Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges pos...Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges posed by viral diseases.Key advancements include the rapid identification of emerging viruses and variants,the revelation of diverse viromes and evolutionary patterns,the elucidation of viral pathogenesis-and antiviral targets,as well as development of novel vaccines and antiviral drugs through far more advanced techniques and pipelines(Holmes et al.,2024).Altogether,these breakthroughs are reshaping our understanding of viruses and our strategies to combat viral infections at an unprecedented pace.展开更多
This editorial provides commentary on the study by Dobrowolska et al,highlighting the influence of biological sex on hepatitis C virus(HCV)infection risk and disease progression.HCV infection is more common in men;how...This editorial provides commentary on the study by Dobrowolska et al,highlighting the influence of biological sex on hepatitis C virus(HCV)infection risk and disease progression.HCV infection is more common in men;however,women,regardless of age,show a lower prevalence of genotype 3 infection,diabetes mellitus,and coinfections with hepatitis B virus and human immunodeficiency virus.Women also experience slower liver fibrosis progression.Despite this,mild adverse events,autoimmune diseases,and depression occur more frequently in women.Sustained virologic response at 12 weeks post-treatment was significantly higher in women(98.4%)than in men(96.6%).In women,postmenopausal status,genotype 3 infection,and cirrhosis were independently associated with treatment failure.Early diagnosis and timely antiviral therapy in women are critical to preventing vertical transmission and mitigating disease advancement.展开更多
BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the saf...BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the safety and efficacy of the generic sofosbuvir(SOF)/ledipasvir(LED)in Egyptian HCV-infected children and to compare the results with the brand form.METHODS This analytical retrospective study included HCV infected children and adolescents aged 12-18 years or weighing>35 kg.Collected data included:Age,sex,risk factors of HCV acquisition,comorbidities,liver functions,HCV viral load,degree of hepatic fibrosis,sustained virologic response(SVR)and frequency of treatment adverse effects.Patients who received the generic form of SOF/LED(Ledisbuvir)were compared to patients who received the brand form(Harvoni®)regarding SVR and frequency of adverse events.RESULTS The study included 43 patients who received Ledisbuvir and 73 who received Harvoni®.All patients achieved SVR.Treatment side effects were mild,transient and comparable in both groups.CONCLUSION The use of generic SOF/LED in HCV infected children is safe and effective.It is comparable to the brand form at a reduced price and represents an affordable and effective alternative.展开更多
Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-convertin...Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-converting enzyme 2(ACE2),highly expressed in the motile cilia of human airway epithelial cells(Sungnak et al.,2020),has been identified as the functional receptor for sarbecoviruses(e.g.,SARS-CoV-2,SARS-CoV)and setracoviruses(e.g.,HCoV-NL63).Recent studies have shown that some bat-circulating MERS-related coronaviruses(MERSr-CoVs),such as MOW15-22,PnNL2018B and HKU5,can use ACE2 to enter cells(Ma et al.,2025;Park et al.,2025).Even more worrying is that one novel bat-infecting merbecovirus HKU5-CoV lineage 2(BtHKU5-CoV-2)has been reported to use human ACE2 as a cell entry receptor(Chen et al.,2025).These ACE2-utilizing merbecoviruses expand the diversity,geographic distribution,and transmission potential of coronaviruses,posing a significant threat of spillover to humans.If an ACE2-utilizing MERSr-CoV acquire the high lethality of MERS-CoV and the high transmissibility of SARS-CoV-2 using ACE2 as a receptor,it could trigger a global pandemic with catastrophic consequences for humanity.Therefore,it is essential to evaluate serological cross-reactivity in sera from SARS-CoV-2-infected individuals against ACE2-using MERSr-CoVs,and urgent to develop preventive vaccines and pan-coronavirus antivirals confront the potential threat(Jiang and Wu,2025).展开更多
BACKGROUND The albumin-bilirubin(ALBI)score was developed as a prognostic tool for pa-tients with hepatocellular carcinoma.However,its new role as an indicator of liver fibrosis in chronic hepatitis C virus(HCV)patien...BACKGROUND The albumin-bilirubin(ALBI)score was developed as a prognostic tool for pa-tients with hepatocellular carcinoma.However,its new role as an indicator of liver fibrosis in chronic hepatitis C virus(HCV)patients is under investigation.AIM To investigate the ALBI score as a non-invasive means of assessing the extent of liver fibrosis in chronic HCV patients.METHODS We evaluated hospital records of 231 eligible chronic HCV patients from King Fahad Specialist Hospital in Buraydah,Saudi Arabia.Demographic/clinical data,liver function tests,non-invasive tests for liver fibrosis,and ALBI score/grades were evaluated before and two years after direct-acting antivirals(DAA)treatment.RESULTS The median ALBI score improved from-2.51 to-2.62 after DAA treatment(P<0.05).Additionally,the ALBI score improved irrespective of the level of fibrosis,with improvement more evident in patients with advanced fibrosis(-2.26 to-2.41,P<0.05).The ALBI score showed significant positive correlation with non-invasive tests for liver fibrosis(aspartate aminotransferase/alanine aminotransferase ratio,aspartate aminotransferase to platelet ratio index,and fibrosis-4 index)at baseline and after DAA treatment(P<0.05).Moreover,the receiver operating characteristic curve demonstrated ALBI score’s ability to predict advanced fibrosis(F3,F4)[area under the curve=0.76,(95%confidence interval:0.70-0.81),P<0.001,best cut-off value=-2.38(sensitivity 60%and specificity 83%)].CONCLUSION The ALBI score appears to be a useful non-invasive marker for assessing liver fibrosis in chronic HCV patients and may serve as a valuable tool for monitoring hepatic function during and after DAA 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
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
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
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
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
文摘Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges posed by viral diseases.Key advancements include the rapid identification of emerging viruses and variants,the revelation of diverse viromes and evolutionary patterns,the elucidation of viral pathogenesis-and antiviral targets,as well as development of novel vaccines and antiviral drugs through far more advanced techniques and pipelines(Holmes et al.,2024).Altogether,these breakthroughs are reshaping our understanding of viruses and our strategies to combat viral infections at an unprecedented pace.
文摘This editorial provides commentary on the study by Dobrowolska et al,highlighting the influence of biological sex on hepatitis C virus(HCV)infection risk and disease progression.HCV infection is more common in men;however,women,regardless of age,show a lower prevalence of genotype 3 infection,diabetes mellitus,and coinfections with hepatitis B virus and human immunodeficiency virus.Women also experience slower liver fibrosis progression.Despite this,mild adverse events,autoimmune diseases,and depression occur more frequently in women.Sustained virologic response at 12 weeks post-treatment was significantly higher in women(98.4%)than in men(96.6%).In women,postmenopausal status,genotype 3 infection,and cirrhosis were independently associated with treatment failure.Early diagnosis and timely antiviral therapy in women are critical to preventing vertical transmission and mitigating disease advancement.
文摘BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the safety and efficacy of the generic sofosbuvir(SOF)/ledipasvir(LED)in Egyptian HCV-infected children and to compare the results with the brand form.METHODS This analytical retrospective study included HCV infected children and adolescents aged 12-18 years or weighing>35 kg.Collected data included:Age,sex,risk factors of HCV acquisition,comorbidities,liver functions,HCV viral load,degree of hepatic fibrosis,sustained virologic response(SVR)and frequency of treatment adverse effects.Patients who received the generic form of SOF/LED(Ledisbuvir)were compared to patients who received the brand form(Harvoni®)regarding SVR and frequency of adverse events.RESULTS The study included 43 patients who received Ledisbuvir and 73 who received Harvoni®.All patients achieved SVR.Treatment side effects were mild,transient and comparable in both groups.CONCLUSION The use of generic SOF/LED in HCV infected children is safe and effective.It is comparable to the brand form at a reduced price and represents an affordable and effective alternative.
文摘Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-converting enzyme 2(ACE2),highly expressed in the motile cilia of human airway epithelial cells(Sungnak et al.,2020),has been identified as the functional receptor for sarbecoviruses(e.g.,SARS-CoV-2,SARS-CoV)and setracoviruses(e.g.,HCoV-NL63).Recent studies have shown that some bat-circulating MERS-related coronaviruses(MERSr-CoVs),such as MOW15-22,PnNL2018B and HKU5,can use ACE2 to enter cells(Ma et al.,2025;Park et al.,2025).Even more worrying is that one novel bat-infecting merbecovirus HKU5-CoV lineage 2(BtHKU5-CoV-2)has been reported to use human ACE2 as a cell entry receptor(Chen et al.,2025).These ACE2-utilizing merbecoviruses expand the diversity,geographic distribution,and transmission potential of coronaviruses,posing a significant threat of spillover to humans.If an ACE2-utilizing MERSr-CoV acquire the high lethality of MERS-CoV and the high transmissibility of SARS-CoV-2 using ACE2 as a receptor,it could trigger a global pandemic with catastrophic consequences for humanity.Therefore,it is essential to evaluate serological cross-reactivity in sera from SARS-CoV-2-infected individuals against ACE2-using MERSr-CoVs,and urgent to develop preventive vaccines and pan-coronavirus antivirals confront the potential threat(Jiang and Wu,2025).
文摘BACKGROUND The albumin-bilirubin(ALBI)score was developed as a prognostic tool for pa-tients with hepatocellular carcinoma.However,its new role as an indicator of liver fibrosis in chronic hepatitis C virus(HCV)patients is under investigation.AIM To investigate the ALBI score as a non-invasive means of assessing the extent of liver fibrosis in chronic HCV patients.METHODS We evaluated hospital records of 231 eligible chronic HCV patients from King Fahad Specialist Hospital in Buraydah,Saudi Arabia.Demographic/clinical data,liver function tests,non-invasive tests for liver fibrosis,and ALBI score/grades were evaluated before and two years after direct-acting antivirals(DAA)treatment.RESULTS The median ALBI score improved from-2.51 to-2.62 after DAA treatment(P<0.05).Additionally,the ALBI score improved irrespective of the level of fibrosis,with improvement more evident in patients with advanced fibrosis(-2.26 to-2.41,P<0.05).The ALBI score showed significant positive correlation with non-invasive tests for liver fibrosis(aspartate aminotransferase/alanine aminotransferase ratio,aspartate aminotransferase to platelet ratio index,and fibrosis-4 index)at baseline and after DAA treatment(P<0.05).Moreover,the receiver operating characteristic curve demonstrated ALBI score’s ability to predict advanced fibrosis(F3,F4)[area under the curve=0.76,(95%confidence interval:0.70-0.81),P<0.001,best cut-off value=-2.38(sensitivity 60%and specificity 83%)].CONCLUSION The ALBI score appears to be a useful non-invasive marker for assessing liver fibrosis in chronic HCV patients and may serve as a valuable tool for monitoring hepatic function during and after DAA 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.
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.
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.
