A retrospective study was performed in drug-induced liver injury(DILI) cases associated with Dictamni Cortex(Baixianpi,BXP) Preparations,which were treated at grade Ⅲ class A liver disease hospitals from 2008 to 2016 and spontaneously reported for adverse reactions between 2012 and 2016 at HILI Cloud(hilicloud.net). The results showed 25 DLII cases associated with BXP Preparations treated at grade Ⅲ class A liver disease hospitals during the 9 years,including only 14 cases in line with the clinical diagnostic criteria of Guidelines for the Diagnosis and Treatment of Herb-Induced Liver Injury. And 74 DILI cases associated with BXP Preparations spontaneously reports adverse reactions,and 18. 92% of them had unreasonable medication,including polypharmacy(21. 43%),overdose(28. 57%) and repeated dosage(50%). And 47 DILI cases used BXP Preparations to treat psoriasis and vitiligo(a total of59. 57%). The time range of taking BXP Preparations until liver injury occurred was 1-366 d,with the median of 18 d. The dose of BXP Preparations was estimated to be 0. 09-12 g·d-1. And the cumulative dosage of taking drugs until liver injury occurred was 1. 1-336 g. Obvious associations with time-toxicity as well as quantity-toxicity could not be found based on the wide range of time-toxicity relations and quantity-toxicity relations. On the basis of the study,we found that DILI cases associated with BXP Preparations commonly occurred in patients with immune diseases,such as psoriasis and vitiligo,indicating specific individual differences. The results suggested that DILI cases associated with BXP Preparations would be correlated with the property of idiosyncratic drug-induced liver injury. In conclusion,the risk of liver injury clinically caused by BXP Preparations should be paid more attention,and the studies on the mechanism of idiosyncratic drug-induced liver injury must be enhanced,and those on risk factors,like irrational drug use,should be strengthened. Moreover,the evaluation of the risk-to-benefit ratio is supposed to be performed for the sake of improving the risk prevention and control standards for BXP preparations,and ensuring safe and rational clinical application of BXP Preparations.
Chemical and Drug Induced Liver Injury ; epidemiology ; China ; Dictamnus ; chemistry ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Liver ; Retrospective Studies ; Risk Factors

Drug-induced liver injury (DILI) remains a significant clinical challenge and is the leading cause of acute liver failure in most countries. An aging population that uses more medications, a constant influx of newly developed drugs and a growing risk from unfamiliar herbal and dietary supplements will make DILI an increasing part of clinical practice. Currently, the most effective strategy for disease management is rapid identification, withholding the inciting agents, supportive care and having a firm understanding of the expected natural history. There are resources available to aid the clinician, including a new online "textbook" as well as causality assessment tools, but a heightened awareness of risk and the disease's varying phenotypes and good history-taking remain cornerstones to diagnosis. Looking ahead, growing registries of cases, pharmacoepidemiology studies and translational research into the mechanisms of injury may produce better diagnostic tools, markers for risk and disease, and prevention and therapeutics.
Age Factors ; Anti-Infective Agents/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anticonvulsants/adverse effects ; Biopsy ; Dietary Supplements/adverse effects ; Drug-Induced Liver Injury/*diagnosis/epidemiology ; Drugs, Chinese Herbal/adverse effects ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Incidence ; Liver/pathology ; Liver Function Tests ; Risk Factors ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

OBJECTIVETo analyze the development of liver damage and reactivation of hepatitis B virus (HBV) during the treatment of extremely severe burn injury in HBsAg positive patients, in order to provide reference for prevention and treatment of liver damage in patients with HBV infection after extremely severe burn.

METHODSMedical records of 54 HBsAg positive patients after extremely severe burn injury admitted from January 2004 to December 2014 were retrospectively analyzed. Development of liver damage and HBV reactivation of these patients during the treatment were analyzed according to the classification of their gender, results of hepatitis B e antigen (HBeAg) and HBV DNA examinations on admission, and development of sepsis in the process of treatment. Data were processed with chi-square test.

RESULTS(1) The incidence of liver damage in the process of treatment of these patients was 85.2% (46/54). Among all the patients, the proportion of liver damage was 35/38 in male, which was significantly higher than that in female (11/16, χ² = 4.867, P<0.05). Liver damage was found in all of 26 patients who were HBeAg positive on admission, 34 patients who were HBV DNA positive on admission, and 36 patients who developed sepsis in the process of treatment; the proportions were significantly higher than those in patients who were HBeAg negative on admission (20/28), patients who were HBV DNA negative on admission (12/20), and patients who did not develop sepsis in the process of treatment (10/18), with χ² values respectively 11.801, 18.384, and 20.574, P values below 0.01. (2) The incidence of HBV reactivation in these patients was 29.6% (16/54). Among all the patients, the proportion of HBV reactivation was 13/38 in male and 3/16 in female, with no statistically significant difference between them (χ² = 0.656, P>0.05). The proportions of HBV reactivation in patients who were HBeAg positive on admission, patients who were HBV DNA positive on admission, and patients who developed sepsis in the process of treatment were respectively 13/26, 16/34, and 15/36, and they were significantly higher than those in patients who were HBeAg negative on admission (3/28), patients who were HBV DNA negative on admission (0/20), and patients who did not develop sepsis in the process of treatment (1/18), with χ² values respectively 9.979, 18.615, and 5.873, P<0.05 or P<0.01.

CONCLUSIONSPatients who are HBsAg positive, HBeAg positive, HBV DNA positive on admission, and develop sepsis in the process of treatment of extremely severe burn injury are more likely to develop liver damage and HBV reactivation. It is necessary to dynamically monitor the changes in HBV DNA and liver function, in order to identity the reactivation of virus.

Alanine Transaminase ; blood ; Burns ; complications ; drug therapy ; Chemical and Drug Induced Liver Injury ; DNA, Viral ; Female ; Hepatitis Antibodies ; blood ; Hepatitis B ; drug therapy ; epidemiology ; virology ; Hepatitis B Surface Antigens ; blood ; immunology ; Hepatitis B virus ; drug effects ; immunology ; isolation & purification ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Humans ; Incidence ; Liver ; pathology ; Male ; Retrospective Studies

Anti-Bacterial Agents ; adverse effects ; Anti-Infective Agents ; adverse effects ; Anti-Inflammatory Agents ; adverse effects ; Biomarkers ; blood ; Chemical and Drug Induced Liver Injury ; diagnosis ; epidemiology ; Child ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Liver ; drug effects ; metabolism ; pathology ; Pediatrics ; Risk Factors

Hepatic adverse drug reactions (ADRs) to certain drugs may differ within each country, reflecting different patterns of prescription, socioeconomic status, and culture. The purpose of this study was to assess the suspected cause of hepatic ADRs using the spontaneously reported pharmacovigilance data from Korea. A total of 9,360 spontaneously reported adverse drug events (ADEs) from nine Pharmacovigilance Centers were analyzed. Risk of hepatic ADEs was assessed by calculating the reporting odds ratio (ROR). Of the 9,360 cases, 567 hepatic ADEs were reported. The most frequently prescribed drug classes inducing hepatic ADEs were anti-tuberculotics, cephalosporins, valproic acids, penicillins, quinolones, non-steroidal anti-inflammatory drugs (NSAIDs), anti-viral agents, and statins. ROR values were especially high in anti-tuberculosis drugs, systemic antifungal drugs for systemic use, anti-epileptics, propylthiouracil, and herbal medicines. Underlying diseases such as tuberculosis (6.9% vs 0.9%), pneumonia (4.9% vs 1.7%), intracranial injury including skull fracture (4.5% vs 0.9%), HIV (3.4% vs 0.4%), subarachnoid hemorrhage (2.8% vs 0.5%), and osteoporosis (2.4% vs 1.4%) were significantly more common in hepatic ADE group. In conclusion, anti-infective drugs, anti-epileptics, NSAIDs and statins are the most common suspects of the spontaneously reported hepatic ADEs, in Korea. Careful monitoring for such reactions is needed for the prescription of these drugs.
Adult ; *Adverse Drug Reaction Reporting Systems/statistics & numerical data ; Aged ; Anti-Infective Agents/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anticonvulsants/adverse effects ; Drug Monitoring ; Drug-Induced Liver Injury/*epidemiology/*etiology ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Male ; Middle Aged ; Odds Ratio ; Pharmacovigilance ; Republic of Korea/epidemiology ; Risk Factors

Liver injury due to prescription and nonprescription medications is a growing medical, scientific, and public health problem. Worldwide, the estimated annual incidence rate of drug-induced liver injury (DILI) is 13.9-24.0 per 100,000 inhabitants. DILI is one of the leading causes of acute liver failure in the US. In Korea, the annual extrapolated incidence of cases hospitalized at university hospital is 12/100,000 persons/year. Most cases of DILI are the result of idiosyncratic metabolic responses or unexpected reactions to medication. There is marked geographic variation in relevant agents; antibiotics, anticonvulsants, and psychotropic drugs are the most common offending agents in the West, whereas in Asia, 'herbs' and 'health foods or dietary supplements' are more common. Different medical circumstances also cause discrepancy in definition and classification of DILI between West and Asia. In the concern of causality assessment, the application of the Roussel Uclaf Causality Assessment Method (RUCAM) scale frequently undercounts the cases caused by 'herbs' due to a lack of previous information and incompatible time criteria. Therefore, a more objective and reproducible tool that could be used for the diagnosis of DILI caused by 'herbs' is needed in Asia. In addition, a reporting system similar to the Drug-Induced Liver Injury Network (DILIN) in the US should be established as soon as possible in Asia.
Dietary Supplements/adverse effects ; Drug-Induced Liver Injury/*diagnosis/epidemiology/*pathology ; Herbal Medicine ; Humans ; Liver Failure, Acute/pathology ; Prognosis ; Risk Factors ; Severity of Illness Index

OBJECTIVETo study the clinical features of drug-induced liver injury in children.

METHODSThe clinical data of the hospitalized children with drug-induced liver injury over 5 years were retrospectively reviewed.

RESULTSOf 641 cases of hospitalized children with liver injury, there were 64 cases (10%) of drug induced liver injury. Hepatocellular injury was the most common type of drug-induced liver injury (81%). The major drugs causing drug-induced liver injury included chemotherapy drugs, antibiotics and anti-tuberculosis drugs. Rash (16%), gastrointestinal reaction (15%), fever (14%) and liver intumescence (12%) were common clinical symptoms. A part of patients with drug-induced liver injury (11%) had no symptoms and signs.

CONCLUSIONSDrug-induced liver injury is one of the common causes of liver damage in hospitalized children. Some children with drug-induced liver injury have no symptoms and signs. Hepatocellular injury is a major type of drug-induced liver injury in children, resulting less severe liver damage.

Adolescent ; Chemical and Drug Induced Liver Injury ; diagnosis ; epidemiology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Retrospective Studies

Chemical and Drug Induced Liver Injury ; epidemiology ; Humans ; Incidence

OBJECTIVETo investigate the incidence of hepatotoxicity in acquired immunodeficiency syndrome (AIDS) patients on combined anti-retroviral therapy (cART) containing nevirapine (NVP) and to assess the risk factors and its impact on cART.

METHODS330 AIDS patients from March 2003 to June 2008 at local county were enrolled and a retrospective study using Kaplan-meier survival and Multivariate logistic regression modeling was conducted.

RESULTS267 out of 330 patients received NVP based cART and 63 cases received EFV-based cART. The deference of prevalences of hepatotoxicity between the two groups is statistically significant (Chi2 = 6.691, P = 0.01). 133 out of 267 (49.8%) patients on NVP based cART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time, amounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV co-infection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+ T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: Chi2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz.

CONCLUSIONNVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.

Acquired Immunodeficiency Syndrome ; drug therapy ; metabolism ; Adolescent ; Adult ; Anti-Retroviral Agents ; adverse effects ; Asian Continental Ancestry Group ; Chemical and Drug Induced Liver Injury ; epidemiology ; virology ; Female ; Humans ; Incidence ; Liver ; drug effects ; metabolism ; Male ; Middle Aged ; Nevirapine ; adverse effects ; Retrospective Studies ; Risk Factors ; Young Adult

Occupational hepatic disorders are classified into toxic hepatitis, viral hepatitis, and chemical-induced malignancy in Korea. Toxic hepatitis cases were reported in workers who were exposed to dimethylformamide, dimethylacetamide, or trichloroethylene. Pre-placement medical examination and regular follow-up are necessary to prevent the development of toxic hepatitis. Viral hepatitis was chiefly reported among health care workers such as doctors, nurses and clinical pathology technicians who could easily be exposed to blood. Preventive measures for these groups therefore include vaccination and serum monitoring programs. Hepatic angiosarcoma caused by vinyl chloride monomer (VCM) exposure is a very well known occupational disease and it has not been officially reported in Korea yet. Some cases of hepatocellular carcinoma were legally approved for compensation as an occupational disease largely by overwork and stress, but not supported by enough scientific evidence. Effort to find the evidence of its causal relationship is needed.
Adult ; Drug-Induced Liver Injury/epidemiology ; Female ; Health Personnel ; Hepatitis, Viral, Human/epidemiology/prevention & control ; Humans ; Liver Diseases/*epidemiology/prevention & control ; Liver Neoplasms/chemically induced/epidemiology ; Male ; Middle Aged ; Occupational Diseases/*chemically induced/*epidemiology/prevention & control ; Occupational Exposure/adverse effects ; Republic of Korea/epidemiology ; Young Adult