of‐treatment response in patients treated but over 86% of patients in this urban clinic were genotype 1. Caucasians were more likely to respond than African Americans, especially in patients with genotype 1.

Prevalence of hepatitis A virus and hepatitis B virus immunity in patients with polymerase chain reaction-confirmed hepatitis C: Implications for vaccination strategy

OBJECTIVES:Administration of vaccine for hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic hepatitis C (CHC) because of the potential for increased severity of acute hepatitis superimposed on existing liver disease. The aim of this study is to determine the prevalence of antibodies directed against HAV and HBV in patients with CHC, analyze demographic and risk factors associated with this prevalence, and develop a cost-effective vaccination strategy.METHODS:We reviewed records from 1092 CHC patients. Demographics and information regarding risk factors were obtained by history and questionnaire administered to all patients. The costs of vaccination and antibody testing were determined, based on standard laboratory and clinic charges at our institution. HAV and HBV markers were correlated to race, age, and risk factors.RESULTS:Of the total population studied (n = 1092), 72% were African-Americans, 27% white, and 1% others. Of 671 CHC patients tested for anti-HAV IgG, 252 (38%) were positive. Of 743 CHC patients tested for HBV antibodies (anti-hepatitis B core IgG or anti-hepatitis B surface), 494 (67%) were positive. African-Americans are more likely to have antibodies to HAV and HBV (67% and 75%, respectively) compared to whites (27% and 20%). The prevalence of anti-HAV was 76% in patients >60 yr, 34% in the 40- to 60-yr-old age group, and 21% in patients <40 yr. The highest prevalence of HBV antibodies was found in patients between the ages of 40–60 yr. No HCV risk factors were associated with increased HAV risk. In CHC patients with HBV antibodies, however, illicit injection drug use was the predominant risk factor.CONCLUSIONS:The prevalence of anti-HAV in patients with CHC was found to be similar to that of the general population in the United States (33% according to recent Centers for Disease Control data), consistent with the hypothesis that the two infections do not share risk factors. Because the prevalence of HAV immunity is low in CHC patients <40 yr, empiric HAV vaccination is cost effective. If two doses of vaccine are to be given, however, antibody testing of all HCV patients is indicated. In the subset of patients >60 yr of age or who are African-American, where the prevalence of HAV exposure is considerably higher, it would be cost effective to check the antibody (

Hepatitis C screening and prevalence among urban public safety workers.

36.00), before vaccination (

Effect of Peptide-Carrier Coupling on Peptide-Specific Immune Responses

97.00). The prevalence of HBV antibodies, however, is significantly increased in patients with CHC compared with the general population (5.3% per the Centers for Disease Control), likely as a result of exposure to similar parenteral risk factors. HBV antibody testing (

Thymosin-α1, but not interferon-α, specifically inhibits anchorage-independent growth of hepatitis B viral transfected HepG2 cells

26.00 per test) should, therefore, be undertaken in all CHC patients who are hepatitis B surface antigen negative, as this approach is cost-effective compared to empiric HBV vaccination (

ADJUVANT PROPERTIES OF MONTANIDE CSA 720 WITH A RECOMBINANT HIV P17 GAG PROTEIN AND SYNTHETIC PEPTIDE ANTIGENS

438.00 for a three injection course).

Utilization of HPLC-Elisa to Assess Serum Levels of Thymosin α1 Following Subcutaneous Administration to Human Subjects

This study examines the prevalence of anti-hepatitis C virus by using an enzyme-linked immunoassay test (EIA-2) in 2447 volunteers (including 1560 police, 678 fire, and 209 emergency medical service personnel) and a self-reported questionnaire on potential occupational and non-occupational risk factors. Subjects consisted of 76% men, 54.8% blacks, and 40.3% whites. Twenty-eight individuals (1.1%) tested positive, with prevalence rates of 1.1% and 1.3%, respectively, among blacks and whites. Although firefighters and emergency medical service workers had a higher prevalence (2.3% and 2.8%) than police (0.6%), the overall prevalence was lower than that typical of urban populations. In a multivariate analysis, the most important risk factors were behavioral, with no significant occupational exposure risk observed. Previously reported racial differences were not detected in this study, most likely because the subjects were of similar socioeconomic status.

Immunotherapy for Hepatitis B in the Direct Acting Anti-viral Era: Reevaluating the Thymosin α1 Efficacy Trials in Light of a Combination Therapy Approach

Synthetic peptides are covalently linked to immunogenic carrier proteins to enhance the anti-peptide immune response. To investigate whether the method of conjugation influences the immune response, we evaluated two distinctly different choices of linker for a peptide-carrier construct. HPG-30, a synthetic peptide derived from the p17 gag protein of human immunodeficiency virus 1, was covalently linked to keyhole limpet hemocyanin by either glutaraldehyde or a maleimide ester. Glutaraldehyde linkage enhanced the anti-peptide antibody and native protein response compared to maleimide. The maleimide-linked conjugate was more effective at inducing a peptide-specific cellular response. Thus, manipulation of the conjugation method can modify the magnitude and character of the immune response to a synthetic peptide vaccine.

Overlapping molecular signaling of IRX-2 and Ta1 resulting in synergistic biological activity

Abstract Background: Thymosin-α 1 is a biological response modifier that has been used clinically, alone and in combination with interferon-α for the treatment of chronic hepatitis B viral infection. Both immunomodulatory and immediate intracelluilar mechanisms have been postulated to explain the effect of these two agents on HBV-infected hepatocytes. Methods: In this study, hepatitis B transfected HepG2 hepatoblastoma cells (HepG2-Nu2), derived from 2.2.15 cells, were used as an in vitro model to determine the efficacy of thymosin-α 1 and interferon-α, individually and combined, a proliferation inhibitors of HBV-infected cells. For comparison, parental HepG2 cells and an SV40-transfected HepG2 cell line (HepG2P9T2) were also evaluated. Results: In a clonogenic soft agar assay, thymosin-α 1 inhibited the anchorage-independent growth of the HepG2-Nu2 cells by 40% compared with untreated controls, but did not inhibit parental HepG2 or HepG2P9T2 clonal growth. The response was dose dependent over concentrations spanning three log units. In comparison, 10 000 units/ml of interferon-α inhibited parental HepG2, HepG2-N4Z and HepG2P9T2 by 33%, 41% and 87%, respectively. The combination of thymosin-α 1 and interferon-α consistently inhibited HepG2-Nu2 clonal growth more effectively than either treatment alone, reaching maximum inhibition levels of 51%. Conclusions: Thymosin-α 1 specifically inhibits the tumorigenic growth of HBV-transfected HepG2 cells in contrast to the general inhibition displayed by interferon-α. This panel of cell lines may be an important resource for dissecting the mechanism by which thymosin, alone or in combination with other drugs, influences HBV-infected hepatocytes and/or HBV-associated carcinoma.

Relationship between clostridium difficile infection and gastrointestinal graft versus host disease in recipients of allogeneic stem cell transplantation

The adjuvant properties of Montanide CSA 720 were assessed in a comparison with alum. BALB/c mice were immunized with recombinant HIV‐1 gag protein p17 administered in either of the two adjuvants. The serum antibody response to p17 with Montanide CSA 720 appeared faster and reached a higher titre than with alum. The serum antibody response to p17 in Montanide CSA 720 was further characterized by a higher titre antibody directed against a 30 amino acid segment from the entire protein. The Montanide CSA 720 adjuvant was sufficiently strong to induce an antibody response against a weak synthetic peptide immunogen after two immunizations, while immunization with the peptide in alum generated no detectable serum antibody. The p17‐specific proliferative response of splenocytes from animals immunized with recombinant protein in either adjuvant was similar.