BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce th...BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce the occurrence of hepatocellular carcinoma(HCC)in patients with HCV-associated cirrhosis who are at high risk have not been concluded.AIM To investigate the effect of DAAs on the occurrence of HCC in patients with HCVassociated cirrhosis after achieving SVR.METHODS Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020.118 patients weren’t received antiviral treatment with any reasons named non-antiviral treatment group,and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group.Demographic information and laboratory data were collected from baseline and the following up.Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups.Cox proportional risk regression was used to re-evaluate the risk factors for HCC.RESULTS HCC incidence was 4.68/100PY(95%CI,3.09-6.81)in the DAAs treatment group,while it was 3.00/100PY(95%CI,1.50-5.37)in the non-antiviral treatment group,and the relative risk was 1.82(95%CI,0.93-3.53,P>0.05).The incidence of HCC at 12,24,36 and 48 months was 3.39%,6.36%,8.47%and 10.17%in the DAAs treatment group,and it was 0%,0%,3.39%and 9.32%in the non-antiviral treatment group,respectively.Age>58[hazard ratio(HR)=1.089;95%CI,1.033-1.147;P=0.002]and liver stiffness measurement>27.85 kPa(HR=1.043;95%CI,1.022-1.065;P=0.000)were risk factors for HCC in all patients(n=427),and DAAs treatment didn’t show protective efficacy.CONCLUSION DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months,and even increased the incidence of HCC in 36 months.展开更多
The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological ...The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).展开更多
Alkaloids are a diverse group of natural phytochemicals.These phytochemicals in plants provide them protection against pests,and herbivorous organisms and also control their development.Numerous of these alkaloids hav...Alkaloids are a diverse group of natural phytochemicals.These phytochemicals in plants provide them protection against pests,and herbivorous organisms and also control their development.Numerous of these alkaloids have a variety of biological effects,and some have even been developed into medications with different medicinal properties.This review aims to provide a broad overview of the numerous naturally occurring alkaloids(isolated from both terrestrial and aquatic species)along with synthetically produced alkaloid compounds having prominent antiviral properties.Previous reviews on this subject have focused on the biological actions of both natural and synthetic alkaloids,but they have not gone into comprehensive detail about their antiviral properties.We reviewed here several antiviral alkaloids that have been described in the literature in different investigational environments i.e.(in-vivo,in-ovo,in-vitro,and in-silico),and found that these alkaloid compounds have significant antiviral properties against several infectious viruses.These alkaloids repressed and targeted various important stages of viral infection at non-toxic doses while some of the alkaloids reported here also exhibited comparable inhibitory activities to commercially used drugs.Overall,these anti-viral effects of alkaloids point to a high degree of specificity,implying that they could serve as effective and safe antiviral medicines if further pursued in medicinal and pharmacological investigations.展开更多
BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based thera...BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.展开更多
AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation param...AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.展开更多
BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained viro...BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.展开更多
AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were trea...AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3%(45/54) achieved rapid virological response at 2 wk after treatment initiation(RVR 2) and 94.4%(51/54)achieved sustained virological response at 24 wk after the end of treatment(SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels(83.6 ± 17.9 vs 88.8 ± 19.4, P 01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P 01 < 0.001), and no significant improvements were observed at 24 w after the end of treatment(83.6 ± 17.9 vs 86.8 ± 19.1, P 02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P 02 = 0.001). The total frequency of adverse events(AEs) during treatment was 33.3%(18/54), with major AEs being fatigue(16.7%), headache(7.4%), anorexia(7.4%), and insomnia(5.6%). CONCLUSION Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.展开更多
The recent introduction of direct-acting antiviral drugs(DAAs) for treatment of the hepatitis C virus(HCV) has greatly improved the management of HCV for infected patients. These viral protein inhibitors act rapidly, ...The recent introduction of direct-acting antiviral drugs(DAAs) for treatment of the hepatitis C virus(HCV) has greatly improved the management of HCV for infected patients. These viral protein inhibitors act rapidly, allowing HCV clearance and increasing the sustained virological response rates. However, hepatitis B virus(HBV) reactivation has been reported in HCV/HBV co-infected patients. Hepatitis B reactivation refers to an abrupt increase in the HBV and is welldocumented in patients with previously undetected HBV DNA due to inactive or resolved HBV infection. Reactivation can occur spontaneously, but in most cases, it is triggered by various factors. Reactivation can be transient, without clinical symptoms; however, it usually causes a hepatitis flare. HBV reactivation may occur regardless of HCV genotype and type of DAA regimen. HBV screening is strongly recommended for co-infected HCV/HBV patients before initiation and during DAA therapy regardless of HBV status, HCV genotype and class of DAAs used. HBV reactivation can be prevented with pretreatment screening and prophylactic treatment when necessary. Additional data are required to evaluate the underlying mechanisms of HBV reactivation in this setting.展开更多
AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustaine...AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(SVR).METHODS We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment(SVR12).RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved SVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved SVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved SVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve SVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.展开更多
The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterfer...The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants(RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These preexisting RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.展开更多
Chronic infection with hepatitis B virus(HBV)constitutes a major global public health threat,causing substantial disease burdens such as liver cirrhosis and hepatocellular carcinoma,thus representing high unmet medica...Chronic infection with hepatitis B virus(HBV)constitutes a major global public health threat,causing substantial disease burdens such as liver cirrhosis and hepatocellular carcinoma,thus representing high unmet medical needs.Currently available therapies are safe,well tolerated,and highly effective in decreasing viremia and improving measured clinical outcomes with low rates of antiviral resistance.However,long-term management remains a clinical challenge,mainly due to the slow kinetics of HBV surface antigen clearance.In this article,we review emerging antivirals directed at novel targets derived from mechanisms of viral cellular entry,viral replication,viral assembly,and the host immune response,leading to preclinical and clinical trials for possible future therapeutic intervention.The recent therapeutic advances in the development of all categories of HBV inhibitors may pave the way for regimens of finite duration that result in long-lasting control of chronic hepatitis B infection.展开更多
Hepatocellular carcinoma(HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection(HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introductio...Hepatocellular carcinoma(HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection(HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals(DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical data that investigate the impact of DAAs on occurrence and recurrence of HCC.展开更多
Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of n...Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylatedinterferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.展开更多
BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL aft...BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL after HCV eradication,no data exists on the modifications of neuropsychological symptoms.AIM To investigate the effect of directly acting antivirals(DAAs)treatment on HRQoL and neuropsychological symptoms.METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment,including Zung-Self Depression-Rating-Scale,Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment.HRQoL was detected by Short-Form-36(SF-36).RESULTS All HRQoL domains,but role limitation physical and bodily pain,significantly improved after treatment.Interestingly,after DAAs treatment,all domains of HRQoL returned similar to those of controls.Each neuropsychological test significantly improved after HCV eradication.A significant correlation was observed among each psychological test and the summary components of SF-36.At multiple linear regression analysis including each psychological test as possible covariates,Zung-Self Depression Rating Scale(Zung-SDS)score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment.CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.展开更多
Hepatitis C virus(HCV) was discovered 26 years ago. For decades, interferon-based therapy has been the mainstay of treatment for HCV. Recently, several direct-acting antivirals(DAAs) have been approved for treatment o...Hepatitis C virus(HCV) was discovered 26 years ago. For decades, interferon-based therapy has been the mainstay of treatment for HCV. Recently, several direct-acting antivirals(DAAs) have been approved for treatment of HCV-infected patients and to help combat the virus. These drugs have revolutionized the management of HCV as all-oral regimens with favorable side effect profiles and superior rates of sustained virological response. Emerging real-world data are demonstrating results comparable to registration trials for DAA agents. Suddenly, the potential for eradicating HCV is on the horizon.展开更多
At present,over 180 million people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)worldwide and there have been more than 3.8 million deaths due to the virus.However,specific effect...At present,over 180 million people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)worldwide and there have been more than 3.8 million deaths due to the virus.However,specific effective antiviral treatment for this infectious disease is absent.At the beginning of the epidemic,relevant cellular and animal experiments of antiviral treatment for SARS-CoV-2 were conducted based on the prior studies of SARS-CoV and Middle East respiratory syndrome coronavirus.Some antivirals were preliminarily validated to be potentially effective in the clinical settings.But as the epidemic continued and more studies were carried out,the efficacy of these antiviral drugs became controversial.This paper reviews the pharmacology and application of interferon,lopinavir/ritonavir,ribavirin,chloroquine,arbidol,favipiravir,remdesivir,and thymosinα1 in coronavirus disease 2019.The actual effect of these drugs remains controversial.Meanwhile,the efficacy and safety of these drugs for patients with coronavirus disease 2019 still need to be explored.展开更多
In the era of highly effective direct acting antiviral(DAA) drugs for the treatment of chronic hepatitis C(CHC) infection, where eradication is almost ensured with minimal side effects, all hepatitis C carriers should...In the era of highly effective direct acting antiviral(DAA) drugs for the treatment of chronic hepatitis C(CHC) infection, where eradication is almost ensured with minimal side effects, all hepatitis C carriers should benefit theoretically. In the real world setting however, only a small proportion will benefit at this time point due to the multiple barriers to accessing therapy. Given that universal treatment is unlikely, treatment with DAAs will likely be restricted to those with the highest health benefits, and for those who can afford the high expense of a treatment course. Those with the highest unmet needs include those who have failed previous interferon-based therapy or who are interferon-ineligible with evidence of active disease, those with advance liver disease, and those with recurrence of hepatitis C after liver transplantation. In the future, the focus should be on increasing access to treatment for those infected with CHC.展开更多
It has been reported that the serum level of vitamin D3(Vit D3) could affect the natural course of chronic hepatitis C(CH-C) and the response to treatment with pegylated interferon(Peg-IFN) and ribavirin. Although sev...It has been reported that the serum level of vitamin D3(Vit D3) could affect the natural course of chronic hepatitis C(CH-C) and the response to treatment with pegylated interferon(Peg-IFN) and ribavirin. Although several mechanisms for the favorable effects of Vit D3 supplementation were reported, the total effect of Vit D3 supplementation remains unclear. Previously, we reported that supplementation with 1(OH)Vit D3 could enhance the Th1 response inducing not only a favorable immune response for viral eradication but also HCC control. Recently, the main treatment of CH-C should be direct acting antivirals(DAAs) without PegIFN. Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of Vit D3 after treatment of DAAs without Peg-IFN. The induction of a favorable immune response by adding Vit D3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients with severe fibrosis lacking sufficient amounts of VitD 3.展开更多
AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrho...AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrhosis [Child-Pugh(CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weightbased RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy. RESULTS We studied 68 patients: 54 with compensated(CP-B) and 14 with decompensated(CP-A) cirrhosis. Patients withdecompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8(P < 0.035). RBV levels were positively correlated with Hb loss over the treatment(P < 0.04). Majority(71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated(95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage. CONCLUSION Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease(CP-B) treated with directacting antivirals.展开更多
BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of c...BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of clinical studies comparing the efficacy of generic vs brand DAA formulations.AIM To compare the efficacy and safety of generic against brand DAAs for chronic hepatitis C treatment in Bahrain.METHODS This was a retrospective observational study involving 289 patients with chronic HCV infection during 2016 to 2018.There were 149 patients who were treated with brand DAAs,while 140 patients were treated with generic DAAs.Commonly used DAAs were Ombitasvir/Paritaprevir/Ritonavir±Dasabuvir±Ribavirin,and Sofosbuvir/Daclatasvir±Ribavirin.SVR at 12 wk post treatment was the main outcome variable.RESULTS Overall,87 patients(30.1%)had cirrhosis and 68.2%had genotype 1 HCV infection.At 12 wk post treatment,SVR was achieved by 271(93.8%)of the patients.In patients who were treated with generic medications,134(95.7%)achieved SVR at 12 wk post treatment,compared to 137(91.9%)among those treated with brand medications(P=0.19).Having cirrhosis[odds ratio(OR):9.41,95%confidence interval(CI):2.47–35.84]and having HCV genotype 3(OR:3.56,95%CI:1.03–12.38)were significant independent predictors of not achieving SVR.Alanine transaminase,gamma-glutamyl transpeptidase,and total bilirubin levels decreased significantly following therapy with both generic and brand DAAs.CONCLUSION Generic and brand DAAs demonstrate comparable effectiveness in the treatment of chronic hepatitis C patients.Both are safe and equally effective in improving biochemical markers of hepatic inflammation.展开更多
基金Supported by Chinese Foundation for Hepatitis Prevention and Control—Tian Qing Hepatitis Research Fund,No.TQGB20210175Tianjin Key Medical Discipline(Specialty)Construction Project,TJYXZDXK-059B+1 种基金Tianjin Health Science and Technology Project Key Discipline Special,TJWJ2022XK034and Research project of Chinese Traditional Medicine and Chinese Traditional Medicine Combined With Western Medicine of Tianjin Municipal Health and Family Planning Commission,No.2021022.
文摘BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce the occurrence of hepatocellular carcinoma(HCC)in patients with HCV-associated cirrhosis who are at high risk have not been concluded.AIM To investigate the effect of DAAs on the occurrence of HCC in patients with HCVassociated cirrhosis after achieving SVR.METHODS Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020.118 patients weren’t received antiviral treatment with any reasons named non-antiviral treatment group,and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group.Demographic information and laboratory data were collected from baseline and the following up.Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups.Cox proportional risk regression was used to re-evaluate the risk factors for HCC.RESULTS HCC incidence was 4.68/100PY(95%CI,3.09-6.81)in the DAAs treatment group,while it was 3.00/100PY(95%CI,1.50-5.37)in the non-antiviral treatment group,and the relative risk was 1.82(95%CI,0.93-3.53,P>0.05).The incidence of HCC at 12,24,36 and 48 months was 3.39%,6.36%,8.47%and 10.17%in the DAAs treatment group,and it was 0%,0%,3.39%and 9.32%in the non-antiviral treatment group,respectively.Age>58[hazard ratio(HR)=1.089;95%CI,1.033-1.147;P=0.002]and liver stiffness measurement>27.85 kPa(HR=1.043;95%CI,1.022-1.065;P=0.000)were risk factors for HCC in all patients(n=427),and DAAs treatment didn’t show protective efficacy.CONCLUSION DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months,and even increased the incidence of HCC in 36 months.
文摘The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).
文摘Alkaloids are a diverse group of natural phytochemicals.These phytochemicals in plants provide them protection against pests,and herbivorous organisms and also control their development.Numerous of these alkaloids have a variety of biological effects,and some have even been developed into medications with different medicinal properties.This review aims to provide a broad overview of the numerous naturally occurring alkaloids(isolated from both terrestrial and aquatic species)along with synthetically produced alkaloid compounds having prominent antiviral properties.Previous reviews on this subject have focused on the biological actions of both natural and synthetic alkaloids,but they have not gone into comprehensive detail about their antiviral properties.We reviewed here several antiviral alkaloids that have been described in the literature in different investigational environments i.e.(in-vivo,in-ovo,in-vitro,and in-silico),and found that these alkaloid compounds have significant antiviral properties against several infectious viruses.These alkaloids repressed and targeted various important stages of viral infection at non-toxic doses while some of the alkaloids reported here also exhibited comparable inhibitory activities to commercially used drugs.Overall,these anti-viral effects of alkaloids point to a high degree of specificity,implying that they could serve as effective and safe antiviral medicines if further pursued in medicinal and pharmacological investigations.
文摘BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile.This has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated.AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses.METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment completion.The entire study population was included in the intent-to-treat(ITT)analysis.Per-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment.RESULTS Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychiatric disorders.The cure rate calculated PP was not significantly different in the two groups analyzed,with a SVR of 96.9% and 97.7%,respectively.Although patients with bipolar disorder achieved a significantly lower SVR,the multivariate analysis excluded it as an independent predictor of treatment non-response.Male sex,GT3 infection,cirrhosis,and failure of previous therapy were identified as independent negative predictors.The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders.In six patients,symptoms of mental illness(depression,schizophrenia)worsened,of which two discontinued treatments for this reason.New episodes of sleep disorders occurred significantly more often in patients with mental disorders.Patients with mental illness were more frequently lost to follow-up(4.2%vs 2.5%).CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders.No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.
文摘AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.
文摘BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.
基金Supported by National Natural Science Foundation of China,No.81373056Beijing Municipal Committee of Science and Technology,No.D161100002716003National Major Project for Infectious Diseases Control,No.2012ZX10002003-004-003
文摘AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3%(45/54) achieved rapid virological response at 2 wk after treatment initiation(RVR 2) and 94.4%(51/54)achieved sustained virological response at 24 wk after the end of treatment(SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels(83.6 ± 17.9 vs 88.8 ± 19.4, P 01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P 01 < 0.001), and no significant improvements were observed at 24 w after the end of treatment(83.6 ± 17.9 vs 86.8 ± 19.1, P 02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P 02 = 0.001). The total frequency of adverse events(AEs) during treatment was 33.3%(18/54), with major AEs being fatigue(16.7%), headache(7.4%), anorexia(7.4%), and insomnia(5.6%). CONCLUSION Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.
文摘The recent introduction of direct-acting antiviral drugs(DAAs) for treatment of the hepatitis C virus(HCV) has greatly improved the management of HCV for infected patients. These viral protein inhibitors act rapidly, allowing HCV clearance and increasing the sustained virological response rates. However, hepatitis B virus(HBV) reactivation has been reported in HCV/HBV co-infected patients. Hepatitis B reactivation refers to an abrupt increase in the HBV and is welldocumented in patients with previously undetected HBV DNA due to inactive or resolved HBV infection. Reactivation can occur spontaneously, but in most cases, it is triggered by various factors. Reactivation can be transient, without clinical symptoms; however, it usually causes a hepatitis flare. HBV reactivation may occur regardless of HCV genotype and type of DAA regimen. HBV screening is strongly recommended for co-infected HCV/HBV patients before initiation and during DAA therapy regardless of HBV status, HCV genotype and class of DAAs used. HBV reactivation can be prevented with pretreatment screening and prophylactic treatment when necessary. Additional data are required to evaluate the underlying mechanisms of HBV reactivation in this setting.
文摘AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(SVR).METHODS We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment(SVR12).RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved SVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved SVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved SVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve SVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.
文摘The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants(RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These preexisting RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.
基金Supported by National Natural Science Foundation of China,No.31340023,No.91029741,No.81001072 and No.81171550National Key Sci-Tech Special Project of China,No.2012ZX10002011-006+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education,No.20130001120075Peking University People’s Hospital Research and Development Funds,No.RDB2013-02
文摘Chronic infection with hepatitis B virus(HBV)constitutes a major global public health threat,causing substantial disease burdens such as liver cirrhosis and hepatocellular carcinoma,thus representing high unmet medical needs.Currently available therapies are safe,well tolerated,and highly effective in decreasing viremia and improving measured clinical outcomes with low rates of antiviral resistance.However,long-term management remains a clinical challenge,mainly due to the slow kinetics of HBV surface antigen clearance.In this article,we review emerging antivirals directed at novel targets derived from mechanisms of viral cellular entry,viral replication,viral assembly,and the host immune response,leading to preclinical and clinical trials for possible future therapeutic intervention.The recent therapeutic advances in the development of all categories of HBV inhibitors may pave the way for regimens of finite duration that result in long-lasting control of chronic hepatitis B infection.
文摘Hepatocellular carcinoma(HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection(HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals(DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical data that investigate the impact of DAAs on occurrence and recurrence of HCC.
文摘Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylatedinterferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.
文摘BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL after HCV eradication,no data exists on the modifications of neuropsychological symptoms.AIM To investigate the effect of directly acting antivirals(DAAs)treatment on HRQoL and neuropsychological symptoms.METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment,including Zung-Self Depression-Rating-Scale,Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment.HRQoL was detected by Short-Form-36(SF-36).RESULTS All HRQoL domains,but role limitation physical and bodily pain,significantly improved after treatment.Interestingly,after DAAs treatment,all domains of HRQoL returned similar to those of controls.Each neuropsychological test significantly improved after HCV eradication.A significant correlation was observed among each psychological test and the summary components of SF-36.At multiple linear regression analysis including each psychological test as possible covariates,Zung-Self Depression Rating Scale(Zung-SDS)score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment.CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.
文摘Hepatitis C virus(HCV) was discovered 26 years ago. For decades, interferon-based therapy has been the mainstay of treatment for HCV. Recently, several direct-acting antivirals(DAAs) have been approved for treatment of HCV-infected patients and to help combat the virus. These drugs have revolutionized the management of HCV as all-oral regimens with favorable side effect profiles and superior rates of sustained virological response. Emerging real-world data are demonstrating results comparable to registration trials for DAA agents. Suddenly, the potential for eradicating HCV is on the horizon.
基金Supported by the 345 Talent Project of Shengjing Hospital of China Medical University。
文摘At present,over 180 million people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)worldwide and there have been more than 3.8 million deaths due to the virus.However,specific effective antiviral treatment for this infectious disease is absent.At the beginning of the epidemic,relevant cellular and animal experiments of antiviral treatment for SARS-CoV-2 were conducted based on the prior studies of SARS-CoV and Middle East respiratory syndrome coronavirus.Some antivirals were preliminarily validated to be potentially effective in the clinical settings.But as the epidemic continued and more studies were carried out,the efficacy of these antiviral drugs became controversial.This paper reviews the pharmacology and application of interferon,lopinavir/ritonavir,ribavirin,chloroquine,arbidol,favipiravir,remdesivir,and thymosinα1 in coronavirus disease 2019.The actual effect of these drugs remains controversial.Meanwhile,the efficacy and safety of these drugs for patients with coronavirus disease 2019 still need to be explored.
文摘In the era of highly effective direct acting antiviral(DAA) drugs for the treatment of chronic hepatitis C(CHC) infection, where eradication is almost ensured with minimal side effects, all hepatitis C carriers should benefit theoretically. In the real world setting however, only a small proportion will benefit at this time point due to the multiple barriers to accessing therapy. Given that universal treatment is unlikely, treatment with DAAs will likely be restricted to those with the highest health benefits, and for those who can afford the high expense of a treatment course. Those with the highest unmet needs include those who have failed previous interferon-based therapy or who are interferon-ineligible with evidence of active disease, those with advance liver disease, and those with recurrence of hepatitis C after liver transplantation. In the future, the focus should be on increasing access to treatment for those infected with CHC.
文摘It has been reported that the serum level of vitamin D3(Vit D3) could affect the natural course of chronic hepatitis C(CH-C) and the response to treatment with pegylated interferon(Peg-IFN) and ribavirin. Although several mechanisms for the favorable effects of Vit D3 supplementation were reported, the total effect of Vit D3 supplementation remains unclear. Previously, we reported that supplementation with 1(OH)Vit D3 could enhance the Th1 response inducing not only a favorable immune response for viral eradication but also HCC control. Recently, the main treatment of CH-C should be direct acting antivirals(DAAs) without PegIFN. Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of Vit D3 after treatment of DAAs without Peg-IFN. The induction of a favorable immune response by adding Vit D3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients with severe fibrosis lacking sufficient amounts of VitD 3.
文摘AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrhosis [Child-Pugh(CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weightbased RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy. RESULTS We studied 68 patients: 54 with compensated(CP-B) and 14 with decompensated(CP-A) cirrhosis. Patients withdecompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8(P < 0.035). RBV levels were positively correlated with Hb loss over the treatment(P < 0.04). Majority(71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated(95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage. CONCLUSION Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease(CP-B) treated with directacting antivirals.
文摘BACKGROUND Direct acting antivirals(DAAs)are a very effective treatment for hepatitis C virus(HCV).However,brand DAAs are expensive.The licensing of cheaper generic DAAs may address this issue,but there is a lack of clinical studies comparing the efficacy of generic vs brand DAA formulations.AIM To compare the efficacy and safety of generic against brand DAAs for chronic hepatitis C treatment in Bahrain.METHODS This was a retrospective observational study involving 289 patients with chronic HCV infection during 2016 to 2018.There were 149 patients who were treated with brand DAAs,while 140 patients were treated with generic DAAs.Commonly used DAAs were Ombitasvir/Paritaprevir/Ritonavir±Dasabuvir±Ribavirin,and Sofosbuvir/Daclatasvir±Ribavirin.SVR at 12 wk post treatment was the main outcome variable.RESULTS Overall,87 patients(30.1%)had cirrhosis and 68.2%had genotype 1 HCV infection.At 12 wk post treatment,SVR was achieved by 271(93.8%)of the patients.In patients who were treated with generic medications,134(95.7%)achieved SVR at 12 wk post treatment,compared to 137(91.9%)among those treated with brand medications(P=0.19).Having cirrhosis[odds ratio(OR):9.41,95%confidence interval(CI):2.47–35.84]and having HCV genotype 3(OR:3.56,95%CI:1.03–12.38)were significant independent predictors of not achieving SVR.Alanine transaminase,gamma-glutamyl transpeptidase,and total bilirubin levels decreased significantly following therapy with both generic and brand DAAs.CONCLUSION Generic and brand DAAs demonstrate comparable effectiveness in the treatment of chronic hepatitis C patients.Both are safe and equally effective in improving biochemical markers of hepatic inflammation.
