Prevalence Of Drug-induced Liver Injury Research Articles

The Epidemiology of Newly Recognized Causes of Drug-Induced Liver Injury: An Update.

The incidence and prevalence of drug-induced liver injury appear to be increasing globally, for example, with the introduction of checkpoint inhibitors. Several reviews have been published in the last decade on the epidemiology of DILI, both among hospitalized patients and in the general population, as well as from retrospective and prospective studies on DILI. Most of these reviews have not focused on newly recognized agents that have recently changed the landscape of DILI. Apart from liver injury associated with antibiotics, oncological agents, particularly checkpoint inhibitors, are increasingly being recognized as causing liver injury. The type of liver injury associated with these agents is not idiosyncratic but rather an indirect type of injury. Furthermore, recently, COVID-19 vaccines and green tea extract have been found to lead to liver injury. Checkpoint inhibitors have revolutionized the treatment of many malignancies, such as malignant melanoma, lung cancer, and renal cancer. Via the activation of T cells, they can increase immune activity against malignant cells, but at the same time, they can decrease immune tolerance and therefore lead to immune-related adverse effects in many organs. The most common adverse effect in clinical practice is liver injury. A recent prospective study demonstrated an 8% frequency of DILI due to the use of checkpoint inhibitors among patients with malignant melanoma and renal cancer. This rate is much higher than observed with drugs, leading to idiosyncratic liver injury. Shortly after the implementation of the worldwide vaccination program against COVID-19, several case reports were published on suspected vaccination-induced autoimmune-like hepatitis occurring shortly after the vaccination. At first, these reports were met with skepticism, but currently, around 100 reports have been published, and cases of positive recurrence have been reported. The clinical, biochemical, immunological, and histological features are indistinguishable from classic autoimmune hepatitis (AIH). These reactions are very similar to drug-induced autoimmune-like hepatitis (DI-ALH) due to drugs such as nitrofurantoin, minocycline, and infliximab, which do not relapse after a short course of corticosteroids, which is the general rule in classic autoimmune hepatitis (AIH). Green tea extract has been found to be a well-documented cause of acute hepatocellular liver injury with jaundice. A strong HLA association has been reported, showing a high prevalence of HLA-B*35:01 among patients suffering from green tea-induced liver injury. Overall, 3% of patients recruited in the DILIN study were supplemented with green tea extract as one of the ingredients. In a prospective population-based study from Iceland, green tea was implicated in approximately 8% of patients with DILI.

Prevalence of drug-induced liver injury in patients on antitubercular therapy

Background: As per the World Health Organization Global Tuberculosis (TB) Report 2019, there were an estimated 10.0 million new TB cases worldwide in 2018, with India (27%) having the maximum burden of the disease. Drug-induced liver injury (DILI) due to antitubercular treatment (ATT) is a serious adverse effect and a major cause of discontinuation of ATT, leading to increased drug resistance, morbidity, and mortality. Methodology: This was an observational study that was conducted at a tertiary care center in South Maharashtra having a dedicated TB nodal center. All newly detected cases of pulmonary and extrapulmonary TB and cases of TB after relapse/failure/treatment after default, who reported to this nodal center from January 2019 to June 2019 and in whom Category 1 and Category 2 ATT was started as per the Revised National Tuberculosis Programme protocol, were enrolled in this study. Results: Out of 100 enrolled patients, 10 (10%) were diagnosed to have ATT-induced DILI, which is concordant with other studies. No deaths were recorded. However, there was no statistically significant difference between male and female patients who developed DILI (12% males vs. 8% females). No correlation was found with body mass index or alcohol consumption. Conclusion: A fine balance should be struck between unnecessary discontinuation of ATT and continued safe treatment. Patient and staff education, careful selection of regimen, and close monitoring of risk factors will minimize cases of DILI.

Safety of co-administration of herbal and conventional medicines on liver and kidney function in stroke patients: A single-center retrospective study

BackgroundAlthough herbal medicines (HMs) are widely used worldwide, information concerning their interactions with conventional medicines (CMs) is sparse. In particular, stroke affects a high proportion of elderly people with impaired hepatic and renal function. Stroke is often accompanied by various complications and is commonly treated via the co-administration of HMs and CMs in Asia. PurposeWe aimed to investigate the effects of co-administration of HMs and CMs on liver and kidney function in patients with stroke. We estimated the prevalence of drug-induced liver injury (DILI) or herb-induced liver injury (HILI) and drug-induced acute kidney injury (DIAKI) or herb-induced acute kidney injury (HIAKI) in patients co-administered HMs and CMs. Study designThis was a retrospective study that reviewed the electronic medical records of 401 patients with stroke in a single hospital. MethodsThe prevalence of DILI or HILI and types of liver injury was examined according to abnormal increases in liver tests. The probable causality between drug or herb administration and liver injury was assessed using the Roussel Uclaf Causality Assessment Method. In addition, the prevalence of DIAKI or HIAKI was estimated using the Kidney Disease Improving Global Outcomes acute kidney injury stage criteria and related medical records. ResultsOut of a total of 401 patients, only four (1.0%) developed liver injury. Two cases of DILI (0.5%) and two cases of HILI (0.5%) were reported. Moxifloxacin and ebastine were the CMs that caused hepatotoxicity. Chungpyesagan-tang and Yeoldahanso-tang were the HMs that caused liver toxicity. Even in cases showing severe liver damage, alkaline phosphatase levels remained less than five times the normal value, and liver function test values recovered within 14 days. There were no cases of DIAKI or HIAKI in this cohort. ConclusionThese results suggest that if appropriately prescribed by experts, the co-administration of CMs and HMs is safe and does not adversely affect liver and kidney function in patients with stroke. To support these results, further large-scale multicenter prospective studies and toxicological studies based on the interaction between HMs and CMs are warranted.

Retrospective study of idiosyncratic drug-induced liver injury from infliximab in an inflammatory bowel disease cohort: the IDLE study.

BackgroundInfliximab therapy may be associated with drug-induced liver injury (DILI), often resembling a drug-induced autoimmune hepatitis. However, the prevalence of DILI in patients receiving infliximab is unclear. Abnormal liver biochemistry is common in patients with inflammatory bowel disease (IBD) and definitive diagnosis may be difficult. The aim of this study was to describe the patterns of abnormal liver biochemistry in an IBD cohort.MethodsIn a retrospective cohort study of adult patients with IBD treated with infliximab through a single institution we used the Roussel Uclaf Causality Assessment Method (RUCAM) to evaluate liver biochemistry and possible DILI. All cases of abnormal liver biochemistry were ascribed a presumptive diagnosis from the electronic medical record.ResultsFifty-seven of the 175 patients (149 Crohn’s disease, 26 ulcerative colitis) had abnormal liver biochemistry. Of the 57 cases, one had highly probable, and 10 possible DILI due to infliximab. There were no significant differences regarding demographics, concomitant therapy/disease, indication for infliximab or outcomes between patients with normal and abnormal liver biochemistry, except for higher baseline alanine transaminase and alkaline phosphatase in the abnormal biochemistry group (P<0.001). Multivariate logistic regression showed male sex (odds ratio [OR] 2.49, 95% confidence interval [CI] 1.22-5.09; P=0.01) and background liver disease (OR 15.09, 95%CI 4.09-55.69; P<0.001) to be associated with the abnormal liver biochemistry group.ConclusionsAbnormal liver biochemistry is common in IBD patients on infliximab. Patients who are male, or have abnormal pre-therapy liver biochemistry or background liver disease, are more likely to develop worsening liver biochemistry during infliximab therapy. RUCAM scoring may help identify true cases of DILI.

Analysis of Antithyroid Drug-Induced Severe Liver Injury in 18,558 Newly Diagnosed Patients with Graves' Disease in Japan.

Background: The prevalence of antithyroid drug (ATD)-related drug-induced liver injury (DILI) has been reported to vary among patients in several countries. The purpose of this study was to summarize the prevalence of liver injury induced by ATD and to determine the actual prevalence of severe liver injury. Methods: The medical records of 18,558 patients who were newly diagnosed with Graves' disease between January 2005 and December 2016 were retrospectively reviewed. Severe DILI was defined as alanine aminotransferase (ALT) 8 times higher than the upper limit of normal (ULN) or total bilirubin (T-bil) 3 times higher than the ULN. The most severe DILI was defined as ALT higher than 20 times the ULN or T-bil higher than 10 times the ULN. Results: A total of 461 subjects (470 cases) were analyzed, and they consisted of 10 males and 451 females, with a median age of 37 years (range 10-82 years). Nine of 461 patients had severe DILI with both drugs. The total prevalence of severe DILI in this study was 2.5%, and the prevalence of DILI by drug was 1.4% with metimazole (MMI) (n = 198) and 6.3% with propylthiouracil (PTU) (n = 272) (p < 0.001). The prevalence of the most severe ATD-related DILI was 0.22% (n = 40), and the prevalence for each drug was 0.08% with MMI (n = 11) and 0.68% with PTU (n = 29). The median time to DILI development was 30 days (range 7-314 days), and all patients recovered from DILI, with no fatalities. The prevalence of MMI-related DILI was significantly age dependent (p < 0.001). Conclusions: Though there were no fatalities in this study, the prevalence of PTU-related severe DILI was significantly higher than that of MMI-related severe DILI.

Zolpidem high-dose abuse: what about the liver? Results from a series of 107 patients

ABSTRACTObjectives: Z-Drugs (ZDs) have been developed to limit benzodiazepines (BZDs) abuse for sleep disorders. Data on the liver toxicity of zolpidem (ZLM) are lacking or anecdotal. The authors evaluated the presence of drug-induced liver injury (DILI) among a cohort of high-dose ZLM abusers.Methods: Retrospective study analyzing clinical records of 1112 consecutive patients admitted for BZDs detoxification from 2003 to 2018. Inclusion criteria: age >18 y.o.; ZLM abuse/dependence; high-dose ZDs abuse. Exclusion criteria: missing lab data; lack of informed consent. Main outcome was the presence of DILI measured as elevation of ALT/AST levels >250 U/l.Results: A total of 107 patients met the eligibility criteria. Liver enzymes alterations were present in 9.3% (95% CI 4.6–16.5%); one patient (0.9%, 95% CI 0.0–2.8%) showed DILI criteria. BMI significantly influenced transaminases levels. No correlations between duration nor doses of ZLM abuse and transaminases levels were found.Conclusion: The present study shows a very low prevalence of DILI among high-dose ZLM abusers. The prevalence of hypertransaminasemia was in line with general population. On one hand ZLM has a substantially safe liver profile but on the other hand ZLM abuse and dependence, especially at very high doses, represents an emerging problem.

Drug-induced liver injury: A 2-year retrospective study of 1169 hospitalized patients in a single medical center

BackgroundAlthough herbal medicines (HMs) are widely used in Asian and Western countries, medicinal information concerning their hepatic toxicity or interaction with conventional medicines (CMs) is sparse. PurposeThe aim of our study was to estimate the prevalence of drug-induced liver injury (DILI) among total inpatients prescribed HMs or CMs. Furthermore, we noted all medications suspected to be associated with hepatotoxicity in the liver injury group during the period of hospitalization. Study designWe retrospectively observed medical records of 1169 inpatients in a single medical center from January 2012 to July 2014. MethodsBased on a database of the 1169 inpatients at a single medical center, we researched the occurrence rate and type of liver injury according to the criteria of the Council for International Organization of Medical Science (CIOMS). We also utilized a simplified Roussel Uclaf Causality Assessment Method (RUCAM) score for probable causality assessment between drugs and liver injury. ResultsAmong a total of 1169 inpatients, 13 cases whose baseline LFTs had been in the normal range at admission had abnormal liver parameters at the time of follow-up, and 11 of them (0.94%) were attributed to drugs: 0.43% (5 of 1169) to HMs, 0.43% (5 of 1169) to CMs, and 0.09% (1 of 1169) to combined drug classes. Two of them were found to have liver injury because of pneumonia and sepsis. As for liver injury type, 8 cases were hepatocellular, 2 were cholestatic, and 1 was of mixed pattern. The common causative HMs for hepatotoxicity were Ephedrae Herba and Scutellariae Radix, while CMs included antidepressants, antihistamines, and antibacterials. ConclusionsWe investigated approximate incidence rates and analyzed suspicious drugs associated with liver damage, which revealed a low frequency of liver injury induced by HMs. However, further study, based on a well-designed, long-term, multicenter prospective study, will be required to determine the safety of HMs.

Drug-induced hepatitis and the risk factors for liver injury in pulmonary tuberculosis patients.

Introduction:Short-course chemotherapy containing rifampicin and isoniazid in combination has proved to be highly effective in the treatment of tuberculosis, but one of its adverse effects is hepatotoxicity. Various risk factors have been found to be associated with drug-induced liver injury (DILI) in general population. The study aimed to determine the prevalence of drug-induced hepatitis and the risk factors associated with the DILI among the patients of pulmonary tuberculosis in Indian patients.Setting and Design:Prospective nested case control study.Materials and Methods:Out of the cohort of 3900 tuberculosis patients who were initiated on anti-tubercular therapy, 150 patients who developed drug-induced liver injury due to short-course chemotherapy under RNTCP were included in the analysis. Thirty cases were being followed up in our hospital and other 120 were referred to us for the management of drug-induced hepatitis from the primary health centers. The diagnostic criteria's for DILI were made according to the American Thoracic Society criteria. Analyses of various risk factors were done for the development of DILI.Results:The prevalence of DILI in the present study was 3.8%. It was observed that DILI patients were older and their serum albumin levels were lower, and they had multiple co-morbid conditions. Regular alcohol intake, more extensive disease associated with radiological and female gender were observed to be independent risk factors for the development of DILI.Conclusions:Of the various risk factors analyzed, advanced age, hypoalbuminemia, regular alcohol intake and advanced nature of the disease were independent risk factors for the development of DILI. The risk of development of hepatitis is increased in the presence of one or more of these risk factors.

Liver enzyme abnormalities during concurrent use of herbal and conventional medicines in Korea: A retrospective study

Concurrent use of herbal medicine (HM) and conventional medicine (CM) is increasing. However, little is known about the prevalence of drug-induced liver injury (DILI) related to this concurrent use. In order to investigate changes in liver enzymes during concurrent use of HM and CM and to assess the prevalence of DILI related to their concurrent use, we screened for liver injury among inpatients at our institution who were administered both HM and CM for at least 14 days while hospitalized between 2006 and 2010. We used the Council for International Organization of Medical Science (CIOMS) laboratory criteria to define liver injury. Of the 892 patients included in the study, 34 (3.81%) had liver injury on admission and 21 (2.35%) had liver injury at discharge. Of the 48 cases that fulfilled the CIOMS laboratory criteria for liver injury, 34 had preexisting liver injury. The remaining 14 were analyzed, and five were concluded to have DILI, resulting in a prevalence of 5/892 (0.56%, with a 95% confidence interval of 0.07–1.05%). Overall, clinical symptoms of liver injury were mild. We thus contend that concurrent use of HM and CM is relatively safe.

Clinical Hepatotoxicity. Regulation and Treatment with Inducers of Transport and Cofactors

Drug-induced liver injury (DILI) is a rare condition. This review presents a clinical update on the incidence and prevalence of DILI, cellular targets and histopathological features of liver injury, and basic diagnostic approaches. At present, with the exception of acetaminophen poisoning where timely administered N-acetylcysteine serves as the antidote, treatment usually is supportive. Since most biotransformation processes in the liver are under the control of nuclear receptors (NR), treatment modalities aiming to stimulate or inhibit NR expression are at present tested in animal models of APAP toxicity or cholestasis. Some NR ligands have also been used in human cholestatic liver disease, but studies on the efficacy in DILI are lacking. This review describes possible future options for the treatment of DILI.

Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden

Objective. There are only a few data on the prevalence of drug-induced liver injury associated with fatal outcome. The aim of this study was to determine the nature and number of suspected adverse drug-induced liver disease associated with fatalities and/or liver transplantation since reporting of adverse drug reactions (ADRs) started in Sweden.Material and methods. All reports of suspected hepatic ADRs with fatal outcome received by the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) from 1966 to 2002 were reviewed and causality assessed.Results. The SADRAC received 151 reports of suspected ADRs with fatal outcome from liver injury; 48 cases were either unlikely or excluded. Of the remaining 103 cases, 13 (13%) were highly probable, 48 (47%) probable and 42 (41%) possible. The median age of the 103 patients was 64 years (47–77 interquartile range (IQR)) and 59 (57%) were males. The majority of cases were classified as hepatocellular (75%), with only 15% cholestatic and 10% mixed. Halothane, paracetamol, flucloxacillin, sulfamethoxazole/trimethoprim and diclofenac were the most common drugs associated with fatal outcome. Seventeen patients underwent liver transplantation, most commonly because of paracetamol and disulfiram toxicity.Conclusions. A wide range of suspected ADRs are associated with fatalities. Antibiotics and analgesics are associated with the greatest number of reports of deaths.