In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasv...In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasvir(Epclusa®),sofosbuvir/velpatasvir/voxilaprevir(Vosevi®),glecaprevir/pibrentasvir(Maviret®),and elbasvir/grazoprevir(Zepatier®).We searched MEDLINE(1948-January 2020),Embase(1964-January 2020),Google,and GoogleScholar using the terms pharmacokinetics,drug interaction,drug metabolism,sofosbuvir,velpatasvir,Epclusa,voxilaprevir,Vosevi,glecaprevir,pibrentasvir,Maviret,elbasvir,grazoprevir,and Zepatier,from inception to January 13,2020.The search was limited to randomized controlled trials,in vitro studies,prospective and retrospective human studies,drug monographs,abstracts,and conference proceedings.All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted.Numerous clinically relevant drug-drug interactions(DDIs)were identified with the newer generation DAAs and commonly prescribed drugs.NS3/4A protease inhibitors are more likely to be involved in DDIs,followed by NS5A inhibitors and NS5B polymerase inhibitor.The majority of clinically relevant DDIs are predictable,according to known pharmacokinetic,pharmacodynamics,and physicochemical properties of DAAs;however,in select cases,unpredictable DDIs do occur.As expected,many drug interactions exist between newer generation DAAs and commonly prescribed medications.While the majority of clinically relevant interactions are predictable,many require therapeutic dose adjustment or careful selection of non-interacting drugs.In select cases,severe and unpredictable drug interactions can occur.Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.展开更多
Chronic inflammation due to hepatitis C virus(HCV)infection leads to liver fibrosis and rearrangement of liver tissue,which is responsible for the development of portal hypertension(PH)and hepatocellular carcinoma(HCC...Chronic inflammation due to hepatitis C virus(HCV)infection leads to liver fibrosis and rearrangement of liver tissue,which is responsible for the development of portal hypertension(PH)and hepatocellular carcinoma(HCC).The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection,providing an overall eradication rate of over 90%.Despite a significant decrease after sustained virological response(SVR),the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease.Although the reasons are still unclear,cirrhosis itself has a residual risk for the development of HCC and other PH-related complications.Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis.Following the achievement of SVR,liver stiffness(LS)usually decreases,as a consequence of reduced inflammation and,possibly,fibrosis.Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease(functional decompensation,gastrointestinal bleeding,HCC)and to optimize long-term prognostic outcomes in clinical practice.展开更多
BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-...BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-I-R)score,evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIM To identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODS Chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.Sustained virologic response(SVR)was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation.The Ishak system and P-I-R score were assessed.Inflammation improvement and fibrosis regression were defined as a≥2-points decrease in the histology activity index(HAI)score and a≥1-point decrease in the Ishak fibrosis score,respectively.Fibrosis progression was defined as a≥1-point increase in the Ishak fibrosis score.Histologic improvement was defined as a≥2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy.The P-I-R score was also assessed.“absolutely reversing or advancing”was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score;and“probably reversing or advancing”was defined as only one parameter showing directionality.RESULTS Thirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.The mean age of these patients was 40.9±14.6 years and there were 53%(20/38)males.Thirty-four percent(13/38)of patients were cirrhotic.Eighty-two percent(31/38)of patients achieved inflammation improvement.The median HAI score decreased significantly after SVR(pretreatment 7.0 vs posttreatment 2.0,Z=-5.146,P=0.000).Thirty-seven percent(14/38)of patients achieved fibrosis improvement.The median Ishak score decreased significantly after SVR(pretreatment 4.0 vs posttreatment 3.0,Z=-2.354,P=0.019).Eighty-two percent(31/38)of patients showed histological improvement.The P-I-R score was evaluated in 61%(23/38)of patients.The progressive group showed lower platelet(P=0.024)and higher HAI scores(P=0.070)before treatment.In patients with stable Ishak stage after treatment:Progressive injury was seen in 22%(4/18)of patients,33%(6/18)were classified as indeterminate and regressive changes were seen in 44%(8/18)of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSION Significant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy.The P-I-R score has potential in predicting fibrosis in HCV patients.展开更多
The recent development of direct-acting antiviral agents(DAAs) against hepatitis C virus(HCV) infection could lead to higher sustained virological response(SVR) rates, with shorter treatment durations and fewer advers...The recent development of direct-acting antiviral agents(DAAs) against hepatitis C virus(HCV) infection could lead to higher sustained virological response(SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions(RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1 b(GT1 b) is founded in 70% of HCVinfected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1 b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1 b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1 b-infected patients with treatment failure.展开更多
Background and aims:To investigate the safety and efficacy of direct-acting antiviral(DAA)regimens in a cohort of Chinese patients with chronic hepatitis C virus(HCV)infection.Methods:A total of 222 adult Chinese pati...Background and aims:To investigate the safety and efficacy of direct-acting antiviral(DAA)regimens in a cohort of Chinese patients with chronic hepatitis C virus(HCV)infection.Methods:A total of 222 adult Chinese patients were enrolled and treated via DAA regimens in accor-dance with HCV management guidelines.Treatment responses were evaluated 4 weeks after treatment,at the end of treatment(EOT)and 12 weeks post-treatment.Virological responses,biochemical re-sponses,model for end-stage liver disease(MELD)and Child-Pugh(CP)scores were recorded.Results:A total of 218 patients(98.2%)achieved sustained virological response 12 weeks post-treatment and 4 patients relapsed.The combined number of rapid virological responses for all six regimens was 170/222(76.6%),and 221/222(99.6%)had achieved virological responses by the end of treatment.In decompensated cirrhosis patients the baseline mean CP score was 6.8±1.3 and the mean MELD score was 10.1±3.3.Compared with the mean CP score at baseline,the mean score is significantly lower at the end of treatment(5.7±1.3)and 12 weeks post-treatment(5.6±1.0).Estimated glomerular filtration rates did not differ significantly from baseline during the treatment or 12 weeks post-treatment.The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 42/172(24.4%),and in patients with decompensated cirrhosis it was 8/22(36.4%).The most frequently reported adverse events were elevated indirect bilirubin,fatigue and rash.There were no cases of serious adverse events,death or treatment discontinuation because of adverse events.Conclusion:DAA regimens were highly effective and well tolerated irrespective of HCV genotype,cirrhosis,liver or kidney transplantation,hepatocellular carcinoma,HCV/hepatitis B virus co-infection,or renal failure.展开更多
BACKGROUND In the last few years we have witnessed a revolution in the treatment of hepatitis C virus(HCV)infection.With the introduction of direct-acting antiviral agents(DAAs),sustained virological response(SVR)is a...BACKGROUND In the last few years we have witnessed a revolution in the treatment of hepatitis C virus(HCV)infection.With the introduction of direct-acting antiviral agents(DAAs),sustained virological response(SVR)is achieved in more than 95%of the patients.The focus is now being turned to the global targets set by the World Health Organization,with the aim of achieving HCV elimination by 2030.Prison inmates constitute one of the high-risk groups,and receive treatment less frequently due to several barriers in access to health care.AIM To describe the management and follow-up of a cohort of HCV monoinfected patients treated with DAA in the prison setting,where tertial referral liver center specialists locally provide,on-site assessment and treatment for the prisoners.METHODS A prospective observational study was conducted from April 2017 to March 2020,which included all HCV monoinfected prison inmates in the largest Northern Portugal prison.Demographic,clinical,and laboratory data,as well as transient elastography measurements,were collected onsite by the medical team and prospectively recorded.Patients were treated with DAA according to international guidelines.The primary endpoint was SVR at post-treatment week 12.RESULTS There were 98 monoinfected HCV male inmates(mean age,42.7±8.6 years)included in the analysis.Injecting drugs or tattooing were reported in 74.5%,with 38.8%of the latter being done in prison.Alcohol consumption of more than 30 g/d was referred in 69.4%.The most prevalent genotype was 1a(54.1%),followed by 3(27.6%),4(9.2%)and 1b(6.1%).Pretreatment fibrosis degree was mild-tomoderate(F0-F2)in 77.6%and severe in 22.4%(F3-F4).Treatment regimens chosen were:45.9%elbasvir/grazoprevir,29.6%sofosbuvir/velpatasvir,and 12.2%sofosbuvir/ledispavir and glecaprevir/pibrentasvir.No major adverse events were observed.SVR at post-treatment week 12 was 99%.CONCLUSION In a population considered to be both hard-to-access and a cornerstone for HCV elimination,the onsite evaluation and treatment of HCV-infected prisoners,achieved an exceptional highly effective success rate.This type of collaborative program should be considered to be expanded,to support hepatitis C elimination efforts.展开更多
BACKGROUND Direct-acting antivirals(DAAs)are recommended for the treatment of hepatitis C virus(HCV)infection in patients treated with methadone or buprenorphine.AIM To assess HCV treatment rates in an Opioid Treatmen...BACKGROUND Direct-acting antivirals(DAAs)are recommended for the treatment of hepatitis C virus(HCV)infection in patients treated with methadone or buprenorphine.AIM To assess HCV treatment rates in an Opioid Treatment Program(OTP).METHODS This longitudinal study included 501 patients(81.4%men,median age:45 years;interquartile range:39-50 years)enrolled in an OTP between October 2015 and September 2017.Patients were followed until September 2019.Data on sociodemographics,substance use,HCV infection,human immunodeficiency virus(HIV)infection and laboratory parameters were collected at entry.We analyzed medical records to evaluate HCV treatment.Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors.RESULTS Prevalence of HCV and HIV infection was 70%and 34%,respectively.Among anti-HCV-positive(n=336)patients,47.2%,41.3%,and 31.9%used alcohol,cannabis,and cocaine,respectively.HCV-RNA tests were positive in 233(69.3%)patients.Twentyeight patients(8.3%)cleared the infection,and 59/308(19.1%)had received interferon-based treatment regimens before 2015.Among 249 patients eligible,111(44.6%)received DAAs.Treatment rates significantly increased over time from 7.8/100 person-years(p-y)(95%CI:5.0-12.3)in 2015 to 18.9/100 p-y(95%CI:11.7-30.3)in 2019.In a multivariate analysis,patients with HIV co-infection were twice as likely to receive DAAs(HR=1.94,95%CI:1.21-3.12)than patients with HCV mono-infection.Current drug use was an independent risk factor for not receiving treatment against infection(HR=0.48,95%CI:0.29-0.80).CONCLUSION HCV treatment is evolving in patients with HCV-HIV co-infection.Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.展开更多
Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)coinfection is a major problem among HIV-infected patients,resulting in increased morbidity and mortality rates due to the acceleration of liver fibrosis progres...Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)coinfection is a major problem among HIV-infected patients,resulting in increased morbidity and mortality rates due to the acceleration of liver fibrosis progression by HIV,leading to liver cirrhosis and hepatocellular carcinoma.Although the efficacy of directacting antiviral therapy in patients with HIV/HCV coinfection and HCV monoinfection are similar in terms of sustained virologic response rate,there are some additional complications that arise in the treatment of patients with HIV/HCV coinfection,including drug-drug interactions and HCV reinfection due to the high risk behavior of these patients.This review will summarize the current management of HIV/HCV coinfection.展开更多
AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze dif...AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response(SVR) as well as serious adverse events(SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial(CT-met and CT-unmet, respectively).RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir(36.4%), followed by sofosbuvir/ledipasvir(24.9%) and ombitasvir/paritaprevir/ritonavir(r)/dasabuvir(19.9%). Ribavirin(RBV) was administered in 198 patients(42.9%). SVRs occurred in 437/462 patients(94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CTmet group vs 91.9% patients in the CT-unmet group(P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure(P = 0.04). Eleven patients(2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively(P = 0.003).CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.展开更多
This study aimed to review the trends of hepatitis C virus(HCV)treatment over the past decade and to analyze the effectiveness of sofosbuvir(SOF)–based direct-acting antiviral regimens in the heterogeneous population...This study aimed to review the trends of hepatitis C virus(HCV)treatment over the past decade and to analyze the effectiveness of sofosbuvir(SOF)–based direct-acting antiviral regimens in the heterogeneous population of patients with chronic hepatitis C(CHC)in clinical practice.This retrospective cohort study included CHC patients attending the Sir Run Run Shaw Hospital between January 1,2012,and December 31,2022.All of the 194 patients treatedwith SOF-based regimens completed 12weeks of treatment and were followed up for at least 12 weeks after completion of the therapy.Sustained virologic response(SVR)12 weeks after the end of treatment was the primary endpoint.A total of 194 patients treated with SOF-based regimens were included,among which 121,56,10 and 7 patients received SOF+velpatasvir±ribavirin,SOF+daclatasvir,SOF+ledipasvir or SOF+ribavirin,respectively.With 36.1%,HCV Genotype 1 predominated in CHC patients treated with SOF-based regimens,followed by Genotype 2a with 17.5%and Genotype 3 with 14.9%.Comorbidities among patients included hypertension(4.1%),diabetes(2.1%),depression(1.0%)and neoplastic disease(2.6%).All patients treated with SOF-based regimens achieved SVR.There was no association between SVR and factors such as HCV genotype,sex,age,presence of cirrhosis or previous treatment history.There were no reports of any serious adverse events in the study.This single-center retrospective study represented the latest 10-year treatment trends for HCV in real-world clinical practice and provided useful information on the excellent efficacy of SOF-based direct-acting antiviral regimens for treatment of CHC patients in Eastern China.展开更多
Our comprehensive review focuses on the treatment of hepatitis C virus in the context of hepatocellular carcinoma and vice versa,highlighting the ongoing complexity of this clinical scenario.There remain multiple unan...Our comprehensive review focuses on the treatment of hepatitis C virus in the context of hepatocellular carcinoma and vice versa,highlighting the ongoing complexity of this clinical scenario.There remain multiple unanswered questions when considering the management of these complex patients and,with a rapidly-changing treatment landscape for both chronic hepatitis C and hepatocellular carcinoma,these questions are only going to grow.Treatment timing,interactions and the impact of one disease condition on the other are vitally important,though guidance generally remains non-specific,suggesting that we make these decisions on a case-by-case basis.We focus on the current evidence for managing these cases,depending on disease stage and treatment type.展开更多
Chronic hepatitis C virus(HCV)infection is a major cause of liver cirrhosis and hepatocellular carcinoma(HCC)worldwide.The recent advancement of direct-acting Antiviral Agents(DAAs)in hepatitis C therapy,resulted in s...Chronic hepatitis C virus(HCV)infection is a major cause of liver cirrhosis and hepatocellular carcinoma(HCC)worldwide.The recent advancement of direct-acting Antiviral Agents(DAAs)in hepatitis C therapy,resulted in sustained virological response rates of over 90%in treated patients in different stages of liver fibrosis.The efficacy of DAAs treatment has also been confirmed in real-life cohorts that include subjects with decompensated cirrhosis and therefore seems a promising step to a significant reduction in the recurrence of HCC in patients who achieved complete destruction of the HCC nodules by local therapy.We present a 72-year old patient with HCV-related liver cirrhosis who successfully responded to DAAs treatment after complete destruction of an early HCC nodule.展开更多
文摘In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasvir(Epclusa®),sofosbuvir/velpatasvir/voxilaprevir(Vosevi®),glecaprevir/pibrentasvir(Maviret®),and elbasvir/grazoprevir(Zepatier®).We searched MEDLINE(1948-January 2020),Embase(1964-January 2020),Google,and GoogleScholar using the terms pharmacokinetics,drug interaction,drug metabolism,sofosbuvir,velpatasvir,Epclusa,voxilaprevir,Vosevi,glecaprevir,pibrentasvir,Maviret,elbasvir,grazoprevir,and Zepatier,from inception to January 13,2020.The search was limited to randomized controlled trials,in vitro studies,prospective and retrospective human studies,drug monographs,abstracts,and conference proceedings.All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted.Numerous clinically relevant drug-drug interactions(DDIs)were identified with the newer generation DAAs and commonly prescribed drugs.NS3/4A protease inhibitors are more likely to be involved in DDIs,followed by NS5A inhibitors and NS5B polymerase inhibitor.The majority of clinically relevant DDIs are predictable,according to known pharmacokinetic,pharmacodynamics,and physicochemical properties of DAAs;however,in select cases,unpredictable DDIs do occur.As expected,many drug interactions exist between newer generation DAAs and commonly prescribed medications.While the majority of clinically relevant interactions are predictable,many require therapeutic dose adjustment or careful selection of non-interacting drugs.In select cases,severe and unpredictable drug interactions can occur.Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.
文摘Chronic inflammation due to hepatitis C virus(HCV)infection leads to liver fibrosis and rearrangement of liver tissue,which is responsible for the development of portal hypertension(PH)and hepatocellular carcinoma(HCC).The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection,providing an overall eradication rate of over 90%.Despite a significant decrease after sustained virological response(SVR),the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease.Although the reasons are still unclear,cirrhosis itself has a residual risk for the development of HCC and other PH-related complications.Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis.Following the achievement of SVR,liver stiffness(LS)usually decreases,as a consequence of reduced inflammation and,possibly,fibrosis.Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease(functional decompensation,gastrointestinal bleeding,HCC)and to optimize long-term prognostic outcomes in clinical practice.
基金The National Natural Science Foundation of China,No.81870406the Beijing Natural Science Foundation,No.7182174and the China National Science and Technology Major Project for Infectious Diseases Control during the 13th Five-Year Plan Period,No.2017ZX10202202.
文摘BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-I-R)score,evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIM To identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODS Chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.Sustained virologic response(SVR)was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation.The Ishak system and P-I-R score were assessed.Inflammation improvement and fibrosis regression were defined as a≥2-points decrease in the histology activity index(HAI)score and a≥1-point decrease in the Ishak fibrosis score,respectively.Fibrosis progression was defined as a≥1-point increase in the Ishak fibrosis score.Histologic improvement was defined as a≥2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy.The P-I-R score was also assessed.“absolutely reversing or advancing”was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score;and“probably reversing or advancing”was defined as only one parameter showing directionality.RESULTS Thirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.The mean age of these patients was 40.9±14.6 years and there were 53%(20/38)males.Thirty-four percent(13/38)of patients were cirrhotic.Eighty-two percent(31/38)of patients achieved inflammation improvement.The median HAI score decreased significantly after SVR(pretreatment 7.0 vs posttreatment 2.0,Z=-5.146,P=0.000).Thirty-seven percent(14/38)of patients achieved fibrosis improvement.The median Ishak score decreased significantly after SVR(pretreatment 4.0 vs posttreatment 3.0,Z=-2.354,P=0.019).Eighty-two percent(31/38)of patients showed histological improvement.The P-I-R score was evaluated in 61%(23/38)of patients.The progressive group showed lower platelet(P=0.024)and higher HAI scores(P=0.070)before treatment.In patients with stable Ishak stage after treatment:Progressive injury was seen in 22%(4/18)of patients,33%(6/18)were classified as indeterminate and regressive changes were seen in 44%(8/18)of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSION Significant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy.The P-I-R score has potential in predicting fibrosis in HCV patients.
文摘The recent development of direct-acting antiviral agents(DAAs) against hepatitis C virus(HCV) infection could lead to higher sustained virological response(SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions(RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1 b(GT1 b) is founded in 70% of HCVinfected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1 b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1 b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1 b-infected patients with treatment failure.
基金This work was supported by the Science and Technology Plan-ning Project of Guangdong Province Grant(2014B020212025).
文摘Background and aims:To investigate the safety and efficacy of direct-acting antiviral(DAA)regimens in a cohort of Chinese patients with chronic hepatitis C virus(HCV)infection.Methods:A total of 222 adult Chinese patients were enrolled and treated via DAA regimens in accor-dance with HCV management guidelines.Treatment responses were evaluated 4 weeks after treatment,at the end of treatment(EOT)and 12 weeks post-treatment.Virological responses,biochemical re-sponses,model for end-stage liver disease(MELD)and Child-Pugh(CP)scores were recorded.Results:A total of 218 patients(98.2%)achieved sustained virological response 12 weeks post-treatment and 4 patients relapsed.The combined number of rapid virological responses for all six regimens was 170/222(76.6%),and 221/222(99.6%)had achieved virological responses by the end of treatment.In decompensated cirrhosis patients the baseline mean CP score was 6.8±1.3 and the mean MELD score was 10.1±3.3.Compared with the mean CP score at baseline,the mean score is significantly lower at the end of treatment(5.7±1.3)and 12 weeks post-treatment(5.6±1.0).Estimated glomerular filtration rates did not differ significantly from baseline during the treatment or 12 weeks post-treatment.The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 42/172(24.4%),and in patients with decompensated cirrhosis it was 8/22(36.4%).The most frequently reported adverse events were elevated indirect bilirubin,fatigue and rash.There were no cases of serious adverse events,death or treatment discontinuation because of adverse events.Conclusion:DAA regimens were highly effective and well tolerated irrespective of HCV genotype,cirrhosis,liver or kidney transplantation,hepatocellular carcinoma,HCV/hepatitis B virus co-infection,or renal failure.
文摘BACKGROUND In the last few years we have witnessed a revolution in the treatment of hepatitis C virus(HCV)infection.With the introduction of direct-acting antiviral agents(DAAs),sustained virological response(SVR)is achieved in more than 95%of the patients.The focus is now being turned to the global targets set by the World Health Organization,with the aim of achieving HCV elimination by 2030.Prison inmates constitute one of the high-risk groups,and receive treatment less frequently due to several barriers in access to health care.AIM To describe the management and follow-up of a cohort of HCV monoinfected patients treated with DAA in the prison setting,where tertial referral liver center specialists locally provide,on-site assessment and treatment for the prisoners.METHODS A prospective observational study was conducted from April 2017 to March 2020,which included all HCV monoinfected prison inmates in the largest Northern Portugal prison.Demographic,clinical,and laboratory data,as well as transient elastography measurements,were collected onsite by the medical team and prospectively recorded.Patients were treated with DAA according to international guidelines.The primary endpoint was SVR at post-treatment week 12.RESULTS There were 98 monoinfected HCV male inmates(mean age,42.7±8.6 years)included in the analysis.Injecting drugs or tattooing were reported in 74.5%,with 38.8%of the latter being done in prison.Alcohol consumption of more than 30 g/d was referred in 69.4%.The most prevalent genotype was 1a(54.1%),followed by 3(27.6%),4(9.2%)and 1b(6.1%).Pretreatment fibrosis degree was mild-tomoderate(F0-F2)in 77.6%and severe in 22.4%(F3-F4).Treatment regimens chosen were:45.9%elbasvir/grazoprevir,29.6%sofosbuvir/velpatasvir,and 12.2%sofosbuvir/ledispavir and glecaprevir/pibrentasvir.No major adverse events were observed.SVR at post-treatment week 12 was 99%.CONCLUSION In a population considered to be both hard-to-access and a cornerstone for HCV elimination,the onsite evaluation and treatment of HCV-infected prisoners,achieved an exceptional highly effective success rate.This type of collaborative program should be considered to be expanded,to support hepatitis C elimination efforts.
基金Supported by the Ministry of Science,Innovation and Universities,CarlosⅢHealth Institute(ISCⅢ),European Fund for Regional Development(FEDER),Network for Cooperative Research in Health(RETICS),Spain(No.RD16/0017/0003,PI17/00174,INT19/00026,CD19/00019)the Ministry of Health,National Plan on Drugs(PNSD),Spain(No.2018/020)+4 种基金the European Commission(806996-JUSTSO-JUST2017-AG-DRUG)the Gilead Fellowship Program,Gilead Sciences(No.GLD17/187)the Ministry of Education,Spain(No.PRX18/00245)the Agency for Management of University and Research Grants,Government of Catalonia(No.2017SGR316)and the Municipal Institute of Personal。
文摘BACKGROUND Direct-acting antivirals(DAAs)are recommended for the treatment of hepatitis C virus(HCV)infection in patients treated with methadone or buprenorphine.AIM To assess HCV treatment rates in an Opioid Treatment Program(OTP).METHODS This longitudinal study included 501 patients(81.4%men,median age:45 years;interquartile range:39-50 years)enrolled in an OTP between October 2015 and September 2017.Patients were followed until September 2019.Data on sociodemographics,substance use,HCV infection,human immunodeficiency virus(HIV)infection and laboratory parameters were collected at entry.We analyzed medical records to evaluate HCV treatment.Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors.RESULTS Prevalence of HCV and HIV infection was 70%and 34%,respectively.Among anti-HCV-positive(n=336)patients,47.2%,41.3%,and 31.9%used alcohol,cannabis,and cocaine,respectively.HCV-RNA tests were positive in 233(69.3%)patients.Twentyeight patients(8.3%)cleared the infection,and 59/308(19.1%)had received interferon-based treatment regimens before 2015.Among 249 patients eligible,111(44.6%)received DAAs.Treatment rates significantly increased over time from 7.8/100 person-years(p-y)(95%CI:5.0-12.3)in 2015 to 18.9/100 p-y(95%CI:11.7-30.3)in 2019.In a multivariate analysis,patients with HIV co-infection were twice as likely to receive DAAs(HR=1.94,95%CI:1.21-3.12)than patients with HCV mono-infection.Current drug use was an independent risk factor for not receiving treatment against infection(HR=0.48,95%CI:0.29-0.80).CONCLUSION HCV treatment is evolving in patients with HCV-HIV co-infection.Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.
文摘Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)coinfection is a major problem among HIV-infected patients,resulting in increased morbidity and mortality rates due to the acceleration of liver fibrosis progression by HIV,leading to liver cirrhosis and hepatocellular carcinoma.Although the efficacy of directacting antiviral therapy in patients with HIV/HCV coinfection and HCV monoinfection are similar in terms of sustained virologic response rate,there are some additional complications that arise in the treatment of patients with HIV/HCV coinfection,including drug-drug interactions and HCV reinfection due to the high risk behavior of these patients.This review will summarize the current management of HIV/HCV coinfection.
基金Supported by Fundación Burgos por la Investigación de la Salud and Gerencia Regional de Salud de Castilla y León,No.BUO/06/15
文摘AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus(HCV).METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response(SVR) as well as serious adverse events(SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial(CT-met and CT-unmet, respectively).RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir(36.4%), followed by sofosbuvir/ledipasvir(24.9%) and ombitasvir/paritaprevir/ritonavir(r)/dasabuvir(19.9%). Ribavirin(RBV) was administered in 198 patients(42.9%). SVRs occurred in 437/462 patients(94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CTmet group vs 91.9% patients in the CT-unmet group(P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure(P = 0.04). Eleven patients(2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively(P = 0.003).CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.
基金supported by the Natural Science Foundation of Zhejiang Province(no.LY21H030011)ZhejiangMedical Health Science and Technology Program—Young Innovative Support Program(no.2022RC196).
文摘This study aimed to review the trends of hepatitis C virus(HCV)treatment over the past decade and to analyze the effectiveness of sofosbuvir(SOF)–based direct-acting antiviral regimens in the heterogeneous population of patients with chronic hepatitis C(CHC)in clinical practice.This retrospective cohort study included CHC patients attending the Sir Run Run Shaw Hospital between January 1,2012,and December 31,2022.All of the 194 patients treatedwith SOF-based regimens completed 12weeks of treatment and were followed up for at least 12 weeks after completion of the therapy.Sustained virologic response(SVR)12 weeks after the end of treatment was the primary endpoint.A total of 194 patients treated with SOF-based regimens were included,among which 121,56,10 and 7 patients received SOF+velpatasvir±ribavirin,SOF+daclatasvir,SOF+ledipasvir or SOF+ribavirin,respectively.With 36.1%,HCV Genotype 1 predominated in CHC patients treated with SOF-based regimens,followed by Genotype 2a with 17.5%and Genotype 3 with 14.9%.Comorbidities among patients included hypertension(4.1%),diabetes(2.1%),depression(1.0%)and neoplastic disease(2.6%).All patients treated with SOF-based regimens achieved SVR.There was no association between SVR and factors such as HCV genotype,sex,age,presence of cirrhosis or previous treatment history.There were no reports of any serious adverse events in the study.This single-center retrospective study represented the latest 10-year treatment trends for HCV in real-world clinical practice and provided useful information on the excellent efficacy of SOF-based direct-acting antiviral regimens for treatment of CHC patients in Eastern China.
基金CMV is a recipient of a grant from Gilead,Canada.
文摘Our comprehensive review focuses on the treatment of hepatitis C virus in the context of hepatocellular carcinoma and vice versa,highlighting the ongoing complexity of this clinical scenario.There remain multiple unanswered questions when considering the management of these complex patients and,with a rapidly-changing treatment landscape for both chronic hepatitis C and hepatocellular carcinoma,these questions are only going to grow.Treatment timing,interactions and the impact of one disease condition on the other are vitally important,though guidance generally remains non-specific,suggesting that we make these decisions on a case-by-case basis.We focus on the current evidence for managing these cases,depending on disease stage and treatment type.
文摘Chronic hepatitis C virus(HCV)infection is a major cause of liver cirrhosis and hepatocellular carcinoma(HCC)worldwide.The recent advancement of direct-acting Antiviral Agents(DAAs)in hepatitis C therapy,resulted in sustained virological response rates of over 90%in treated patients in different stages of liver fibrosis.The efficacy of DAAs treatment has also been confirmed in real-life cohorts that include subjects with decompensated cirrhosis and therefore seems a promising step to a significant reduction in the recurrence of HCC in patients who achieved complete destruction of the HCC nodules by local therapy.We present a 72-year old patient with HCV-related liver cirrhosis who successfully responded to DAAs treatment after complete destruction of an early HCC nodule.
