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Importance of Hepatitis C Virus RNA Testing in Patients with Suspected Drug-Induced Liver Injury.

ABSTRACT: 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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Ahmad J

PROVIDER: S-EPMC6706305 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Importance of Hepatitis C Virus RNA Testing in Patients with Suspected Drug-Induced Liver Injury.

Ahmad Jawad J Reddy K Rajender KR Tillmann Hans L HL Hayashi Paul H PH Chalasani Naga N Fontana Robert J RJ Navarro Victor J VJ Stolz Andrew A Barnhart Huiman H Cloherty Gavin A GA Hoofnagle Jay H JH

Digestive diseases and sciences 20190329 9

<h4>Background and aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Between 2004 and 2016, 1518 patients were enrolled and adjudicated ...[more]

PMID: 30927209

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Project description:Background & aimsDrug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine.MethodsWe analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH-associated HLA-DRB1*03:01 and HLA-DRB1*04:01 allele frequencies were compared with those of the general population (controls).ResultsOf the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score ≥2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P < .001) and in autoimmune scores (P < .001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03:01 (15%) and HLA-DRB1*04:01 (9%) as controls (12% and 9%, respectively).ConclusionsIn analysis of data from the DILIN prospective study, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH.

Dataset Information

Importance of Hepatitis C Virus RNA Testing in Patients with Suspected Drug-Induced Liver Injury.

Publications

Importance of Hepatitis C Virus RNA Testing in Patients with Suspected Drug-Induced Liver Injury.

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