Letter to the editor: Prediction of biochemical nonresolution in patients with chronic drug‐induced liver injury: A large multicenter study

To the editor, We read with great interest the article published in Hepatology by Wang et al.[1] This study developed a novel, easy‐to‐use nomogram model to predict biochemical nonresolution (BNR) in patients with chronic drug‐induced liver injury (DILI), named BNR‐6, and patients with significant hepatocellular inflammation are at greater risk of BNR. This is a large, retrospective, and multicenter cohort study, which is significant for the guiding of clinical practice, because it is estimated[2] that China is the country with the largest disease burden of DILI. However, there are issues requiring further clarification. First, with regard to the use of the Roussel Uclaf Causality Assessment Method (RUCAM) score (only >6 points, probably), the investigators failed to completely exclude other liver diseases given that not all patients underwent a liver biopsy first. In addition, there are currently no exact diagnostic criteria for chronic DILI, and drugs could also induce fatty liver or autoimmune hepatitis (AIH)[3]; so, we believe that the investigators should describe the type of hepatic histopathology in detail. Second, the meaning of liver biochemistry abnormalities varies widely.[4] The problem is, however, that not only could liver inflammation cause an elevation of liver enzymes, but also other types of organ damage, especially injury to the myocardium and skeletal muscle.[3] Thus, it would be better to explain this clearly in the article. Furthermore, even if patients do have liver inflammation after 1 year, it is necessary to carry out another liver biopsy to determine whether the cause is still chronic DILI rather than other causes, because DILI can induce an autoimmune liver disease such as AIH, which is hard to detect without hepatic histopathology. In addition, the prevalence of NAFLD in China is ~29.88%, so the case of combining with NAFLD or the progression of NAFLD likely occurs in the DILI recovery period, and a liver biopsy is also necessary to determine or exclude an association with NASH.[3,5] Hence, the definition of BNR should be thoughtfully discussed to obtain the best clinical value. Third, with respect to the applicable population, the guideline by the European Association for the Study of the Liver[3] indicated that there might be differences in the incidence of DILI among different races. Although the study was a multicenter study, participants were all within China, thereby excluding an explanation for such differences with other ethnicities and countries. Last, the status of drug administration should be clarified during 1 year of follow‐up, such as whether or not patients are taking hepatotoxic drugs consecutively, or whether they are taking other hepatotoxic drugs, which makes sense for determining the applicable population of BNR‐6. Thus, the definition and applicable population of BNR‐6 in patients with chronic DILI deserve further discussion. FUNDING INFORMATION Supported by the Chinese Foundation for Hepatitis Prevention and Control–"Tian Qing" Hepatitis Research Fund (no. TQGB20210175) and the Research project of Chinese traditional medicine and Chinese traditional medicine combined with Western medicine of Tianjin municipal health and Family Planning Commission(2015061/2017070/2021022). CONFLICT OF INTEREST Nothing to report. AUTHOR CONTRIBUTIONS Xuemei Tao: writing; Liang Xu and Yuqiang Mi: critical revision; Youfei Zhao: writing and critical revision; Lin Chen: writing and critical revision; Minghui Zeng: writing and critical revision.