Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved t...Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.展开更多
Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular carcinoma.Currently,no effective vaccine is available for HCV infection.Polye...Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular carcinoma.Currently,no effective vaccine is available for HCV infection.Polyethylene glycol interferon-α(PegIFN-α)in combination with ribavirin(RBV)is the standard of care(SOC)for chronic hepatitis C.However,the efficacy of PegIFN-αand RBV combination therapy is less than 50%for genotype 1HCV,which is the dominant virus in humans.In addition,IFN and RBV have several severe side effects.Therefore,strategies to improve sustained virological response(SVR)rates have been an important focus for clinical physicians.The serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in 2011.The addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV infection.Several direct-acting antiviral drugs currently in late-stage clinical trials,both with and without pegIFN and RBV,have several advantages over the previous SOC,including higher specificity and efficacy,fewer side effects,and the ability to be administered orally,and might be optimal regimens in the future.Factors affecting the efficacy of anti-HCV treatments based on IFN-αinclude the HCV genotype,baseline viral load,virological response during treatment,host IL28B gene polymorphisms and hepatic steatosis.However,determining the effect of the above factors on DAA therapy is necessary.In this review,we summarize the development of antiHCV agents and assess the main factors affecting the efficacy of antiviral treatments.展开更多
Despite advances in therapy, hepatitis C virus(HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many ...Despite advances in therapy, hepatitis C virus(HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants(quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success.展开更多
While hepatitis B virus(HBV)screening relies on hepatitis B surface antigen to confirm HBV infection since the early days of hepatitis B disease management,hepatitis C virus(HCV)infection screening is based on anti-HC...While hepatitis B virus(HBV)screening relies on hepatitis B surface antigen to confirm HBV infection since the early days of hepatitis B disease management,hepatitis C virus(HCV)infection screening is based on anti-HCV testing which does not discriminate active from past infection.Thus to confirm infection HCV RNA testing has been required;recently a HCV core antigen assay became widely commercially available which could serve to confirm infection.That assay is less sensitive than current HCV RNA assays,but as more than 50%of anti-HCV positive persons will be HCV core antigen positive,HCV core antigen testing can be a cost effective and reflex test to confirm HCV infection in anti-HCV positive individuals and will be easier as it can be applied on the same platform.For treatment monitoring,more data need to be generated,but the early data available at present suggest that HCV core antigen may be an alternative to HCV RNA monitoring.With direct antivirals,HCV core antigen could even be superior to HCV RNA testing,as direct antivirals might already prevent virus formation when HCV core antigen is still produced and thereby correlates better with eventual viral clearance.展开更多
More than twenty years of study has provided a better understanding of hepatitis C virus(HCV) life cycle,including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive...More than twenty years of study has provided a better understanding of hepatitis C virus(HCV) life cycle,including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviraltreatments. At present,serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response. In the early 2000 s,pegylated interferon plus ribavirin became the standard antiHCV treatment. However,this therapy is not ideal. To 2014,boceprevir,telaprevir,simeprevir,sofosbuvir and Harvoni are approved by Food and Drug Administration for the treat of HCV infections. It is likely that the new all-oral,interferon-free,pan-genotyping anti-HCV therapy will be available within the next few years. Majority of HCV infections will be cured by these antiviral treatments. However,not all patients are expected to be cured due to viral resistance and the high cost of antiviral treatments. Thus,an efficient prophylactic vaccine will be the next challenge in the fight against HCV infection.展开更多
A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. F...A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.展开更多
To quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this process.METHODSAs standard of care, a clinical pharmac...To quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this process.METHODSAs standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral (DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir (LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir (OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTSSix hundred and sixty four patients (83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients.CONCLUSIONDDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care.展开更多
AIM:To examine the association between the interleukin 28B(IL-28B)genotype and treatment response in hepatitis C virus(HCV)-infected patients with persistently normal alanine aminotransferase(PNALT).METHODS:We compare...AIM:To examine the association between the interleukin 28B(IL-28B)genotype and treatment response in hepatitis C virus(HCV)-infected patients with persistently normal alanine aminotransferase(PNALT).METHODS:We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT.Between February 2010 and April2013,278 patients infected with HCV were enrolled in this study.All of the patients were treated with peginterferon-alpha 2a or 2b plus ribavirin.In addition,180μg of peginterferon alpha-2a or 1.5μg/kg peginterferon alpha-2b per week plus weight-based ribavirin(600-1000 mg/d)were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected patients.In all of the patients,the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism assay.HCV RNA was measured using the COBAS TaqMan HCV test.RESULTS:Female patients were dominant in the PNALT group(P【0.0001).Among 72 HCV genotype 1-infected patients with PNALT,the early virologic response(EVR)rates(P【0.01)and the sustained virologic response(SVR)rates(P【0.01)were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG genotype.In HCV genotype 1-infected patients with PNALT,multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type(P【0.05)and having an EVR(P【0.01).The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with PNALT.CONCLUSION:The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.展开更多
Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interfero...Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response (EVR) and a rapid virologic response (RVR) is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV co- infected patients, patients with liver cirrhosis, and pre- or post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development.展开更多
AIM:To assess whether schistosomiasis coinfection with chronic hepatitis C virus (HCV) influences hepatic fibrosis and pegylated-interferon/ribavirin (PEG-IFN/ RIB) therapy response. METHODS:This study was designed as...AIM:To assess whether schistosomiasis coinfection with chronic hepatitis C virus (HCV) influences hepatic fibrosis and pegylated-interferon/ribavirin (PEG-IFN/ RIB) therapy response. METHODS:This study was designed as a retrospective analysis of 3596 chronic HCV patients enrolled in the Egyptian National Program for HCV treatment with PEG-IFN/RIB. All patients underwent liver biopsy and anti-schistosomal antibodies testing prior to HCV treatment. The serology results were used to categorize the patients into group A (positive schistosomal serology) or group B (negative schistosomal serology). Patients in group A were given oral antischistosomal treatment(praziquantel, single dose) at four weeks prior to PEG-IFN/RIB. All patients received a 48-wk course of PEG-IFN (PEG-IFNα2a or PEG-IFNα2b)/RIB therapy. Clinical and laboratory follow-up examinations were carried out for 24 wk after cessation of therapy (to week 72). Correlations of positive schistosomal serology with fibrosis and treatment response were assessed by multiple regression analysis. RESULTS:Schistosomal antibody was positive in 27.3% of patients (15.9% females and 84.1% males). The patients in group A were older (P = 0.008) and had a higher proportion of males (P = 0.002) than the patients in group B. There was no significant association between fibrosis stage and positive schistosomal serology (P = 0.703). Early virological response was achieved in significantly more patients in group B than in group A (89.4% vs 86.5%, P = 0.015). However, significantly more patients in group A experienced breakthrough at week 24 than patients in group B (36.3% vs 32.3%, P = 0.024). End of treatment response was achieved in more patients in group B than in group A (62.0% vs 59.1%) but the difference did not reach statistical significance (P = 0.108). Sustained virological response occurred in significantly more patients in group B than in group A (37.6% vs 27.7%, P = 0.000). Multivariate logistic regression analysis of patient data at treatment weeks 48 and 72 showed that positive schistosomal serology was associated with failure of response to treatment at week 48 (OR = 1.3, P = 0.02) and at week 72 (OR = 1.7, P < 0.01). CONCLUSION:Positive schistosomal serology has no effect on fibrosis staging but is significantly associated with failure of response to HCV treatment despite antischistosomal therapy.展开更多
Elucidation of the natural history of chronic hepatitis C (CHC) and the identification of risk factors for its progression to advanced liver disease have allowed many physicians to recommend deferral treatment (triple...Elucidation of the natural history of chronic hepatitis C (CHC) and the identification of risk factors for its progression to advanced liver disease have allowed many physicians to recommend deferral treatment (triple therapy) in favour of waiting for new drug availability for patients who are at low risk of progression to significant liver disease. Newer generation drugs are currently under development, and are expected to feature improved efficacy and safety profiles, as well as less complex and shorter duration delivery regimens, compared to the current standards of care. In addition, patients with cirrhosis and prior null responders have a low rate (around 15%) of achieving sustained virological response (SVR) with triple therapy, and physicians must also consider the decision to wait for new treatments in the future for these patients as well. Naïve patients are the most likely to achieve a close to 100% SVR rate; therefore, it may be advisable to recommend that patients with mild to moderate CHC should wait for the newer therapy options. In contrast, patients with advanced fibrosis and cirrhosis will be those with the greatest need for expedited therapeutic intervention. There remains a need, however, for establishing definitive clinical management guidelines to maximize the benefit of waiting for new drugs and minimize risk of side effects and non-response to the current triple therapy.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
AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment...AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.展开更多
AIM: To investigate the safety/efficacy of Boceprevirbased triple therapy in hepatitis C virus(HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assi...AIM: To investigate the safety/efficacy of Boceprevirbased triple therapy in hepatitis C virus(HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure(7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEGIFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNApositive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response(SVR)(HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4(RVR), 8(RVR BOC), 12(EVR), or at the end-of-treatment(ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used.RESULTS: After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤1 log10 decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56(57.1%) and at week 12 in 41/56(73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56(44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders(P = 0.250), in 44% F0-F2 vs 54% F3-F4(P = 0.488), and in 11/19(57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy(OR = 2.662, 95%CI: 0.957-6.881, P = 0.043), was related with SVR. When considering "on treatment" factors, 1 log10 HCV RNA decline at week 4(3.733, 95%CI: 1.676-12.658, P = 0.034) and achievement of RVR BOC(7.347, 95%CI: 2.156-25.035, P = 0.001) were significantly related with the SVR, although RVR BOC only(6.794, 95%CI: 1.596-21.644, P = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy. CONCLUSION: Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR.展开更多
The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)tr...The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic failure.In fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been reported.In the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still controversial.Therefore,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.展开更多
Introduction of effective drugs in the treatment of hepatitis C virus(HCV)infection has prompted the World Health Organization to declare a global eradication target by 2030.Propositions have been made to screen the g...Introduction of effective drugs in the treatment of hepatitis C virus(HCV)infection has prompted the World Health Organization to declare a global eradication target by 2030.Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status.A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease.Huge financial resources were redirected,and the pandemic became the first priority in every country.In this review,we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection.We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination.Alcohol consumption,HIV coinfection and the presence of components of metabolic syndrome including obesity,hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liverrelated morbidity and mortality of HCV.We also examined the significance of special subpopulations like people who inject drugs and males having sex with males.Finally,we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income.We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.展开更多
Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV). Although treatment with antiretroviral therapy ...Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus(HBV) and hepatitis C virus(HCV) causes significant numbers of non-acquired immune deficiency syndrome(AIDS)-related deaths in coinfected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals(DAA) and antiretroviral therapy(ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV coinfected individuals.展开更多
Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications s...Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indicates that HCV-associated insulin resistance may cause(1) hepatic steatosis;(2) resistance to anti-viral treatment;(3) hepatic f ibrosis and esophageal varices;(4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma;and(5) extrahepatic manifestations.Thus,HCV-associated insulin resistance is a therapeutic target at any stage of HCV infection.Although the risk of insulin resistance in HCV-infected patients has been documented,therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been established.In addition,mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin resistance.In order to ameliorate HCV-associated insulin resistance and its complications,the eff icacy of the following interventions is discussed:a late evening snack,coffee consumption,dietary iron restriction,phlebotomy,and zinc supplements.Little is known regarding the effect of anti-diabetic agents on HCV infection,however,a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been reported.On the other hand,insulin-sensitizing agents are reported to improve sustained virologic response rates.In this review,we summarize distinctive complications of,and therapeutic strategies for,HCVassociated insulin resistance.Furthermore,we discuss supplementation with branched-chain amino acids as a unique insulin-sensitizing strategy for patients with HCVassociated insulin resistance.展开更多
Hepatitis C virus(HCV) is a major cause of liver diseases including liver cirrhosis and hepatocellular carcinoma. Approximately 3% of the world population is infected with HCV. Thus, HCV infection is considered a publ...Hepatitis C virus(HCV) is a major cause of liver diseases including liver cirrhosis and hepatocellular carcinoma. Approximately 3% of the world population is infected with HCV. Thus, HCV infection is considered a public healthy challenge. It is worth mentioning, that the HCV prevalence is dependent on the countries with infection rates around 20% in high endemic countries. The review summarizes recent data on HCV molecular biology, the physiopathology of infection(immune-mediated liver damage, liver fibrosis and lipid metabolism), virus diagnostic and treatment. In addition, currently available in vitro, ex vivo and animal models to study the virus life cycle, virus pathogenesis and therapy are described. Understanding of both host and viral factors may in the future lead to creation of new approaches in generation of an efficient therapeutic vaccine.展开更多
Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabet...Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus(T1DM) and T2 DM. T2 DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1 DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2 DM and chronic hepatitis C(CHC) infection. The processes through which CHC is associated with T2 DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immunemediated mechanisms. Few data have been reported on the association of CHC and T1 DM and reports on the potential association between T1 DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoim-munity and in certain cases lead to the development of T1 DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with nondiabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effec-tive programmes for the surveillance and treatment of diabetic CHC patients.展开更多
文摘Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.
文摘Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular carcinoma.Currently,no effective vaccine is available for HCV infection.Polyethylene glycol interferon-α(PegIFN-α)in combination with ribavirin(RBV)is the standard of care(SOC)for chronic hepatitis C.However,the efficacy of PegIFN-αand RBV combination therapy is less than 50%for genotype 1HCV,which is the dominant virus in humans.In addition,IFN and RBV have several severe side effects.Therefore,strategies to improve sustained virological response(SVR)rates have been an important focus for clinical physicians.The serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in 2011.The addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV infection.Several direct-acting antiviral drugs currently in late-stage clinical trials,both with and without pegIFN and RBV,have several advantages over the previous SOC,including higher specificity and efficacy,fewer side effects,and the ability to be administered orally,and might be optimal regimens in the future.Factors affecting the efficacy of anti-HCV treatments based on IFN-αinclude the HCV genotype,baseline viral load,virological response during treatment,host IL28B gene polymorphisms and hepatic steatosis.However,determining the effect of the above factors on DAA therapy is necessary.In this review,we summarize the development of antiHCV agents and assess the main factors affecting the efficacy of antiviral treatments.
文摘Despite advances in therapy, hepatitis C virus(HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants(quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success.
文摘While hepatitis B virus(HBV)screening relies on hepatitis B surface antigen to confirm HBV infection since the early days of hepatitis B disease management,hepatitis C virus(HCV)infection screening is based on anti-HCV testing which does not discriminate active from past infection.Thus to confirm infection HCV RNA testing has been required;recently a HCV core antigen assay became widely commercially available which could serve to confirm infection.That assay is less sensitive than current HCV RNA assays,but as more than 50%of anti-HCV positive persons will be HCV core antigen positive,HCV core antigen testing can be a cost effective and reflex test to confirm HCV infection in anti-HCV positive individuals and will be easier as it can be applied on the same platform.For treatment monitoring,more data need to be generated,but the early data available at present suggest that HCV core antigen may be an alternative to HCV RNA monitoring.With direct antivirals,HCV core antigen could even be superior to HCV RNA testing,as direct antivirals might already prevent virus formation when HCV core antigen is still produced and thereby correlates better with eventual viral clearance.
基金Supported by Grants from the National Science Council of Taiwan,No.NSC 101-2320-B-320-011-MY3(Dr.Shih-Yen Lo)the Tzu Chi University to Dr.Shih-Yen Lo,No.TCIRP 103002-03and to Dr.Hui-Chun Li,No.TCIRP 103002-02
文摘More than twenty years of study has provided a better understanding of hepatitis C virus(HCV) life cycle,including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviraltreatments. At present,serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response. In the early 2000 s,pegylated interferon plus ribavirin became the standard antiHCV treatment. However,this therapy is not ideal. To 2014,boceprevir,telaprevir,simeprevir,sofosbuvir and Harvoni are approved by Food and Drug Administration for the treat of HCV infections. It is likely that the new all-oral,interferon-free,pan-genotyping anti-HCV therapy will be available within the next few years. Majority of HCV infections will be cured by these antiviral treatments. However,not all patients are expected to be cured due to viral resistance and the high cost of antiviral treatments. Thus,an efficient prophylactic vaccine will be the next challenge in the fight against HCV infection.
基金Supported by In part by grants of AViLL/AIL(Associazione Vicentina per le Leucemie,i Linfomi e il Mieloma/Associazione Italiana Leucemie)(Vicenza,Italy)the Hematology Project Foundation(HPF,Fondazione Progetto Ematologia,Vicenza,Italy)
文摘A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.
文摘To quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this process.METHODSAs standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral (DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir (LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir (OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTSSix hundred and sixty four patients (83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients.CONCLUSIONDDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care.
基金Supported by Grants for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology,JapanGrants from the Ministry of Health,Labour and Welfare of Japan
文摘AIM:To examine the association between the interleukin 28B(IL-28B)genotype and treatment response in hepatitis C virus(HCV)-infected patients with persistently normal alanine aminotransferase(PNALT).METHODS:We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT.Between February 2010 and April2013,278 patients infected with HCV were enrolled in this study.All of the patients were treated with peginterferon-alpha 2a or 2b plus ribavirin.In addition,180μg of peginterferon alpha-2a or 1.5μg/kg peginterferon alpha-2b per week plus weight-based ribavirin(600-1000 mg/d)were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected patients.In all of the patients,the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism assay.HCV RNA was measured using the COBAS TaqMan HCV test.RESULTS:Female patients were dominant in the PNALT group(P【0.0001).Among 72 HCV genotype 1-infected patients with PNALT,the early virologic response(EVR)rates(P【0.01)and the sustained virologic response(SVR)rates(P【0.01)were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG genotype.In HCV genotype 1-infected patients with PNALT,multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type(P【0.05)and having an EVR(P【0.01).The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with PNALT.CONCLUSION:The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.
文摘Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response (EVR) and a rapid virologic response (RVR) is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV co- infected patients, patients with liver cirrhosis, and pre- or post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development.
基金Supported by The Science and Technology Development Fund,No.1708
文摘AIM:To assess whether schistosomiasis coinfection with chronic hepatitis C virus (HCV) influences hepatic fibrosis and pegylated-interferon/ribavirin (PEG-IFN/ RIB) therapy response. METHODS:This study was designed as a retrospective analysis of 3596 chronic HCV patients enrolled in the Egyptian National Program for HCV treatment with PEG-IFN/RIB. All patients underwent liver biopsy and anti-schistosomal antibodies testing prior to HCV treatment. The serology results were used to categorize the patients into group A (positive schistosomal serology) or group B (negative schistosomal serology). Patients in group A were given oral antischistosomal treatment(praziquantel, single dose) at four weeks prior to PEG-IFN/RIB. All patients received a 48-wk course of PEG-IFN (PEG-IFNα2a or PEG-IFNα2b)/RIB therapy. Clinical and laboratory follow-up examinations were carried out for 24 wk after cessation of therapy (to week 72). Correlations of positive schistosomal serology with fibrosis and treatment response were assessed by multiple regression analysis. RESULTS:Schistosomal antibody was positive in 27.3% of patients (15.9% females and 84.1% males). The patients in group A were older (P = 0.008) and had a higher proportion of males (P = 0.002) than the patients in group B. There was no significant association between fibrosis stage and positive schistosomal serology (P = 0.703). Early virological response was achieved in significantly more patients in group B than in group A (89.4% vs 86.5%, P = 0.015). However, significantly more patients in group A experienced breakthrough at week 24 than patients in group B (36.3% vs 32.3%, P = 0.024). End of treatment response was achieved in more patients in group B than in group A (62.0% vs 59.1%) but the difference did not reach statistical significance (P = 0.108). Sustained virological response occurred in significantly more patients in group B than in group A (37.6% vs 27.7%, P = 0.000). Multivariate logistic regression analysis of patient data at treatment weeks 48 and 72 showed that positive schistosomal serology was associated with failure of response to treatment at week 48 (OR = 1.3, P = 0.02) and at week 72 (OR = 1.7, P < 0.01). CONCLUSION:Positive schistosomal serology has no effect on fibrosis staging but is significantly associated with failure of response to HCV treatment despite antischistosomal therapy.
文摘Elucidation of the natural history of chronic hepatitis C (CHC) and the identification of risk factors for its progression to advanced liver disease have allowed many physicians to recommend deferral treatment (triple therapy) in favour of waiting for new drug availability for patients who are at low risk of progression to significant liver disease. Newer generation drugs are currently under development, and are expected to feature improved efficacy and safety profiles, as well as less complex and shorter duration delivery regimens, compared to the current standards of care. In addition, patients with cirrhosis and prior null responders have a low rate (around 15%) of achieving sustained virological response (SVR) with triple therapy, and physicians must also consider the decision to wait for new treatments in the future for these patients as well. Naïve patients are the most likely to achieve a close to 100% SVR rate; therefore, it may be advisable to recommend that patients with mild to moderate CHC should wait for the newer therapy options. In contrast, patients with advanced fibrosis and cirrhosis will be those with the greatest need for expedited therapeutic intervention. There remains a need, however, for establishing definitive clinical management guidelines to maximize the benefit of waiting for new drugs and minimize risk of side effects and non-response to the current triple therapy.
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.
基金Supported by Fundacion Manchega de Investigacion y Docencia en Gastroenterologiapartially by Red Nacional en Investigacin de Hepatologa y Gastroenterologia (RNIHG) Javier MorenoGloria Moraleda contributed equally to this work
文摘AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.
文摘AIM: To investigate the safety/efficacy of Boceprevirbased triple therapy in hepatitis C virus(HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure(7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEGIFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNApositive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response(SVR)(HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4(RVR), 8(RVR BOC), 12(EVR), or at the end-of-treatment(ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used.RESULTS: After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤1 log10 decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56(57.1%) and at week 12 in 41/56(73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56(44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders(P = 0.250), in 44% F0-F2 vs 54% F3-F4(P = 0.488), and in 11/19(57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy(OR = 2.662, 95%CI: 0.957-6.881, P = 0.043), was related with SVR. When considering "on treatment" factors, 1 log10 HCV RNA decline at week 4(3.733, 95%CI: 1.676-12.658, P = 0.034) and achievement of RVR BOC(7.347, 95%CI: 2.156-25.035, P = 0.001) were significantly related with the SVR, although RVR BOC only(6.794, 95%CI: 1.596-21.644, P = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy. CONCLUSION: Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR.
文摘The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic failure.In fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been reported.In the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still controversial.Therefore,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.
基金Corresponding author:Elias Kouroumalis,MD,PhD,Emeritus Professor,Department of Gastroenterology,University of Crete Medical School,Voutes,Heraklion 71500,Crete,Greece.kouroumi@uoc.gr。
文摘Introduction of effective drugs in the treatment of hepatitis C virus(HCV)infection has prompted the World Health Organization to declare a global eradication target by 2030.Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status.A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease.Huge financial resources were redirected,and the pandemic became the first priority in every country.In this review,we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection.We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination.Alcohol consumption,HIV coinfection and the presence of components of metabolic syndrome including obesity,hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liverrelated morbidity and mortality of HCV.We also examined the significance of special subpopulations like people who inject drugs and males having sex with males.Finally,we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income.We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
基金National Institutes of Health,No.NIAAAK01AA026864
文摘Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus(HBV) and hepatitis C virus(HCV) causes significant numbers of non-acquired immune deficiency syndrome(AIDS)-related deaths in coinfected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals(DAA) and antiretroviral therapy(ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV coinfected individuals.
基金Supported by (in part) A Grant-in-Aid for Young Scientists (B),No. 19790643 to Kawaguchi Ta Grant-in-Aid for Scientif ic Research (C),No. 21590865 to Sata M,from the Ministry of Education,Culture,Sports,Science and Technology of Japan+1 种基金Health and Labour Sciences Research Grants for Research on Hepatitis from the Ministry of Health,Labour and Welfare of Japana Grant for Cancer Research from Fukuoka Cancer Society
文摘Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indicates that HCV-associated insulin resistance may cause(1) hepatic steatosis;(2) resistance to anti-viral treatment;(3) hepatic f ibrosis and esophageal varices;(4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma;and(5) extrahepatic manifestations.Thus,HCV-associated insulin resistance is a therapeutic target at any stage of HCV infection.Although the risk of insulin resistance in HCV-infected patients has been documented,therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been established.In addition,mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin resistance.In order to ameliorate HCV-associated insulin resistance and its complications,the eff icacy of the following interventions is discussed:a late evening snack,coffee consumption,dietary iron restriction,phlebotomy,and zinc supplements.Little is known regarding the effect of anti-diabetic agents on HCV infection,however,a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been reported.On the other hand,insulin-sensitizing agents are reported to improve sustained virologic response rates.In this review,we summarize distinctive complications of,and therapeutic strategies for,HCVassociated insulin resistance.Furthermore,we discuss supplementation with branched-chain amino acids as a unique insulin-sensitizing strategy for patients with HCVassociated insulin resistance.
文摘Hepatitis C virus(HCV) is a major cause of liver diseases including liver cirrhosis and hepatocellular carcinoma. Approximately 3% of the world population is infected with HCV. Thus, HCV infection is considered a public healthy challenge. It is worth mentioning, that the HCV prevalence is dependent on the countries with infection rates around 20% in high endemic countries. The review summarizes recent data on HCV molecular biology, the physiopathology of infection(immune-mediated liver damage, liver fibrosis and lipid metabolism), virus diagnostic and treatment. In addition, currently available in vitro, ex vivo and animal models to study the virus life cycle, virus pathogenesis and therapy are described. Understanding of both host and viral factors may in the future lead to creation of new approaches in generation of an efficient therapeutic vaccine.
文摘Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus(T1DM) and T2 DM. T2 DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1 DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2 DM and chronic hepatitis C(CHC) infection. The processes through which CHC is associated with T2 DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immunemediated mechanisms. Few data have been reported on the association of CHC and T1 DM and reports on the potential association between T1 DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoim-munity and in certain cases lead to the development of T1 DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with nondiabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effec-tive programmes for the surveillance and treatment of diabetic CHC patients.
