Drug-induced liver injury (DILI) is a significant threat to patient health and a major concern during drug development. Recently, multiple circulating microRNAs (miRNAs) have been reported to be potential biomarkers for DILI. To adapt and validate miRNAs for clinical use, we investigated the time-course changes in miR-122 expression levels in an acetaminophen-induced liver injury model in rats. In addition, miR-155 and miR-21 were evaluated as makers of inflammation and regeneration, respectively, to characterize liver status. Our results revealed that miR-122 is an early and sensitive biomarker of hepatocellular injury at a stage when alanine transaminase, aspartate transaminase, and total bilirubin were not detectable. However, no significant differences in the expression levels of other miRNAs (miR-155 and -21) were observed between treatment and vehicle groups. Collectively, these time-course changes in the expression levels of miRNAs may be useful as markers for clinical decision-making, in the diagnosis and treatment of DILI.
Acetaminophen/*toxicity ; Animals ; Biomarkers/*blood ; Chemical and Drug Induced Liver Injury/*blood/*diagnosis/pathology ; Gene Expression Profiling ; Gene Expression Regulation/*drug effects ; Hepatocytes/*drug effects ; Inflammation/blood/diagnosis ; Liver Regeneration ; MicroRNAs/*blood/genetics ; Predictive Value of Tests ; Rats ; Time

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

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

Nodular regenerative hyperplasia (NRH) is an uncommon liver condition characterized by diffuse transformation of the hepatic parenchyma into regenerative nodules without fibrosis. Portal vasculopathy caused by abnormal hepatic venous flow may induce hepatocyte hyperplasia, which forms regenerative nodules. Underlying diseases or certain drugs may also be the cause of NRH. This condition is often underdiagnosed as the patients remain asymptomatic until development of portal hypertension, and histopathologic confirmation by liver biopsy is the only way of making a definite diagnosis. The management mainly involves prevention and treatment of the complications of portal hypertension. The frequency of diagnosis of NRH has increased rapidly in recent years, however, only a few cases have been reported in Korea. Here, we report on a case of NRH of the liver combined with toxic hepatitis.
Alanine Transaminase/analysis ; Aspartate Aminotransferases/analysis ; Bilirubin/blood ; Chemical and Drug Induced Liver Injury/complications/*diagnosis/pathology ; Duodenal Ulcer/pathology ; Endoscopy, Digestive System ; Female ; Focal Nodular Hyperplasia/complications/*diagnosis/pathology ; Humans ; Liver/enzymology/pathology ; Magnetic Resonance Imaging ; Middle Aged ; Tomography, X-Ray Computed