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Cited by 62Drug-Induced Hepatotoxicity and ProtectionPharmacovigilance and Adverse Drug ReactionsLiver Disease Diagnosis and Treatment

The DOI matches its Crossref record; 196 of the 198 references it cites were found in a registry or an index; 16 of the 239 sources its claims cite were checked for support.

Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update

Open access
Mao, Yimin, Ma, Shiwu, Liu, Chenghai, Liu, Xiaoyan, Su, Minghua, Li, Dongliang, Li, Yiling, Chen, Gongying, Chen, Jun, Chen, Jinjun, Zhao, Jingmin, Guo, Xiaoyan, Tang, Jieting, Zhuge, Yuzheng, Xie, Qing, Xie, Wen, Lai, Rongtao, Cai, Dachuan, Cai, Qingxian, Zhi, Yang, Li, Xiaoyun, the Technology Committee on DILI Prevention, Management, Chinese Medical Biotechnology Association; Study Group on Drug-Induced Liver Disease, Chinese Society of Hepatology, Chinese Medical Association·2024·Hepatology International
DOI 10.1007/s12072-023-10633-7
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Abstract

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.

Overview

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Written from the paper’s full text.

TL;DR

This 2024 update from Chinese societies provides evidence-based guidance for diagnosing and managing drug-induced liver injury (DILI), emphasizing exclusion-based diagnosis, causality assessment, and management of special populations and common etiologies. It covers epidemiology, classification, risk factors, diagnosis, chronic DILI, HDS/anti-TB/antineoplastic DILI, HBV reactivation, biomarkers, clinical-trial signals, and treatment.

Key findings

  • In China, the estimated annual DILI incidence is at least 23.80/100,000, higher than other countries and increasing annually; hospitalized DILI incidence is approximately 1–6%, and DILI accounts for about 2–10% of patients with jaundice, 11.3% of patients hospitalized for severe acute liver injury, and 2.7% of hospitalized patients with liver diseases.
  • Common causes in China include TCM, HDS, anti-TB drugs, antineoplastic agents, and immunomodulators; HDS-DILI/HILI accounts for approximately 20–30% of DILI in China, anti-TB DILI incidence is 9.5–10.6% in China and accounts for 22–31.3% of investigated DILI cases, and antineoplastic agents account for approximately 10% of DILI cases in China.
  • Diagnosis uses R ratio classification: hepatocellular R ≥ 5, cholestatic R ≤ 2, mixed 2 < R < 5; acute DILI thresholds are ALT ≥ 5 × ULN, ALP ≥ 2 × ULN, or ALT ≥ 3 × ULN plus TBil ≥ 2 × ULN; RUCAM is recommended as the primary causality assessment method, with expert opinion in specific scenarios.
  • Approximately 7–13% of patients may not normalize liver biochemistry 6 months or 1 year after acute DILI; about 10% of cases fulfilling Hy’s law progress to ALF; liver transplantation can increase survival up to 66.2% in DI-ALF/ACLF; NAC is recommended for adult DI-ALF/SALF, and magnesium isoglycyrrhizinate and bicyclol are recommended for acute hepatocellular or mixed DILI with significant ALT elevation.

Methods

  • This is an updated clinical guideline developed according to the basic processes and procedures of guideline development promulgated by authoritative academic organizations; all expert writers signed a conflict-of-interest statement.
  • Evidence assessment used the 2011 Oxford Centre for Evidence-Based Medicine levels of evidence and grades of recommendation; evidence collection and assessment were performed by the Health Data Science Institute of Lanzhou University, an independent third party.
  • Recommendations are graded and cover diagnosis, differential diagnosis, causality assessment, severity/prognosis, chronic DILI and specific phenotypes, DILI with pre-existing liver disease, HBV reactivation, common etiologies, biomarkers, clinical-trial signals, treatment, prevention, and future research directions.

Limitations

  • Stated: the guideline cannot cover or address all issues of DILI diagnosis and treatment arising in clinical practice and is not mandatory standards; it will be updated in due course as research progresses.
  • Stated/evident: many recommendations rely on low-level evidence or expert consensus; the text notes no high-level evidence for conventional corticosteroid use in DILI, limited evidence for prophylactic liver-protective drugs, and that currently reported biomarkers have not been clinically validated for approval.
  • Evident from text: RUCAM has ambiguities and suboptimal reliability, with reduced reliability in TCM/HDS-DILI, multiple suspected drugs, pre-existing liver disease, and new-drug trials; RECAM requires external validation outside the US and Spain, and its reliability in herb-induced liver injury remains unknown.

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Integrity signals

Registry

Crossref · 10.1007/s12072-023-10633-7

Cites

196 of 196 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

16 of 239 cited sources checked · 6 supported · 1 flagged · accuracy not yet measured

Show all 102 claims

  • It may state two separate claims as one. 38
  • Probably not a substantial claim. 28
  • The quote only partly states this claim. 1
60 of 60

  • The paper relies on this without support.

    Currently, the diagnosis of DILI still follows the strategy of exclusion.

    “Currently, the diagnosis of DILI still follows the strategy of exclusion.”

  • The paper relies on this without support.

    Early detection, diagnosis, prognosis, management, and prevention of DILI is challenging owing to complex drug classes, differences in prescribing habits, limitations in understanding of population heterogeneity, mechanisms of injury, risk factors, and phenotypes, and lack of specific diagnostic biomarkers and effective interventions.

    “The early detection, diagnosis, prognosis, management, and prevention of DILI is challenging owing to the following factors: complex drug classes causing liver injury; differences in prescribing habits; limitations in the understanding of population heterogeneity, mechanisms of injury, risk factors, and phenotypes; and lack of specific diagnostic biomarkers and effective interventions.”

  • The paper relies on this without support.

    DILI is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases.

    “Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases.”

  • The paper relies on this without support.

    Liver injury caused by the use of herbal and dietary supplements (HDS) and herbal medicines (HMs) has been a global concern, especially in Asian and African countries where such complementary and alternative medicine (CAM) are frequently used and recently in western countries where HDS-DILI has also increased.

    “Liver injury caused by the use of herbal and dietary supplements (HDS) and herbal medicines (HMs) has been a global concern, especially in Asian and African countries where such complementary and alternative medicine (CAM) are frequently used and recently in western countries where HDS-DILI has also increased.”

  • The paper relies on this without support.

    With the recent approval of targeted therapies and immune checkpoint inhibitors (ICIs), new challenges such as immune-mediated ICI-related hepatotoxicity have been posed in the field of DILI.

    “Moreover, with the recent approval of targeted therapies and immune checkpoint inhibitors (ICIs), new challenges such as immune-mediated ICIrelated hepatotoxicity have been posed in the field of DILI.”

  • The paper relies on this without support.

    In direct DILI, the risk of liver injury is dose dependent.

    “In direct DILI, the risk of liver injury is dose dependent.”

  • The paper relies on this without support.

    iDILI is largely dose-independent.

    “Idiosyncratic DILI (iDILI) is largely doseindependent, although some studies have suggested that a dose threshold is usually required [28,29].”

  • The paper relies on this without support.

    Drugs that affect both ATP-dependent BSEP and mitochondrial function are associated with an increased risk of DILI.

    “Drugs that affect both adenosine triphosphate-dependent BSEP and mitochondrial function are associated with an increased risk of DILI.”

  • The paper relies on this without support.

    Concomitant use of certain drugs may increase the risk of hepatotoxicity.

    “Drug interactions: Concomitant use of certain drugs may increase the risk of hepatotoxicity.”

  • The paper relies on this without support.

    Age is not a general risk factor for DILI.

    “Age is not a general risk factor for DILI.”

  • The paper relies on this without support.

    There is insufficient evidence suggesting that female are at a higher risk of DILI than men.

    “There is insufficient evidence suggesting that female are at a higher risk of DILI than men.”

  • The paper relies on this without support.

    High alcohol consumption increases the risk of liver injury induced by certain drugs such as APAP, isoniazid, methotrexate, and halothane.

    “However, high alcohol consumption increases the risk of liver injury induced by certain drugs such as APAP, isoniazid, methotrexate, and halothane.”

  • The paper relies on this without support.

    DILI during pregnancy is rare because of conservative drug use.

    “DILI during pregnancy is rare because of conservative drug use.”

  • The paper relies on this without support.

    Limited evidence suggests that comorbidities increase the risk of developing DILI.

    “Limited evidence suggests that comorbidities increase the risk of developing DILI.”

  • The paper relies on this without support.

    Polymorphisms in drug-metabolizing enzymes, transporters, and human leukocyte antigen (HLA) may be important determinants of DILI.

    “Polymorphisms in drug-metabolizing enzymes, transporters, and human leukocyte antigen (HLA) may be important determinants of DILI.”

  • The paper relies on this without support.

    The clinical presentation of DILI is usually nonspecific, similar to that of other acute and chronic liver diseases.

    “The clinical presentation of DILI is usually nonspecific, similar to that of other acute and chronic liver diseases.”

  • The paper relies on this without support.

    Serum ALT, AST, and ALP levels are markers of liver injury, whereas TBil, albumin, and international normalized ratio (INR) are markers of severity.

    “Serum ALT, AST, and ALP levels are the markers of liver injury, whereas TBil, albumin, and international normalized ratio (INR) are markers of severity.”

  • The paper relies on this without support.

    The histologic features of DILI are complex and include almost all pathologic changes in the liver.

    “The histologic features of DILI are complex and include almost all pathologic changes in the liver.”

  • The paper relies on this without support.

    The type of injured target cell at the onset of DILI largely determines the clinical phenotype.

    “The type of injured target cell at the onset of DILI largely determines the clinical phenotype.”

  • The paper relies on this without support.

    Currently, there is no uniform histologic scoring system for DILI.

    “Currently, there is no uniform histologic scoring system for DILI.”

  • The paper relies on this without support.

    Usually, DILI occurs within the first 6 months after starting a new medication; however, there are exceptions.

    “Usually, DILI occurs within the first 6 months after starting a new medication; however, there are exceptions.”

  • The paper relies on this without support.

    DILI remains a diagnosis of exclusion based on a detailed history, clinical manifestations, serum biochemistry, imaging, and liver biopsy, owing to the lack of specific diagnostic biomarkers.

    “DILI remains a diagnosis of exclusion based on a detailed history, clinical manifestations, serum biochemistry, imaging, and liver biopsy, owing to the lack of specific diagnostic biomarkers.”

  • The paper relies on this without support.

    Causality assessment is the key to DILI diagnosis and can be used to determine whether a drug is the cause of liver injury.

    “Causality assessment is the key to DILI diagnosis and can be used to determine whether a drug is the cause of liver injury.”

  • The paper relies on this without support.

    In most cases, the diagnosis of DILI cannot be made solely based on pathology.

    “Although in most cases, the diagnosis of DILI cannot be made solely based on pathology, liver biopsy is of great value for providing information on the histopathological type, area, and severity of injury.”

  • The paper relies on this without support.

    In certain clinical scenarios (TCM/HDS-DILI, multiple suspected drugs, pre-existing liver disease, clinical trials of new drugs), rote use of the RUCAM score may result in misdiagnosis or missed diagnosis owing to lowered reliability.

    “In certain clinical scenarios (e.g., TCM/HDS-DILI, DILI caused by multiple suspected drugs, DILI in patients with pre-existing liver disease, and evaluation of hepatotoxicity in clinical trials of new drugs), rote use of the RUCAM score may result in misdiagnosis or missed diagnosis owing to lowered reliability.”

  • The paper relies on this without support.

    Expert opinion is an important causality assessment method for the diagnosis of DILI.

    “Expert opinion is an important causality assessment method for the diagnosis of DILI.”

  • The paper relies on this without support.

    The advantages of expert opinion include the ability to account for different or rare-specific phenotypes of DILI, thereby achieving a more detailed differential diagnosis.

    “The advantages of expert opinion include the ability to account for different or rare-specific phenotypes of DILI, thereby achieving a more detailed differential diagnosis.”

  • The paper relies on this without support.

    The SEOP overcomes some shortcomings of the RUCAM score, is not externally validated, and is not suitable for daily clinical practice because of its complex procedures.

    “Although the SEOP overcomes some shortcomings of the RUCAM score, it is not externally validated and is not suitable for daily clinical practice because of its complex procedures.”

  • The paper relies on this without support.

    In clinical practice, most rechallenges are performed unintentionally or because of their importance in the treatment of the primary disease.

    “In clinical practice, most rechallenges are performed unintentionally or because of their importance in the treatment of the primary disease.”

  • The paper relies on this without support.

    A positive rechallenge is the most powerful evidence in the causality assessment of suspected DILI and helps in a definite diagnosis.

    “A positive rechallenge is the most powerful evidence in the causality assessment of suspected DILI and helps in a definite diagnosis.”

  • The paper relies on this without support.

    Rechallenge may result in a rapid and severe liver injury that may progress to ALF, particularly when the initial exposure has already caused liver injury fulfilling Hy's law or when the liver injury after initial exposure is due to immune-related reactions.

    “However, rechallenge may result in a rapid and severe liver injury that may progress to ALF, particularly when the initial exposure has already caused liver injury fulfilling Hy's law or when the liver injury after initial exposure is due to immune-related reactions.”

  • The paper relies on this without support.

    Most patients with acute DILI can recover from liver injury with a good prognosis within 6 months of discontinuation of the suspected drug.

    “Most patients with acute DILI can recover from liver injury with a good prognosis within 6 months of discontinuation of the suspected drug.”

  • The paper relies on this without support.

    A small number of patients with acute DILI can become critically ill or progress to ALF/SALF requiring liver transplantation or even death.

    “However, a small number of patients can become critically ill or progress to ALF/SALF requiring liver transplantation or even death.”

  • The paper relies on this without support.

    Some patients may present with chronic manifestations after an acute DILI episode, which eventually transforms into chronic liver injury as a clinical outcome.

    “Some patients may present with chronic manifestations after an acute DILI episode, which eventually transforms into chronic liver injury as a clinical outcome.”

  • The paper relies on this without support.

    The updated RUCAM score remains to be validated.

    “The updated score was published in 2016 [58], but remains to be validated.”

  • The paper relies on this without support.

    RECAM's reliability in herb-induced liver injury (HILI) remains unknown since there is still insufficient data regarding these HMs/HDS.

    “In addition, its reliability in herb-induced liver injury (HILI) remains unknown since there is still insufficient data regarding these HMs/HDS.”

  • The paper relies on this without support.

    Some patients with chronic DILI may develop varying degrees of liver fibrosis or cirrhosis despite discontinuation of the suspected drug, which is an important etiology of cryptogenic cirrhosis.

    “Some patients with chronic DILI may develop varying degrees of liver fibrosis or cirrhosis despite discontinuation of the suspected drug, which is an important etiology of cryptogenic cirrhosis.”

  • The paper relies on this without support.

    DILI in AIH belongs to the category of DILI with pre-existing liver disease.

    “Notably, DILI in AIH also presents with liver injury with autoimmune features, but it belongs to the category of DILI with pre-existing liver disease.”

  • The paper relies on this without support.

    In most cases, the mechanism of injury of DILI in AIH differs from that of DI-ALH, which is under the category of indirect DILI.

    “In most cases, the mechanism of injury differs from that of DI-ALH which is under the category of indirect DILI and should be distinguished.”

  • The paper relies on this without support.

    Pretreatment with high-dose chemotherapy after HSCT, chemotherapy for solid tumors, and post-transplantation immunosuppressive therapy are important causes of HSOS.

    “Pretreatment with high-dose chemotherapy after hematopoietic stem cell transplantation (HSCT), chemotherapy for solid tumors, and post-transplantation immunosuppressive therapy are also important causes of HSOS.”

  • The paper relies on this without support.

    The RUCAM score may have reduced reliability in patients with pre-existing liver disease.

    “The RUCAM score may have reduced reliability in this setting and expert opinion may be useful for making a comprehensive judgment after obtaining detailed information about the suspected drug, liver injury, and underlying liver disease.”

  • The paper relies on this without support.

    HBV reactivation is more common among cases of drug-induced reactivation of hepatitis virus because of the heavy HBV burden in China.

    “HBV reactivation (HBVr) is more common among cases of drug-induced reactivation of hepatitis virus because of the heavy HBV burden in China.”

  • The paper relies on this without support.

    Reactivation is caused by risk drugs such as immunosuppressants, high-dose glucocorticoids, cytotoxic chemotherapeutic agents, anti-CD20 monoclonal antibody, and anti-tumor necrosis factor drugs that alter the original liver and immune status of HBV-infected patients or carriers, leading to increased viral replication and immune-mediated liver injury.

    “Reactivation is caused by risk drugs such as immunosuppressants, high-dose glucocorticoids, cytotoxic chemotherapeutic agents, anti-CD20 monoclonal antibody, and anti-tumor necrosis factor drugs that alter the original liver and immune status of HBV-infected patients or carriers, leading to increased viral replication and immune-mediated liver injury.”

  • The paper relies on this without support.

    Patients with HBVr may present with significant elevation in ALT levels with or without jaundice, positive HBV DNA, or increased viral load compared with pre-exposure to risky drugs and may progress to ALF and even death in severe cases.

    “Patients may present with a significant elevation in ALT levels with or without jaundice, positive HBV DNA, or increased viral load compared with pre-exposure to risky drugs and may progress to ALF and even death in severe cases.”

  • The paper relies on this without support.

    Immunosuppressive therapy such as chemotherapy is usually suspended once HBVr occurs, owing to possible severe clinical outcomes, thereby delaying the treatment of the primary disease.

    “Immunosuppressive therapy such as chemotherapy is usually suspended once HBVr occurs, owing to possible severe clinical outcomes, thereby delaying the treatment of the primary disease.”

  • The paper relies on this without support.

    Stratified management of high-risk drugs and patients can effectively reduce the incidence of HBVr.

    “Stratified management of high-risk drugs and patients can effectively reduce the incidence of HBVr.”

  • The paper relies on this without support.

    Lamivudine increases the risk of drug resistance.

    “Lamivudine is not recommended as the first-line treatment because it increases the risk of drug resistance.”

  • The paper relies on this without support.

    The discontinuation of NAs may result in HBV relapse.

    “The discontinuation of NAs may result in HBV relapse.”

  • The paper relies on this without support.

    The incidence of HDS-DILI is rapidly increasing worldwide and is becoming a key concern for academics and regulatory agencies.

    “The incidence of HDS-DILI is rapidly increasing worldwide and is becoming a key concern for academics and regulatory agencies.”

  • The paper relies on this without support.

    Most patients with mild elevation of liver enzymes after anti-tuberculosis treatment can tolerate reintroduction of first-line drugs.

    “For patients who present with mild elevation of liver enzymes after ATT, although most can tolerate the reintroduction of first-line drugs, a comprehensive assessment of benefits/risks should be performed before planning to use the same ATT regimen”

  • The paper relies on this without support.

    Most patients with grade ≥3 immune checkpoint inhibitor-related hepatitis respond well to high-daily-dose corticosteroids without relapse after discontinuation.

    “Most patients with grade ≥ 3 ICI-related hepatitis respond well to high-daily-dose corticosteroids (1-2 mg/kg day methylprednisolone or equivalents) without relapse after discontinuation.”

  • The paper relies on this without support.

    DILI in patients with chronic liver disease is usually severe.

    “Because DILI in patients with chronic liver disease is usually severe, conservative thresholds should be used in this population”

  • The paper relies on this without support.

    In most cases, the risk of DILI and associated risk factors for new drugs in clinical development are unknown and information and literature on previous liver injury caused by these drugs are limited.

    “In most cases, the risk of DILI and the associated risk factors for new drugs in the clinical development phase are unknown, information and literature on previous liver injury caused by these drugs are limited”

  • The paper relies on this without support.

    Once participants in clinical trials develop liver injury, they are usually not rechallenged.

    “once participants in clinical trials develop a liver injury, they are usually not rechallenged.”

  • The paper relies on this without support.

    Liver injury in most acute DILI cases is self-limiting after discontinuation of the suspected drug.

    “Liver injury in most acute DILI cases is self-limiting after discontinuation of the suspected drug.”

  • The paper relies on this without support.

    A small number of patients with acute DILI become critically ill or develop chronic injuries that require other therapies.

    “A small number of patients become critically ill or develop chronic injuries that require other therapies.”

  • The paper relies on this without support.

    The DILI prevention and treatment situation in China is serious.

    “The DILI prevention and treatment situation in China is serious”

  • The paper relies on this without support.

    China is becoming an aging society with a huge population taking multiple medications for multiple morbidities.

    “China is becoming an aging society with a huge population taking multiple medications for multiple morbidities”

  • The paper relies on this without support.

    Widespread irrational medication use exists.

    “widespread irrational medication use”

  • The paper relies on this without support.

    Healthcare providers other than hepatologists are unfamiliar with the diagnosis and management of DILI.

    “healthcare providers other than hepatologists are unfamiliar with the diagnosis and management of DILI”

  • The paper relies on this without support.

    Post-market surveillance of pharmaceutical companies is poorly developed.

    “the post-market surveillance of pharmaceutical companies is poorly developed”

  • The paper relies on this without support.

    There is a lack of public awareness concerning drug safety, particularly DILI.

    “lack of public awareness concerning drug safety, particularly DILI”

  • The paper relies on this without support.

    N-acetylcysteine is the only antidote approved by the FDA for the treatment of APAP-induced intrinsic DILI.

    “N-Acetylcysteine (NAC) is the only antidote approved by the FDA for the treatment of APAP-induced intrinsic DILI.”

  • The paper relies on this without support.

    Currently, magnesium isoglycyrrhizinate is the only drug indicated for acute DILI.

    “Currently, MgIG is the only drug indicated for acute DILI.”

  • The paper relies on this without support.

    Bicyclol is the first oral drug indicated for acute DILI registered for clinical trial.

    “Bicyclol is the first oral drug indicated for acute DILI registered for clinical trial.”

  • The paper relies on this without support.

    There is no standardized dose or duration for immune-mediated DILI.

    “However, there is no standardized dose or duration for iDILI.”

  • The paper relies on this without support.

    There is no evidence suggesting better efficacy of a combination of two or more drugs that reduce ALT levels.

    “There is no evidence suggesting better efficacy of a combination of two or more of these drugs.”

  • The paper relies on this without support.

    The prophylactic use of these drugs for liver injury to reduce the occurrence of DILI in the context of high-risk drug therapies such as antineoplastic therapy and anti-tuberculosis treatment is not well documented.

    “The prophylactic use of these drugs for liver injury to reduce the occurrence of DILI in the context of high-risk drug therapies such as antineoplastic therapy and ATT is not well documented.”

  • The paper relies on this without support.

    Evidence of the efficacy of other drugs in DILI is mostly provided by small-sample-size randomized controlled trials or retrospective real-world studies.

    “Evidence of the efficacy of other drugs in DILI is mostly provided by small-sample-size RCTs or retrospective realworld studies.”

  • The paper relies on this without support.

    The LiverTox and Hepatox websites provide healthcare providers and the public with information on several hepatotoxic drugs.

    “The Liver-Tox and Hepatox websites provide healthcare providers and the public with information on several hepatotoxic drugs.”

  • The paper relies on this without support.

    The combination of orally targeted drugs with CYP3A4 inhibitors (e.g., erythromycin and itraconazole) may lead to increased blood levels of targeted drugs and increase the risk of DILI.

    “For example, the combination of orally targeted drugs with CYP3A4 inhibitors (e.g., erythromycin and itraconazole) may lead to increased blood levels of targeted drugs and increase the risk of DILI.”

  • The paper relies on this without support.

    Inappropriate medication habits may increase the risk of DILI.

    “In addition, inappropriate medication habits may increase the risk of DILI.”

  • The paper relies on this without support.

    Catechol and caffeine in tea and coffee beverages can lead to increased concentrations of drugs metabolized by CYP2E1, such as acyclovir and quinolone.

    “For example, catechol and caffeine in tea and coffee beverages can lead to increased concentrations of drugs metabolized by CYP2E1, such as acyclovir and quinolone.”

  • The paper relies on this without support.

    Grapefruit juice can increase the concentration of immunosuppressants, statins, and other drugs metabolized by CYP3A4.

    “Grapefruit juice can increase the concentration of immunosuppressants, statins, and other drugs metabolized by CYP3A4.”
74 of 74

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Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting biopsy timing for cholestatic DILI

    Major

    The diagnostic discussion recommends considering liver biopsy if peak ALP has not fallen by more than 50% within 30-60 days after stopping the suspected drug. Recommendation 9 gives 180 days for the same cholestatic criterion.

1 of 1

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Metadata

Authors
Mao, Y., Ma, S., Liu, C., Liu, X., Su, M., Li, D., Li, Y., Chen, G., Chen, J., Chen, J., Zhao, J., Guo, X., Tang, J., Zhuge, Y., Xie, Q., Xie, W., Lai, R., Cai, D., Cai, Q., Zhi, Y., Li, X., & the Technology Committee on DILI Prevention, M.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Shanghai University of Traditional Chinese Medicine (CN)
  • First Affiliated Hospital of GuangXi Medical University (CN)
  • Chinese People's Liberation Army (CN)
  • First Hospital of China Medical University (CN)
  • Affiliated Hospital of Hangzhou Normal University (CN)
  • Nanfang Hospital (CN)
  • Chinese PLA General Hospital (CN)
  • Second Affiliated Hospital of Xi'an Jiaotong University (CN)
  • Nanjing Drum Tower Hospital (CN)
  • Capital Medical University (CN)
  • Second Affiliated Hospital of Chongqing Medical University (CN)
  • Shenzhen Third People’s Hospital (CN)
Corresponding author
Mao, Yimin
ORCID
Venue
Hepatology International
Publisher
Springer Science and Business Media LLC
Published
2024-02-24
Volume
18
Issue
2
Pages
384-419
ISSN
  • 1936-0533 (ISSN-L)
  • 1936-0541
DOI
10.1007/s12072-023-10633-7
OpenAlex
W4392146720
Cited by
62
References
198
Citations by year
2026: 28 · 2025: 26 · 2024: 8
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology International (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Key Technologies Research and Development Program (2022YFC3502101)
  • National Major Science and Technology Projects of China (2017ZX09304016)
  • National Natural Science Foundation of China (NSFC 81970513, NSFC 82270619)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Keywords
drug-induced liver injury, adverse drug reactions, acute liver failure, diagnosis of exclusion, chronic liver disease, herbal and dietary supplements, antitubercular agents, anticancer agents, diagnosis and treatment
MeSH terms
Antineoplastic Agents, China, Humans, Risk Factors, Liver Failure, Acute, Chemical and Drug Induced Liver Injury

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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