Zeolite synthesis in contemporary chemical industries is predominantly conducted using organic structure‐directing agents(OSDAs),which are chronically hazardous to humans and the environment.It is a growing trend to ...Zeolite synthesis in contemporary chemical industries is predominantly conducted using organic structure‐directing agents(OSDAs),which are chronically hazardous to humans and the environment.It is a growing trend to develop an eco‐friendly and nuisanceless OSDA for zeolite synthesis.Herein,choline is employed as a non‐toxic and green OSDA to synthesize high silica Y zeolite with SiO2/Al2O3 ratios of 6.5–6.8.The prepared Y zeolite samples exhibited outstanding(hydro)thermal stability at ultrahigh temperature owing to the higher SiO2/Al2O3 ratio.The XRF,SEM,29Si‐NMR and 13Na+results suggested that choline plays a structure‐directing role in the synthesis of Y zeolite,while the feed molar fraction of Na+is a crucial determinant for the framework SiO2/Al2O3 ratio and the crystal morphology.展开更多
Silicoaluminophosphates SAPO-11 molecular sieves with small particle size and hierarchical pores were synthesized using the directing agent method.The effect of crystallization time on the particle structure,morpholog...Silicoaluminophosphates SAPO-11 molecular sieves with small particle size and hierarchical pores were synthesized using the directing agent method.The effect of crystallization time on the particle structure,morphology,pore structure properties,and acid properties of SAPO-11 molecular sieves were investigated.Unlike the SAPO-11 molecular sieves synthesized with the conventional method,the results of XRD,SEM,BET and NH3-TPD analyses showed that the SAPO-11 molecular sieves synthesized by the directing agent method in a shorter crystallization time exhibited fine and uniform morphology.By increasing the crystallization time,the particle size of SAPO-11 molecular sieve was significantly reduced,and the mesoporous structure(intercrystalline pores)was formed.Furthermore,the external specific surface area and the total specific surface area reached 81.7 m^2/g and 192.0 m^2/g,respectively,which effectively reduced the pore mass transfer resistance and significantly increased the number of acid sites.The results of n-dodecane hydroisomerization revealed that the Pt/SAPO-11 prepared with the novel method exhibited higher catalytic activity and better hydroisomerization selectivity than that synthesized by the conventional hydrothermal method.Thus,the small particle molecular sieve showed a promising industrial application prospect to be used as catalyst support.展开更多
Recurrence of hepatitis C virus(HCV)infection following liver transplantation(LT)is almost universal and can accelerate graft cirrhosis in up to 30%of patients.The development of effective strategies to treat or preve...Recurrence of hepatitis C virus(HCV)infection following liver transplantation(LT)is almost universal and can accelerate graft cirrhosis in up to 30%of patients.The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge,considering the shortage of donor organs and the accelerated progression of HCV in LT recipients.Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients,even though the combination is not as effective as it is in immunocompetent patients.A sustained virological response in the setting of LT improves patient and graft survival,but this is only achieved in 30%-45%of patients and the treatment is poorly tolerated.To improve the efficacy of pre-and post-transplant antiviral therapy,a new class of potent direct-acting antiviral agents (DAAs)has been developed.The aim of this review is to summarize the use of DAAs in LT HCV patients.PubMed,Cochrane Library,MEDLINE,EMBASE,Web of Science and clinical trial databases were searched for this purpose.To date,only three clinical studies on the topic have been published and most of the available data are in abstract form.Although a moderately successful early virological response has been reported,DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness.Moreover,the ongoing nature of data,the lack of randomized studies,the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable.In conclusion,large welldesigned clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.展开更多
Silica hollow spheres（SHSs） have attracted great attention because of their low toxicity, low density, large surface area, high chemical and thermal stability, and surface permeability. They can be widely applied in...Silica hollow spheres（SHSs） have attracted great attention because of their low toxicity, low density, large surface area, high chemical and thermal stability, and surface permeability. They can be widely applied in storage^[l], catalysis^[2], drug deli- very^[3,4], low-dielectric-constant materials^[5], low-refractive materials^[6-8], and so on. Up to now, there have been various methods to produce SHSs. Inorganic^[9] or organic particles^[10], such as polystyrene or calcium carbonate, were used as hard templates to create hollow cavities, However, the multistep synthetic process and the lack of structural robustness of the shells upon template removal process weaken their applica- tion. Soft templates, including oil-in-water emulsions^[11,12], vesicles^[13], micelle^[14,15] and gas bubbles^[16], are applied widely.展开更多
Curcurbit[n]uril(Q[n])-based supramolecular frameworks(QSFs) constructed from the outer surface interaction of Q[n]s(OSIQ) have the characteristic of simplicity,diversity and modulability.Their simplicity is reflected...Curcurbit[n]uril(Q[n])-based supramolecular frameworks(QSFs) constructed from the outer surface interaction of Q[n]s(OSIQ) have the characteristic of simplicity,diversity and modulability.Their simplicity is reflected in their simple composition and preparation methods used for QSFs.The diversity of supramolecular organic frameworks(SOFs) is reflected in the synthesis methods and structural characteristics of the as-obtained QSFs,as well as the variety of structural directing agents and basic building blocks used to prepare QSFs.The modulability is reflected by the controllable channel size in the QSFs,which can be adjusted using different sizes of Q[n]s.In this work,the first re ported cucurbituril Q[6]was selected as the basic building block and three Q[6]-based su p ramolecular frameworks were obtained from aqueous HCl solutions in the presence of [CdCl_(4)]^(2-)respectively.The OSIQs are the main driving forces for the formation of these frameworks.This study shows the diversity of the QSFs.展开更多
Chronic viral hepatitis is a significant health problem throughout the world,which already represents high annual mortality.By 2040,chronic viral hepatitis due to virus B and virus C and their complications cirrhosis ...Chronic viral hepatitis is a significant health problem throughout the world,which already represents high annual mortality.By 2040,chronic viral hepatitis due to virus B and virus C and their complications cirrhosis and hepatocellular carcinoma will be more deadly than malaria,vitellogenesis-inhibiting hormone,and tuberculosis altogether.In this review,we analyze the global impact of chronic viral hepatitis with a focus on the most vulnerable groups,the goals set by the World Health Organization for the year 2030,and the key points to achieve them,such as timely access to antiviral treatment of direct-acting antiviral,which represents the key to achieving hepatitis C virus elimination.Likewise,we review the strategies to prevent transmission and achieve control of hepatitis B virus.Finally,we address the impact that the coronavirus disease 2019 pandemic has had on implementing elimination strategies and the advantages of implementing telemedicine programs.展开更多
Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to(pegylated) inter...Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to(pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response(SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte(CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.展开更多
B cells lymphoma is one of the most challenging extrahepatic manifestations of hepatitis C virus(HCV). Recently, a new kind of B-cell lymphoma, named doublehit B(DHL), was characterized with an aggressive clinical cou...B cells lymphoma is one of the most challenging extrahepatic manifestations of hepatitis C virus(HCV). Recently, a new kind of B-cell lymphoma, named doublehit B(DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents(DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in oncohaematological diseases.展开更多
Treatment of patients with chronic kidney disease(CKD) and chronic hepatitis C(CHC) differs from that used in the general CHC population mostly when glomerular filtration rate(GFR) is below 30 m L/min, as sofosbuvir, ...Treatment of patients with chronic kidney disease(CKD) and chronic hepatitis C(CHC) differs from that used in the general CHC population mostly when glomerular filtration rate(GFR) is below 30 m L/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvirbased regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response(SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current managementof CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.展开更多
Injection drug users(IDUs)are at risk of hepatitis C virus(HCV)infection,due to needle and syringe sharing.Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cured with antivira...Injection drug users(IDUs)are at risk of hepatitis C virus(HCV)infection,due to needle and syringe sharing.Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cured with antiviral treatment leading to sustained viral response(SVR).It is well demonstrated that,when close cooperation between specialists in drug addiction and psychiatrists is assured,patients on maintenance treatment with methadone/buprenorphine can be treated for HCV with response rate,tolerability and side effects similar to those reported in non-IDUs.Current guidelines recommend that active injection drug use should not exclude patients from HCV treatment,but many services remain reluctant to treat IDUs.No significant pharmacodynamic interactions were reported between approved direct anti-viral agents(DAAs)and buprenorphine or methadone.Dose adjustments are not recommended;therefore DAAs appear to be the"perfect"therapy for patients taking opiate substitutive therapy.These suggestions have been recently recognized by the European Association for the Study of the Liver(EASL)and included in EASL Recommendations on Treatment of Hepatitis C 2016.Guidelines confirm that HCV treatment for IDUs should be considered on an individualized basis and delivered within a multidisciplinary team setting;a history of intravenous drug use and recent drug use at treatment initiation are not associated with reduced SVR and decisions to treat must be made on a case-by-case basis.展开更多
AIM To evaluate the occurrence of resistant mutations in treatment-na?ve hepatitis C virus(HCV) sequences deposited in the European hepatitis C virus database(euH CVdb). METHODS The sequences were downloaded from the ...AIM To evaluate the occurrence of resistant mutations in treatment-na?ve hepatitis C virus(HCV) sequences deposited in the European hepatitis C virus database(euH CVdb). METHODS The sequences were downloaded from the eu HCVdb(https://euhcvdb.ibcp.fr/eu HCVdb/). The search was performed for full-length NS3 protease, NS5 A and NS5 B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5 A and 535 NS5 B sequences from HCV genotypes1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents(DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioE dit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis.RESULTS The Q80 K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V(3.21%) in genotype 1a, and Y56F(15.93%), V132I(23.28%) and I170V(65.20%) in genotype 1b. For the NS5 A, 2.21% of the genotype 1a sequences have the P58 S mutation, 5.95% of genotype 1b sequences have the R30 Q mutation, 15.79% of subtypes 2a sequences have the Q30 R mutation, 23.08% of subtype 2b sequences have a L31 M mutation, and in subtype 3a sequences, 23.08% have the M31 L resistant variants. For the NS5 B, the V321 L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142 T variant was observed in 0.32% of subtype 1b sequences. The C316 Y, S556 G, D559 N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes.CONCLUSION HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome.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 evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively ...AIM: To evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index,steatosis, INFL3 polymorphism, pre-treatment HCVRNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1(± 1.8) wk. Overall, 58%(62/107) of the patients achieved an SVR and 42%(45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/m L(OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis(OR = 0.278, 95%CI: 0.113-0.684,P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥600000 UI/m L and advanced fibrosis, the probability of achieving an SVR was 29%(95%CI: 13.1-45.2).In patients with pre-treatment HCV-RNA < 600000UI/m L and mild to moderate fibrosis, the probability of achieving an SVR was 81%(95%CI: 68.8-93.4).CONCLUSION: In patients with HCV genotype 3infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agentsbased regimes.展开更多
The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA)combination hepatitis C virus(HCV)treatment of Paritaprevir,Ombitasvir,Dasabuvir,Ritonavir,and Ribavirin(PODr+R)can c...The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA)combination hepatitis C virus(HCV)treatment of Paritaprevir,Ombitasvir,Dasabuvir,Ritonavir,and Ribavirin(PODr+R)can cause severe liver injury in patients with advanced liver disease.Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs,but has not been reported in patients with compensated cirrhosis.We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis)treated with PODr+R.The patient presented on day 14 of PODr+R therapy with jaundice and new-onset ascites.Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65,while aminotransferase levels remained relatively stable.Hepatitis C treatment was discontinued on day 24 and she gradually recovered.Follow-up testing showed that she achieved a sustained virologic response.In conclusion,hepatic decompensation developed within two weeks of starting treatment withPODr+R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels.Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr+R.展开更多
Chronic hepatitis C is a leading cause of morbidity and mortality,mainly related to fibrosis/cirrhosis and portal hypertension.Direct antiviral agents are highly effective and safe and can now cure>90%of the patien...Chronic hepatitis C is a leading cause of morbidity and mortality,mainly related to fibrosis/cirrhosis and portal hypertension.Direct antiviral agents are highly effective and safe and can now cure>90%of the patients.Sustained viral response(SVR)after interferon-based regimens has been associated with improvement in liver function,fibrosis and portal hypertension in a significant proportion of patients,although a point of no return seems to exist from which viral elimination is no longer capable of preventing portal hypertension progression and liver decompensation.Indeed,although SVR is associated with improvement of hepatic venous pressure gradients and therefore a decreased risk of de novo esophageal varices,several studies show that viral clearance does not eliminate the risk of variceal progression,liver decompensation and death in patients with pre-established portal hypertension.Although evidence about the effects of direct antiviral agents(DAAs)on clinically significant outcomes is still scarce and with short follow-up,DAAs can decrease the burden of the disease if patients are timely treated before significant fibrosis and portal hypertension develops.Studies with longer follow-up are waited to establish the real magnitude of hepatitis C treatment on portal hypertension.Future studies should also focus on predictors of portal hypertension resolution since it can influence management and avoid unnecessary monitoring.展开更多
The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development o...The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 m L/min per 1.73 m^2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.展开更多
Chronic hepatitis C virus(HCV)infection is a major global public health problem,particularly in developing part of the world.Significant advances have been made in the early diagnosis and treatment of the disease.Its ...Chronic hepatitis C virus(HCV)infection is a major global public health problem,particularly in developing part of the world.Significant advances have been made in the early diagnosis and treatment of the disease.Its management has been particularly revolutionized during the past two decades.In this review,we summarize the major advances in the diagnostic and management armamentarium for chronic HCV infection.The focus of the present review is on the newer directly acting anti-viral agents,which have revolutionized the management of chronic HCV infection.Management of uncomplicated chronic HCV infection and of specific complications and special at-risk populations of patients will be covered in detail.Despite the advent and approval of highly effective and well tolerable oral agents,still many challenges remain,particularly the affordability,the equitable distribution and access to later drugs.The World Health Organization aims to eliminate viral hepatitis including HCV by 2030 since its poses a major public health threat.There is an urgent need to ensure uniform and early access to diagnostic and therapeutic facilities throughout the world if the later goal has to be realized.展开更多
Hepatitis C virus(HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greate...Hepatitis C virus(HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease(CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in endstage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents(DAAs) while avoiding peginterferon and ribavirin. The first results were convincing. To aid in the correct use of these drugs in patients with renal insufficiency, their pharmacokinetic properties and potential renal toxicity must be known. The renal toxicity of these new drugs was not a safety signal in clinical trials, and the drugs are generally efficient in these frail populations. These drugs are usually well tolerated, but recent cohort studies have demonstrated that these new regimens may be associated with renal side effects, especially when using sofosbuvir combinations. HCV, renal diseases and comorbidities are intimately linked. The close monitoring of renal function is required, particularly for at-risk patients(transplanted, HIV-coinfected, CKD, hypertensive or diabetic patients). New DAA regimens, which will soon be approved, will probably change the landscape.展开更多
Loss of follow-up or reinfections hinder the expectations of hepatitis C eradicationdespite the existence of highly effective treatments. Moreover, the elimination ofthe infection does not imply the reversion of those...Loss of follow-up or reinfections hinder the expectations of hepatitis C eradicationdespite the existence of highly effective treatments. Moreover, the elimination ofthe infection does not imply the reversion of those chronic alterations derivedfrom the previous infection by hepatitis C virus (HCV). This review analyzes therisk factors associated with loss to follow-up in diagnosis or treatment, and thepossibility of reinfection. Likewise, it assesses the residual alterations induced bychronic HCV infection considering the liver alterations (inflammation, fibrosis,risk of decompensation, hepatocellular carcinoma, liver transplantation) and, onthe other hand, the comorbidities and extrahepatic manifestations (cryoglobulinemia,non-Hodgkin lymphoma, peripheral insulin resistance, and lipid, boneand cognitive alterations). Peculiarities present in subjects coinfected with humanimmunodeficiency virus are analyzed in each section.展开更多
As crucial factors in hepatitis C virus(HCV)management,resistance-associated substitutions(RASs)are associated with the treatment outcome of some direct-acting antiviral(DAA)-based regimens.In this study,we mainly ana...As crucial factors in hepatitis C virus(HCV)management,resistance-associated substitutions(RASs)are associated with the treatment outcome of some direct-acting antiviral(DAA)-based regimens.In this study,we mainly analyzed the impact of baseline Y93 H or Y93 Y/H on the short-term efficacy after single administration of NS5 A inhibitors in three phaseⅠb clinical trials(yimitasvir phosphate,KW-136 and fopitasvir),and analyzed the prevalence of baseline RASs and treatment-emergent RASs.A total of 94 treatment-naive HCV genotype(GT)-1 b(n=63)and GT-2 a(n=31)Chinese patients were enrolled in three phase lb clinical trials.We investigated RASs in 77 patients with next generation or Sanger sequencing.In the 7-day trial of yimitasvir phosphate,the mean maximum HCV RNA decrease of patients with baseline Y93 H or Y93 Y/H was lower than that of patients without the mutation in the 30 mg and 200 mg cohorts(0.83 vs.2.45 log10 IU/mL and 1.92 vs.2.63 log10 IU/mL).In the3-day trial of KW-136,the mean maximum HCV RNA decrease in patients with baseline Y93 H or Y93 Y/H was lower than that of patients without the mutation in the 30,60 and 120 mg cohorts(1.58 vs.2.89 log10 IU/mL,3.16 vs.4.09 log10 IU/mL and3.00 vs.5.04 log10 IU/mL,respectively).In the 3-day trial of fopitasvir,only 30 mg group had baseline Y93 H or Y93 Y/H,and the average maximum HCV RNA decrease of patients with baseline Y93 H or Y93 Y/H was lower than that of patients without the mutation(1.45 vs.3.59 log10 IU/mL).In the three trials,baseline RASs were observed in 54 patients(70.1%;54/77).The most prevalent baseline RASs were Y93 H and Y93 Y/H(18.2%;14/77),followed by L3 IM(16.9%;13/77).The most common RASs after single administration of DAA were Y93 H and Y93 Y/H.Our data could provide reference for future clinical treatment and clinical trial.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.21802136)~~
文摘Zeolite synthesis in contemporary chemical industries is predominantly conducted using organic structure‐directing agents(OSDAs),which are chronically hazardous to humans and the environment.It is a growing trend to develop an eco‐friendly and nuisanceless OSDA for zeolite synthesis.Herein,choline is employed as a non‐toxic and green OSDA to synthesize high silica Y zeolite with SiO2/Al2O3 ratios of 6.5–6.8.The prepared Y zeolite samples exhibited outstanding(hydro)thermal stability at ultrahigh temperature owing to the higher SiO2/Al2O3 ratio.The XRF,SEM,29Si‐NMR and 13Na+results suggested that choline plays a structure‐directing role in the synthesis of Y zeolite,while the feed molar fraction of Na+is a crucial determinant for the framework SiO2/Al2O3 ratio and the crystal morphology.
基金We thank the National Natural Science Fund of China(2016-Z0030)Natural Science Foundation of Liaoning Province(L2017 LQN008,L2019014).
文摘Silicoaluminophosphates SAPO-11 molecular sieves with small particle size and hierarchical pores were synthesized using the directing agent method.The effect of crystallization time on the particle structure,morphology,pore structure properties,and acid properties of SAPO-11 molecular sieves were investigated.Unlike the SAPO-11 molecular sieves synthesized with the conventional method,the results of XRD,SEM,BET and NH3-TPD analyses showed that the SAPO-11 molecular sieves synthesized by the directing agent method in a shorter crystallization time exhibited fine and uniform morphology.By increasing the crystallization time,the particle size of SAPO-11 molecular sieve was significantly reduced,and the mesoporous structure(intercrystalline pores)was formed.Furthermore,the external specific surface area and the total specific surface area reached 81.7 m^2/g and 192.0 m^2/g,respectively,which effectively reduced the pore mass transfer resistance and significantly increased the number of acid sites.The results of n-dodecane hydroisomerization revealed that the Pt/SAPO-11 prepared with the novel method exhibited higher catalytic activity and better hydroisomerization selectivity than that synthesized by the conventional hydrothermal method.Thus,the small particle molecular sieve showed a promising industrial application prospect to be used as catalyst support.
文摘Recurrence of hepatitis C virus(HCV)infection following liver transplantation(LT)is almost universal and can accelerate graft cirrhosis in up to 30%of patients.The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge,considering the shortage of donor organs and the accelerated progression of HCV in LT recipients.Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients,even though the combination is not as effective as it is in immunocompetent patients.A sustained virological response in the setting of LT improves patient and graft survival,but this is only achieved in 30%-45%of patients and the treatment is poorly tolerated.To improve the efficacy of pre-and post-transplant antiviral therapy,a new class of potent direct-acting antiviral agents (DAAs)has been developed.The aim of this review is to summarize the use of DAAs in LT HCV patients.PubMed,Cochrane Library,MEDLINE,EMBASE,Web of Science and clinical trial databases were searched for this purpose.To date,only three clinical studies on the topic have been published and most of the available data are in abstract form.Although a moderately successful early virological response has been reported,DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness.Moreover,the ongoing nature of data,the lack of randomized studies,the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable.In conclusion,large welldesigned clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.
基金Supported by the National Natural Science Foundation of China(No.20890121)the National Basic Research Program of China(No.2009CB930403)
文摘Silica hollow spheres（SHSs） have attracted great attention because of their low toxicity, low density, large surface area, high chemical and thermal stability, and surface permeability. They can be widely applied in storage^[l], catalysis^[2], drug deli- very^[3,4], low-dielectric-constant materials^[5], low-refractive materials^[6-8], and so on. Up to now, there have been various methods to produce SHSs. Inorganic^[9] or organic particles^[10], such as polystyrene or calcium carbonate, were used as hard templates to create hollow cavities, However, the multistep synthetic process and the lack of structural robustness of the shells upon template removal process weaken their applica- tion. Soft templates, including oil-in-water emulsions^[11,12], vesicles^[13], micelle^[14,15] and gas bubbles^[16], are applied widely.
基金the financial support of the National Natural Science Foundation of China(Nos.21761007,51663005 and 21871064)Science and Technology Plan Project of Guizhou Province(Nos.20175788 and 20185781)。
文摘Curcurbit[n]uril(Q[n])-based supramolecular frameworks(QSFs) constructed from the outer surface interaction of Q[n]s(OSIQ) have the characteristic of simplicity,diversity and modulability.Their simplicity is reflected in their simple composition and preparation methods used for QSFs.The diversity of supramolecular organic frameworks(SOFs) is reflected in the synthesis methods and structural characteristics of the as-obtained QSFs,as well as the variety of structural directing agents and basic building blocks used to prepare QSFs.The modulability is reflected by the controllable channel size in the QSFs,which can be adjusted using different sizes of Q[n]s.In this work,the first re ported cucurbituril Q[6]was selected as the basic building block and three Q[6]-based su p ramolecular frameworks were obtained from aqueous HCl solutions in the presence of [CdCl_(4)]^(2-)respectively.The OSIQs are the main driving forces for the formation of these frameworks.This study shows the diversity of the QSFs.
文摘Chronic viral hepatitis is a significant health problem throughout the world,which already represents high annual mortality.By 2040,chronic viral hepatitis due to virus B and virus C and their complications cirrhosis and hepatocellular carcinoma will be more deadly than malaria,vitellogenesis-inhibiting hormone,and tuberculosis altogether.In this review,we analyze the global impact of chronic viral hepatitis with a focus on the most vulnerable groups,the goals set by the World Health Organization for the year 2030,and the key points to achieve them,such as timely access to antiviral treatment of direct-acting antiviral,which represents the key to achieving hepatitis C virus elimination.Likewise,we review the strategies to prevent transmission and achieve control of hepatitis B virus.Finally,we address the impact that the coronavirus disease 2019 pandemic has had on implementing elimination strategies and the advantages of implementing telemedicine programs.
文摘Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to(pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response(SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte(CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.
文摘B cells lymphoma is one of the most challenging extrahepatic manifestations of hepatitis C virus(HCV). Recently, a new kind of B-cell lymphoma, named doublehit B(DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents(DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected. A possible effect of DAAs on DHL regression should be investigated, but eradicating HCV would avoid life-threatening reactivation of viral hepatitis during pharmacological immunosuppression in oncohaematological diseases.
文摘Treatment of patients with chronic kidney disease(CKD) and chronic hepatitis C(CHC) differs from that used in the general CHC population mostly when glomerular filtration rate(GFR) is below 30 m L/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvirbased regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response(SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current managementof CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.
文摘Injection drug users(IDUs)are at risk of hepatitis C virus(HCV)infection,due to needle and syringe sharing.Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cured with antiviral treatment leading to sustained viral response(SVR).It is well demonstrated that,when close cooperation between specialists in drug addiction and psychiatrists is assured,patients on maintenance treatment with methadone/buprenorphine can be treated for HCV with response rate,tolerability and side effects similar to those reported in non-IDUs.Current guidelines recommend that active injection drug use should not exclude patients from HCV treatment,but many services remain reluctant to treat IDUs.No significant pharmacodynamic interactions were reported between approved direct anti-viral agents(DAAs)and buprenorphine or methadone.Dose adjustments are not recommended;therefore DAAs appear to be the"perfect"therapy for patients taking opiate substitutive therapy.These suggestions have been recently recognized by the European Association for the Study of the Liver(EASL)and included in EASL Recommendations on Treatment of Hepatitis C 2016.Guidelines confirm that HCV treatment for IDUs should be considered on an individualized basis and delivered within a multidisciplinary team setting;a history of intravenous drug use and recent drug use at treatment initiation are not associated with reduced SVR and decisions to treat must be made on a case-by-case basis.
文摘AIM To evaluate the occurrence of resistant mutations in treatment-na?ve hepatitis C virus(HCV) sequences deposited in the European hepatitis C virus database(euH CVdb). METHODS The sequences were downloaded from the eu HCVdb(https://euhcvdb.ibcp.fr/eu HCVdb/). The search was performed for full-length NS3 protease, NS5 A and NS5 B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5 A and 535 NS5 B sequences from HCV genotypes1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents(DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioE dit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis.RESULTS The Q80 K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V(3.21%) in genotype 1a, and Y56F(15.93%), V132I(23.28%) and I170V(65.20%) in genotype 1b. For the NS5 A, 2.21% of the genotype 1a sequences have the P58 S mutation, 5.95% of genotype 1b sequences have the R30 Q mutation, 15.79% of subtypes 2a sequences have the Q30 R mutation, 23.08% of subtype 2b sequences have a L31 M mutation, and in subtype 3a sequences, 23.08% have the M31 L resistant variants. For the NS5 B, the V321 L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142 T variant was observed in 0.32% of subtype 1b sequences. The C316 Y, S556 G, D559 N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes.CONCLUSION HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome.
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 evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index,steatosis, INFL3 polymorphism, pre-treatment HCVRNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1(± 1.8) wk. Overall, 58%(62/107) of the patients achieved an SVR and 42%(45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/m L(OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis(OR = 0.278, 95%CI: 0.113-0.684,P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥600000 UI/m L and advanced fibrosis, the probability of achieving an SVR was 29%(95%CI: 13.1-45.2).In patients with pre-treatment HCV-RNA < 600000UI/m L and mild to moderate fibrosis, the probability of achieving an SVR was 81%(95%CI: 68.8-93.4).CONCLUSION: In patients with HCV genotype 3infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agentsbased regimes.
文摘The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA)combination hepatitis C virus(HCV)treatment of Paritaprevir,Ombitasvir,Dasabuvir,Ritonavir,and Ribavirin(PODr+R)can cause severe liver injury in patients with advanced liver disease.Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs,but has not been reported in patients with compensated cirrhosis.We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis)treated with PODr+R.The patient presented on day 14 of PODr+R therapy with jaundice and new-onset ascites.Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65,while aminotransferase levels remained relatively stable.Hepatitis C treatment was discontinued on day 24 and she gradually recovered.Follow-up testing showed that she achieved a sustained virologic response.In conclusion,hepatic decompensation developed within two weeks of starting treatment withPODr+R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels.Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr+R.
文摘Chronic hepatitis C is a leading cause of morbidity and mortality,mainly related to fibrosis/cirrhosis and portal hypertension.Direct antiviral agents are highly effective and safe and can now cure>90%of the patients.Sustained viral response(SVR)after interferon-based regimens has been associated with improvement in liver function,fibrosis and portal hypertension in a significant proportion of patients,although a point of no return seems to exist from which viral elimination is no longer capable of preventing portal hypertension progression and liver decompensation.Indeed,although SVR is associated with improvement of hepatic venous pressure gradients and therefore a decreased risk of de novo esophageal varices,several studies show that viral clearance does not eliminate the risk of variceal progression,liver decompensation and death in patients with pre-established portal hypertension.Although evidence about the effects of direct antiviral agents(DAAs)on clinically significant outcomes is still scarce and with short follow-up,DAAs can decrease the burden of the disease if patients are timely treated before significant fibrosis and portal hypertension develops.Studies with longer follow-up are waited to establish the real magnitude of hepatitis C treatment on portal hypertension.Future studies should also focus on predictors of portal hypertension resolution since it can influence management and avoid unnecessary monitoring.
文摘The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 m L/min per 1.73 m^2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.
文摘Chronic hepatitis C virus(HCV)infection is a major global public health problem,particularly in developing part of the world.Significant advances have been made in the early diagnosis and treatment of the disease.Its management has been particularly revolutionized during the past two decades.In this review,we summarize the major advances in the diagnostic and management armamentarium for chronic HCV infection.The focus of the present review is on the newer directly acting anti-viral agents,which have revolutionized the management of chronic HCV infection.Management of uncomplicated chronic HCV infection and of specific complications and special at-risk populations of patients will be covered in detail.Despite the advent and approval of highly effective and well tolerable oral agents,still many challenges remain,particularly the affordability,the equitable distribution and access to later drugs.The World Health Organization aims to eliminate viral hepatitis including HCV by 2030 since its poses a major public health threat.There is an urgent need to ensure uniform and early access to diagnostic and therapeutic facilities throughout the world if the later goal has to be realized.
文摘Hepatitis C virus(HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease(CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in endstage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents(DAAs) while avoiding peginterferon and ribavirin. The first results were convincing. To aid in the correct use of these drugs in patients with renal insufficiency, their pharmacokinetic properties and potential renal toxicity must be known. The renal toxicity of these new drugs was not a safety signal in clinical trials, and the drugs are generally efficient in these frail populations. These drugs are usually well tolerated, but recent cohort studies have demonstrated that these new regimens may be associated with renal side effects, especially when using sofosbuvir combinations. HCV, renal diseases and comorbidities are intimately linked. The close monitoring of renal function is required, particularly for at-risk patients(transplanted, HIV-coinfected, CKD, hypertensive or diabetic patients). New DAA regimens, which will soon be approved, will probably change the landscape.
基金Consejería de Salud,Junta de Andalucía,Integrated Territorial Initiative for the province of Cádiz,No.(ITI)2014-2020Cofinanced by Fondo Europeo de Desarrollo Regional(FEDER),No.PI-0076-2017+1 种基金Consejería de Salud,Junta de Andalucía,No.PI 0128/2018and Instituto de Salud Carlos III,Ministerio de Sanidad,Acción Estratégica en Salud 2017-2020,No.PI19/01361.
文摘Loss of follow-up or reinfections hinder the expectations of hepatitis C eradicationdespite the existence of highly effective treatments. Moreover, the elimination ofthe infection does not imply the reversion of those chronic alterations derivedfrom the previous infection by hepatitis C virus (HCV). This review analyzes therisk factors associated with loss to follow-up in diagnosis or treatment, and thepossibility of reinfection. Likewise, it assesses the residual alterations induced bychronic HCV infection considering the liver alterations (inflammation, fibrosis,risk of decompensation, hepatocellular carcinoma, liver transplantation) and, onthe other hand, the comorbidities and extrahepatic manifestations (cryoglobulinemia,non-Hodgkin lymphoma, peripheral insulin resistance, and lipid, boneand cognitive alterations). Peculiarities present in subjects coinfected with humanimmunodeficiency virus are analyzed in each section.
基金Jilin University Science and Technology Innovative Research Team(Grant No.2017TD-08)。
文摘As crucial factors in hepatitis C virus(HCV)management,resistance-associated substitutions(RASs)are associated with the treatment outcome of some direct-acting antiviral(DAA)-based regimens.In this study,we mainly analyzed the impact of baseline Y93 H or Y93 Y/H on the short-term efficacy after single administration of NS5 A inhibitors in three phaseⅠb clinical trials(yimitasvir phosphate,KW-136 and fopitasvir),and analyzed the prevalence of baseline RASs and treatment-emergent RASs.A total of 94 treatment-naive HCV genotype(GT)-1 b(n=63)and GT-2 a(n=31)Chinese patients were enrolled in three phase lb clinical trials.We investigated RASs in 77 patients with next generation or Sanger sequencing.In the 7-day trial of yimitasvir phosphate,the mean maximum HCV RNA decrease of patients with baseline Y93 H or Y93 Y/H was lower than that of patients without the mutation in the 30 mg and 200 mg cohorts(0.83 vs.2.45 log10 IU/mL and 1.92 vs.2.63 log10 IU/mL).In the3-day trial of KW-136,the mean maximum HCV RNA decrease in patients with baseline Y93 H or Y93 Y/H was lower than that of patients without the mutation in the 30,60 and 120 mg cohorts(1.58 vs.2.89 log10 IU/mL,3.16 vs.4.09 log10 IU/mL and3.00 vs.5.04 log10 IU/mL,respectively).In the 3-day trial of fopitasvir,only 30 mg group had baseline Y93 H or Y93 Y/H,and the average maximum HCV RNA decrease of patients with baseline Y93 H or Y93 Y/H was lower than that of patients without the mutation(1.45 vs.3.59 log10 IU/mL).In the three trials,baseline RASs were observed in 54 patients(70.1%;54/77).The most prevalent baseline RASs were Y93 H and Y93 Y/H(18.2%;14/77),followed by L3 IM(16.9%;13/77).The most common RASs after single administration of DAA were Y93 H and Y93 Y/H.Our data could provide reference for future clinical treatment and clinical trial.
