Direct-Acting Antivirals Are not Associated With Early Tumor Recurrence After Curative Treatments in Hepatitis C-related Hepatocellular Carcinoma
Bibliographic record
Abstract
Introduction: Interferon (IFN)-free regimens using new direct acting antivirals (DAA) have revolutionized the treatment of chronic hepatitis C (HCV) infection and demonstrate a sustained viral response (SVR) of over 90%. A recent publication has suggested an association between DAA therapy and early hepatocellular carcinoma (HCC) recurrence raising concerns about their safety. Therefore, we conducted a retrospective study to investigate the impact of DAA initiation on early tumor recurrence after curative treatments in HCV-related HCC. Methods: From surgery and interventional radiology (January 2012-December 2015) databases, 103 unique HCV infected patients with primary or recurrent HCC were identified. Thirty-seven consecutive HCV infected patients with complete response to their curative HCC therapy for at least 3 months were identified, after excluding those who failed to achieve complete radiological response (n=19), received transarterial chemoembolization (TACE) (n=17), received anti-viral therapy prior to HCC diagnosis or therapy (n=14), received interferon containing DAA regimens (n=3), died within 3 months of HCC therapy (n=6), or those lost to follow-up (n=7). Fourteen of these patients subsequently received DAAs, and 23 acted as controls. To prevent crossover into the DAA treatment cohort, a maximum follow-up period of 36 months after the last HCC treatment was set. Results: Baseline age, gender, total bilirubin, albumin, MELD score, alpha-feto protein levels, total tumor volume, percentage of patients with primary HCC and prior interferon exposure did not differ. Both groups were predominately infected with genotype 1 (DAA 71% vs controls 70%). Median interval between HCC treatment and the start of DAA treatment was 11 months, but ranged from 2 to 17 months. The median observation period was 23 months in DAA and 17 months in controls. In the current observation period, HCC recurrence occurred in 5/14 (36%) treated with DAAs and 15/23 (65%) of controls. Kaplan-Meier analysis did not show improved HCC recurrence free survival in the DAA group (p=0.0639). BCLC staging of recurrent disease was similar in both groups (BCLC 0/A: DAA 60% vs controls 73%; BCLC B/C: DAA 40% vs controls 27%) Conclusion: In our analysis, DAA treatment after curative HCC therapy was not associated with early or more aggressive tumor recurrence. Ultimately, a randomized clinical trial should be performed to further clarify this controversial subject.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".