Rural finance is an issue concerned with rural people, improving rural financial management is important to close the relations of cadres and masses, maintain rural stability, and promote rural economic development. T...Rural finance is an issue concerned with rural people, improving rural financial management is important to close the relations of cadres and masses, maintain rural stability, and promote rural economic development. This article explained the main problems of village financial, the needs of introducing commission and agent system of "village-level accounting" for building a new socialist countryside, and the measures of improving commission and agent system of "village-level accounting".展开更多
AIMTo evaluate the bidirectional association between metabolic syndrome (MS) components and antiviral treatment response for chronic hepatitis C virus (HCV) infection. METHODSThis retrospective cohort study included 1...AIMTo evaluate the bidirectional association between metabolic syndrome (MS) components and antiviral treatment response for chronic hepatitis C virus (HCV) infection. METHODSThis retrospective cohort study included 119 HCV + patients treated with pegylated-interferon-α and ribavirin. Metabolic characteristics and laboratory data were collected from medical records. Differences in baseline clinical and demographic risk factors between responders and non-responders were assessed using independent samples t-tests or χ<sup>2</sup> tests. The effects of sustained viral response (SVR) to antiviral treatment on de novo impairments in MS components, including impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), were assessed using univariable and multivariable logistic regression analysis, while the effect of MS components on SVR was assessed using univariable logistic regression analysis. RESULTSOf the 119 patients, 80 (67%) developed SVR over the average 54 ± 13 mo follow-up. The cumulative risks for de novo T2DM and IFG were 5.07- (95%CI: 1.261-20.4, P = 0.022) and 3.87-fold higher (95%CI: 1.484-10.15, P = 0.006), respectively for non-responders than responders, when adjusted for the baseline risk factors age, sex, HCV genotype, high viral load, and steatosis. Post-treatment triglyceride levels were significantly lower in non-responders than in responders (OR = 0.27; 95%CI: 0.069-0.962, P = 0.044). Age and HCV genotype 3 were significantly different between responders and non-responders, and MS components were not significantly associated with SVR. Steatosis tended to attenuate SVR (OR = 0.596; 95%CI: 0.331-1.073, P = 0.08). CONCLUSIONSVR was associated with lower de novo T2DM and IFG incidence and higher triglyceride levels. Patients infected with HCV should undergo T2DM screening and antidiabetic treatment.展开更多
AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preem...AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.展开更多
Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, among these there is an increased risk of atherosclerosis and cardiovascular disease as well as an increased cardiovascular mortality. ...Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, among these there is an increased risk of atherosclerosis and cardiovascular disease as well as an increased cardiovascular mortality. Several direct and indirect HCV pro-atherogenic mechanisms have been proposed. HCV lives and replicates within carotid plaques, promoting a local environment of pro-atherogenic factors. In addition, it causes conditions such as insulin resistance, diabetes, hepatic steatosis, cryoglobulinemia and endotoxinemia that are associated with the development of atherosclerosis and cardiovascular disease. Therapeutic regimens based on direct-acting antiviral agents (DAA) are currently available with high efficacy in HCV clearance and improvement of liver disease, but does HCV eradication also improve atherosclerosis and the risk of cardiovascular disease? Recently, a multi-center study has shown that elimination of HCV improves carotid atherosclerosis. Two studies have shown that DAA treatments significantly reduce the risk of cardiovascular events. Several studies have assessed the impact of HCV clearance on pro-atherosclerosis metabolic conditions showing improvement in cardiovascular risk biomarkers, disappearance or improvement of insulin resistance, reduction of risk of developing diabetes and improvement of glycemic control. There are also evidences that HCV clearance promotes the recovery of cytokines and inflammatory markers associated with atherosclerosis and the disappearance of cryoglobulinemia. Available data show that clearance of HCV by DAAs is associated with an improvement in atherosclerosis and metabolic and immunological conditions that promote the development of cardiovascular disease. However, the data are not sufficient to allow definitive conclusions and further studies will be needed to definitively clarify the impact of HCV clearance on atherosclerosis and cardiovascular disease.展开更多
AIM To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C(CHC) treated with new Direct-Acting Antiviral agents(DAAs) compared to pegylated interferon-2α p...AIM To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C(CHC) treated with new Direct-Acting Antiviral agents(DAAs) compared to pegylated interferon-2α plus ribavirin(P/R) therapy.METHODS This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus(HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index(PASI) scores and the Dermatology Quality of Life Index(DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different b DMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response(SVR) were considered as outcomes of HCV therapy.RESULTS Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower(P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group(0/27) compared to 8 patients of the P/R group(8/32) needed a shift in biological treatment.CONCLUSION DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.展开更多
In order to select the long-acting,low toxic,low-risk and multi-functional new pesticides for the control of sugarcane borders and woolly aphids and precise and efficient application technology,the control effect of 1...In order to select the long-acting,low toxic,low-risk and multi-functional new pesticides for the control of sugarcane borders and woolly aphids and precise and efficient application technology,the control effect of 10% monosultap · thiamethoxam granular formulation and 1% Bt · clothianidin granular formulation on sugarcane borders and woolly aphids were studied.The results showed that 10% monosultap·thiamethoxam GR and 1% Bt·clothianidin GR had good control effects on sugarcane borders and woolly aphids.They were ideal slow-release,long-acting,low toxic and multi-functional new pesticides used to control sugarcane borders and woolly aphids.They could be used alternately with other pesticides to delay the emergence and development of pest resistance to pesticides.The best dosage of the two pesticides in the field was 45 kg/hm^2.They could be mixed with fertilizer( 1200-1800 kg/hm^2),scattered in sugarcane ditches or at the base of sugarcane plants,and covered with soil or film from January to July.The control effect on dead heart seedlings damaged by borers could be up to above 79.2%,and the control effect on sugarcane woolly aphids could reach more than 98.8%.In comparison with the control group,the actual yield and sugar content of sugarcane increased by above 41 555 kg/hm^2 and 6.5% respectively.The application of slow-release,long-acting,strong systemic and multi-functional new agents with fertilizer around roots is convenient,precise and efficient,labor-saving,time-saving and environmentally friendly,and is worthy of being widely applied in sugarcane areas.展开更多
Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have step...Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.展开更多
Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the pres...Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5 A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-totreat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.展开更多
BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved...BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure.展开更多
Direct-acting antiviral agents(DAAs)for hepatitis C virus(HCV)infection are one of the major advances in its medical treatment.The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the ...Direct-acting antiviral agents(DAAs)for hepatitis C virus(HCV)infection are one of the major advances in its medical treatment.The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States,Europe,and Japan.When combined with peginterferon plus ribavirin,these agents increase sustained virologic response rates to70%-80%in treatment-na?ve patients and previoustreatment relapsers with chronic HCV genotype 1 infection.Without peginterferon plus ribavirin,DAA monotherapies increased DAA-resistance mutations.Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future.However,it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases.Furthermore,these mutations exhibit cross-resistance to multiple drugs.The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown,and it is as yet uncertain whether such variants are sensitive to DAAs.We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors.Here,we reviewed the literature on resistance variants of HCV protease inhibitors in treatment na?ve patients with chronic HCV genotype 1,as well as our experience.展开更多
BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asi...BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asia.AIM To investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODS This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December 2018.They were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more wk.The participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary endpoint.The occurrence of adverse events and drug-drug interactions were recorded.RESULTS In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)patients.Fifty(13.7%)patients were treatment-experienced.Intention-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype 3.Most of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HCV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the adverse events were mild.We found two cases of special adverse events.One case involved facial and bilateral lower extremity edema,and the other case showed an interesting change in lipid levels while on medication.No severe adverse events were noted.CONCLUSION The DAA-based regimens tested in this study have excellent effectiveness and safety in all patients infected with HCV genotypes 1,2 and 3,including those with cirrhosis.展开更多
With the introduction of direct-acting antiviral agents(DAA), the rate of sustained virological response(SVR) in the treatment of hepatitis C virus(HCV) has radically improved to over 95%. Robust scientific evidence s...With the introduction of direct-acting antiviral agents(DAA), the rate of sustained virological response(SVR) in the treatment of hepatitis C virus(HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma(HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4%(maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4%(maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection.展开更多
Based on the premise that ethics education leads to creation of the required (acceptable level of) ethical awareness, the general streamline of accounting ethics literature is strongly in favor of teaching adequate,...Based on the premise that ethics education leads to creation of the required (acceptable level of) ethical awareness, the general streamline of accounting ethics literature is strongly in favor of teaching adequate, efficient, and effective accounting ethics. This paper takes the position that this premise must be checked in an educational setting in which accounting ethics education lacks the characteristics of being adequate, efficient, and effective. Accordingly, a questionnaire with two parts was distributed to accounting students about to graduate from the University of Bahrain (UoB). The first part is an exploratory investigation consisting of 21 variables/questions. The second part is an experimental investigation consisting of 13 hypothetical accounting cases representing various ethics violations. The general tendency by an accounting student based on the two parts indicates that he/she holds an acceptable level of ethical awareness, despite the fact that accounting education programs lack an adequate, efficient, and effective approach to teaching accounting ethics.展开更多
This study seeks to explore the impact of the Environment Management Act (EMA) (2005) on the accountability of three companies in Fiji. The study uses a multi-case study approach based on three subsidiaries of a c...This study seeks to explore the impact of the Environment Management Act (EMA) (2005) on the accountability of three companies in Fiji. The study uses a multi-case study approach based on three subsidiaries of a conglomerate. Data collection methods include semi-structured interviews with accountants, internal auditors, and environmental officers, document reviews, and content analysis of annual reports and websites of the respective companies. The findings suggest that the EMA (2005) had some effects in terms of engendering accountability on the companies studied. Further evidence suggests that while this increased accountability has led to disclosures in annual reports and websites, these disclosures are minimal at best; furthermore, they primarily address that the stakeholder group comprised government regulatory authorities. The study provides policy implications on how environmental legislations could be designed to improve the accountability of commercial entities in developing economies. The experience and issues highlighted are also useful to other developing economies who are contemplating in developing their own environmental legislations. This paper is one of the few papers that explore the impact of environmental legislations on accountability in a developing economy context.展开更多
BACKGROUND The effectiveness of sofosbuvir/ribavirin(SOF/RBV) combination therapy,which is one of the 1 st-choice therapeutic options for patients with hepatitis C virus(HCV) genotype 2(HCV-G2) in Japan according to t...BACKGROUND The effectiveness of sofosbuvir/ribavirin(SOF/RBV) combination therapy,which is one of the 1 st-choice therapeutic options for patients with hepatitis C virus(HCV) genotype 2(HCV-G2) in Japan according to the most recent version of the Japan Society of Hepatology guideline, for patients who experienced failure of the ombitasvir/paritaprevir/ritonavir plus ribavirin(OBV/PTV/r+RBV) combination therapy, which was another option for patients with HCV-G2, is unknown.CASE SUMMARY We evaluated the effects of SOF/RBV combination therapy in two patients with genotype 2 a who could not achieve a sustained virological response(SVR) by OBV/PTV/r+RBV combination therapy. One patient was complicated with VogtKoyanagi-Harada(VKH) disease. Resistance-associated variations before SOF/RBV combination therapy were not detected in two patients. Both patients had an SVR at 12 wk after the treatment(SVR12). Regarding adverse events(AEs), itching, chill, a dull feeling in the throat and cough as well as increase of alanine transaminase level were shown in one patient, while a headache and deterioration of light aversion probably due to the recurrence of VKH disease were shown in the other patients. In addition, the latter patient developed arthralgia and morning stiffness approximately 7 wk after the therapy and turned out to be diagnosed with rheumatoid arthralgia.CONCLUSION SOF/RBV therapy might be effective for patients experiencing failure of OBV/PTV/r+RBV therapy, but caution should be taken regarding the AEs.展开更多
基金The Stage Achievement of the Item "Theory and Policy Research on Building A New Socialist Countryside"in Heilongjiang Philosophy and Social Service Research Base (Economic of Agricultural and Rural Area) (05zd001)
文摘Rural finance is an issue concerned with rural people, improving rural financial management is important to close the relations of cadres and masses, maintain rural stability, and promote rural economic development. This article explained the main problems of village financial, the needs of introducing commission and agent system of "village-level accounting" for building a new socialist countryside, and the measures of improving commission and agent system of "village-level accounting".
文摘AIMTo evaluate the bidirectional association between metabolic syndrome (MS) components and antiviral treatment response for chronic hepatitis C virus (HCV) infection. METHODSThis retrospective cohort study included 119 HCV + patients treated with pegylated-interferon-α and ribavirin. Metabolic characteristics and laboratory data were collected from medical records. Differences in baseline clinical and demographic risk factors between responders and non-responders were assessed using independent samples t-tests or χ<sup>2</sup> tests. The effects of sustained viral response (SVR) to antiviral treatment on de novo impairments in MS components, including impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), were assessed using univariable and multivariable logistic regression analysis, while the effect of MS components on SVR was assessed using univariable logistic regression analysis. RESULTSOf the 119 patients, 80 (67%) developed SVR over the average 54 ± 13 mo follow-up. The cumulative risks for de novo T2DM and IFG were 5.07- (95%CI: 1.261-20.4, P = 0.022) and 3.87-fold higher (95%CI: 1.484-10.15, P = 0.006), respectively for non-responders than responders, when adjusted for the baseline risk factors age, sex, HCV genotype, high viral load, and steatosis. Post-treatment triglyceride levels were significantly lower in non-responders than in responders (OR = 0.27; 95%CI: 0.069-0.962, P = 0.044). Age and HCV genotype 3 were significantly different between responders and non-responders, and MS components were not significantly associated with SVR. Steatosis tended to attenuate SVR (OR = 0.596; 95%CI: 0.331-1.073, P = 0.08). CONCLUSIONSVR was associated with lower de novo T2DM and IFG incidence and higher triglyceride levels. Patients infected with HCV should undergo T2DM screening and antidiabetic treatment.
文摘AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.
文摘Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, among these there is an increased risk of atherosclerosis and cardiovascular disease as well as an increased cardiovascular mortality. Several direct and indirect HCV pro-atherogenic mechanisms have been proposed. HCV lives and replicates within carotid plaques, promoting a local environment of pro-atherogenic factors. In addition, it causes conditions such as insulin resistance, diabetes, hepatic steatosis, cryoglobulinemia and endotoxinemia that are associated with the development of atherosclerosis and cardiovascular disease. Therapeutic regimens based on direct-acting antiviral agents (DAA) are currently available with high efficacy in HCV clearance and improvement of liver disease, but does HCV eradication also improve atherosclerosis and the risk of cardiovascular disease? Recently, a multi-center study has shown that elimination of HCV improves carotid atherosclerosis. Two studies have shown that DAA treatments significantly reduce the risk of cardiovascular events. Several studies have assessed the impact of HCV clearance on pro-atherosclerosis metabolic conditions showing improvement in cardiovascular risk biomarkers, disappearance or improvement of insulin resistance, reduction of risk of developing diabetes and improvement of glycemic control. There are also evidences that HCV clearance promotes the recovery of cytokines and inflammatory markers associated with atherosclerosis and the disappearance of cryoglobulinemia. Available data show that clearance of HCV by DAAs is associated with an improvement in atherosclerosis and metabolic and immunological conditions that promote the development of cardiovascular disease. However, the data are not sufficient to allow definitive conclusions and further studies will be needed to definitively clarify the impact of HCV clearance on atherosclerosis and cardiovascular disease.
文摘AIM To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C(CHC) treated with new Direct-Acting Antiviral agents(DAAs) compared to pegylated interferon-2α plus ribavirin(P/R) therapy.METHODS This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus(HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index(PASI) scores and the Dermatology Quality of Life Index(DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different b DMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response(SVR) were considered as outcomes of HCV therapy.RESULTS Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower(P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group(0/27) compared to 8 patients of the P/R group(8/32) needed a shift in biological treatment.CONCLUSION DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.
基金Supported by Sugar Crop Research System(CARS-170303)Training Project of"Yunling Industry Technology Leading Talent"(2018LJRC56)Special Funds for Construction of Modern Agricultural Industrial Technology System of Yunnan Province(YNGZTX-4-92)
文摘In order to select the long-acting,low toxic,low-risk and multi-functional new pesticides for the control of sugarcane borders and woolly aphids and precise and efficient application technology,the control effect of 10% monosultap · thiamethoxam granular formulation and 1% Bt · clothianidin granular formulation on sugarcane borders and woolly aphids were studied.The results showed that 10% monosultap·thiamethoxam GR and 1% Bt·clothianidin GR had good control effects on sugarcane borders and woolly aphids.They were ideal slow-release,long-acting,low toxic and multi-functional new pesticides used to control sugarcane borders and woolly aphids.They could be used alternately with other pesticides to delay the emergence and development of pest resistance to pesticides.The best dosage of the two pesticides in the field was 45 kg/hm^2.They could be mixed with fertilizer( 1200-1800 kg/hm^2),scattered in sugarcane ditches or at the base of sugarcane plants,and covered with soil or film from January to July.The control effect on dead heart seedlings damaged by borers could be up to above 79.2%,and the control effect on sugarcane woolly aphids could reach more than 98.8%.In comparison with the control group,the actual yield and sugar content of sugarcane increased by above 41 555 kg/hm^2 and 6.5% respectively.The application of slow-release,long-acting,strong systemic and multi-functional new agents with fertilizer around roots is convenient,precise and efficient,labor-saving,time-saving and environmentally friendly,and is worthy of being widely applied in sugarcane areas.
文摘Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.
文摘Before the advent of direct acting antiviral agents(DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5 A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-totreat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.
文摘BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure.
基金Supported by Grants from the Japan Society for Promotion of Science(JSPS)Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology of Japanand Grants from the Ministry of Health,Labour,and Welfare of Japan
文摘Direct-acting antiviral agents(DAAs)for hepatitis C virus(HCV)infection are one of the major advances in its medical treatment.The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States,Europe,and Japan.When combined with peginterferon plus ribavirin,these agents increase sustained virologic response rates to70%-80%in treatment-na?ve patients and previoustreatment relapsers with chronic HCV genotype 1 infection.Without peginterferon plus ribavirin,DAA monotherapies increased DAA-resistance mutations.Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future.However,it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases.Furthermore,these mutations exhibit cross-resistance to multiple drugs.The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown,and it is as yet uncertain whether such variants are sensitive to DAAs.We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors.Here,we reviewed the literature on resistance variants of HCV protease inhibitors in treatment na?ve patients with chronic HCV genotype 1,as well as our experience.
文摘BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asia.AIM To investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODS This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December 2018.They were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more wk.The participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary endpoint.The occurrence of adverse events and drug-drug interactions were recorded.RESULTS In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)patients.Fifty(13.7%)patients were treatment-experienced.Intention-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype 3.Most of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HCV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the adverse events were mild.We found two cases of special adverse events.One case involved facial and bilateral lower extremity edema,and the other case showed an interesting change in lipid levels while on medication.No severe adverse events were noted.CONCLUSION The DAA-based regimens tested in this study have excellent effectiveness and safety in all patients infected with HCV genotypes 1,2 and 3,including those with cirrhosis.
文摘With the introduction of direct-acting antiviral agents(DAA), the rate of sustained virological response(SVR) in the treatment of hepatitis C virus(HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma(HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4%(maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4%(maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection.
文摘Based on the premise that ethics education leads to creation of the required (acceptable level of) ethical awareness, the general streamline of accounting ethics literature is strongly in favor of teaching adequate, efficient, and effective accounting ethics. This paper takes the position that this premise must be checked in an educational setting in which accounting ethics education lacks the characteristics of being adequate, efficient, and effective. Accordingly, a questionnaire with two parts was distributed to accounting students about to graduate from the University of Bahrain (UoB). The first part is an exploratory investigation consisting of 21 variables/questions. The second part is an experimental investigation consisting of 13 hypothetical accounting cases representing various ethics violations. The general tendency by an accounting student based on the two parts indicates that he/she holds an acceptable level of ethical awareness, despite the fact that accounting education programs lack an adequate, efficient, and effective approach to teaching accounting ethics.
文摘This study seeks to explore the impact of the Environment Management Act (EMA) (2005) on the accountability of three companies in Fiji. The study uses a multi-case study approach based on three subsidiaries of a conglomerate. Data collection methods include semi-structured interviews with accountants, internal auditors, and environmental officers, document reviews, and content analysis of annual reports and websites of the respective companies. The findings suggest that the EMA (2005) had some effects in terms of engendering accountability on the companies studied. Further evidence suggests that while this increased accountability has led to disclosures in annual reports and websites, these disclosures are minimal at best; furthermore, they primarily address that the stakeholder group comprised government regulatory authorities. The study provides policy implications on how environmental legislations could be designed to improve the accountability of commercial entities in developing economies. The experience and issues highlighted are also useful to other developing economies who are contemplating in developing their own environmental legislations. This paper is one of the few papers that explore the impact of environmental legislations on accountability in a developing economy context.
文摘BACKGROUND The effectiveness of sofosbuvir/ribavirin(SOF/RBV) combination therapy,which is one of the 1 st-choice therapeutic options for patients with hepatitis C virus(HCV) genotype 2(HCV-G2) in Japan according to the most recent version of the Japan Society of Hepatology guideline, for patients who experienced failure of the ombitasvir/paritaprevir/ritonavir plus ribavirin(OBV/PTV/r+RBV) combination therapy, which was another option for patients with HCV-G2, is unknown.CASE SUMMARY We evaluated the effects of SOF/RBV combination therapy in two patients with genotype 2 a who could not achieve a sustained virological response(SVR) by OBV/PTV/r+RBV combination therapy. One patient was complicated with VogtKoyanagi-Harada(VKH) disease. Resistance-associated variations before SOF/RBV combination therapy were not detected in two patients. Both patients had an SVR at 12 wk after the treatment(SVR12). Regarding adverse events(AEs), itching, chill, a dull feeling in the throat and cough as well as increase of alanine transaminase level were shown in one patient, while a headache and deterioration of light aversion probably due to the recurrence of VKH disease were shown in the other patients. In addition, the latter patient developed arthralgia and morning stiffness approximately 7 wk after the therapy and turned out to be diagnosed with rheumatoid arthralgia.CONCLUSION SOF/RBV therapy might be effective for patients experiencing failure of OBV/PTV/r+RBV therapy, but caution should be taken regarding the AEs.