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001-es BibID:	BIBFORM120681
Első szerző:	Weltzsch, Jan Philipp
Cím:	Optimizing thiopurine therapy in autoimmune hepatitis : a multi-center study on monitoring metabolite profiles and co-therapy with allopurinol / Jan Philipp Weltzsch, Claudius Bartel, Moritz Waldmann, Thomas Renné, Stephanie Schulze, Benedetta Terziroli Beretta-Piccoli, Papp Maria, Ye Oo, Vincenzo Ronca, Marcial Sebode, Ansgar Lohse, Christoph Schramm, Johannes Hartl
Dátum:	2024
ISSN:	0270-9139
Megjegyzések:	Background & aims: In autoimmune hepatitis (AIH), achieving complete biochemical remission (CBR) with current weight-based thiopurine dosing is challenging. We investigated whether patients could be stratified regarding CBR according to a target range of thiopurine metabolites. Moreover, we explored the effects of azathioprine dosage increases and co-therapy of allopurinol with low-dose thiopurines on metabolite profiles and treatment response. Approach & results: The relation between metabolites and treatment response was assessed in 337 individuals from four European centers. In a global, cross-sectional analysis, active metabolites 6-thioguanin nucleotides (6TGN) were similar in those with and without CBR. However, analyzing patients with sequential measurements over 4 years (N=146) revealed higher average 6TGN levels in those with stable CBR (260 pmol/0.2ml) compared to those failing to maintain CBR (181 pmol/0.2ml;p=0.0014) or never achieving CBR (153 pmol/0.2ml;p<0.0001), with an optimal 6TGN-cutoff of ?223 pmol/0.2ml (sensitivity: 76%, specificity: 78%). Only 42% exhibited 6TGN ?223 pmol/0.2ml following weight-based dosing, as doses weakly correlated with 6TGN but with 6-methylmercaptopurine (6MMP), a metabolite associated with toxicity. Azathioprine dose increases led to preferential 6MMP formation (+127% vs. 6TGN +34%;p<0.0001). Conversely, adding allopurinol to thiopurines in difficult-to-treat patients (N=36) raised 6TGN (168?321 pmol/0.2ml;p<0.0001) and lowered 6MMP (2125?184 pmol/0.2ml;p<0.0001), resulting in improved transaminases in all patients and long-term CBR in 75%. Conclusions: Maintaining CBR in AIH was associated with 6TGN ?223 pmol/0.2ml. For patients who fail to achieve CBR and therapeutic 6TGN levels despite thiopurine dose increase due to preferential 6MMP formation, co-medication of allopurinol alongside low-dose thiopurines represents an efficient alternative.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Hepatology. - "Accepted by Publisher" (2024). -
További szerzők:	Bartel, Claudius Waldmann, Moritz Renné, Thomas Schulze, Stephanie Beretta-Piccoli, Benedetta Terziroli Papp Mária (1975-) (belgyógyász, gasztroenterológus) Oo, Ye Ronca, Vincenzo Sebode, Marcial Lohse, Ansgar W. Schramm, Christoph Hartl, Johannes
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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