Diagnostic Performance of Insulin Resistance Indices for Identifying Metabolic Dysfunction-Associated Fatty Liver Disease.

Background/objectives: Insulin resistance (IR) plays an important role in metabolic dysfunction-associated fatty liver disease (MAFLD) pathogenesis. A modified triglyceride-glucose (TyG) index, including TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC), has been introduced to represent IR. This study aimed to investigate the diagnostic abilities of IR indices in MAFLD, in which fatty liver was diagnosed using computed tomography (CT). Subjects/methods: We retrospectively analyzed the clinical data and images of 852 adults aged ≥19 years who underwent abdominal CT. MAFLD was diagnosed based on the appearance of fatty liver on CT alongside at least one of the following three criteria: being overweight or obese, at least two metabolic risk abnormalities, and/or diabetes mellitus. IR indices were calculated by examining the following variables: homeostasis model assessment-IR, TyG index, TyG-BMI, TyG-WC, and visceral adiposity index. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve. Results: For all patients, the area under the curve (AUC) of the TyG index, TyG-BMI, and TyG-WC were 0.834, 0.938, and 0.942, respectively. In men, the AUC of the TyG index, TyG-BMI, and TyG-WC were 0.812, 0.928, and 0.934, respectively. In women, the AUC of the TyG index was 0.841, and TyG-BMI and TyG-WC were 0.940 and 0.953, respectively. The AUC values tended to increase in the following order: TyG index < TyG-BMI < TyG-WC. Women showed a higher AUC than men in all items, and the TyG-WC of women showed the highest value with AUC 0.953 (95% confidence interval [CI]: 0.892-1.000, P < 0.0001). The AUC of the TyG index was 0.858 (95% CI: 0.828-0.888, P < 0.0001). Conclusions: In conclusion, TyG-WC is a powerful surrogate marker for identifying MAFLD in clinical settings.

Metabolic dysfunction associated fatty liver disease (MAFLD) and serum vitamin D concentration in South Korea.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has recently been renamed as metabolic dysfunction-associated fatty liver disease (MAFLD) by the Asian Pacific Association for the Study of the Liver (APASL) to reflect metabolic dysfunction. Vitamin D regulates free fatty acid flux from the periphery to the liver. The association MAFLD and vitamin D has been controversial. We investigated the association of MAFLD, nutrient intake, and vitamin D status in South Korean adults. METHODS AND STUDY DESIGN: We analyzed patient responses from the Korea National Health and Nutrition Examination survey (KNHANES) 2010-2011. The disease group was selected as per the latest guidelines. Steatosis was evaluated by the fatty liver index (FLI). Frequency analysis was performed on general characteristics. We compared differences in nutritional status using complex sample adjusted chi-square tests and generalized linear models. After adjusting for age, complex sample logistic regression analysis was used to examine the relationship between MAFLD and vitamin D. RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), LDL, triglyceride, creatinine, glucose, nutrient intake, and serum 25(OH)D concentrations were significantly elevated while HDL was reduced in the disease group than in the control group. The OR for 25(OH)D was 1.015 (95% CI: 1.004-1.026, p<0.0001). However, MAFLD presented no significant association with vitamin D concentration (OR 1.010, 95% CI: 0.985-1.037, p=0.431) after adjusting for age. CONCLUSIONS: We found no significant relationship between MAFLD and serum vitamin D concentration in South Korean adults.

Synergistic anticancer effect of docosahexaenoic acid and isoliquiritigenin on human colorectal cancer cells through ROS-mediated regulation of the JNK and cytochrome c release.

A large body of research has demonstrated a synergistic anticancer effect between docosahexaenoic acid (DHA) and standard chemotherapy regimens against colorectal cancer (CRC). In this study, we investigated the chemotherapeutic potential of cotreatment with DHA and isoliquiritigenin (ISL) against CRC HCT-116 cells. Apoptosis was confirmed by Annexin V/PI staining and expression of apoptosis-associated proteins. The synergistic effect of DHA and ISL combination on apoptosis was detected using combination index approaches. Flow cytometry was carried out using fluorescent probes to measure the production of reactive oxygen species (ROS). DHA and ISL in combination synergistically enhanced the decrease in cell viability versus the compounds used alone. Moreover, we demonstrated that the synergistic anti-CRC activity of cotreatment with these two compounds was achieved by inducing the apoptosis caspase-dependently mediated through augmented ROS generation followed by increased Fas ligand mRNA expression and cytochrome c release. Our data also demonstrated that cotreating with DHA and ISL strongly upregulated the phosphorylation of ERK and JNK, which are functionally associated with ROS induced by the two compounds in combination. Interestingly, further study revealed that inhibiting ERK phosphorylation strongly enhanced Fas ligand mRNA expression and the combination of the two compounds induced stronger cytotoxicity, whereas inhibiting JNK phosphorylation significantly reduced the apoptotic signals mediated by cotreatment with these two compounds. Excessive ROS-induced JNK activation and cytochrome c release from mitochondria played a key role in the synergistic anticancer activity of CRC cells by cotreating with DHA and ISL.

Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis.

Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.

The Correlation between the Triglyceride to High Density Lipoprotein Cholesterol Ratio and Computed Tomography-Measured Visceral Fat and Cardiovascular Disease Risk Factors in Local Adult Male Subjects.

BACKGROUND: We studied the association between the triglyceride to high-density lipoprotein cholesterol ratio and computed tomography-measured visceral fat as well as cardiovascular risk factors among Korean male adults. METHODS: We measured triglycerides, high density lipoprotein cholesterol, body mass, waist circumference, fasting plasma glucose, hemoglobin A1c, systolic blood pressure, diastolic blood pressure, visceral fat, and subcutaneous fat among 372 Korean men. The visceral fat and subcutaneous fat areas were measured by computed tomography using a single computed tomography slice at the L4-5 lumbar level. We analyzed the association between the triglyceride to high density lipoprotein cholesterol ratio and visceral fat as well as cardiovascular risk factors. RESULTS: A positive correlation was found between the triglyceride to high density lipoprotein cholesterol ratio and variables such as body mass index, waist circumference, fasting plasma glucose, hemoglobin A1c, visceral fat, and the visceral-subcutaneous fat ratio. However, there was no significant correlation between the triglyceride to high density lipoprotein cholesterol ratio and subcutaneous fat or blood pressure. Multiple logistic regression analyses revealed significant associations between a triglyceride to high density lipoprotein cholesterol ratio ≥3 and diabetes, a body mass index ≥25 kg/m(2), a waist circumference ≥90 cm, and a visceral fat area ≥100 cm(2). The triglyceride to high density lipoprotein cholesterol ratio was not significantly associated with hypertension. CONCLUSION: There were significant associations between the triglyceride to high density lipoprotein cholesterol ratio and body mass, waist circumference, diabetes, and visceral fat among a clinical sample of Korean men. In the clinical setting, the triglyceride to high density lipoprotein cholesterol ratio may be a simple and useful indicator for visceral obesity and cardiovascular disease.

The usefulness of soluble transferrin receptor in the diagnosis and treatment of iron deficiency anemia in children.

PURPOSE: Soluble transferrin receptor (sTfR) is a truncated extracellular form of the membrane transferrin receptor produced by proteolysis. Concentrations of serum sTfR are related to iron status and erythropoiesis in the body. We investigated whether serum sTfR levels can aid in diagnosis and treatment of iron deficiency anemia (IDA) in children. METHODS: Ninety-eight patients with IDA were enrolled and were classified according to age at diagnosis. Group 1 comprised 78 children, aged 6-59 months, and group 2 comprised 20 adolescents, aged 12-16 years. RESULTS: In group 1, patients' serum sTfR levels correlated negatively with mean corpuscular volume; hemoglobin (Hb), ferritin, and serum iron levels; and transferrin saturation and positively with total iron binding capacity (TIBC) and red cell distribution width. In group 2, patients' serum sTfR levels did not correlate with ferritin levels and TIBC, but had a significant relationship with other iron indices. Hb and serum sTfR levels had a significant inverse relationship in both groups; however, in group 1, there was no correlation between Hb and serum ferritin levels. In 30 patients of group 1, serum sTfR levels were significantly decreased with an increase in Hb levels after iron supplementation for 1 month. CONCLUSION: Serum sTfR levels significantly correlated with other diagnostic iron parameters of IDA and inversely correlated with an increase in Hb levels following iron supplementation. Therefore, serum sTfR levels can be a useful marker for the diagnosis and treatment of IDA in children.

EED gene polymorphism in patients with colorectal cancer.

BACKGROUND: Our previous work indicated that, first, the embryonic ectoderm development (EED) gene is a candidate gene associated with the pathogenesis of ulcerative colitis (UC) and, second, that the haplotypes of the EED polymorphism are one of the markers for UC susceptibility. The risk of developing colorectal cancer (CRC) increases in patients with inflammatory bowel disease. 
 AIM: The present study aimed at determining the association between polymorphisms in the EED gene and CRC. 
 METHODS: Genotype analysis of EED single nucleotide polymorphisms (SNPs) was performed with high-resolution melting analysis, and the genotype and allele frequencies of the EED SNPs were compared between CRC patients and healthy controls. The haplotype frequencies of EED for multiple loci were estimated using the expectation maximization (EM) algorithm. 
 RESULTS: Our study had a power of 76.6% at a 0.05 significance level. Genotype and allele frequencies of the SNPs and haplotype frequencies of the EED gene in CRC patients were not significantly different from those in healthy controls. Only the allele frequency of g.-1850G>C in the rectal cancer (RC) patient group was significantly different from that of the control group (p=0.04). Similarly, the genotype and allelic frequencies of the EED SNPs for either tumor site (left or right) or tumor stage were not significantly different from those in healthy controls. However, our data show an association between the g.-993G>C polymorphism in the EED gene and the presence of lymph node metastasis in CRC.
 CONCLUSIONS: These results suggest that the SNPs of the EED gene might not be associated with susceptibility to CRC. However, this study shows that the allele frequency of g.-1850G>C in the RC patient group was significantly different from that in the control group (p=0.04) and that g.-993G>C may play a role in the lymph node metastatic process of CRC.

Improved chronic fatigue symptoms after removal of mercury in patient with increased mercury concentration in hair toxic mineral assay: a case.

Clinical manifestations of chronic exposure to organic mercury usually have a gradual onset. As the primary target is the nervous system, chronic mercury exposure can cause symptoms such as fatigue, weakness, headache, and poor recall and concentration. In severe cases chronic exposure leads to intellectual deterioration and neurologic abnormality. Recent outbreaks of bovine spongiform encephalopathy and pathogenic avian influenza have increased fish consumption in Korea. Methyl-mercury, a type of organic mercury, is present in higher than normal ranges in the general Korean population. When we examine a patient with chronic fatigue, we assess his/her methyl-mercury concentrations in the body if environmental exposure such as excessive fish consumption is suspected. In the current case, we learned the patient had consumed many slices of raw tuna and was initially diagnosed with chronic fatigue syndrome. Therefore, we suspected that he was exposured to methyl-mercury and that the mercury concentration in his hair would be below the poisoning level identified by World Health Organization but above the normal range according to hair toxic mineral assay. Our patient's toxic chronic fatigue symptoms improved after he was given mercury removal therapy, indicating that he was correctly diagnosed with chronic exposure to organic mercury.

Evaluation of direct immunofluorescence test with PCR for detection of novel influenza A (H1N1) virus during 2009 pandemic.

During the 2009 novel influenza (H1N1) pandemic, the sensitivity of direct immunofluorescence assay (DFA) for H1N1 infection was 62% (266/429) of that of the polymerase chain reaction (PCR) test. The sensitivity of the DFA differed significantly with the age of patients: the sensitivity was the highest (71.8%) for patients aged <10 years and the lowest for patients aged ≥30 years. The sensitivity of DFA in patients aged ≥30 years was 40.7%. Furthermore, the sensitivity (67.3%, 171/254) of DFA was higher for patients who had a high temperature at admission. An increase in the incidence of H1N1 infection did not influence the sensitivity of DFA (62.1% vs. 62%; p=0.984) test, but resulted in a decrease in the negative predictive value, from 92.4% (700/757) to 69.6% (247/355). PCR may be useful as the initial test for diagnosing H1N1 infection in patients aged ≥30 years with a normal temperature at presentation.

Association of serum alanine aminotransferase and γ-glutamyltransferase levels within the reference range with metabolic syndrome and nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) has recently been found to be a novel component of metabolic syndrome (MS), which is one of the leading causes of chronic liver disease. The serum alanine aminotransferase (ALT) and ⟨-glutamyltransferase (GGT) levels are suggested to affect liver fat accumulation and insulin resistance. We assessed the associations of serum ALT and GGT concentrations within the reference ranges with MS and NAFLD. METHODS: In total, 1,069 subjects enrolled at the health promotion center of Wonkwang University Hospital were divided into 4 groups according to serum ALT and GGT concentrations levels within the reference ranges. We performed biochemical tests, including liver function tests and lipid profiles, and diagnosed fatty liver by ultrasonography. Associations of ALT and GGT concentrationgrading within the reference range with fatty liver and/or MS were investigated. RESULTS: The presence of MS, its components, and the number of metabolic abnormalities [except for high-density lipoprotein-cholesterol (HDL-C) and fasting blood glucose] increased with the ALT level, while the presence of MS, its components, and the number of metabolic abnormalities (except for HDL-C) increased with the GGT level. The odds ratios for fatty liver and MS increased with the ALT level (P⟨0.001 and P=0.049, respectively) and the GGT level (P=0.044 and P=0.039, respectively). CONCLUSIONS: Serum ALT and GGT concentrations within the reference ranges correlated with the incidence of NAFLD and MS in a dose-dependent manner. There associations need to be confirmed in large, prospective studies.

Activation of lipopolysaccharide-TLR4 signaling accelerates the ototoxic potential of cisplatin in mice.

Dysfunction in immune surveillance during anticancer chemotherapy of patients often causes weakness of the host defense system and a subsequent increase in microbial infections. However, the deterioration of organ-specific function related to microbial challenges in cisplatin-treated patients has not yet been elucidated. In this study, we investigated cisplatin-induced TLR4 expression and its binding to LPS in mouse cochlear tissues and the effect of this interaction on hearing function. Cisplatin increased the transcriptional and translational expression of TLR4 in the cochlear tissues, organ of Corti explants, and HEI-OC1 cells. Furthermore, cisplatin increased the interaction between TLR4 and its microbial ligand LPS, thereby upregulating the production of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, via NF-κB activation. In C57BL/6 mice, the combined injection of cisplatin and LPS caused severe hearing impairment compared with that in the control, cisplatin-alone, or LPS-alone groups, whereas this hearing dysfunction was completely suppressed in both TLR4 mutant and knockout mice. These results suggest that hearing function can be easily damaged by increased TLR expression and microbial infections due to the weakened host defense systems of cancer patients receiving therapy comprising three to six cycles of cisplatin alone or cisplatin combined with other chemotherapeutic agents. Moreover, such damage can occur even though patients may not experience ototoxic levels of cumulative cisplatin concentration.

Nucleotide changes related to hepatocellular carcinoma in the enhancer 1/x-promoter of hepatitis B virus subgenotype C2 in cirrhotic patients.

Hepatocellular carcinoma (HCC) is widely known to develop more frequently in cirrhotic patients with a high expression of Hepatitis B virus X protein (HBx), which is controlled by the enhancer 1 (Enh1)/X-promoter. To examine the effect of the mutations in the Enh1/X-promoter region in hepatitis B virus (HBV) genomes on the development of HCC, we investigated the differences in HBV isolated from cirrhotic patients with or without HCC along with the promoter activities of certain specific mutations within the Enh1/X-promoter. We examined 160 hepatitis B surface antigen (HBsAg)-positive cirrhotic patients (80 HCC patients, 80 non-HCC patients) by evaluating the biochemical, virological, and molecular characteristics. We evaluated the functional differences in certain specific mutations within the Enh1/X-promoter. The isolated sequences included all of the subgenotypes C2. The sites that showed higher mutation rates in the HCC group were G1053A and G1229A, which were found to be independent risk factors through multiple logistic analysis (P < 0.05). Their promoter activities were elevated 2.38- and 4.68-fold, respectively, over that of the wild type in the HepG2 cells. Similarly, both the mRNA and protein levels of HBx in these two mutants were much higher than that in wild type-transfected HepG2 cells. Mutated nucleotides of the Enh1/X-promoter, especially G1053A and G1229A mutations in the HBV subgenotype C2 of patients with cirrhosis, can be risk factors for hepatocarcinogenesis, and this might be due to an increase in the HBx levels through the transactivation of the Enh1/X-promoter.

Korean travelers' knowledge, attitudes, and practices regarding the prevention of malaria: measures taken by travelers departing for India from Incheon International Airport.

BACKGROUND: Although many Koreans travel each year to countries where malaria is present, few data are available on the knowledge, attitudes, and practices of Koreans with regards to malaria. METHODS: The study was conducted in the departure lounge of Incheon International Airport in May 2006. A 22-item questionnaire was administered to Korean travelers whose travel destination was India. RESULTS: Of 188 respondents, 24% had sought pretravel health information. Independent predictors for seeking pretravel health information were the following: being a Korean woman, longer duration of travel, planning to travel independently or to a rural area, and perceived risk of malaria. A total of 47% of travelers answered that they had not perceived any risk of malaria, and only 7% of travelers carried malaria prophylaxis. CONCLUSIONS: There is an urgent need for increased awareness about travel-related infectious diseases (especially malaria) among Korean travelers, and they should be encouraged to seek pretravel health information.