Dataset Information

Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C.

ABSTRACT: To evaluate T cell immunity in advanced liver disease, antigen-specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low-dose peginterferon-alfa-2a (PEG-IFN) only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5-6) were less likely to have positive LP responses to HCV at baseline than patients with fibrosis (15%vs 29%, P = 0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (P = 0.11, P = 0.05, P = 0.02, respectively). For 97 patients with complete longitudinal data, the frequency of positive LP responses to HCV, tetanus and Candida antigens declined over time (P < 0.003), and the slope of this decline was greater in the PEG-IFN treatment group than the observation group (P < 0.02). Lower levels of tetanus LP responses were associated with fibrosis progression and clinical outcomes (P = 0.009). Poorer CD4+ T cell proliferative function was associated with more advanced liver disease in chronic hepatitis C and may be further affected by long-term PEG-IFN treatment.

SUBMITTER: Morishima C

PROVIDER: S-EPMC3349971 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C.

Morishima C C Di Bisceglie A M AM Rothman A L AL Bonkovsky H L HL Lindsay K L KL Lee W M WM Koziel M J MJ Fontana R J RJ Kim H-Y HY Wright E C EC

Journal of viral hepatitis 20111216 6

To evaluate T cell immunity in advanced liver disease, antigen-specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low-dose peginterferon-alfa-2a (PEG-IFN) only or observation. Liver histology was evalua ...[more]

PMID: 22571902

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Project description:RationaleOccupational exposure to beryllium (Be) can result in chronic granulomatous inflammation characterized by the presence of Be-specific CD4+ T cells. Studies show that oxidative stress plays a role in the pathogenesis of chronic inflammatory disorders.ObjectivesWe hypothesized that Be-induced oxidative stress modulates the proliferation of Be-specific CD4+ T cells.MethodsThirty-three subjects with chronic beryllium disease (CBD), 15 subjects with beryllium sensitization, and 28 healthy normal control subjects were consecutively enrolled from the Occupational and Environmental Health Clinic of the National Jewish Medical and Research Center.Measurements and main resultsAll studies were performed with Ficoll-Hypaque-isolated peripheral blood mononuclear cells from subsets of the study subjects. Decreased intracellular levels of the thiol antioxidants, glutathione and cysteine, were observed in peripheral blood mononuclear cells from subjects with beryllium sensitization and CBD, as compared with healthy control subjects. Beryllium stimulation decreased intracellular thiol antioxidants by more than 40%, accompanied by increased reactive oxygen species levels and the proliferation of Be-specific blood CD4+ T cells from subjects with CBD. Be-induced T-cell proliferation was inhibited by treatment with the thiol antioxidant N-acetylcysteine or the catalytic antioxidant manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP). MnTBAP treatment also inhibited T-cell proliferation in response to the unrelated, MHC class II-restricted antigen tetanus toxoid. Treatment of CBD blood lymphocytes, but not antigen-presenting cells, with MnTBAP decreased Be-induced T-cell proliferation by more than 40%.ConclusionsBeryllium can mediate a thiol imbalance leading to oxidative stress that may modulate the proliferation and clonal expansion of Be-specific blood CD4+ T cells. These data suggest that Be-induced oxidative stress plays a role in the pathogenesis of granulomatous inflammation in CBD.

Project description:PurposeRadiation oncology (RO) has seen declines in Medicare reimbursement (MCR). However, there are no recent studies analyzing the contributions of specific billing codes to overall RO reimbursement. We compared total MCR for specific Healthcare Common Procedure Coding System (HCPCS) codes in 2019 with MCR for those codes in 2010 and 2015, corrected for inflation, to see how the same basket of RO services in 2019 would have been reimbursed in 2010 and 2015 (adjusted MCR).Methods and materialsThe Centers for Medicare & Medicaid Services Physician/Supplier Procedure Summary database was used to obtain MCR data for RO HCPCS codes in 2010, 2015, and 2019. For each code, the total allowed charge was divided by the number of submitted claims to calculate the average MCR per claim in 2010, 2015, and 2019. The 2019 billing frequency for each code was then multiplied by the inflation-adjusted average MCR for those codes in 2010 and 2015 to determine what the MCR would have been in 2010 and 2015 using 2019 dollars and utilization rates. Results were compared with actual 2019 MCR to calculate the projected difference.ResultsTotal inflation-adjusted RO MCR was $2281 million (M), $1991 M, and $1848 M in 2010, 2015, and 2019 respectively. This represents a cut of $433 M (19%) and $143 M (7%) from 2010 and 2015, respectively, to 2019. After utilization adjustment, total reimbursement was $2534 M, $2034 M, and $1848 M for 2010, 2015, and 2019, respectively, representing a cut of $686 M (27%) and $186 M (9%) from 2010 and 2015, respectively, to 2019. Intensity modulated radiation therapy (IMRT) treatment delivery and planning accounted for $917 M (36%), $670 M (33%), and $573 M (31%) of the adjusted MCR in 2010, 2015, and 2019, respectively.ConclusionsMedicare reimbursement decreased substantially from 2010 to 2019. A decline in IMRT treatment reimbursement was the primary driver of MCR decline. When considering further cuts, policymakers should consider these trends and their consequences for health care quality and access.

Dataset Information

Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C.

Publications

Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C.

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