BACKGROUND/AIMS: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. METHODS: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. RESULTS: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows: hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs 18/39, p=0.031). CONCLUSIONS: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.
Anti-Bacterial Agents/*adverse effects ; Bilirubin/blood ; Child ; Child, Preschool ; China ; Drug-Induced Liver Injury/blood/*etiology/pathology ; Drugs, Chinese Herbal/*adverse effects ; Female ; Humans ; Liver/pathology ; Male ; Prothrombin Time ; Respiratory Tract Infections/*complications/drug therapy ; Retrospective Studies

OBJECTIVETo explore the liver-toxic fraction in Rhigoma of Dioscorea bulbifera.

METHODThe rats were randomized into four groups: control group (20% PVP-water), T001(10% total methanol extraction), F002(5% chloroform fraction) and F003(5% methanol fraction). Direct bilirubin (DBil) and Glutamic-pyruvic transaminase (GPT) were examined, and liver index was measured. The histological and morphological observations were performed with optical and electrical microscope.

RESULTT001 and F002 showed significant liver toxicity.

CONCLUSIONThe chloroform fraction was the liver-toxic fraction of D. bulbifera.

Alanine Transaminase ; blood ; Animals ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; blood ; etiology ; pathology ; Dioscorea ; chemistry ; Drugs, Chinese Herbal ; toxicity ; Female ; Liver ; pathology ; ultrastructure ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.
Adult ; Aged ; Alanine Transaminase/blood ; Alkaline Phosphatase/blood ; Aloe/*chemistry/metabolism ; Drug-Induced Liver Injury/*diagnosis/etiology/pathology ; Female ; Humans ; Liver/pathology ; Male ; Middle Aged ; Plant Extracts/*adverse effects/*chemistry ; Splenomegaly/diagnosis ; Tomography, X-Ray Computed ; Young Adult

BACKGROUND/AIMS: Accurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH. METHODS: The clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2+/-12.8 years (mean+/-SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively. RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase levels were 662.2+/-574.8 U/L, 905.4+/-794.9 U/L, 12.9+/-10.8 mg/dL, 195.8+/-123.3 U/L, and 255.3+/-280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1+/-519.1 vs. 1043.3+/-600.5 U/L), globulin levels (2.7+/-0.4 vs. 3.3+/-0.5 g/dL), and prothrombin time (12.9+/-2.4 vs. 15.2+/-3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7+/-0.9 in the DILI group and 6.5+/-0.9 in the AIH group (P<0.001). CONCLUSIONS: Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.
Adult ; Alanine Transaminase/blood ; Antibodies, Antinuclear/blood ; Aspartate Aminotransferases/blood ; Biopsy ; Drug-Induced Liver Injury/*diagnosis/pathology ; Female ; Globulins/analysis ; Hepatitis, Autoimmune/*diagnosis/pathology ; Herbal Medicine ; Humans ; Jaundice/etiology ; Male ; Middle Aged ; Prothrombin Time

OBJECTIVETo study the hepatoprotective effect of the extract of Terminala catappa leaves (TCE) and the possible mechanisms underlying its protection on acute liver injury induced by D-Galactosamine (D-GalN).

METHODIn vivo: D-GalN-induced liver injury model was used to evaluate the effect of TCE on the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice. Structure of liver was observed and liver mitochondrial swelling was measured following D-GalN injection without or with TCE. In vitro: D-GalN-induced primary cultured hepatocytes injury model was used to value the effect of TCE on cultured hepatocytes. Cell viability was measured by means of MTT assay, and the AST and superoxide dismutase (SOD) activities in supernatant of cultured cells were investigated also.

RESULTIn acute hepatic injury test, with oral pretreatment of TCE, remarkable rises in serum AST and ALT activities (2.95 fold and 3.35 fold) induced by D-GalN were obviously reversed and significant morphological changes were remarkably lessened. In addition, the decrease in sensitivity of mitochondrial swelling to the exotic Ca2+ stimulation induced by D-GalN was also prevented by TCE. In primary cultured hepatocytes of mice, it was found that incubation with TCE could prevent the decrease in cell viability in a dose-dependent manner. It was also found that both the increase in AST level (1.9 fold) and the decrease in SOD activity (48.0%) in supernatant of primary cultured hepatocytes induced by D-GalN could be inhibited by pretreatment of TCE.

CONCLUSIONTCE has hepatoprotective activity and the mechanisms underlying its protective effect may be related to its antioxidant activity and protection on both hepatocytes and liver mitochondria.

Animals ; Cells, Cultured ; Chemical and Drug Induced Liver Injury ; blood ; etiology ; pathology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Galactosamine ; Liver ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred ICR ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Pregnancy ; Protective Agents ; pharmacology ; Terminalia ; chemistry

Drug-induced liver injury (DILI) is an increasingly common cause of acute hepatitis. We examined clinical features and types of liver injury of 65 affected patients who underwent liver biopsy according DILI etiology. The major causes of DILI were the use of herbal medications (43.2%), prescribed medications (21.6%), and traditional therapeutic preparations and dietary supplements (35%). DILI from herbal medications, traditional therapeutic preparations, and dietary supplements was associated with higher elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than was DILI from prescription medications. The types of liver injury based on the R ratio were hepatocellular (67.7%), mixed (10.8%), and cholestatic (21.5%). Herbal medications and traditional therapeutic preparations were more commonly associated with hepatocellular liver injury than were prescription medications (P = 0.002). Herbal medications and traditional therapeutic preparations induce more hepatocellular DILI and increased elevations in AST and ALT than prescribed medications.
Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Dietary Supplements/adverse effects ; Drug-Induced Liver Injury/enzymology/*etiology/pathology ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy/adverse effects ; Plant Preparations/adverse effects ; Prescription Drugs/adverse effects ; Republic of Korea ; Retrospective Studies

OBJECTIVEChildren with refractory epilepsy who suffered from severe liver function impairment during valproic acid (VPA) treatment at routine dosage were studied. The clinical manifestations and therapeutic approaches were investigated in order to improve its diagnosis and management.

METHODClinical information as well as features and management of 4 inpatients who were suffered from intractable epilepsy with severe liver function impairment induced by VPA since 2006 were collected and analyzed, including age of onset of epilepsy, VPA using age and the time when liver injury occurred, clinical manifestations, auxiliary examinations and management.

RESULTAmong the 4 cases, three were male and one was female. The admitted age ranged from 1 - 9 years and 1 month. The course of disease was 25 d - 6 months. They manifested as refractory epilepsy of epilepsia partialis continua which was difficult to control. After using VPA for 62 d (50 - 76 d), all developed severe impairment of liver synthetic function which was not related to the concentration of VPA. One was diagnosed with Alpers syndrome, two were suspicious of Alpers syndrome, and the other was diagnosed gliocytoma after brain biopsy. VPA was stopped immediately and symptomatic therapies were used. Other than that, intravenous injection of L-carnitine in 3 cases recovered the liver function.

CONCLUSIONVPA-associated severe hepatotoxicity can manifest first as impaired liver synthetic function. Besides alanin transaminase and aspartate transaminase, the liver synthetic function test is more important than monitoring of liver enzymatic functions in monitoring for the hepatotoxicity. Intravenous injection of L-carnitine in early stage showed good treatment effect.

Anticonvulsants ; adverse effects ; Biomarkers ; blood ; Carnitine ; administration & dosage ; therapeutic use ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; Child ; Child, Preschool ; DNA Mutational Analysis ; Diffuse Cerebral Sclerosis of Schilder ; chemically induced ; drug therapy ; genetics ; Epilepsy ; drug therapy ; Female ; Humans ; Infant ; Liver ; drug effects ; pathology ; Liver Function Tests ; Male ; Retrospective Studies ; Valproic Acid ; adverse effects

OBJECTIVETo discuss the mechanism of mice acute hepatic injury caused by tripterygium glycosides tablets with different dose at different time.

METHODMice were given Tripterygium Glycosides respectively with the dosage of 10 times, 20 times, 30 times of clinical dose to observe the change of mice acute hepatic injury with different does; then, the acute hepatic injury mice were duplicated with 20 times clinical dosage and mice serum ALT were detected at 9, 18, 27, 36 h to observe the change of mice acute hepatic injury at different time. The activity of SOD, GSH-Px in serum and the level of LPO in liver homogenate wevedetected to discuss the mechanism of mice acute hepatic injury caused by Tripterygium Glycosides tablets; and liver tissue pathology was observed.

RESULTThe acute hepatic injury was obvious with 20 times adult dosage in 18 hours and the acute hepatic injury mice death rate was low.

CONCLUSIONTripterygium Glycosides tablets can cause acute hepatic injury to mice and its mechanism is related to Lipid peroxidation reaction.

Alanine Transaminase ; blood ; Animals ; Chemical and Drug Induced Liver Injury ; etiology ; metabolism ; pathology ; Dose-Response Relationship, Drug ; Female ; Glutathione Peroxidase ; blood ; Glycosides ; isolation & purification ; toxicity ; Lipid Peroxidation ; drug effects ; Lipid Peroxides ; metabolism ; Liver ; metabolism ; pathology ; Male ; Mice ; Superoxide Dismutase ; blood ; Time Factors ; Tripterygium ; chemistry

OBJECTIVETo study the protective effects of Isodon lophanthoides var. gerardianus (ILVG) aqueous extract on the acute hepatic injury induced by carbon tetrachloride (CCl4) in rats.

METHODSixty rats were allocated into control group, model group, low, middle and high dosage group and Bifendate group randomly. At the test group, rats received either ILVG aqueous extract (15, 7.5, 3.75 g x kg(-1)) or Bifendate (45 mg x kg(-1)) by gastric perfusion daily for 10 consecutive days. In 1st, 4th, 7th and 10th days, 10% CCl4 (2 mL x kg(-1)) was given to rats by intraperitoneal (ip) injection. The rats were killed 24 h after the last adminiction with drug, the levels of ALT, AST, ALP and total bilirubin in serum were analyzed, the body weight, liver weight, spleen weight and thymus weight of each rat were measured, and the hepatic tissue pathology was observed.

RESULTILVG could decrease the ALT, AST, ALP and T-Bil in serum, restrain the enlargement of liver and the shrinkage of thymus, and reduce the necrosis in pathological observation.

CONCLUSIONILVG aqueous extract possesses the effects of protecting on the acute hepatic injury induced by CCl4 in rats.

Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; blood ; etiology ; pathology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Isodon ; chemistry ; Liver ; pathology ; Male ; Plants, Medicinal ; chemistry ; Protective Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the protective effect of dl-tetrahydropalmatine(dl-THP) on liver injury induced by carbon tetrachloride (CC4) in mice.

METHODMice were administracted with dl-tetrahydropalmatine ip 20, 40 mg x kg(-1) daily for 9 d respectively, and then actue liver injury model was induced by 0.1% carbon tetrachloride ip 20 mL x kg(-1). The mice were killed 17 h after injection ip of CCl4, serum alanine and aspartate aminotransferase (ALT and AST) activity were measured, and maleic dialdehyde (MDA) and superoxide dismutase(SOD) activity in liver were detected.

RESULTdl-THP significantly reduced the level of serum ALT and AST, inhibited lipoperxidation in liver, while increased SOD activity in liver tissue. Degeneration of hepatocytes was obviously prevented in mice treated with dl-THP, and the liver histological structure was well maintained.

CONCLUSIONdl-THP has inhibitory effects on liver injury induced by CCl4 in mice. The mechanisms may be related with its effects of reducing lipid peroxidation product.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Berberine Alkaloids ; pharmacology ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; etiology ; metabolism ; pathology ; Female ; Lipid Peroxidation ; drug effects ; Liver ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Protective Agents ; pharmacology ; Random Allocation ; Superoxide Dismutase ; metabolism