Literature DB >> 26346867

Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury.

Robert J Fontana1, Paul H Hayashi2, Huiman Barnhart3, David E Kleiner4, K Rajender Reddy5, Naga Chalasani6, William M Lee7, Andrew Stolz8, Thomas Phillips3, Jose Serrano9, Paul B Watkins2.   

Abstract

OBJECTIVES: The long-term outcomes of patients with drug induced liver injury (DILI) are not well described. The aim of this study was to determine the frequency and severity of persistent liver biochemistry abnormalities in DILI patients followed over 2 years.
METHODS: Subjects with evidence of liver injury at 6 months after DILI onset were offered a month 12 and 24 study visit.
RESULTS: Amongst the 99 patients with definite, probable, or very likely DILI and available laboratory data at 12 months after DILI onset, 74 (75%) had persistent liver injury (persisters) defined as a serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) or an alkaline phosphatase >ULN, while 25 (25%) had resolved liver injury (resolvers). On multivariate analysis, month 12 persisters were significantly older (52.6 vs. 43.7 years, P=0.01) and more likely to have a cholestatic lab profile at DILI onset (54 vs. 20%, P<0.01) than resolvers. The month 12 persisters also had significantly poorer SF-36 physical summary scores at DILI onset and throughout follow-up compared with the resolvers (P<0.01). Amongst the 17 subjects with a liver biopsy obtained at a median of 387 days after DILI onset, 9 had chronic cholestasis, 3 had steatohepatitis, and 3 had chronic hepatitis.
CONCLUSIONS: In all, 75% of subjects with liver injury at 6 months after DILI onset have laboratory evidence of persistent liver injury during prolonged follow-up. Higher serum alkaline phosphatase levels at presentation and older patient age were independent predictors of persistent liver injury. Subjects with persistent liver injury at 12 months after DILI onset should be carefully monitored and assessed for liver disease progression.

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Year:  2015        PMID: 26346867      PMCID: PMC4784423          DOI: 10.1038/ajg.2015.283

Source DB:  PubMed          Journal:  Am J Gastroenterol        ISSN: 0002-9270            Impact factor:   10.864


  25 in total

1.  The natural history of histologically proved drug induced liver disease.

Authors:  P G Aithal; C P Day
Journal:  Gut       Date:  1999-05       Impact factor: 23.059

2.  Antibiotic-associated acute vanishing bile duct syndrome: a pattern associated with severe, prolonged, intrahepatic cholestasis.

Authors:  M H Davies; R F Harrison; E Elias; S G Hübscher
Journal:  J Hepatol       Date:  1994-01       Impact factor: 25.083

3.  Health-related quality of life in chronic hepatitis C: impact of disease and treatment response. The Interventional Therapy Group.

Authors:  J E Ware; M S Bayliss; M Mannocchia; G L Davis
Journal:  Hepatology       Date:  1999-08       Impact factor: 17.425

4.  Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity.

Authors:  Jeffrey D Browning; Lidia S Szczepaniak; Robert Dobbins; Pamela Nuremberg; Jay D Horton; Jonathan C Cohen; Scott M Grundy; Helen H Hobbs
Journal:  Hepatology       Date:  2004-12       Impact factor: 17.425

5.  Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry.

Authors:  Raúl J Andrade; M Isabel Lucena; Neil Kaplowitz; Beatriz García-Muņoz; Yolanda Borraz; Ketevan Pachkoria; Miren García-Cortés; M Carmen Fernández; Gloria Pelaez; Luis Rodrigo; José A Durán; Joan Costa; Ramón Planas; Anabel Barriocanal; Carlos Guarner; Manuel Romero-Gomez; Teresa Muņoz-Yagüe; Javier Salmerón; Ramón Hidalgo
Journal:  Hepatology       Date:  2006-12       Impact factor: 17.425

6.  Characteristics associated with liver graft failure: the concept of a donor risk index.

Authors:  S Feng; N P Goodrich; J L Bragg-Gresham; D M Dykstra; J D Punch; M A DebRoy; S M Greenstein; R M Merion
Journal:  Am J Transplant       Date:  2006-04       Impact factor: 8.086

7.  Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct.

Authors:  Robert J Fontana; Paul B Watkins; Herbert L Bonkovsky; Naga Chalasani; Timothy Davern; Jose Serrano; James Rochon
Journal:  Drug Saf       Date:  2009       Impact factor: 5.606

8.  Long-term follow-up of patients with mild to moderate drug-induced liver injury.

Authors:  E Björnsson; E Kalaitzakis; V Av Klinteberg; N Alem; R Olsson
Journal:  Aliment Pharmacol Ther       Date:  2007-07-01       Impact factor: 8.171

9.  Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis.

Authors:  D Moradpour; J Altorfer; R Flury; P Greminger; C Meyenberger; R Jost; M Schmid
Journal:  Hepatology       Date:  1994-12       Impact factor: 17.425

10.  The long-term follow-up after idiosyncratic drug-induced liver injury with jaundice.

Authors:  Einar Björnsson; Loa Davidsdottir
Journal:  J Hepatol       Date:  2008-12-25       Impact factor: 25.083

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  23 in total

1.  Response to Collyer et al.

Authors:  Robert J Fontana
Journal:  Am J Gastroenterol       Date:  2016-02       Impact factor: 10.864

2.  Response to Fontana et al.

Authors:  Elizabeth Collyer; Marsha Kay
Journal:  Am J Gastroenterol       Date:  2016-02       Impact factor: 10.864

3.  Heavy Consumption of Alcohol is Not Associated With Worse Outcomes in Patients With Idiosyncratic Drug-induced Liver Injury Compared to Non-Drinkers.

Authors:  Lara Dakhoul; Marwan Ghabril; Jiezhun Gu; Victor Navarro; Naga Chalasani; Jose Serrano
Journal:  Clin Gastroenterol Hepatol       Date:  2018-01-03       Impact factor: 11.382

Review 4.  Drug-induced Liver Injury: The Hepatic Pathologist's Approach.

Authors:  David E Kleiner
Journal:  Gastroenterol Clin North Am       Date:  2017-06       Impact factor: 3.806

5.  The role of HLA-A*33:01 in patients with cholestatic hepatitis attributed to terbinafine.

Authors:  Robert John Fontana; Elizabeth Theresa Cirulli; Jiezhun Gu; David Kleiner; David Ostrov; Elizabeth Phillips; Ryan Schutte; Huiman Barnhart; Naga Chalasani; Paul Brent Watkins; Jay H Hoofnagle
Journal:  J Hepatol       Date:  2018-08-21       Impact factor: 25.083

6.  Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

Authors:  Rachel J Church; Gerd A Kullak-Ublick; Jiri Aubrecht; Herbert L Bonkovsky; Naga Chalasani; Robert J Fontana; Jens C Goepfert; Frances Hackman; Nicholas M P King; Simon Kirby; Patrick Kirby; John Marcinak; Sif Ormarsdottir; Shelli J Schomaker; Ina Schuppe-Koistinen; Francis Wolenski; Nadir Arber; Michael Merz; John-Michael Sauer; Raul J Andrade; Florian van Bömmel; Thierry Poynard; Paul B Watkins
Journal:  Hepatology       Date:  2018-06-27       Impact factor: 17.425

7.  Associations of gender and a proxy of female menopausal status with histological features of drug-induced liver injury.

Authors:  Ayako Suzuki; Huiman Barnhart; Jiezhun Gu; Herbert L Bonkovsky; Hans L Tillmann; Robert J Fontana; David E Kleiner
Journal:  Liver Int       Date:  2017-03-02       Impact factor: 5.828

8.  Death and liver transplantation within 2 years of onset of drug-induced liver injury.

Authors:  Paul H Hayashi; Don C Rockey; Robert J Fontana; Hans L Tillmann; Neil Kaplowitz; Huiman X Barnhart; Jiezhan Gu; Naga P Chalasani; K Rajender Reddy; Averell H Sherker; Jay H Hoofnagle
Journal:  Hepatology       Date:  2017-08-26       Impact factor: 17.425

Review 9.  Recent Advances in the Histopathology of Drug-Induced Liver Injury.

Authors:  David E Kleiner
Journal:  Surg Pathol Clin       Date:  2018-06

10.  Identification and Characterization of Fenofibrate-Induced Liver Injury.

Authors:  Jawad Ahmad; Joseph A Odin; Paul H Hayashi; Naga Chalasani; Robert J Fontana; Huiman Barnhart; Elizabeth T Cirulli; David E Kleiner; Jay H Hoofnagle
Journal:  Dig Dis Sci       Date:  2017-11-08       Impact factor: 3.199

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