[Research progress of direct-acting antiviral drugs in the treatment of chronic hepatitis C-related cirrhosis].

Chronic hepatitis C is a kind of viral hepatitis caused by hepatitis C virus infection, which can further progress to cirrhosis, liver failure, hepatocellular carcinoma, and even death. Presently, there is no preventive vaccine yet. Therefore, preventing infection and safe and effective drug treatment are currently the most effective strategies for dealing with hepatitis C virus infection. Since 2014, the clinical application of direct-acting antiviral drugs has brought revolutionary changes to the treatment of chronic hepatitis C. Direct-acting antiviral drugs have an excellent hepatitis C virus clearance effect, are well tolerated, have a good safety profile, and can significantly improve liver function, metabolic disorders, immune dysfunction, etc. However, some studies have pointed out that even if the hepatitis C virus is cleared during the treatment of chronic hepatitis C-related cirrhosis with direct-acting antiviral drugs, a considerable proportion of patients still have severe liver failure, hepatocellular carcinoma, and even liver disease-related death, so there are still some problems in the treatment of chronic hepatitis C- related cirrhosis with direct-acting antiviral drugs that need to be further explored. This article reviews the research progress of direct-acting antiviral drugs so as to provide meaningful references for the treatment of patients with chronic hepatitis C-related cirrhosis.

[Analysis of advanced fibrosis in metabolic dysfunction-associated fatty liver disease patients with chronic hepatitis B].

Objective: To investigate the clinical and pathological characteristics of chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD), as well as associations with advanced fibrosis. Methods: CHB patients who underwent liver biopsy at Tianjin Second People's Hospital from June 2016 to September 2019 were included in the study. The patients were divided into two groups based on whether they had concomitant MAFLD; a CHB group and a MAFLD-CHB group. t-tests and Chi-square tests were used to compare pathological characteristics and basic features in the two groups. Logistic regression analysis was used to analyze factors associated with advanced fibrosis. Results: The CHB group included 110 patients, and the MAFLD-CHB group included 272 patients. There were significant differences in smoking, alcohol consumption, hypertension incidence, body metabolic index, alanine aminotransferase, gamma-glutamyl transferase (GGT), high-density lipoprotein, low-density lipoprotein, fasting plasma glucose, and platelets (PLT) between the two groups (all P<0.05). The MAFLD-CHB group had a higher incidence of advanced fibrosis than the CHB group (P<0.05). In logistic regression analysis MAFLD [odds ratio (OR)=2.204, 95% confidence interval (CI) 1.018-4.774, P=0.045], GGT (OR=1.008, 95%CI 1.002-1.013, P=0.005), and PLT (OR=0.995, 95%CI 0.991-0.999, P=0.019) were associated with advanced fibrosis (all P<0.05). In the MAFLD-CHB group type 2 diabetes (OR=3.281, 95%CI 1.375-7.832, P=0.007), GGT (OR=1.011, 95%CI 1.003-1.018, P=0.005), and PLT (OR=0.993, 95%CI 0.988-0.998, P=0.004) were associated with advanced fibrosis (P<0.05). Conclusion: Patients with MAFLD-CHB are more likely to develop advanced fibrosis than patients with CHB alone. In the MAFLD-CHB group type 2 diabetes mellitus was associated with advanced fibrosis. It is important to strictly control relevant risk factors in MAFLD-CHB patients, especially in patients with type 2 diabetes.

[Liver fibrosis screening, evaluation pathway, and management in patients with fatty liver].

Non-alcoholic fatty liver disease (NAFLD) is not a benign condition, especially in patients with non-alcoholic steatohepatitis (NASH) combined with liver fibrosis grades F2-4, who have a higher risk of liver-related events and mortality. Thus, this population is considered "at-risk" for developing NASH. China has a large NAFLD patient population, so how to screen for those with liver fibrosis is an important socio-economic concern. At the moment, serological models, liver stiffness detection based on vibration-controlled transient elastography, and magnetic resonance elastography (MRE) are the only non-invasive tests (NITs) for liver fibrosis. The prevention and treatment guidelines for NAFLD at home and abroad are reviewed here, based on the research progress of NITs in recent years, so as to suggest screening, evaluation pathways, and management for liver fibrosis in patients with NAFLD.

[Diagnostic value of non-invasive model for hepatic steatosis in patients infected with human immunodeficiency virus].

Objective: Hepatic steatosis has a high incidence in human immunodeficiency virus (HIV) infected people, and there is no effective non-invasive method to evaluate it. This study aims to evaluate the diagnostic value of non-invasive models for hepatic steatosis in this population. Methods: A single-center retrospective study was applied to evaluate: (1) the diagnostic value of controlled attenuation parameters (CAP) and hepatic steatosis index (HSI) in HIV-infected patients with hepatic steatosis; (2) the ability of the non-invasive model to distinguish hepatic steatosis caused by abnormal glucose and lipid metabolism and hepatic steatosis caused by hepatitis C virus infection; (3) the diagnostic value of the above models for hepatic steatosis in patients co-infected with HIV/hepatitis C virus. The diagnostic value of the model was analyzed and evaluated by diagnostic test and receiver operating characteristic curve. Results: (1) the diagnostic value of hepatic steatosis for HIV-infected patients: when CAP = 232 dB/m, the sensitivity and specificity were 89.2% and 78.1%, respectively; when HSI = 34, the sensitivity and specificity were 79.1% and 83.2%, respectively. (2) The ability to identify the causes of hepatic steatosis in HIV-infected patients: when CAP = 258dB/m, the sensitivity and specificity were 81.5% and 88.2%, respectively; when HSI = 37, the sensitivity and specificity were 70.7% and 92.4%, respectively. (3) The diagnostic value of hepatic steatosis in patients co-infected with HIV/hepatitis C virus: when CAP = 241 dB/m, the sensitivity and specificity were 80% and 71.4%, respectively; when HSI = 32, the sensitivity and specificity were 73% and 68.9%, respectively. Conclusion: CAP and HSI have superior diagnostic value for hepatic steatosis in patients infected with HIV.

[Potential clinical value of new type of HBV serological markers ranking in the review column].

Liver fibrosis, liver cirrhosis and hepatocellular carcinoma caused by chronic hepatitis B are still the main diseases that seriously affect the health of Chinese population. Notably, even if serum HBV-DNA cannot be detected after treatment, many patients will still develop liver disease. Therefore, in addition to the quantitative analysis of HBV-DNA and HBsAg, other new serological markers should be sought to facilitate the selection of CHB antiviral drugs and methods, monitoring efficacy and follow-up, efficacy prediction, and the risks of viral rebound after drug withdrawal. This article focuses on three new serological markers, namely HBcrAg, HBV-RNA and anti-HBc, with a view to applying them in clinical practice.

[Characteristics, diagnostic and therapeutic strategies for chronic hepatitis B combined with non-alcoholic fatty liver disease].

Presently, the situation of chronic hepatitis B combined with non-alcoholic fatty liver disease is relatively common in our country, and yet the relationship between them has not reached a consensus. The co-existing fatty liver may affect the efficacy of anti-HBV therapy and increase the all-cause mortality rates in patients. Therefore, it is very important to correctly diagnose and evaluate fatty liver changes, inflammation, and fibrosis for active prevention and treatment.

[Study of reactive oxygen species and adiponectin for chronic HBV infection combined with nonalcoholic fatty liver diseases].

Objective: To investigate the application value of reactive oxygen species (ROS) and adiponectin (ADPN) in the judgment of liver inflammation in chronic hepatitis B virus infection combined with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 159 cases with NAFLD (21 cases), chronic hepatitis B virus infection (57 cases), and chronic hepatitis B virus infection combined with NAFLD (81 cases) were collected between June 2016 to December 2018, and the visited patients diagnosis were confirmed by histopathological examination of the liver. ROS and ADPN level retained in serum was determined by enzyme-linked immunosorbent assay. Histopathological examination of liver tissue was used as the gold standard to discuss the diagnostic value of the serum in patients with chronic hepatitis B virus infection combined with NAFLD for the occurrence of nonalcoholic steatohepatitis. One-way analysis of variance was used for the comparison among multiple groups, and LSD-t test was used for pairwise comparison between groups. Measurement data for non-normal distributions were expressed as M (P25, P75). Comparisons between groups were performed using the Mann-Whitney U or Kruskal-Wallis H test. Chi-square test was used to compare the count data between groups. Correlation analysis was performed using Spearman correlation analysis. Histopathological grouping of liver tissue was used as the gold standard, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the regression formula. Results: (1) In patients with chronic hepatitis B virus infection combined with NAFLD, the levels of ROS in the non-hepatic steatosis group and the mild hepatic steatosis group were significantly lower than those in the moderate and severe hepatic steatosis group, while the ADPN level in the non-hepatic steatosis group was significantly higher than liver steatosis group, P < 0.05. (2) The results of correlation analysis showed that ROS was significantly correlated with NAS score, change in the degree of fatty liver and lobular inflammation (all P < 0.05).There was a significant negative correlation between ADPN and the change in the degree of fatty liver (P < 0.05). (3) Logistic regression analysis results showed that the diagnostic formula for chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis was 0.02 × controlled attenuation index + 0.584 × white blood cells/10(9) + 0.587 × ROS-10.982. The area under receiver operating characteristic curve of the subject was = 0.896. The sensitivity, specificity, positive and negative predictive value were 97.1%, 71.2%, 64.2%, and 97.9%. Conclusion: ADPN and ROS have certain reference value in differentiating the change in the degree of fatty liver and inflammation in chronic hepatitis B virus infection combined with NAFLD and the diagnostic formula has higher application value in the diagnosis and exclusion of chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis.

[Clinical value of noninvasive method in diagnosing hepatic fibrosis about chronic HBV carriers].

Objective: To compare the clinical value of FibroScan, FIB-4, APRI and AAR diagnosing hepatic fibrosis in chronic hepatitis B virus (HBV) carriers. Methods: A total of 213 patients with chronic HBV carriers diagnosed by clinical and liver biopsy were selected. And according to HBeAg status, 149 patients were divided into HBeAg-positive group and 64 patients were divided into HBeAg-negative group. The liver stiffness measurements (LSM) was measured by FibroScan (FS), FIB-4, APRI and AAR values were calculated using FIB-4, APRI and AAR formula. And all patients underwent liver biopsy in the same period. According to the degree of hepatic fibrosis in Knodell, one decision point was set: significant hepatic fibrosis (S ≥ 2). The Spearman correlation analysis method was used to analyze the correlation of indicators and the area under receiver operator characteristic curves (AUROCs) of LSM, FIB-4, APRI and AAR were drawn according to liver biopsy pathology results as gold standard. The value of LSM, FIB-4, APRI and AAR diagnosing hepatic fibrosis in chronic HBV carriers was retrospectively analyzed. Retrospective analysis of FS, FIB-4, APRI and AAR were divided into 149 HBeAg-positive chronic HBV carriers (HBeAg-positive group) and 64 HBeAg-negative chronic HBV carriers (HBeAg) in 213 patients with chronic HBV carriers and HBeAg Negative group) in the diagnosis of liver fibrosis. Results: The LSM of 213 patients with chronic HBV carriers, 149 patients with HBeAg-positive chronic HBV carriers and 64 patients with HBeAg-negative chronic HBV carriers were significantly correlated with liver fibrosis grade≥ 2 (P < 0.001). Regardless of HBeAg status, only LSM in the three groups had moderate evaluation efficacy for evaluating significant fibrosis(S≥2), and the positive predictive value was more than 94%, but the diagnostic accuracy was not high, the minimum was 46.31% (HBeAg-positive group), the maximum value of 67.19% (HBeAg-negative group), while the remaining three kinds of serum noninvasive liver fibrosis diagnostic model indicators and diagnostic efficacy are low. The LSM in the three groups showed a significant positive correlation with liver fibrosis grade (S)≥2. Conclusion: LSM is more accurate than FIB-4, APRI and AAR in diagnosing chronic HBV carriers. Dynamically monitoring changes of LSM can earlier understand the progress of liver fibrosis than the three kinds of serology noninvasive diagnostic model and is contributed to the choice of liver biopsy timing.

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China.

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large-sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)-positive chronic HBV infection (n = 588), HBeAg-positive chronic hepatitis B (n = 596), and HBeAg-negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%-90% confidence interval: 3.52 log10 IU/mL-4.99 log10 IU/mL]) in patients with HBeAg-positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg-positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg-negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg-positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg-negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement.

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

[A serum lipidomic study of patients with non-alcoholic fatty liver disease].

Objective: To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD. Methods: The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis. Results: A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05). Conclusion: There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.

[The significance of 8-hydroxy-deoxyguanosine acid in the diagnosis of nonalcoholic steatohepatitis].

Objective: To evaluate the significance of serum 8-hydroxy-deoxyguanosine acid(8-OHdG) in the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: Patients or healthy subjects were enrolled at the Second Hospital of Tianjin Medical University and the Second People's Hospital of Tianjin from May 2013 to December 2015. A total of 41 patients with nonalcoholic fatty liver disease were enrolled in the study, including 20 nonalcoholic simple fatty liver (NAFL) patients and 21 NASH patients whose diagnosis were proven by liver biopsy. The other 32 healthy subjects were studied as controls. Serum 8-OHdG, ALT, AST and GGT were tested. Nonalcoholic fatty liver disease activity score (NAS) and expression of 8-OHdG in liver was investigated between NAFL patients and NASH patients. The correlations between serum 8-OHdG and serum ALT, AST, GGT, and 8-OHdG in liver tissue in NASH group were investigated. In addition, the receiver operating characteristic (ROC) curve analyses for ALT and 8-OHdG levels were performed in NAFL patients and NASH patients, and the cut-off value was determined. Results: Serum 8-OHdG values in healthy controls, NAFL and NASH patients were (0.19±0.16) µg/L, (0.22±0.16) µg/L, (0.42±0.21) µg/L respectively. The serum 8-OHdG and serum ALT, GGT and 8-OHdG in liver tissue were all positively correlated in NASH group with respective correlation coefficient r values as 0.454 7, 0.382 9, and 0.497 6. AUC of 8-OHdG was 0.901 with cut-off value 0.39 µg/L. Its sensitivity was 88.3% and specificity was 81.5%, which were higher than those of ALT. Conclusion: The value of serum 8-OHdG would be used as a marker for the diagnosis of NASH.

[Serological and pathological features of drug-induced liver injury and autoimmune hepatitis].

Objective: To investigate the differences and similarities between drug-induced liver injury (DILI) and autoimmune hepatitis (AIH) in serum biochemical parameters and liver pathology, and to provide some thoughts for clinical diagnosis and differentiation of these two diseases. Methods: A retrospective analysis was performed for the biochemical, immunological, autoantibody, and liver pathological data of 106 DILI patients and 63 AIH patients who were hospitalized, diagnosed, and treated in our hospital from January 2012 to October 2014. The patients' general data, biochemical parameters, immunological data, Ishak score, and qualitative changes in liver tissue were analyzed and compared. The Kruskal-Wallis test was used for comparison of nonparametric data between multiple groups, the Nemenyi test was used for comparison of nonparametric data between any two groups, the Wilcoxon rank sum test was used for comparison of Ishak scores, and the chi-square test was used for comparison of constituent ratio of categorical data. Results: There were significant differences between AIH group and DILI hepatocyte injury group/mixed-type DILI group in the following serum biochemical parameters: alanine aminotransferase (187.2 U/Lvs 1 326.5 U/L and 455.6,P< 0.05), aspartate aminotransferase (172.2 U/L vs 759.5 U/L and 349.5 U/L,P<0.05), alkaline phosphatase (209.3 U/L vs 157.3 U/L and 169.4 U/L,P< 0.05), gamma-glutamyl transferase (254.8 U/L vs 176.5 U/L and 170.5 U/L,P< 0.05), total bilirubin (37.2µmol/L vs 95.8µmol/L and 52.6µmol/L,P< 0.05), serum iron (18.9µmol/L vs 36.2µmol/L and 23.9µmol/L,P< 0.05), serum ferritin (122.5µmol/L vs 410.4µmol/L and 186.5µmol/L,P< 0.05), immunoglobulin G (18.4 g/L vs 12.6 g/L and 12.3 g/L,P< 0.05), and immunoglobulin M (1.8 g/L vs 1.3 g/L and 1.1 g/L,P< 0.05). There were also significant differences between AIH group and DILI hepatocyte injury group/mixed-type DILI group in the Ishak score for interface inflammation (2.2±0.8 vs 1.3±0.7 and 1.3±0.6,P< 0.05), Ishak score for portal inflammation (2.3±0.9 vs 1.5±0.7 and 1.4±0.8,P< 0.05), and fibrosis score (2.8±1.1 vs 1.5±0.7 and 1.3±0.7,P< 0.05). There were significant differences between AIH group and DILI hepatocyte injury group/mixed-type DILI group in the proportion of wax-like deposition (0 vs 29.2% and 34.5%, P <0.05) and proportion of iron deposition (11.1% vs 52.1% and 25.9%,P< 0.05). Conclusion: There are differences in biochemistry, immunology, and liver histology between DILI and AIH patients. AIH patients have more serious interface inflammation and portal inflammation and a higher fibrosis degree compared with DILI patients, while DILI patients have greater proportions of wax-like deposition and iron deposition compared with AIH patients.

[Value of a two-step approach with cytokeratin-18 and controlled attenuation parameter in noninvasive differential diagnosis of nonalcoholic steatohepatitis].

OBJECTIVE: To investigate the value of a two-step approach with cytokeratin-18 (CK-18) and controlled attenuation parameter (CAP) in the noninvasive diagnosis of nonalcoholic steatohepatitis (NASH). METHODS: A total of 65 patients with biopsy-proven nonalcoholic fatty liver disease were enrolled, including 30 patients with NASH. The M30 and M65 enzyme-linked immunosorbent assay kits were used to measure serum CK-18, and FibroScan was used to measure CAP. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUROC) was used to determine the value of noninvasive diagnosis. The binary logistic regression model was used to calculate the predicted probability of combined diagnosis. The maximum Youden index, a sensitivity of >90%, and a specificity of > 90% were used to determine the optimal cut-off value, the low value, and the high value, respectively. RESULTS: The results of the multivariate analysis showed that M65 (OR = 1.004, 95% CI 1.002-1.007, P = 0.003) and CAP (OR = 1.017, 95% CI 1.001-1.033, P = 0.036) were independent predictors of NASH. The AUROC of M65+CAP was 0.851 (95% CI 0.761-0.942), higher than 0.808 (95% CI 0.702-0.913) of M65 and 0.677 (95% CI 0.545-0.808) of CAP alone. A two-step approach with high (820.8 U/L) and low (527.7 U/L) values for M65 and the optimal cut-off value (293.5 dB/m) for CAP was used for the differential diagnosis of NASH, with a positive predictive value of 85.7%, a negative predictive value of 100%, and a coincidence rate of 92.0%. CONCLUSION: A two-step approach with M65 and CAP can improve the value of noninvasive diagnosis of NASH, and a high negative predictive value can avoid unnecessary liver biopsy.

Congenital heart defects and maternal fever: systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyze the relation between maternal fever in the first trimester and congenital heart defect (CHD) in offspring. STUDY DESIGN: We searched PubMed (1977-2012), Embase (1974-2012) and the Cochrane Library (2012) databases to identify relevant articles. Random effects model were performed, with the conduction of subgroup analysis. RESULT: Meta-analysis yielded a pooled odds ratio of 1.53 (95% confidence interval=1.36 to 1.73) for the magnitude of the relation between maternal fever in the first trimester and CHD in offspring. As to subgroup analysis, it is associated with ventricular septal defects (VSDs) and right obstructive defects. CONCLUSION: Our analysis suggests that maternal fever in the first trimester is the risk factor of congenital heart diseases in offspring. Through the subgroup analysis, we find that exposure to maternal fever is the risk factor of VSD and right obstructive defects.

A double-blind comparative study of Chinese herbal medicine Jinlianqingre Effervescent Tablets in combination with conventional therapy for the treatment of uncomplicated hand, foot, and mouth disease.

Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95% confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.