As a liver disease with the most complex clinical phenotype, drug-induced liver injury (DILI) poses great challenges in diagnosis and management in clinical practice. Although guidelines based on the latest research advances can provide clinicians with guidance on the identification, diagnosis, and management of DILI, the overall level of evidence in this field is relatively low and high-level evidence is limited. Therefore, we should interpret guidelines with caution and look forward to more clinical and translational research to address the huge unmet clinical needs in DILI.
Humans ; Translational Research, Biomedical ; Chemical and Drug Induced Liver Injury/therapy* ; Liver Diseases ; Liver Function Tests

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.
Aspartate Aminotransferases ; Biomarkers ; Child ; Elasticity Imaging Techniques ; Humans ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Liver Function Tests ; Non-alcoholic Fatty Liver Disease/pathology* ; ROC Curve ; Retrospective Studies

BACKGROUND: Biliary atresia is an extrahepatic progressive obliterate cholangiopathy that occurs in infants. Kasai procedure, a surgical method that can help re-establish bile flow from the liver into the intestine, is its first line treatment. Since infants with biliary atresia already have advanced hepatic dysfunction, all kinds of schemes should be considered to minimize further liver damage during surgery. The objective of this study was to compare the postoperative hepatic functions between the two commonly used inhalational anesthetics in infants undergoing the Kasai procedure (i.e., desflurane and sevoflurane). METHODS: This prospective, randomized, double-blind, single-center, and parallel group study included 40 children undergoing Kasai procedure. They were randomly allocated to Group S (sevoflurane) or Group D (desflurane). All the patients were anesthetized with designated anesthetic agent with the end-tidal concentration of about 0.8–1 minimum alveolar concentration. Postoperative hepatic functions were assessed by aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, prothrombin time, and total bilirubin. RESULTS: A total of 38 patients were selected for the study. In both groups, AST, ALT were increased in magnitude to the peak on postoperative day 0 and decreased to preoperative value at postoperative day 3. There were no significant differences between the groups in any laboratory results related to liver function. CONCLUSIONS: Sevoflurane and desflurane, inhalation anesthetics for maintaining anesthesia used in infants undergoing the Kasai procedure, did not show any difference in preserving postoperative hepatic function.
Alanine Transaminase ; Anesthesia ; Anesthetics ; Anesthetics, Inhalation ; Aspartate Aminotransferases ; Bile ; Biliary Atresia ; Bilirubin ; Child ; Humans ; Infant ; Intestines ; Liver ; Liver Function Tests ; Methods ; Portoenterostomy, Hepatic ; Prospective Studies ; Prothrombin Time

PURPOSE: Screening nonalcoholic fatty liver disease (NAFLD) by body mass index (BMI) as a single surrogate measure for obesity has limitations. We suggest considering body composition zones by drawing a body composition chart composed of body composition indices, including BMI and percent body fat (PBF), to visualize the risk of NAFLD in obese children and adolescents.METHODS: Thirty-eight boys diagnosed with NAFLD were selected retrospectively from patients who visited Konkuk University Medical Center from 2006 to 2015. They had gone through body composition analysis by bioelectrical impedance analysis (BIA), and biochemical analyses, including a liver function test (LFT) and lipid panel, were performed. Fat-free mass index (FFMI) and fat mass index (FMI) were calculated from body composition analysis and height. We plotted FFMI and FMI of patients on a body composition chart and classified the patients into zones A to D. In addition, we analyzed the correlations between LFT, lipid panel, and body composition indices.RESULTS: Thirty-three of 38 boys (86.8%) were located in zone C, corresponding to high BMI and PBF. Four boys (10.5%) were located in zone D, which correlates with sarcopenic obesity. One boy located in zone B was a muscular adolescent. Alanine aminotransferase level was positively correlated with PBF, FMI, and BMI z-score.CONCLUSION: Body composition zones on a body composition chart might be useful in risk assessment in obesity-related diseases such as NAFLD. Zones on a body composition chart could have practical applications, especially in sarcopenic obese children and adolescents.
Academic Medical Centers ; Adipose Tissue ; Adolescent ; Alanine Transaminase ; Body Composition ; Body Mass Index ; Child ; Electric Impedance ; Humans ; Liver Function Tests ; Male ; Mass Screening ; Non-alcoholic Fatty Liver Disease ; Obesity ; Retrospective Studies ; Risk Assessment

BACKGROUND/AIMS: Hepatitis B virus reactivation (HBVr) following chemotherapy (CMT) is well-known among hematologic malignancies, and screening recommendations are established. However, HBVr data in solid organ malignancy (SOM) patients are limited. This study aims to determine hepatitis B surface antigen (HBsAg) screening rates, HBV prevalence, and the rate of significant hepatitis caused by HBVr in SOM patients undergoing CMT.METHODS: Based on the Oncology unit’s registration database from 2009–2013, we retrospectively reviewed records of all SOM patients ≥18 years undergoing CMT at Songklanagarind Hospital who were followed until death or ≥6 months after CMT sessions. Exclusion criteria included patients without baseline liver function tests (LFTs) and who underwent CMT before the study period. We obtained and analyzed baseline clinical characteristics, HBsAg screening, and LFT data during follow-up.RESULTS: Of 3,231 cases in the database, 810 were eligible. The overall HBsAg screening rate in the 5-year period was 27.7%. Screening rates were low from 2009–2012 (7.8–21%) and increased in 2013 to 82.9%. The prevalence of HBV among screened patients was 7.1%. Of those, 75% underwent prophylactic antiviral therapy. During the 6-month follow-up period, there were three cases of significant hepatitis caused by HBVr (4.2% of all significant hepatitis cases); all were in the unscreened group.CONCLUSIONS: The prevalence of HBV in SOM patients undergoing CMT in our study was similar to the estimated prevalence in general Thai population, but the screening rate was quite low. Cases of HBVr causing significant hepatitis occurred in the unscreened group; therefore, HBV screening and treatment in SOM patients should be considered in HBV-endemic areas.
Asian Continental Ancestry Group ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Follow-Up Studies ; Hematologic Neoplasms ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis ; Humans ; Liver Function Tests ; Mass Screening ; Prevalence ; Retrospective Studies ; Thailand ; Virus Activation

To explore the feasibility and clinical value of CT-based arterial enhancement fraction (AEF) for evaluating liver function in liver cirrhosis patients.
 Methods: Fifty-two patients with liver cirrhosis (Child-Pugh A, B, and C group included 13, 20, and 19 patients, respectively) and 17 patients without liver diseases as control were prospectively enrolled, respectively. All individuals underwent three-phase hepatic CT, and the color mapping of AEF were obtained in CT kinetics software, as well as the corresponding parameters, i.e., hepatic AEF (HAEF) and the ratio of HAEF to spleen AEF (H/S). The AEF parameters were compared among different groups, and the area under the receiver operating characteristic curve (AUROC) was calculated. The Spearman correlation analysis was performed between the AEF parameters and model for end-stage liver disease (MELD) score in liver cirrhosis patients.
 Results: The interobserver agreement of HAEF and H/S were perfect, and the intraclass correlation coefficient (ICC) were 0.918 (95% CI 0.871 to 0.949), 0.946 (95% CI 0.915 to 0.966), respectively. The HAEF and H/S among those groups were significant different (both P<0.001), and they elevated with the increase of Child-Pugh classification in liver cirrhosis patients (all P<0.05, except the H/S between Child-Pugh A and B). In all patients with liver cirrhosis, the AUROC of HAEF and H/S were 0.933 and 0.821 for Child-Pugh A, and were 0.925 and 0.915 for Child-Pugh C, respectively. The HAEF and H/S of patients with liver cirrhosis were significantly correlated with the MELD score (HAEF: r=0.752, P<0.001; H/S: r=0.676, P<0.001).
 Conclusion: CT-based AEF parameters including HAEF and H/S are closely associated with the severity and prognosis of patients with liver cirrhosis, which have the potential to estimate the liver function in liver cirrhosis patients quantitatively and effectively.
Humans ; Liver Cirrhosis ; diagnostic imaging ; Liver Function Tests ; Tomography, X-Ray Computed

Physicians of all specialties are required to assess abnormal results of liver function tests. Many patients with abnormal results in liver function tests do not have primary liver disease; most of the frequently requested tests are influenced by myriad non-hepatic factors. The most common tests are those for serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and bilirubin. Hepatocellular injury is indicated by abnormally elevated AST and ALT levels compared to the ALP level. Cholestatic injury is indicated by an abnormally elevated ALP level compared to AST and ALT levels. The majority of bilirubin circulates as unconjugated bilirubin, and an elevated conjugated bilirubin level is a marker of hepatocellular or cholestatic injury. Obtaining a detailed medical history, a clinical examination, and optimal interpretation of abnormal results of liver tests can enable the determination of the cause of liver diseases, facilitating their diagnosis and therapy.
Alanine Transaminase ; Alkaline Phosphatase ; Aspartate Aminotransferases ; Bilirubin ; Diagnosis ; Diagnosis, Differential ; Hepatitis ; Humans ; Liver Diseases ; Liver Function Tests ; Liver

Hepatic duct diverticulum is a rare form of choledochal cyst that does not fit into the most widely used Todani classification system. Because of its rarity, it may be difficult for clinicians to diagnose and treat it. Here, we present a case of left hepatic diverticulum in a 57-year-old woman with epigastric pain. At presentation, there were mild elevations in the liver function tests. Computed tomography and magnetic resonance cholangiopancreatography showed diverticulum-like cystic lesion with sludge ball near the confluence portion of both intrahepatic bile duct, but the origin of the lesion could not be identified. The clinical impression was type II choledochal cyst. Surgical excision was planned due to recurrent abdominal pain. The operative findings revealed diverticulum arising from left hepatic duct. Histopathology confirmed the lesion to be diverticulum lined by biliary epithelium. The patient had no postoperative complication and no further symptoms since the operation.
Abdominal Pain ; Bile Ducts ; Bile Ducts, Intrahepatic ; Cholangiopancreatography, Magnetic Resonance ; Choledochal Cyst ; Classification ; Diverticulum ; Epithelium ; Female ; Hepatic Duct, Common ; Humans ; Liver Function Tests ; Middle Aged ; Postoperative Complications ; Sewage

Benign recurrent intrahepatic cholestasis (BRIC), a rare cause of cholestasis, is characterized by recurrent episodes of cholestasis without permanent liver damage. BRIC type 2 (BRIC2) is an autosomal recessive disorder caused by ABCB11 mutations. A 6-year-old girl had recurrent episodes of jaundice. At two months of age, jaundice and hepatosplenomegaly developed. Liver function tests showed cholestatic hepatitis. A liver biopsy revealed diffuse giant cell transformation, bile duct paucity, intracytoplasmic cholestasis, and periportal fibrosis. An ABCB11 gene study revealed novel compound heterozygous mutations, including c.2075+3A>G in IVS17 and p.R1221K. Liver function test results were normal at 12 months of age. At six years of age, steatorrhea, jaundice, and pruritus developed. Liver function tests improved following administration of phenylbutyrate and rifampicin. Her younger brother developed jaundice at two months of age and his genetic tests revealed the same mutations as his sister. This is the first report of BRIC2 confirmed by ABCB11 mutations in Korean siblings.
Bile Ducts ; Biopsy ; Child ; Cholestasis ; Cholestasis, Intrahepatic ; Female ; Fibrosis ; Giant Cells ; Hepatitis ; Humans ; Jaundice ; Liver ; Liver Function Tests ; Pruritus ; Rifampin ; Siblings ; Steatorrhea

BACKGROUND: Insulin therapy is the treatment of choice in type 2 diabetes mellitus (T2DM) patients who are not achieving glycemic goals despite triple oral hypoglycemic agent (OHA) combination therapy. However, there is still no additional treatment option for patients who cannot afford insulin therapy or who have various clinical limitations. The purpose of this study was to evaluate the clinical efficacy and safety of four OHA combination therapy in poorly controlled T2DM patients who could not afford insulin therapy. METHODS: Forty-seven T2DM patients were enrolled according to the following criteria: 1) glycosylated hemoglobin [HbA1c] > 8.5%, 2) ongoing treatment with 3 OHA combination therapy (metformin, sulfonylurea, dipeptidyl peptidase-4 inhibitor), or 3) combined limitations for applying insulin therapy. Patients were given the fourth OHA (pioglitazone) in addition to their previous treatment for 12 months. We evaluated changes in HbA1c, body weight, hypoglycemic events, and side effects. RESULTS: At study completion, mean HbA1c and fasting plasma glucose were significantly reduced from 9.6% to 8.04% and from 198.4 mg/dL to 161.5 mg/dL, respectively (P < 0.001). Mean body weight was significantly increased from 66.7 kg to 69.3 kg. Hypoglycemia and side effects were observed 18 times and only 3 cases showed abnormal liver function tests or edema. In addition, subjects with higher initial HbA1c levels and HOMA-beta showed an independent association with a greater reduction in HbA1c. CONCLUSION: The 4 OHA combination therapy is effective and safe when insulin is not feasible.
Blood Glucose ; Body Weight ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Drug Therapy ; Edema ; Fasting ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Insulin ; Liver Function Tests ; Treatment Outcome