Abnormal Liver Function Group Research Articles

Associations between one-carbon metabolism and valproic acid-induced liver dysfunction in epileptic patients.

Valproic acid (VPA) has been widely used as an antiepileptic drug for decades. Although VPA is effective and well-tolerated, long-term VPA treatment is usually associated with hepatotoxicity. However, the underlying mechanisms of VPA-caused hepatotoxicity remain unclear. In this study, a total of 157 pediatric patients with epilepsy were recruited and divided into normal liver function (NLF, 112 subjects) group and abnormal liver function (ABLF, 45 subjects) group. We observed that MTHFR A1298C and MTHFR C677T variants may be linked to VPA-induced liver dysfunction (p = 0.001; p = 0.023, respectively). We also found that the MTHFR A1298C polymorphism was associated with a higher serum Hcy level (p = 0.001) and a lower FA level (p = 0.001). Moreover, the serum Hcy levels was strongly correlated with the GSH and TBARS concentrations (r = -0.6065, P < 0.001; r = 0.6564, P < 0.001, respectively). Furthermore, logistic analysis indicated that MTHFR A1298C/C677T polymorphisms and increased Hcy concentrations may be risk factors for VPA-induced liver dysfunction. These results suggested that individual susceptibility to VPA-induced liver dysfunction may result from MTHFR A1298C/C677T polymorphisms and increased Hcy levels. This study may be helpful for the prevention and guidance of VPA-induced liver dysfunction.

Predictive Value of Inflammatory Cytokines in Early Pregnancy for Liver Dysfunction in Pregnant Women with Hepatitis B.

The purpose of this study is to explore the predictive value of cytokine levels in the first trimester of pregnancy on abnormal liver function of pregnant women with hepatitis B in the third trimester of pregnancy. A total of 111 pregnant women with HBV infection at 12 weeks gestation participated in the study. The levels of IL-6, IL-8, TNF-α in peripheral blood of the patients and liver function indexes were detected. Subsequently, the pregnant women were followed up, and the liver function was detected at 36 weeks of gestation. According to liver function indexes, patients were divided into normal liver function group and abnormal liver function group to determine the correlation between cytokines in early pregnancy and abnormal liver function in late pregnancy. Kaplan-Meier survival curve and multivariate Cox analysis were used to evaluate the predictive value of cytokines for liver dysfunction. At 12 weeks of gestation, cytokine levels in the normal liver function group were significantly lower than that in the abnormal liver function group. Kaplan-Meier survival analysis showed that the increased IL-6 level was associated with abnormal liver function in late pregnancy. Multivariate Cox regression analysis revealed that IL-6 level was an independent predictor of abnormal liver function in patients with normal liver function in the late pregnancy. The high expression level of cytokine IL-6 at 12 weeks of pregnancy has noteworthy predictive significance for the abnormal liver function of hepatitis B pregnant women in third trimester of pregnancy.

Characteristics of liver function changes in 111 elderly patients with COVID-19 pneumonia

Objective: To retrospectively analyze the characteristics and influencing factors of liver function changes in 111 elderly patients with COVID-19 pneumonia. Methods: 111 elderly patients with COVID-19 admitted to the Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 5 to March 3, 2020 were enrolled. According to the severity of disease and liver function condition, they were divided into severe group (n=40), normal group (n=71), abnormal liver function group (n=86) and normal liver function group (n=25). The indexes related to liver function changes [total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT)] and related influencing factors were analyzed. Results: Among 111 cases, 86 (77.5%) had abnormal liver function of varying degrees, and 28 (25.2%) had liver injury. The abnormal rates of TBil, AST, ALP and GGT were significantly higher in the severe group than normal group (P<0.05). There were no significant differences in age, ribavirin, glucocorticoid and the application of lopinavir-ritonavir tablets between the abnormal liver function and the normal group (P>0.05). The proportion of male was significantly higher in the abnormal liver function than normal liver function group (P<0.05). Conclusion: Elderly COVID-19 patients have a higher proportion of abnormal liver function, and patients in the severe group are more likely to have higher level of TB, AST, ALP and GGT. The abnormal liver function may be related to the direct viral infection of the liver and the inflammatory immune response of the body after infection in elderly patients.

이상 간기능 남성 집단의 유산소운동에서 밀크씨슬의 복용여부가 AST 및 ALT개선에 미치는 효과

This study proposes effective treatment means for liver health and disease prevention of the abnormal liver function group by verifying the liver function improvement effect of taking milk thistle as a health functional supplement and exercise therapy for the group with impaired liver function.<BR>To achieve the purpose of the study, 16 adult males with AST or ALT exceeding 40 IU/L were recruited. It was carried out for 10 weeks, divided into 8 people in the non-intake group who performed only aerobic exercise but did not take milk thistle and 8 people in the group that took both aerobic exercise and milk thistle.<BR>As a result of the study, both AST and ALT decreased in the non-intake group, but there was no significant difference by measurement period (p＞.05), and the ingestion group decreased, showing a significant difference (p＜.05), and there was a significant difference between the two groups. In both AST/ALT, it was found that there was a significant effect difference in Time (p＜.001) and Time<SUP>*</SUP>Group (p＜.01). Therefore, when applying aerobic exercise as an exercise therapy for improving liver function in the abnormal liver function group, it is judged that it is recommended to adjust the treatment according to the severity of the AST and ALT test values, because the intake of Mike Thistle is more effective.

The Liver Injury and Coagulation Dysfunction in the Patients with Severe/Critical COVID-19

The clinical data of 53 COVID-19 patients were collected from a single center in Wuhan from February 8, 2020 to March 25, 2020. The patients were divided into severe type group (38 patients) and critical type group (15 patients). The clinical characteristics, indexes of liver function, coagulation function and inflammatory markers were analyzed retrospectively. According to the degree of abnormal liver function in the process of diagnosis and treatment, the patients were divided into three groups: combined liver injury, mild abnormal liver function and normal liver function group. Statistical analysis was performed by using Student t test, Mann-Whitney U test, Kruskal-Wallis test and Chi-square test. Among the 53 patients, 29 were male (54.7%) and 24 were female (45.3%), the median age was 57(27－80) years old. The time from onset to admission was (11.5±7.7) days. The levels of AST, TBIL, DBIL, ALP, GGT, LDH, D-dimer, PCT and hsCRP in critical patients were higher than those in severe patients (P<0.05). The levels of Alb in critical patients was lower than those in severe patients (P<0.05). Among the 53 patients, 34 (64%) patients showed abnormal elevation of ALT, AST or TBIL, while 4 (7.5%) patients showed the criteria of COVID-19 with liver injury. After the patients were grouping according to the degree of liver dysfunction, the levels of ALP, GGT and D-dimer of the patients in the liver injury group were significantly higher than those in the normal liver function group, D-dimer levels of the patients in the liver injury group was significantly higher than those in the mild abnormal liver function group, while the levels of ALP and GGT in the mild abnormal liver function group were significantly higher than those in the normal liver function group, and the differences were statistically significant(P<0.05). In this group, the patients with COVID-19 severe/critical type have a certain proportion of liver injury accompanied by significantly increased D-dimer levels, critical type patients have more severe liver function and coagulation dysfunction, which may promote the progression of COVID-19.

Hemodynamic analysis of hepatic arteries for the early evaluation of hepatic fibrosis in biliary atresia

Background and objectiveHepatic fibrosis is the prominent characteristic of biliary atresia (BA), may even progress continually after Kasai procedure (KP). BA, as a devastating pediatric hepatic disease, mainly leads to newborn cholestasis, even liver cirrhosis, eventually hepatic failure. Earlier diagnosis of hepatic fibrosis, which used to be detected by liver biopsy commonly, is consistent with better outcomes of KP. Due to potential risks and uncertainty of liver biopsy, it is an urge to seek a safer and more precise evaluation method as alternative. The purpose of this study is to investigate the hemodynamics of hepatic artery (HA) in hepatic fibrosis of early BA based on computational fluid dynamics (CFD) for evaluating the value of CFD for hepatic fibrosis diagnosis. Methods40 patients were divided into three groups, including the control group, the abnormal liver function group and the mild to moderate hepatic fibrosis group. CFD was applied to quantify primary hemodynamic parameters of HA and related arteries, including blood flow distribution ratio (FDR), pressure, wall shear stress (WSS) and energy loss (EL). Statistical analyses were also performed to compare the differences amongst these above groups. ResultsWith the progression of hepatic fibrosis, the increasing tendency of hemodynamic parameters values of HA and related arteries were observed. Values of FDR, pressure, WSS and EL of the mild to moderate group was higher than those of the control group and the abnormal liver function group. There were significant differences on FDRAA, FDRHA and EL between the control group and the mild to moderate hepatic fibrosis group (t = 0.037, 0.030 and <0.001, P < 0.05). ConclusionSignificant variations of HA hemodynamics acquired by CFD between the control group and the mild to moderate hepatic fibrosis group demonstrated the relationship between the progression of hepatic fibrosis and the hemodynamic disorder, and suggested that CFD had the potential to assist the diagnosis of hepatic fibrosis in early BA.

Clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors

Objective To investigate the clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors. Methods A total of 129 patients who were diagnosed with liver injury induced by anti-tuberculosis drugs in Shenzhen Third People's Hospital from January 2017 to December 2018 were enrolled and divided into abnormal liver function group with 51 patients (39.53%) and drug-induced liver injury (DILI) group with 78 patients (60.47%), and among these 129 patients, 13 (10.08%) had liver failure. A retrospective analysis was performed for their laboratory markers as well as treatment and prognosis data. The chi-square test was used for comparison of categorical data between two groups; the independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The multivariable logistic regression model was used to investigate the risk factors for DILI and liver failure. Results There were significant differences between the DILI group and the abnormal liver function group in chronic HBV co-infection (χ2=5.616, P=0.018), asymptomatic liver injury (χ2=9.451, P=0.002), liver failure (χ2=9.453, P=0.002), need to adjust anti-tuberculosis regimen (χ2=16.787, P 8 weeks (odds ratio [OR]=3.94, 95% confidence interval [CI]: 1.02-15.25, P=0.047) and asymptomatic liver injury (OR=7.64, 95% CI: 1.63-35.86, P=0.010) were independent risk factors for DILI; chronic HBV co-infection (OR=14.42, 95% CI: 2.66-78.09, P=0.002) and time to identification of liver injury > 8 weeks (OR=11.97, 95% CI: 2.03-70.50, P=0.006) were independent risk factors for liver failure, while albumin ≥35 g/L (OR=0.07, 95% CI: 0.01-0.51, P=0.010) was a protective factor. Conclusion Anti-tuberculosis drugs may induce severe liver injury, and HBV co-infection, asymptomatic liver injury, long time to identification of liver injury, and low albumin level may increase the risk of severe liver injury. Regular follow-up, liver function monitoring, appropriate nutritional support, and HBV screening are important for reducing the risk of liver injury during anti-tuberculosis therapy.

Effect of ipragliflozin on liver function in Japanese type 2 diabetes mellitus patients: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM).

The STELLA-LONG TERM prospective post-marketing surveillance study assessed ipragliflozin in Japanese patients with type 2 diabetes mellitus (T2DM). This subgroup analysis of patients with liver impairment used the final 3-year results. Data on patients, adverse drug reactions (ADRs), and changes in glycemic parameters and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transpeptidase [γ-GTP] and alkaline phosphatase [ALP]) were collected, and the fatty liver index (FLI) was calculated. In the effectiveness analysis (n = 8,763), baseline liver function was normal in 2,605 patients (ALT <31/<21 U/L [men/women]) and abnormal in 3,277 (ALT ≥31/≥21 U/L). The abnormal liver function group had higher mean body weight and BMI than the normal liver function group (p < 0.001). In the safety analysis (n = 11,051), urinary tract infections, genital infections and hepatic disorders were more common in the abnormal than normal liver function group (2.25% vs. 1.07%; 1.78% vs. 1.14% and 1.85% vs. 1.01%). In the abnormal liver function group, there were significant (p < 0.001) decreases from baseline at 36 months in AST and ALT (from 38.8 and 53.7 U/L to 29.3 and 37.7 U/L, respectively), γ-GTP (from 75.4 to 51.7 U/L) and ALP (from 254.8 to 234.5 U/L), which were greater than in the normal liver function group. FLI reductions at 36 months were significant (p < 0.001) in subgroups with baseline FLI of ≥30 or ≥60. In conclusion, ipragliflozin improved liver function over 3 years in patients with impaired liver function, although ADRs occurred more frequently than in the normal liver function group.

Assessing Liver Function in Liver Tumors Patients: The Performance of T1 Mapping and Residual Liver Volume on Gd-EOBDTPA-Enhanced MRI.

Purpose: To assess the performance of T1 mapping and residual liver volume (RLV) on Gd-EOBDTPA-enhanced MRI in pretreatment estimation of liver function in patients with liver tumors. Indocyanine green retention rate at 15 min (ICG R-15) was used as a reference standard.Methods: Ethical approval from the institutional review board and informed consent were obtained for this prospective study. We enrolled 155 patients with liver tumors who underwent pretreatment Gd-EOB-DTPA-enhanced MRI. T1 relaxation time before (T1-pre), 20 min after (T1-post) Gd-EOB-DTPA injection and RLV were measured. The absolute reduction (ΔT1) and reduction rate (ΔT1%) of T1 relaxation time, volume-assisted ΔT1 (ΔT1*RLV) and volume-assisted ΔT1% (ΔT1%*RLV) were calculated accordingly. The correlation of MR parameters with ICG R-15 was determined using Spearman's rank correlation analysis. Patients were classified into the normal liver function (NLF) group if their ICG R-15 levels were <10% or otherwise into the abnormal liver function (ALF) group. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performances of the MR parameters in predicting ALF.Results: T1-post (r = 0.472, P < 0.001), ΔT1 (r = −0.355, P = 0.011), ΔT1% (r = −0.482, P < 0.001), RLV (r = −0.336, P < 0.001), volume-assisted ΔT1 (r = −0.458, P < 0.001) and volume-assisted ΔT1% (r = −0.522, P < 0.001) showed weak to moderate correlation with ICG R-15. The area under the ROC curves (AUROC) of volume-assisted ΔT1 in predicting ALF was 0.777, which was significantly higher than the other parameters (P < 0.05 for all).Conclusions: Combined T1 mapping and RLV on Gd-EOB-DTPA-enhanced MRI can help assess liver function with good diagnostic accuracy in patients with liver tumors before treatment.

Correlation of vitamin D with inflammatory factors, oxidative stress and T cell subsets in patients with autoimmune hepatitis.

Correlation of vitamin D with inflammatory factors, oxidative stress and T cell subsets in patients with autoimmune hepatitis were investigated. Patients with liver diseases (n=635) treated in The Sixth People's Hospital of Qingdao City from March 2015 to January 2018 were selected, among which 80 cases diagnosed with autoimmune hepatitis were included into observation group, and 80 healthy cases were included into control group. Patients with autoimmune hepatitis were further divided into normal 25-hydroxyvitamin D [25-(OH) D] group (n=40) and abnormal 25-(OH) D group (n=40) according to the level of 25-(OH) D, and divided into normal liver function group (n=40) and abnormal liver function group (n=40). 25-(OH) D, liver function, inflammatory factors, oxidative stress level and T cell subsets were compared. In the observation group, levels of 25-(OH) D, superoxide dismutase (SOD), total antioxidant capacity, and T cell subsets were lower than those in the control group (P<0.05), while levels of total bilirubin (TBIL), indirect BIL (IBIL), direct BIL (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), inflammatory factors and malondialdehyde (MDA) were higher than those in the control group (P<0.05). In the normal 25-(OH) D group, levels of inflammatory factors and oxidative stress factor were lower than those in the abnormal 25-(OH) D group (P<0.05), while the SOD level, total antioxidant capacity and T cell subset counts were higher than those in the abnormal 25-(OH) D group (P<0.05). Moreover, the 25-(OH) D level in patients with autoimmune hepatitis was negatively correlated with hs-CRP, tumor necrosis factor-α (TNF-α), ALT and MDA, but positively correlated with CD3+ and CD4+ counts, SOD and total antioxidant capacity. Patients with autoimmune hepatitis, especially those with decreased level of vitamin D, are more prone to enhanced inflammatory and stress responses, decreased levels of T cell subsets and decline in immunity.

Analysis of risk factors for susceptibility of abnormal liver function in male patients with gout

Objective To investigate the risk factors for susceptibility of abnormal liver function in patients with gout. Methods A total of 5 044 cases of male gout patients in remission were selected and divided into normal liver function group with 3 693 patients and abnormal liver function group with 1 351 patients. The clinical information was collected and relevant biochemical indices were detected. Serum uric acid(SUA) was divided into quartiles, and its associations with elevated ALT were evaluated. Results There were significant differences in the history of drinking, family history, combining with hyperlipidemia, fatty liver, and coronary heart disease between the abnormal liver function group and normal function group(P 0.05). Further logistic regression analysis indicated that body mass, waist circumference, combining fatty liver, higher SUA level, higher cholesterol and triglyceride were risk factors of the early onset of abnormal liver function. ALT and the proportion of abnormal liver function were increased with the increase of UA. After adjustment for BMI, TG, TC and fatty liver, the ALT level and the proportion of abnormal liver function decreased significantly while still showed an upward trend. Conclusion Patients with obesity, high level of uric acid, high blood lipids and fatty liver were more likely to develop abnormal liver function, SUA was independently associated with elevated ALT. Key words: Gout; Liver transaminases; Risk factors

Clinical Features of COVID-19-Related Liver Damage

BACKGROUND: A recent outbreak of SARS-CoV-2 infection occurs mainly in China, with rapidly increasing the number of cases (namely COVID-19). Abnormal liver functions are frequently present in these patients, here we aimed to clarify the clinical features of COVID-19-related liver damage to provide some references for the clinical treatment. METHODS: In this retrospective, single-center study, we included all confirmed COVID-19 cases in Shanghai Public Health Clinical Center from January 20 to January 31, 2020. The outcomes were followed up until February 19, 2020. A total of 148 cases were analyzed for clinical features, laboratory parameters (including liver function tests), medications and the length of stay. FINDINGS: Of 148 confirmed SARS-CoV-2-infected patients, 49.3% were females and 50.7% were males. The median age was 50.5 years (interquartile range, 36-64). Patients had clinical manifestations of fever (70.1%), cough (45.3%), expectoration (26.7%) at admission. 75 patients (50.7%) showed abnormal liver functions at admission. Patients (n = 75) who had elevated liver function index were more likely to have a moderate-high degree fever (44% vs 27.4%; p = 0.035) and significantly present in male patients (62.67% vs 38.36%; p = 0.005). The numbers of CD4+ and CD8+ T cells were significantly lower in abnormal liver function group than those in normal liver function group. There was no statistical difference in prehospital medications between normal and abnormal liver function groups, while the utilization rate of lopinavir/ritonavir after admission was significantly higher in patients with emerging liver injury than that in patients with normal liver functions. Importantly, the emerging abnormal liver functions after admission caused a prolonged length of stay. INTERPRETATION: SARS-CoV-2 may cause the liver function damage and the Lopinavir/ritonavir should be applied carefully for the treatment of COVID-19.

Lipidomic Profiling Reveals Disruption of Lipid Metabolism in Valproic Acid-Induced Hepatotoxicity.

Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs, as VPA-induced hepatotoxicity is one of the most severe adverse reaction that can lead to death. The objective of this study was to gain an understanding of dysregulated lipid metabolism in mechanism of hepatotoxicity. Nontargeted lipidomics analysis with liquid chromatography–quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS) was performed to explore differential lipids from the patient serum and L02 cells. Lipidomics data interpretation was augmented by gene expression analyses for the key enzymes in lipid metabolism pathways. From patient serum lipidomics, pronouncedly changed lipid species between abnormal liver function (ALF) patients and normal liver function (NLF) patients were identified. Among these lipid species, LPCs, Cers, and SMs were markedly reduced in the ALF group and showed negative relationships with liver injury severity [alanine aminotransferase (ALT) levels], while significantly increased triacylglycerols (TAG) with higher summed carbon numbers demonstrated a positive relationship with ALT levels. Regarding lipidomics in hepatic L02 cells, TAG was markedly elevated after VPA exposure, especially in TAGs with more than 53 summed carbons. Besides, gene expression analysis revealed dysregulated lipid metabolism in VPA-treated L02 cells. Peroxime proliferators-activated receptor (PPARγ) pathway played an important role in VPA-induced lipid disruption through inducing long-chain fatty acid uptake and TAG synthesis, which was also regulated by Akt pathway. Our findings present that VPA-induced lipid metabolism disruption might lead to lipotoxicity in the liver. This approach is expected to be applicable for other drug-induced toxicity assessments.

Catalase C-262T Polymorphism Is a Risk Factor for Valproic Acid–Induced Abnormal Liver Function in Chinese Patients With Epilepsy

Individual susceptibility to valproic acid (VPA)-caused hepatotoxicity might result from genetic deficiencies in the detoxification and antioxidant enzymes including glutathione S-transferases (GSTs), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). This study aimed to investigate the relationships between GST mu 1 (GSTM1), GST theta 1 (GSTT1), CAT C-262T, GPx1 Pro200Leu, and SOD2 Val16Ala polymorphisms and the risk of abnormal liver function in Chinese epileptic patients treated with VPA monotherapy. According to the levels of liver function indicators, a total of 267 epileptic patients between 1 and 65 years of age were divided into normal liver function group and abnormal liver function group. GSTM1 and GSTT1 polymorphisms were determined using polymerase chain reaction (PCR) amplification based on the absence of a PCR amplification product. CAT, GPx1, and SOD2 polymorphisms were identified using PCR-restriction fragment length polymorphism or direct automated DNA sequencing. Carriers of CAT had an increased risk of developing abnormal liver function compared with noncarriers in VPA-treated patients (odds ratio 3.968, P = 0.003). Logistic regression analyses indicated that the CAT genotype was a significant genetic risk factor for VPA-induced liver dysfunction. It suggests that individual susceptibility to VPA-induced liver dysfunction may at least partially result from genetic deficiencies in CAT C-262T.

Associations of CYP2C9 and CYP2A6 Polymorphisms with the Concentrations of Valproate and its Hepatotoxin Metabolites and Valproate-Induced Hepatotoxicity.

The aim of this study was to compare genetic polymorphisms and concentrations of hepatotoxic metabolites in patients with epilepsy and liver injury and those with normal liver function receiving valproate monotherapy to identify risk factors for VPA-induced hepatotoxicity. A total of 279 Chinese patients with epilepsy were divided into an abnormal liver function (ANLFT) group (n = 79) and a normal liver function (NLFT) group (n = 200). Polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP and nested PCR were applied to identify the frequency of two SNPs in candidate genes. Serum concentrations of VPA and its major metabolites were determined by Ultra-Performance Liquid Chromatography-tandem mass spectrometry UPLC-MS/MS. Significant differences were found in genotype distributions of CYP2A6 and CYP2C9 between the two groups. The values of 4-ene-VPA and 2,4-diene-VPA in the ANLFT group were significantly higher than in the NLFT group. Only CYP2A6 polymorphisms had associations with the concentrations of 4-ene-VPA and 2,4-diene-VPA. CYP2A6*1/*4 and CYP2A6*4/*4 variant carriers had higher CDR4-ene-VPA and CDR2,4-diene-VPA values than CYP2A6*1/*1 carriers. The logistic regression analysis showed that CYP2C9 and CYP2A6 were significant risk factors for hepatotoxicity by increasing the risk by 7.50 and 5.13 times, respectively. These findings provide preliminary evidence that CYP2A6 and CYP2C9 are associated with hepatotoxicity. However, only the CYP2A6 polymorphism was found to be associated with concentrations of 4-ene-VPA and 2,4-diene-VPA. Potential important risk factors include mutated genotypes of CYP2C9 and CYP2A6 and higher concentrations of VPA, 4-ene-VPA and 2,4-diene-VPA.

Clinical analysis of acute liver damage in children with acute Epstein-Barr virus infection

Objective To study the clinical manifestations and laboratory findings like liver function, immunoglobulin and peripheral blood lymphocyte subsets, and to provide evidence for diagnosing and the therapy for acute Epstein-Barr virus (EBV) infection. Methods From July 2012 to June 2015, clinical data from 321 patients with acute EBV infection admitted to Children′s Hospital of Fudan University for treatment were retrospectively analyzed.The clinical characteristics and the findings by liver function test, detection of virus, immunoglobulin and lymphocyte subsets were analyzed.The patients were divided into an abnormal liver function group (186 cases) and the normal liver function group (135 cases). The copy number of EBV-DNA, serum EBV-IgM, immunoglobulin, CD series between the 2 groups were analyzed.Stata 12.0 software was used for statistical analysis. Results (1) There were 321 cases diagnosed with acute EBV infection.Among them, the gender of 183 cases were boys, 138 cases were girls, male to female ratio was 1.33∶1.00.The average age of onset was (52.07±35.05) months.There were 186 cases (57.94%) with abnormal liver function and 135 cases (42.06%) with normal liver function.(2) Clinical course was (9.11±8.21) days, and period of fever lasted (7.12±5.00) days; 281 cases (87.54%) had fever, and the highest temperature reached (39.04±0.69) ℃; lymphadenectasis occurred in 267 cases (83.18%), 245 cases (76.32%) had angina, hepatomegaly occurred in 235 cases (73.21%), 142 cases (44.24%) had splenomegaly, and rash occurred in 60 cases (18.69%); 155 cases (48.29%) occurred trilogy of fever, lymphadenectasis and angina.(3) There were 186 cases had abnormal liver function without jaundice, and their levels of total bilirubin, direct bilirubin, total bile acid, albumin and coagulation function were normal.Alanine aminotransferase (ALT) increased from 40 to 400 IU/L in 125 cases, 400 to 800 IU/L in 2 cases, and more than 800 IU/L in 6 cases.Aspartate aminotransferase(AST) increased from 40 to 400 IU/L in 157 cases, 400 to 800 IU/L in 5 cases, more than 800 IU/L in 1 case.Ninety-seven cases were followed up for liver function, and the recovery time was 21-74 days.(4) In comparison of the abnormal liver function group to the normal liver function group, the differences were statistically significant in age, IgG, IgA, CD4+ T cell, the ratio of CD4+ T cell and CD8+ T cell (all P 0.05). Conclusions Children with acute EBV infection may have a high incidence of liver damage.The clinical manifestations are characterized by elevated transaminase and self-limiting.The occurrence of liver damage may be related to case of cell-mediated immunity Key words: Epstein-Barr virus; Liver function damage; Child

Improvement of abnormal liver enzymes after rosiglitazone treatment in Chinese type 2 diabetes

Objectives:Insulin resistance is one of the important underlying abnormalities of type 2 diabetes. The effect of thiazolidinedione on liver functions has been controversial in different studies. In this study, we evaluated the effect of rosiglitazone on liver enzymes in subjects with type 2 diabetes with and without abnormal liver function.Materials and Methods:Seventy-three patients with type 2 diabetes taking rosiglitazone 4 mg daily were enrolled in this 3-month study. Forty-two of them had normal liver function (NLF), and 31 had abnormal liver function (ABLF). Blood biochemistries were collected monthly during the treatment period.Results:At baseline, other than age and liver enzymes, there were no differences in body mass index, fasting plasma glucose, hemoglobin A1c (HbA1c), and lipid profiles between the NLF and ABLF groups. At the end of the treatment, HbA1c was lowered in both groups, but only significantly in the ABLF group (P = 0.027). More importantly, serum concentrations of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the ABLF group decreased significantly (AST: 57.8 ± 26.5 to 47.5 ± 20.2 U/L, P = 0.006; ALT 66.6 ± 35.0 to 51.9 ± 23.5 UL, P = 0.004), while in the NLF group, a similar change was not found.Conclusion:After 3-month rosiglitazone treatment in subjects with type 2 diabetes with mildly elevated liver enzymes, significant improvement in AST and ALT were observed. Our study provides some hints that rosiglitazone might not be contraindicated in subjects with diabetes with abnormal liver function as previously thought, but further well-designed studies are necessary to clarify this issue.