Importance of Hepatitis C Virus RNA Testing in Patients with Suspected Drug-Induced Liver Injury
Background and Aims
The aims were to review the diagnosis, testing and presentation of acute hepatitis C (HCV) in patients initially diagnosed to have drug-induced liver injury (DILI) enrolled in the US DILI Network.
All patients with suspected DILI underwent testing for competing causes of liver injury and returned for 6-month follow-up. Causality was adjudicated by consensus expert opinion.
Between 2004 and 2016, 1518 patients were enrolled and adjudicated and underwent 6 months of follow-up. Initial locally acquired anti-HCV results were available in 1457 (96%), but HCV RNA in only 795 (52%). Stored sera were available for repeat testing, so that results were available on all 1518 patients (1457 for anti-HCV and 1482 for HCV RNA). A total of 104 subjects (6.9%) had evidence of HCV infection—10 positive for HCV RNA alone, 16 for anti-HCV alone and 78 for both. All 104 HCV-positive cases were reviewed, and 23 cases were adjudicated as acute HCV. All presented with acute hepatocellular injury with median ALT 1448 U/L, alkaline phosphatase 232 U/L and total bilirubin 10.8 mg/dL. Twenty-two (96%) patients were jaundiced. While all 23 cases initially had been suspected of having DILI, 19 were adjudicated as acute HCV and not DILI at the 6-month follow-up; while 4 were still considered DILI.
Twenty-three of 1518 (1.5%) cases of suspected DILI were due to acute HCV infection. We recommend that initial and follow-up HCV RNA testing should be performed to exclude HCV in patients with acute hepatocellular injury and suspected DILI.
KeywordsDrug-induced liver injury Acute hepatitis C Hepatitis C RNA
- Alk P
Drug-induced liver injury
Drug induced liver injury network
Hepatitis C virus
International normalized ratio
Upper limit of normal
All authors contributed to the collection of clinical data, data analysis, and initial and final drafting of the manuscript.
The drug-induced liver injury network (DILIN) is structured as an U01 cooperative agreement supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) with funds provided by the following grants: U01DK065211 (Indiana University [Purdue]), U01DK065184 (University of Michigan [Ann Arbor]), U01DK065201 (University of North Carolina [Chapel Hill], Asheville, Wake Forest Baptist Medical Center), U01DK083020 (University of Southern California, University of California, Los Angeles [Pfleger Liver Institute]), U01DK083027 (Albert Einstein Medical Center), U01DK100928 (Icahn School of Medicine at Mount Sinai), U01DK065176 (Duke Clinical Research Institute). Additional support was provided by the Intramural Division of the National Cancer Institute (NCI), NIH and Abbott Laboratories (blinded samples sent under an agreement and at no cost to the study group).
Compliance with Ethical Standards
Conflict of interest
JA, PHH, AS, VN, HB, JHH: No conflict of interest to disclose. KRR: Scientific Advisory Board-Merck, Abbvie, Gilead, Shionogi, Dova. Research Support (paid to the University of Pennsylvania) Abbvie, Gilead, Merck, Conatus, Intercept, Mallinckrodt. HLT: Abbott stocks from previous employment of Spouse, AbbVie Stocks and employment of spouse, Gilead Stocks, Novartis (DSMB). NC: Consultant for Abbvie, Lilly, Afimmune, NuSirt, Shire, Axovant, Madrigal, Allergan, Immuron and research support from Cumberland, Galectin, Lilly, and Exact Sciences. RJF: Research support from Gilead, BristolMyersSquibb, and Abbvie. Consulted for Alnylam Pharmaceuticals. GAC: Employee and Share Holder or Abbott Laboratories.
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