Safety and Efficacy of Peginterferon Alfa-2a and Ribavirin for Hepatitis C in Thalassemia.
Bibliographic record
Abstract
Abstract Hepatitis C virus (HCV) is an important cause of liver disease in patients with thalassemia. Standard treatment for adult patients without thalassemia is pegylated interferon-alfa (PEG) and ribavirin, but has been contraindicated in patients with thalassemia due to ribavirin-induced hemolysis, with associated increase in transfusion requirement and iron loading. This study examines whether increased iron burden accelerates liver, heart, and endocrine disease, increases the risk of antiviral treatment in these patients, and influences response to therapy. An open-label, single arm trial of PEG (180 μg/week) and ribavirin (~16mg/kg/day) was performed through the NIH-sponsored Thalassemia Clinical Research Network. Patients were treated for 24 weeks (genotypes 2&3) or 48 weeks (genotype 1). Iron burden was measured as liver iron concentration (LIC) in dry weight biopsy samples and HCV-RNA levels by using the Roche COBAS HCV Tests (qualitative and quantitative). Safety for iron-related toxicities was assessed by liver pathology, cardiac echo and ECG, fasting blood sugar and thyroid function tests. Standard PEG/ribavirin toxicities were followed using biochemical parameters, vision and hearing tests, and adverse event monitoring. 21 patients (48% male, mean age 32y, 15 genotype 1, 6 genotype 2 or 3) were enrolled and started treatment. 4 participants discontinued between weeks 4 through 12 [death from presumed sepsis, persistent cough, extreme fatigue, and pregnant spouse], and 1 participant dropped out at 36 weeks. Transfusion requirement had increased by 40% after 24 weeks (range: −5 to 68 %) in all participants and by 31% after 48 weeks (range: −2 to 77%) in participants with genotype 1. Week 48 liver biopsies were obtained in 14 /16 patients. The mean baseline LIC was 11.2 mg/g (range: 1.1 to 44.1) and did not change significantly at 48 weeks (median increase: 1.7 mg/g). LIC increased in 29% (4/14) of participants by more than 5 mg/g. Ejection fraction remained stable over 48 weeks (range: −15 to +17 %) and no pathologic arrhythmias were reported. No participants developed diabetes mellitus or thyroid disease. A ≥ 2 log HCV-RNA reduction was achieved by week 4 in all participants with genotype 2 or 3, and in 47% by week 4 and 73% by week 12 in those with genotype 1. Although end of treatment viral response (ETR) in genotype 2 or 3 was 100 % (4/4), 75% did not obtain sustained viral response (SVR; HCV undetectable in blood six months after treatment). In contrast, genotype 1 participants had ETR of 75% (9/12) and SVR of 55% (6/11). No significant correlations were found in baseline LIC, baseline HCV-RNA level, or change in transfusion requirement with ETR or SVR. In summary, baseline LIC was not a predictor of early or SVR. Response rates for participants with genotype 1 were similar to the non-thalassemia population. Genotype 2 or 3 patients appear to have a lower SVR rate after 24 weeks of therapy; therefore, 48 weeks of therapy should be considered. Despite an increase in iron burden in some participants, combination therapy did not appear to pose significant iron-related safety issues. (Study medications provided by Hoffmann-La Roche).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".