Rapid Response to Treatment of Autoimmune Hepatitis Associated With Remission at 6 and 12 Months

被引:43
作者
Pape, Simon [1 ]
Gevers, Tom J. G. [1 ]
Vrolijk, Jan Maarten [2 ]
van Hoek, Bart [3 ]
Bouma, Gerd [4 ]
van Nieuwkerk, Carin M. J. [4 ]
Taubert, Richard [5 ]
Jaeckel, Elmar [5 ]
Manns, Michael P. [5 ]
Papp, Maria [6 ]
Sipeki, Nora [6 ]
Stickel, Felix [7 ]
Efe, Cumali [8 ]
Ozaslan, Ersan [9 ]
Purnak, Tugrul [10 ]
Nevens, Frederik [11 ]
Kessener, Dominik J. N. [12 ]
Kahraman, Alisan [12 ]
Wedemeyer, Heiner [12 ]
Hartl, Johannes [13 ]
Schramm, Christoph [13 ,14 ]
Lohse, Ansgar W. [13 ]
Drenth, Joost P. H. [1 ]
Heneghan, Michael A. [15 ]
机构
[1] Radboud Univ Nijmegen, Dept Gastroenterol & Hepatol, Med Ctr, Internal Postal Code 455,POB 9101, NL-6500 HB Nijmegen, Netherlands
[2] Rijnstate Hosp, Dept Gastroenterol & Hepatol, Arnhem, Netherlands
[3] Leiden Univ, Dept Gastroenterol & Hepatol, Med Ctr, Leiden, Netherlands
[4] Vrije Univ Amsterdam, Dept Gastroenterol & Hepatol, Med Ctr, Amsterdam, Netherlands
[5] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany
[6] Univ Debrecen, Fac Med, Dept Internal Med, Div Gastroenterol, Debrecen, Hungary
[7] Univ Hosp Zurich, Dept Gastroenterol & Hepatol, Zurich, Switzerland
[8] Harran Univ Hosp, Dept Gastroenterol, Urfa, Turkey
[9] Numune Res & Educ Hosp, Dept Gastroenterol, Ankara, Turkey
[10] Hacettepe Univ, Dept Gastroenterol, Ankara, Turkey
[11] Katholieke Univ Leuven, Dept Gastroenterol & Hepatol, Univ Hosp, Leuven, Belgium
[12] Univ Clin Essen Duisburg Essen, Dept Gastroenterol & Hepatol, Duisburg, Germany
[13] Univ Med Ctr Hamburg Eppendorf, Dept Internal Med 1, Hamburg, Germany
[14] Univ Med Ctr Hamburg Eppendorf, Martin Zeitz Ctr Rare Dis, Hamburg, Germany
[15] Kings Coll Hosp London, Inst Liver Studies, London, England
关键词
Induction Therapy; Prognostic Factor; Liver Enzyme; Steroid; DISEASE COURSE; DIAGNOSIS; MANAGEMENT; CIRRHOSIS; CRITERIA;
D O I
10.1016/j.cgh.2019.11.013
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Changes in serum levels of transaminases immediately after initiation of treatment for autoimmune hepatitis (AIH) might be associated with biochemical markers of remission and liver-related events. We assessed the outcomes of patients with vs without rapid response to treatment of AIH in a large international cohort. METHODS: We performed a retrospective cohort study, collecting data from 2 independent cohorts of adults with AIH from 12 centers in 7 countries in Europe. We collected information on patient demographics; serologic, histologic, and biochemical analyses; and treatment. We used a receiver operating characteristic curve and Youden index to calculate the optimal percentage decrease in level of aspartate aminotransferase (AST) after 8 weeks of treatment that associated with normalization of transaminase levels after 26 weeks of treatment with predniso(lo)ne (primary outcome) in the first (discovery) cohort (n = 370). We evaluated the results in the second (validation) cohort (n = 370). Secondary outcomes were liver-related death or transplantation. We performed univariate and multivariable logistic and Cox regression with correction for confounders. RESULTS: A significant decrease in level of AST after 8 weeks of treatment was significantly associated with normalization of transaminase levels at 26 and 52 weeks (P <.001); a decrease of more than 80% in level of AST was associated with optimal normalization. In both cohorts, rapid responders (>= 80% decrease in level of AST after 8 weeks) were more likely to achieve normalization of transaminases at 26 and 52 weeks when compared to non-rapid responders. Rapid responders in the discovery cohort had lower risk of liver-related death or transplantation (adjusted hazard ratio 0.18; 95% CI 0.05-0.63; P =.007), although this was not confirmed in the validation cohort. Results from measurement of alanine aminotransferase did not differ significantly from those of AST for the primary outcome. Slow responders (without normalization of transaminases after 1 year) had the highest risk of liver transplantation or liver-related death. CONCLUSIONS: In a retrospective study of patients with AIH, we found that a rapid response to treatment, based on level of AST after 8 weeks, associates with normalization of transaminase levels in the following year. Patients with a rapid response also have a lower risk of liver-related death or transplantation than patients without this rapid response.
引用
收藏
页码:1609 / +
页数:13
相关论文
共 21 条
[1]   Effects of Serum Aspartate Aminotransferase Levels in Patients With Autoimmune Hepatitis Influence Disease Course and Outcome [J].
Al-Chalabi, Thawab ;
Underhill, James A. ;
Portmann, Bernard C. ;
McFarlane, Ian G. ;
Heneghan, Michael A. .
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2008, 6 (12) :1389-1395
[2]   International Autoimmune Hepatitis Group Report:: review of criteria for diagnosis of autoimmune hepatitis [J].
Alvarez, E ;
Berg, PA ;
Bianchi, FB ;
Bianchi, L ;
Burroughs, AK ;
Cancado, EL ;
Chapman, RW ;
Cooksley, WGE ;
Czaja, AJ ;
Desmet, VJ ;
Donaldson, RT ;
Eddleston, ALWF ;
Fainboim, L ;
Heathcote, J ;
Homberg, JC ;
Hoofnagle, JH ;
Kakumu, S ;
Krawitt, EL ;
Mackay, IR ;
MacSween, RNM ;
Maddrey, WC ;
Manns, MP ;
McFarlane, IG ;
zum Büschenfelde, KHM ;
Mieli-Vergani, G ;
Nakanuma, Y ;
Nishioka, M ;
Penner, E ;
Porta, G ;
Portmann, BC ;
Reed, WD ;
Rodes, J ;
Schalm, SW ;
Scheuer, PJ ;
Schrumpf, E ;
Seki, T ;
Toda, G ;
Tsuji, T ;
Tygstrup, N ;
Vergani, D ;
Zeniya, M .
JOURNAL OF HEPATOLOGY, 1999, 31 (05) :929-938
[3]  
CZAJA AJ, 1981, GASTROENTEROLOGY, V80, P687
[4]   Rapidity of treatment response and outcome in type 1 autoimmune hepatitis [J].
Czaja, Albert J. .
JOURNAL OF HEPATOLOGY, 2009, 51 (01) :161-167
[5]   Real-world management of juvenile autoimmune liver disease [J].
de Boer, Y. S. ;
Liberal, R. ;
Vergani, D. ;
Mieli-Vergani, G. .
UNITED EUROPEAN GASTROENTEROLOGY JOURNAL, 2018, 6 (07) :1032-1038
[6]   Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome [J].
Feld, JJ ;
Dinh, H ;
Arenovich, T ;
Marcus, VA ;
Wanless, IR ;
Heathcote, EJ .
HEPATOLOGY, 2005, 42 (01) :53-62
[7]   Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury [J].
Friedman, SL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (04) :2247-2250
[8]   Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepatitis [J].
Hartl, Johannes ;
Ehlken, Hanno ;
Sebode, Marcial ;
Peiseler, Moritz ;
Krech, Till ;
Zenouzi, Roman ;
von Felden, Johann ;
Weiler-Normann, Christina ;
Schramm, Christoph ;
Lohse, Ansgar W. .
JOURNAL OF HEPATOLOGY, 2018, 68 (04) :754-763
[9]   Simplified criteria for the diagnosis of autoimmune hepatitis [J].
Hennes, Elke M. ;
Zeniya, Mikio ;
Czaja, Albert. J. ;
Pares, Albert ;
Dalekos, George N. ;
Krawitt, Edward L. ;
Bittencourt, Paulo L. ;
Porta, Gilda ;
Boberg, Kirsten M. ;
Hofer, Harald ;
Bianchi, Francesco B. ;
Shibata, Minoru ;
Schramm, Christoph ;
de Torres, Barbara Eisenmann ;
Galle, Peter R. ;
McFarlane, Ian ;
Dienes, Hans-Peter ;
Lohse, Ansgar W. .
HEPATOLOGY, 2008, 48 (01) :169-176
[10]   Prediction of short- and long-term outcome in patients with autoimmune hepatitis [J].
Kirstein, Martha M. ;
Metzler, Frauke ;
Geiger, Elena ;
Heinrich, Eyk ;
Hallensleben, Michael ;
Manns, Michael P. ;
Vogel, Arndt .
HEPATOLOGY, 2015, 62 (05) :1524-1535