Abstract
Currently, there are no satisfactory noninvasive methods for the diagnosis of fibrosis in patients with chronic drug-induced liver injury (DILI). Our goal was to develop an algorithm to improve the diagnostic accuracy of significant fibrosis in this population. In the present study, we retrospectively investigated the biochemical and pathological characteristics of consecutive patients with biopsy-proven chronic DILI, who presented at our hospital from January 2013 to December 2017. A noninvasive algorithm was developed by using multivariate logistic regression, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) to diagnose significant fibrosis in the training cohort, and the algorithm was subsequently validated in the validation cohort. Totally, 1,130 patients were enrolled and randomly assigned into a training cohort (n = 848) and a validation cohort (n = 282). Based on the multivariate analysis, LSM, CHE, and APRI were independently associated with significant fibrosis. A novel algorithm, LAC, was identified with the AUROC of 0.81, which was significantly higher than LSM (AUROC 0.78), CHE (AUROC 0.73), and APRI (AUROC 0.68), alone. The best cutoff value of LAC in the training cohort was 5.4. When the LAC score was used to diagnose advanced fibrosis and cirrhosis stages, the optimal cutoff values were 6.2 and 6.7, respectively, and the AUROC values were 0.84 and 0.90 in the training cohort and 0.81 and 0.83 in the validation cohort. This study proved that the LAC score can contribute to the accurate assessment of high-risk disease progression and the establishment of optimal treatment strategies for patients with chronic DILI.
Highlights
Drug-induced liver injury (DILI) refers to liver injury caused by a variety of drugs, herbs, and dietary supplements with liver toxicity under the reasonable exclusion of other causes (Kullak-Ublick et al, 2017; Navarro et al, 2017; European Association for Study of Liver (EASL), 2019)
We enrolled patients who met all of the following inclusion criteria: (1) patients who presented to our hospital from January 2013 to December 2017; (2) patients who were over 18 years old; (3) patients who were diagnosed with chronic DILI, which was defined as DILI with an acute presentation in which there is evidence of persistent liver injury >1 year after its onset (Sarges et al, 2016). and (4) patients who agreed to liver biopsy
BMI, body mass index; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, gamma glutamyl transpeptidase; TBIL, total bilirubin; PLT, platelet; LSM, liver stiffness measurement; APRI, aspartate aminotransferase-to-platelet ratio index; FIB-4, fibrosis index based on four factors; CHE, cholinesterase; OR, odds ratio; CI, confidence interval
Summary
Drug-induced liver injury (DILI) refers to liver injury caused by a variety of drugs, herbs, and dietary supplements with liver toxicity under the reasonable exclusion of other causes (Kullak-Ublick et al, 2017; Navarro et al, 2017; European Association for Study of Liver (EASL), 2019). Chronic DILI may lead to worse clinical outcomes, such as persistent hepatocyte inflammation, the hepatic fibrosis progression, or an incidence of hepatocellular carcinoma (Kleiner, 2017). The diagnosis of significant fibrosis is of fundamental significance for subsequent clinical treatment decision making. Liver biopsy is a special examination to diagnose substantial liver injury, so as to provide assistant information and help with the accurate diagnosis and prognosis of liver disease (Kleiner et al, 2014; Andrade et al, 2019). Liver biopsy is hindered by a sampling bias (Regev et al, 2002; Martinez et al, 2011) With the application of noninvasive liver fibrosis markers in clinical practice in recent years, the monitoring of chronic liver disease is increasingly less dependent on liver biopsy
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