Drug-induced liver injury(DILI)is a major cause of acute liver injury,liver failure,and liver transplantation worldwide.In recent years,immune checkpoint inhibitors have become widely used.This has led to an increase ...Drug-induced liver injury(DILI)is a major cause of acute liver injury,liver failure,and liver transplantation worldwide.In recent years,immune checkpoint inhibitors have become widely used.This has led to an increase in DILI,for which pathophysiology and management methods differ significantly from the past.As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase,information about a DILI is becoming more valuable.DILI is classified into two types according to its etiology:intrinsic DILI,in which the drug or its metabolites cause liver damage that is dose-dependent and predictable;and idiosyncratic DILI,in which liver damage is also dose-independent but unpredictable.In addition,depending on the course of the disease,chronic DILI or drug-induced autoimmune hepatitis may be present.The number of DILI cases caused by antimicrobial agents is decreasing,whereas that caused by drugs for malignant tumors and health foods is increasing.The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI.Liver injury is a type of immune-related adverse event.The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular,but mixed type and bile stasis have also been reported.Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury.Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration;however,mycophenolate mofetil may be considered if the disease is refractory to steroids.展开更多
Background and Aims:Immune-mediated liver injury is a fatal side effect of sintilimab.This study aimed to shed light on the associated risk factors and characteristics of this adverse event.Methods:The clinical record...Background and Aims:Immune-mediated liver injury is a fatal side effect of sintilimab.This study aimed to shed light on the associated risk factors and characteristics of this adverse event.Methods:The clinical records of 772 patients treated with sintilimab were retrospectively reviewed to investigate risk factors associated with sintilimab immune-related hepatotoxicity,as well as its incidence and outcome.The Roussel Uclaf Causality Assessment Method was used o identify cases of sintilimab-induced hepatotoxicity.Furthermore,logistic regressions were performed to compare the clinical and bloodwork characteristics of patients with and without immune-mediated liver injury caused by checkpoint inhibitors.Resu/ts:Of the 585 patients included in the study,71(12.1%)developed liver injury during sintili-mab use.The median RUCAM score with interquartile range was 7(6,8).Hypoproteinemia,dyslipidemia,and the pres-ence of thyroid peroxidase antibodies were risk factors for sintilimab-related hepatotoxicity.A nomogram model was constructed for sintilimab-induced immune-mediated liver injury based on these risk factors,which had a C-index value of 0.713 and a good calibration curve.When applied o patients with grade≥3 and≥4 sintilimab-induced immune-mediated liver injury,it achieved C-index values of 0.752 and 0.811,respectively.The nomogram model also showed a good prediction potential in patients≥65 years and males.Six of the patients with sintilimab-related hepatotoxicity showed improved liver function upon treatment with steroids.Conclusions:This study demonstrated that hypoproteinemia,dyslipidemia,and the presence of thyroid peroxidase antibodies were clinically feasible prognostic biomarkers to predict liver injury in patients treated with sintilimab.展开更多
Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between dr...Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.展开更多
Herb-induced liver injuries (HILI) by traditional herbal medi-cines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provi...Herb-induced liver injuries (HILI) by traditional herbal medi-cines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provide an overview on how causality was assessed in HILI cases from Asian countries and whether the Roussel Uclaf Causality Assessment Method (RUCAM) was the preferred diagnostic algorithm, as shown before in world-wide evaluated cases of drug-induced liver injury (DILI). Using the PubMed database, publications in English language were preferred to allow for reevaluation by peers. Overall 11,160 HILI cases have assessed causality using RUCAM and were published by first authors working in Asian countries. With 21 evaluable reports, most publications came from China's Mainland, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1), while other Asian countries were not contributory. Most publications provided case and RUCAM data of good quality. For better presentation of future cases, how-ever, the following recommendations are given:(1) preference of prospective study design with use of the updated RUCAM version;(2) clear separation of HILI cohorts from those of other herbal products or DILI;(3) case series for epidemiology stud-ies should contain many essential data, possibly also as supple-mentary material;(4) otherwise, preference of single case reports providing individual case data and RUCAM-based cau-sality gradings, and applying liver test threshold values;and (5) publication in English language journals. In conclusion, China and Korea are top in presenting RUCAM-based HILI cases, other Asian countries are encouraged to follow.展开更多
基金supported by Yokohama City University Personal Research Grant.
文摘Drug-induced liver injury(DILI)is a major cause of acute liver injury,liver failure,and liver transplantation worldwide.In recent years,immune checkpoint inhibitors have become widely used.This has led to an increase in DILI,for which pathophysiology and management methods differ significantly from the past.As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase,information about a DILI is becoming more valuable.DILI is classified into two types according to its etiology:intrinsic DILI,in which the drug or its metabolites cause liver damage that is dose-dependent and predictable;and idiosyncratic DILI,in which liver damage is also dose-independent but unpredictable.In addition,depending on the course of the disease,chronic DILI or drug-induced autoimmune hepatitis may be present.The number of DILI cases caused by antimicrobial agents is decreasing,whereas that caused by drugs for malignant tumors and health foods is increasing.The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI.Liver injury is a type of immune-related adverse event.The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular,but mixed type and bile stasis have also been reported.Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury.Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration;however,mycophenolate mofetil may be considered if the disease is refractory to steroids.
基金supported by the Startup Fund for Scientific Research,Fujian Medical University(2020QH1346 and 2020QH1345)Fujian Provincial Health Technology Project(2021QNA018)+3 种基金Fuzhou Health Science and Technology Project(grant numbers 2022-S-wq1)the Natural Science Foundation of Fujian Province(2021J011304)Joint Funds for the Innovation of Science and Technology,Fujian Province(Grant number:2018Y9045)Key Project for Youth Academic Talents(2019-ZQN-39)from Health and Family Planning Commission of Fujian Province.
文摘Background and Aims:Immune-mediated liver injury is a fatal side effect of sintilimab.This study aimed to shed light on the associated risk factors and characteristics of this adverse event.Methods:The clinical records of 772 patients treated with sintilimab were retrospectively reviewed to investigate risk factors associated with sintilimab immune-related hepatotoxicity,as well as its incidence and outcome.The Roussel Uclaf Causality Assessment Method was used o identify cases of sintilimab-induced hepatotoxicity.Furthermore,logistic regressions were performed to compare the clinical and bloodwork characteristics of patients with and without immune-mediated liver injury caused by checkpoint inhibitors.Resu/ts:Of the 585 patients included in the study,71(12.1%)developed liver injury during sintili-mab use.The median RUCAM score with interquartile range was 7(6,8).Hypoproteinemia,dyslipidemia,and the pres-ence of thyroid peroxidase antibodies were risk factors for sintilimab-related hepatotoxicity.A nomogram model was constructed for sintilimab-induced immune-mediated liver injury based on these risk factors,which had a C-index value of 0.713 and a good calibration curve.When applied o patients with grade≥3 and≥4 sintilimab-induced immune-mediated liver injury,it achieved C-index values of 0.752 and 0.811,respectively.The nomogram model also showed a good prediction potential in patients≥65 years and males.Six of the patients with sintilimab-related hepatotoxicity showed improved liver function upon treatment with steroids.Conclusions:This study demonstrated that hypoproteinemia,dyslipidemia,and the presence of thyroid peroxidase antibodies were clinically feasible prognostic biomarkers to predict liver injury in patients treated with sintilimab.
文摘Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.
文摘Herb-induced liver injuries (HILI) by traditional herbal medi-cines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provide an overview on how causality was assessed in HILI cases from Asian countries and whether the Roussel Uclaf Causality Assessment Method (RUCAM) was the preferred diagnostic algorithm, as shown before in world-wide evaluated cases of drug-induced liver injury (DILI). Using the PubMed database, publications in English language were preferred to allow for reevaluation by peers. Overall 11,160 HILI cases have assessed causality using RUCAM and were published by first authors working in Asian countries. With 21 evaluable reports, most publications came from China's Mainland, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1), while other Asian countries were not contributory. Most publications provided case and RUCAM data of good quality. For better presentation of future cases, how-ever, the following recommendations are given:(1) preference of prospective study design with use of the updated RUCAM version;(2) clear separation of HILI cohorts from those of other herbal products or DILI;(3) case series for epidemiology stud-ies should contain many essential data, possibly also as supple-mentary material;(4) otherwise, preference of single case reports providing individual case data and RUCAM-based cau-sality gradings, and applying liver test threshold values;and (5) publication in English language journals. In conclusion, China and Korea are top in presenting RUCAM-based HILI cases, other Asian countries are encouraged to follow.
