Prospective study on the overuse of blood test-guided antibiotics on patients with acute diarrhea in primary hospitals of China.

BACKGROUND: Overuse with antibiotics in the treatment of infectious diseases has become a central focus of public health over the years. The aim of this study was to provide an up-to-date evaluation of the blood test-guided antibiotic use on patients with acute diarrhea in primary hospitals of China. MATERIALS AND METHODS: A cross-sectional survey was conducted on 330 patients with acute diarrhea in Shanghai, People's Republic of China, from March 2013 to February 2016. These patients were treated with or without antibiotics based on the results of their blood tests, including examinations of C-reactive protein (CRP), white blood cells (WBC), and the percentage of neutrophils (Neu%). The infection types, which included bacterial, viral, and combination diarrhea, were determined by microbiological culture methods. Antibiotics used in non-bacterial diarrhea patients were considered misused and overused. RESULTS: There were significant overall differences in the clinical characteristics and blood tests between patients with diarrhea with a bacterial infection and patients with other types of infections. The patients were divided into four grading groups (0-3) according to the number of the positive results from three blood testes (CRP, WBC, and Neu%). The misuse rates of antibiotics in each group (0-3) were 81.3%, 71.1%, 72.4%, and 64.9%, respectively. CONCLUSION: In this prospective study, the current diagnostic criteria (CRP, WBC, and Neu%) based on blood tests are not reliable in diagnosing bacterial diarrhea or guiding antibiotics use. To limit antibiotic overuse, a rapid and accurate differentiation of bacterial diarrhea from other types of diarrhea is pivotal.

Hepatitis B e antigen-positive and high levels of alanine aminotransferase are associated with prevalence of metabolic syndrome in chronic HBV patients.

OBJECTIVE: The interactions between hepatitis B virus (HBV) infection and metabolic syndrome (MS) have not been elucidated. This study was aimed to investigate the relationship between metabolic profile and HBV infection. METHODS: A retrospective cross-sectional study including patients infected by HBV (HBV group, n=121) and healthy volunteers (control group, n=263) was conducted, serum HBV viral load and markers, serum alanine aminotransferase (ALT) levels and MS were analyzed. Factors associated with prevalence of MS were explored with multivariate adjusted logistic regression analyses. RESULTS: The prevalence of MS was 9.9% in HBV infected patients and 19.4% in controls (p=0.011). Factors associated with the prevalence of MS were (odds ratio, 95% confidence interval, p value): hepatitis B e antigen (HBeAg) positive (0.368, 0.107-0.653, 0.008) and high levels of ALT (0.183, 0.120-0.268, <0.001) in HBV patients. But clinical and virological factors (including age, HBV DNA level, male gender, BMI, and fatty liver) were not found to be associated with prevalence of MS in HBV patients who were HBeAg positive with high levels of ALT. CONCLUSION: These findings suggest that HBeAg positive and high levels of ALT are independently associated with lower prevalence of MS in HBV patients. But HBV DNA may not have impact on the lipid metabolism. HBV-related immune reactions may play a certain role in the mechanism of MS.

Rescue therapy for lamivudine-resistant chronic hepatitis B: adefovir monotherapy, adefovir plus lamivudine or entecavir combination therapy.

OBJECTIVE: We aimed to compare the cumulative efficacy and resistance of ADV monotherapy, ADV add-on LAM (ADV + LAM), ADV and ETV (ADV + ETV) combination therapy in LAM-resistant patients. METHODS: Ninety-one adult CHB patients with LAM-resistance mutations (YMDD) were identified. Of these 91, 29 patients were treated with ADV monotherapy, 30 were treated with ADV + LAM and 32 were treated with ADV + ETV combination therapy, for at least 24 months. RESULTS: The mean serum HBV-DNA decreases from baseline at 3, 6, 12, and 24 months were -3.23, -4.41, -5.32, and -5.58 log(10) IU/mL in the ADV + ETV combination therapy groups, respectively; the most significant among the three treatment groups (p<0.01). The rate of HBV-DNA PCR undetectability (<60 IU/mL) at 6 months in ADV + ETV combination therapy was 78.1%; also the most significant among the three treatment groups (p=0.024). Viral breakthrough and genotypic mutations were detected in 8 (27.6%) and 4 (13.3%) patients in the ADV monotherapy and ADV+LAM therapy groups, respectively; whereas no case of viral breakthrough and genotypic resistance was detected in the ADV+ETV combination therapy group after 24 months (p<0.05). CONCLUSION: ADV + ETV combination therapy demonstrated faster and significantly greater suppression of HBV DNA compared with ADV add-on LAM combination therapy for patients with LAM-resistance mutations. ADV + ETV was superior to ADV + LAM in achieving initial virological response and long-term suppression activity against HBV. ADV + ETV combination therapy was the most effective to refrain from selecting HBV strains with cross-resistance to three NAs (LAM, ADV and ETV) for LAM-resistance patients.

A prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients with stringent cessation criteria for adefovir.

Adefovir is usually applied for therapy of chronic hepatitis B (CHB), but its effectiveness after cessation is still unknown. This study was to evaluate the effectiveness of adefovir treatment with strict cessation criteria in hepatitis B e antigen (HBeAg)-negative patients and to identify potentially important factors. One hundred forty-five HBeAg-negative CHB patients who had received adefovir treatment for at least 24 months and for whom serum hepatitis B virus (HBV) DNA had remained undetectable for at least 18 months before cessation were included. They were followed up monthly during the first four months and at 3-month or 6-month intervals thereafter. Patients with ≥10(4) copies of HBV DNA per mL were defined as relapsed. In total, 95 patients relapsed within the follow-up time, and more than 93% relapsed within 12 months after adefovir cessation. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 53.8%, 61.4%, 65.5%, 65.5%, 65.5% and 65.5%, respectively. Age was the only factor associated with relapse, with lower relapse rates in younger patients shown by Cox regression analysis. HBsAg seroconversion occurred in 12 patients, and none of them relapsed during follow-up. The effectiveness of adefovir therapy does not persist in HBeAg-negative CHB patients, even when strict cessation criteria are applied, except for patients aged ≤ 25 years. HBsAg seroconversion is the ideal endpoint of adefovir treatment.

Effect of interferon-gamma on hepatic stellate cells stimulated by acetaldehyde.

BACKGROUND/AIMS: Liver fibrosis in alcoholics has been linked to the oxidation of ethanol to the highly reactive compound acetaldehyde and accumulating evidence has indicated a close link between alcohol and TGF-beta1. Although, it is considered that IFN-gamma inhibits the transcription of matrix, it has not been well defined whether IFN-gamma could inhibit the expression of matrix induced by acetaldehyde in METHODOLOGY: HSC were divided into 5 groups, 4 groups were treated with different doses (0, 1000, 1500, 2000 IU/mL) of IFN-gamma and acetaldehyde (200pM) for 24 and 48 h. For the control group, HSC were treated only with medium. The collagen, alpha-SMA, TGF-beta1, Smad4, Smad7 and TGFbetaRI protein expression in HSC were examined by western blot analysis. 5-Bromo-2'-deoxy-uridine (BrdU) labeling assay was used to determine the effect of IFN-gamma on the proliferation of HSC. RESULTS: IFN-gamma exhibited a dose-dependent inhibitory effect on a-SMA, collagen type I, collagen type III protein expression in HSC (p<0.01); also IFN-gamma implemented a dose-dependent inhibitory effect on TGF-beta1, Smad4 and especially TGFBRI protein expression in HSC (p<0.01). There was no influence of IFN-gamma on HSC proliferation by BrdU labeling assay. CONCLUSIONS: The present data indicated that IFN-gamma could inhibit the collagen expression in HSC stimulated by acetaldehyde. IFN-gamma could down-regulate the TGF-beta1, Smad4 and especially TGFbetaRI in HSC after acetaldehyde stimulation. This experiment showed 1000, 1500, 2000 IU/mL IFN-gamma were effective and safe to down-regulate the extracellular matrix induced by acetaldehyde in vitro.

[The effects of endothelial progenitor cell transplantation in carbon tetrachloride induced hepatic fibrosis rats].

OBJECTIVES: To study the effects of rat endothelial progenitor cell (EPC) transplantation on hepatic fibrosis in carbon tetrachloride (CCl4) induced hepatic fibrosis rats. METHODS: Hepatic fibrosis was developed in 24 healthy female SD rats by feeding them 25% CCl4/olive oil for 8 weeks. Eight of them were sacrificed at the end of the 8 weeks. The rats were subdivided into a EPCs transplanting group (n=8) and a saline control group (n=8). After the EPCs were isolated and cultured for 9 days, the cells were injected into the portal veins of the rats in the EPCs transplanting group. Four weeks later all of the rats were sacrificed. The blood biochemical parameters from the serum were examined. The degree of liver fibrosis was evaluated by reading Masson staining liver slides and by detecting the expression of a-SMA and collagen III. RESULTS: Compared with the saline control group, hepatic activity index (HAI), levels of ALT, AST and TBil in the serum were all lower in the EPCs transplanting group, but the level of Alb was higher and the expression of a-SMA and collagen III were lower. Compared with the 8 week hepatic fibrosis group, the levels of ALT, AST and TBil in the serum of the EPCs transplanting group were all lower. In the saline control group, the serum levels of ALT, AST and TBil were higher, the level of Alb was lower, and the expressions of a-SMA and Collagen III were higher. CONCLUSION: In hepatic fibrosis rats, transplantation of rat EPCs could minimize the hepatic fibrosis process and the injuries.

The hepatitis C virus 5' untranslated region gene amplified by rapid amplification of cDNA ends and its secondary structure.

OBJECTIVES: To obtain very end full-length cDNA of hepatitis C virus (HCV) 5'untranslated region (5'UTR) and analyze its primary and secondary structure. METHODS: A patient infected genotype 2a HCV was identified by reverse transcription-nested polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). Total RNA isolated from the serum was used as template, and the cDNA of the 5'untranslated region was amplified using rapid amplification of cDNA ends (RACE). The fragments were recombinated by A-T clone strategy, and the recombinants were confirmed by RFLP and PCR, and sequenced subsequently. Secondary structures were analysed by RNAdraw. RESULTS: Very end full-length cDNA of genotype 2a HCV 5'UTR was obtained by RACE. In five clones obtained, three contained full-length 5'UTR cDNA; A21G, G170A, T222C, T247C, C339T substitutions were found as compared to HC-J6. Homological results of HCV-1, HC-J6, HC-C2, HC-J8 were 93.6%-94.4%, 92.1%-93%, 98.8%-99.7%, 96.2%-96.5%, respectively; however, the substitutions did not alter secondary structure. Two of 5 clones were deletions of 53bp and 135bp at the 5'terminal of HCV 5'UTR, respectively. CONCLUSIONS: RACE can be used to obtain the full-length cDNA of 2a genotype HCV 5'UTR. Genes deleted at the 5'terminal of HCV circulate in hepatitis C patients.

[Amplification of hepatitis C virus 5' untranslated region gene by RACE and its secondary structure analysis].

OBJECTIVE: To obtain very end full-length cDNA of hepatitis C virus (HCV) 5' untranslated region (5' UTR), and analyse its primary and secondary structure. METHODS: By reverse transcription-nested polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP), a patient infected with genotype 2a HCV was found. Total RNA isolated from the serum as template, the cDNA of 5' noncoding region was amplified using rapid amplification of cDNA ends methods (RACE), the fragments were recombined by A-T clone strategy, the recombinants were confirmed by RFLP and PCR then sequenced. Secondary structures were analysed by RNA draw. RESULTS: Very end full-length cDNA of 2a genotype HCV 5' UTR was obtained by RACE. In five clones obtained, three contained full-length 5' UTR cDNA, and A21G, G170A, T222C, T247C, C339T substitutions were found compared with HC-J6. he homologies with HCV-1,HC-J6,HC-C2, HC-J8 were 93.6%-94.4%, 92.1%-93.0%, 98.8%-99.7%, 96.2%-96.5%, respectively; however, the substitutions did not alter the secondary structure. Two out of five clones were deleted to have 53 and 144 bases at 5' terminus of HCV 5' UTR, respectively. CONCLUSIONS: RACE is rapid and effective, works well to obtain very end of virus genome. With that, Authors obtained full-length cDNA of genotype 2a of HCV 5' UTR. There are genes deleted at 5' terminus circulated in hepatitis C patients.