Acetamides ; Aminopyrine ; Animals ; Breath Tests ; methods ; Carbon Isotopes ; Chemical and Drug Induced Liver Injury ; diagnosis ; pathology ; physiopathology ; Humans ; Liver ; injuries ; pathology ; physiopathology ; Liver Cirrhosis ; diagnosis ; pathology ; physiopathology ; Liver Diseases ; diagnosis ; pathology ; physiopathology ; Liver Function Tests ; Phenylalanine ; Prognosis

Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity.
Aloe/*adverse effects ; Animals ; Dietary Supplements/adverse effects ; *Drug-Induced Liver Injury/enzymology/pathology/physiopathology ; Female ; Humans ; Middle Aged ; Phytotherapy/adverse effects ; Plant Extracts/adverse effects

PURPOSE: Toxicity caused by acetaminophen and its toxic mechanisms in the liver have been widely studied, including effects involving metabolism and oxidative stress. However, its adverse effects on heart have not been sufficiently investigated. This study evaluated the cardiac influence and molecular events occurring within the myocardium in rats treated with a dose of acetaminophen large enough to induce conventional liver damage. MATERIALS AND METHODS: Male rats were orally administered a single dose of acetaminophen at 1,000 mg/kg-body weight, and subsequently examined for conventional toxicological parameters and for gene expression alterations to both the heart and liver 24 hours after administration. RESULTS: Following treatment, serum biochemical parameters including aspartate aminotransferase and alanine aminotransferase were elevated. Histopathological alterations of necrosis were observed in the liver, but not in the heart. However, alterations in gene expression were observed in both the liver and heart 24 hours after dosing. Transcriptional profiling revealed that acetaminophen changed the expression of genes implicated in oxidative stress, inflammatory processes, and apoptosis in the heart as well as in the liver. The numbers of up-regulated and down-regulated genes in the heart were 271 and 81, respectively, based on a two-fold criterion. CONCLUSION: The induced expression of genes implicated in oxidative stress and inflammatory processes in the myocardium reflects molecular levels of injury caused by acetaminophen (APAP), which could not be identified by conventional histopathology.
Acetaminophen/*toxicity ; Administration, Oral ; Analgesics, Non-Narcotic/*toxicity ; Animals ; Drug-Induced Liver Injury/pathology/*physiopathology ; Gene Expression Profiling ; Heart/*physiology ; Liver/pathology/physiology ; Male ; Myocardium/pathology ; Rats ; Transcriptome/*drug effects

OBJECTIVETo investigate the clinical significance of liver function and autoantibodies in patients with acute or chronic drug-induced liver injury.

METHODS51 patients with drug-induced liver injury were divided into acute drug induced liver injury group and chronic drug induced liver injury group, liver function and autoantibodies were compared between these two groups.

RESULTSThere was no significant difference (P more than 0.05) in alanine aminotransferase [(412.1+/-387.5) U/L and (376.0+/-319.7) U/L], aspartate aminotransferase [(352.5+/-457.9) U/L and (198.8+/-142.7) U/L], total bilirubin [(109.7+/-104.80)micromol/L and(102.4+/-135.7)micromol/L], direct bilirubin [(66.4+/-73.3)micromol/L and (61.2+/-72.1)micromol/L], alkaline phosphatase [(133.4+/-50.1) U/L and (147.4+/-97.3) U/L], gamma-glutamyltransferase [(139.9+/-134.1) U/L and (180.6+/-227.9) U/L], and albumin [(41.3+/-4.9) g/L and (39.8+/-5.3)g/L] between these two groups, however, the level of globulin [(25.1+/-5.3) g/L and (28.6+/-5.1) g/L] was significantly different between these two groups (P less than 0.05). The titers of Anti-nuclear antibody (ANA) and smooth muscle antibody (SMA) were less than or equal to 1:320 in patients with acute drug induced liver injury. The titers of ANA, antimitochondrial antibody (AMA), and SMA were more than or equal to 1:320 in most of the patients with chronic drug induced liver injury.

CONCLUSIONLiver function has no value in the diagnosis of acute or chronic drug induced liver injury. High titer autoantibodies are found in patients with chronic drug induced liver injury.

Acute Disease ; Adult ; Antibodies, Antinuclear ; blood ; Autoantibodies ; blood ; Chemical and Drug Induced Liver Injury ; blood ; diagnosis ; immunology ; Diagnosis, Differential ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Liver ; pathology ; physiopathology ; Liver Function Tests ; Male ; Microsomes ; immunology ; Middle Aged ; Muscle, Smooth ; immunology

OBJECTIVETo study the incidence, clinical features and related factors of propylthiouracil (PTU)-induced hepatic injury in patients with hyperthyroidism.

METHODSA prospective study were carried out in 70 patients of hyperthyroidism with normal liver function. Every patient was treated with PTU 300 mg/d until the thyroid functions recovered to normal, following by decease and maintenance PTU dose in period of six months. Liver function, including serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL), thyroid function (serum thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine and thyrotropin) and blood routine items were measured before therapy and once a month for six months after PTU therapy was begun.

RESULTSSixty-four cases of 70 patients completed the therapy for 6 months. Hepatic injury developed in 33 patients (51.6%). Asymptomatic, transient hepatic injury was shown in 22 patients (34.4%). Slight symptomatic hepatic injury occured in 6 cases (9.4%) and overt hepatic injury in 5 patients (7.8%) after PTU administration. However, all the patients who developed overt hepatic injury did not stop PTU. Hepatic function returned normal one month after stopping PTU. No one finally suffered from viral hepatitis and autoimmune hepatitis in patients of symptomatic and overt hepatic injury.

CONCLUSIONSPTU-induced symptomatic hepatic injury is not rare and usually develops within the first few months of PTU administration. Its clinical course is relatively benign. However, it may be difficult to predict its development, so all patients should be monitored for liver function test during the administration in early stage.

Adolescent ; Adult ; Aged ; Antithyroid Agents ; adverse effects ; therapeutic use ; Chemical and Drug Induced Liver Injury ; Female ; Follow-Up Studies ; Humans ; Hyperthyroidism ; drug therapy ; Liver ; pathology ; physiopathology ; Liver Diseases ; physiopathology ; Liver Function Tests ; Male ; Middle Aged ; Propylthiouracil ; adverse effects ; therapeutic use ; Prospective Studies

OBJECTIVETo study the location, immigration of allogenic grafted Feridex-labeled rat bone marrow stem cells (BMSCs) in chemically-induced acute injured livers and their role on repairing the injured liver function.

METHODSThe rat models of chemically-induced acute hepatic injury established with CCl4 Feridex-labeled BMSCs were injected into the injured livers. Magnetic resonance imaging (MRI) examination was conducted on rat livers, the levels of ALT, AST and Fe3+ in the serum and hepatic tissues were studied 6 h before and 6 h, 1 w and 5 w after injection.

RESULTSCellular necrosis, congestion in the hepatic sinusoid and infiltration of inflammatory cells were seen in the model livers. Above 90 percent of the cells were Feridex-labeled BMSCs positive by prussian blue staining and iron particles were found in their endochylema through electron microscopy. MRI examination at the sequence of SE-T2WI showed remarkably low signal changes 6 h after injecting Feridex-labeled BMSCs and the site with signal changes gradually expanded 1 and 5 w after injection. Comparatively, the changes of low signal images at each time point in the injured livers were more obvious than those of the controls at all time points, respectively. Simultaneously, pathological injuries in the livers were ameliorated and the levels of ALT and AST in serums declined: these changes in the Feridex-labeled BMSCs group were more obvious than those in the non-Feridex-labeled BMSCs group. Uniformly, there were no significant differences between the Feridex-labeled BMSCs group and the non-Feridex-labeled BMSCs group in view of histopathological examination and serological examination (including ALT, AST, Fe3+ levels) at all time points.

CONCLUSIONSThe liver function in the model of chemically-induced acutely-injured liver may be repaired by BMSCs implantation. Traced by MRI, BMSCs in the injured liver of rats disperse at a higher rate than in the normally fed ones.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bone Marrow Transplantation ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; Disease Models, Animal ; Hematopoietic Stem Cell Transplantation ; methods ; Liver ; pathology ; physiopathology ; surgery ; Liver Diseases ; blood ; surgery ; Liver Regeneration ; Magnetic Resonance Imaging ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transplantation, Homologous

Evidence-based medicine is advocated by WHO and adopted by developed countries for many years. In China, however, the selection of essential medicine and various medical insurance reimbursement schemes medicine is usually based on experts' experience of prescription practice which is under heavy critics resulting from the lack of related comparative efficacy and evidence-based research. The efficacy of Jian'ganle in prevention of drug-induced liver injury (DILI) caused by antituberculotics was evaluated in this study by comparison with Hugan Pian, glucuronolactone and reduced glutathione. Evidence was provided for relevant sectors such as Ministry for Human Resources and Social Security of the People's Republic of China and National Health and Family Planning Commission of the People's Republic of China to select and renew the Essential Medicine List (EML), the new rural cooperative medical scheme in China (NRCMS) list or the reimbursement list of industrial injury insurance. A total of 189 patients with initial pulmonary tuberculosis were divided into four groups who took antituberculotics combined with Jian'ganle, Hugan Pian, glucuronolactone and reduced glutathione respectively. Their liver function profile including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), total protein (TP), albumin (A) and globulin (G) were detected at admission as baseline and after treatment. The Jian'ganle group was compared with the three others by chi-square tests. In an aspect of maintaining bilirubin indexes normal, Jian'ganle was more efficacious than glucuronolactone. And Jian'ganle had a little more efficacy than reduced glutathione to maintain protein indexes normal as well. And the therapeutic regimen of antituberculotics combined with Jian'ganle was the best in treating tuberculosis and preventing DILI at the same time. The study showed that among the four hepatinicas which demonstrated similar prevention of DILI caused by antituberculotics, Jian'ganle has more advantages over the three others to some extent, which provides a reliable basis for health sectors to select and renew the EML, NRCMS List or the reimbursement list of industrial injury insurance.
Adult ; Alanine Transaminase ; metabolism ; Antitubercular Agents ; adverse effects ; therapeutic use ; Asian Continental Ancestry Group ; statistics & numerical data ; Aspartate Aminotransferases ; metabolism ; Bilirubin ; Chemical and Drug Induced Liver Injury ; etiology ; prevention & control ; China ; Evidence-Based Medicine ; statistics & numerical data ; Female ; Glucuronates ; therapeutic use ; Glutathione ; therapeutic use ; Humans ; Liver ; drug effects ; pathology ; physiopathology ; Liver Function Tests ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Treatment Outcome ; Tuberculosis, Pulmonary ; drug therapy ; ethnology