BACKGROUND The World Health Organization recommends testing all human immunodeficiency virus(HIV)patients for hepatitis C virus(HCV).In resource-constrained contexts with low-to-intermediate HCV prevalence among HIV p...BACKGROUND The World Health Organization recommends testing all human immunodeficiency virus(HIV)patients for hepatitis C virus(HCV).In resource-constrained contexts with low-to-intermediate HCV prevalence among HIV patients,as in Cambodia,targeted testing is,in the short-term,potentially more feasible and cost-effective.AIM To develop a clinical prediction score(CPS)to risk-stratify HIV patients for HCV coinfection(HCV RNA detected),and derive a decision rule to guide prioritization of HCV testing in settings where‘testing all’is not feasible or unaffordable in the short term.METHODS We used data of a cross-sectional HCV diagnostic study in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh.Key populations were very rare in this cohort.Score development relied on the Spiegelhalter and Knill-Jones method.Predictors with an adjusted likelihood ratio≥1.5 or≤0.67 were retained,transformed to natural logarithms,and rounded to integers as score items.CPS performance was evaluated by the area-under-the-ROC curve(AUROC)with 95% confidence intervals(CI),and diagnostic accuracy at the different cut-offs.For the decision rule,HCV coinfection probability≥1% was agreed as test-threshold.RESULTS Among the 3045 enrolled HIV patients,106 had an HCV coinfection.Of the 11 candidate predictors(from history-taking,laboratory testing),seven had an adjusted likelihood ratio≥1.5 or≤0.67:≥50 years(+1 point),diabetes mellitus(+1),partner/household member with liver disease(+1),generalized pruritus(+1),platelets<200×10^(9)/L(+1),aspartate transaminase(AST)<30 IU/L(-1),AST-to-platelet ratio index(APRI)≥0.45(+1),and APRI<0.45(-1).The AUROC was 0.84(95%CI:0.80-0.89),indicating good discrimination of HCV/HIV coinfection and HIV mono-infection.The CPS result≥0 best fits the test-threshold(negative predictive value:99.2%,95%CI:98.8-99.6).Applying this threshold,30%(n=926)would be tested.Sixteen coinfections(15%)would have been missed,none with advanced fibrosis.CONCLUSION The CPS performed well in the derivation cohort,and bears potential for other contexts of low-to-intermediate prevalence and little onward risk of transmission(i.e.cohorts without major risk factors as injecting drug use,men having sex with men),and where available resources do not allow to test all HIV patients as recommended by WHO.However,the score requires external validation in other patient cohorts before any wider use can be considered.展开更多
Alcohol use disorder(AUD) and hepatitis C virus(HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to...Alcohol use disorder(AUD) and hepatitis C virus(HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus(HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.展开更多
Objective Newly identified human rhinovirus C （HRV-C） and human bocavirus （HBoV） cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related va...Objective Newly identified human rhinovirus C （HRV-C） and human bocavirus （HBoV） cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses.Methods A platform for culturing human airway epithelia in a three-dimensional （3D） pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction {PCR）. Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA.Results Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-2, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial （HAE） cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system.Conclusion Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.展开更多
AIM To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus(HCV)/human immunodeficiency virus(HIV) co-infection in an urban HIV clinic.METHODS A retro...AIM To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus(HCV)/human immunodeficiency virus(HIV) co-infection in an urban HIV clinic.METHODS A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016.All patients included were receiving antiretroviral therapy(ART) with HIV RNA values of 100 copies/m L or fewer regardless of baseline HCV RNA level.The primary end point was a sustained virologic response of HCV at 12 wk(SVR12) after the end of therapy.RESULTS Of the 40 patients enrolled,55% were black,22.5% had been previously treated for HCV,and 25% hadcirrhosis.The patients were on a wide range of ART.Overall,39 patients(97.5%) had a SVR 12 after the end of therapy,including rates of 97.1% in patients with HCV genotype 1 a and 100% in those with HCV genotype 1 b.One patient with HCV genotype 3 a was included and achieved SVR12.Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis.Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn't reveal any resistance associated mutation in the NS5A or NS5B region.Interestingly,7(17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen.Two(5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy,which resolved after resuming the same ART regimen.No severe adverse events were observed and no patient discontinued treatment because of adverse events.The most common adverse events included headache(12.5%),fatigue(10%),and diarrhea(2.5%).CONCLUSION This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV,regardless of HCV baseline levels,HCV treatment history or cirrhosis condition.The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART.Occasional HIV virologic rebound occurred but later resolved without the need to change ART.展开更多
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share a common route of transmission so that about one third of HIV infected individuals show HCV coinfection. Highly active antiretroviral therapy has of...Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share a common route of transmission so that about one third of HIV infected individuals show HCV coinfection. Highly active antiretroviral therapy has offered a longer and better life to infected patients. While has removed AIDS-related diseases from the list of most common causes of death their place has been taken by complications of HCV infection, such as cirrhosis, end stage liver disease and hepatocellular carcinoma (HCC). HIV/HCV co-infection requires complex management, especially when HCC is present. Co-infected patients with HCC undergo the same therapeutic protocol as their mono-infected counterparts, but special issues such as interaction between regimens, withdrawal of therapy and choice of immunosuppressive agents, demand a careful approach by specialists. All these issues are analyzed in this minireview.展开更多
AIM:To document the epidemiologic patterns and risk factors of human immunodeficiency virus(HIV)and hepatitis C virus(HCV)infections in Mali in order to develop prevention means for both diseases.METHODS:Two prospecti...AIM:To document the epidemiologic patterns and risk factors of human immunodeficiency virus(HIV)and hepatitis C virus(HCV)infections in Mali in order to develop prevention means for both diseases.METHODS:Two prospective studies were conducted in Bamako in 2009 among 1000 pregnant women(i.e.,young women)who consulted six reference health centers,and in 2010,among 231 older women who attended general practice in two hospitals.Antibody tests and molecular analysis(performed only for HCV)were used to quantify the frequencies of both infections.The data were collected from patients recruited through a questionnaire.Transmission risk factors of both diseases were identified by univariate and multivariate analysis.RESULTS:HCV seroprevalence was 0.2% for young and 6.5% for older women.HIV prevalence was similar in both populations(4.1% vs 6.1%).In older women,the analysis of risk factors highlighted an association between HCV infection and episodes of hospitalization(P < 0.01).The study did not show an association between HIV infection and the variables such as hospitalization,transfusion,tattoo,dental care,and endoscopy.A significant decrease of HIV seroprevalence was detected in young women who used condoms for contraception more than for other purposes(P < 0.01).By contrast,HIV seroprevalence was significantly increased in young women using condoms mainly to prevent sexual infections rather than for contraception(P < 0.01).No HCV/HIV coinfection was detected in our study.CONCLUSION:Risk factors and epidemiologic data of HIV and HCV as well as the absence of co-infection strongly suggest epidemiological disparities between these diseases.展开更多
Liver transplantation(LT)remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply.The advent of highly effective anti-...Liver transplantation(LT)remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply.The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C(HCV)and hepatitis B(HBV)related liver disease and yet the number of patients waiting for LT continues to increase,driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcoholrelated liver disease.In addition,human immunodeficiency virus(HIV)infection,which was previously a contra-indication for LT,is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT.The rising demand for LT is projected to increase further in the future,thus driving the need to investigate potential means of expanding the pool of potential donors.One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive,HBV-positive,and HIVpositive donors.The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV,HBV or HIV infected recipients and in some cases uninfected recipients.展开更多
Bouare et al found that hepatitis C virus (HCV) infection in Malian women is mainly transmitted through medical procedures with contaminated supplies, and that human immunodeficiency virus (HIV) transmission is predom...Bouare et al found that hepatitis C virus (HCV) infection in Malian women is mainly transmitted through medical procedures with contaminated supplies, and that human immunodeficiency virus (HIV) transmission is predominantly sexual. The results of this study confirm those of a recent case-control study in New York and Oregon which demonstrated that healthcare exposures represent an important source of new HCV infections in United States. HCV seroprevalence was only 0.2% in pregnant, young Malian women, indicating that hygiene improved in healthcare facilities over time. Heterosexual transmission of HCV is exceptional, and can occur, from males to females, in extremely rare occasions in case of vaginal mucosal damage or less rarely through anal intercourse. The Malian study did not show an association between HIV infection and hospitalization, transfusion, tattoo, dental care. Transmission by needle-stick injury occurs in 0.9%-2.2% of exposures from HCV-infected subjects and in 0.1%-0.3% of exposures from HIV-infected in- dividuals. HCV is therefore more transmissible through percutaneous exposure.展开更多
Human immunodeficiency virus(HIV)and hepatitis C virus(HCV)share the same transmission routes;therefore,coinfection is frequent.An estimated 5-10 million individuals alone in the western world are infected with both v...Human immunodeficiency virus(HIV)and hepatitis C virus(HCV)share the same transmission routes;therefore,coinfection is frequent.An estimated 5-10 million individuals alone in the western world are infected with both viruses.The majority of people acquire HCV by injection drug use and,to a lesser extent,through blood transfusion and blood products.Recently,there has been an increase in HCV infections among men who have sex with men.In the context of effective antiretroviral treatment,liver-related deaths are now more common than Acquired Immune Deficiency Syndromerelated deaths among HIV-HCV coinfected individuals.Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20%of chronically infected individuals.HCV treatment has rapidly changed with the development of new direct-acting antiviral agents;therefore,cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle.In this review,we focus on the epidemiology,diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.展开更多
This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global imp...This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the on-going and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the Pub Med literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes.展开更多
AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis ...AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.展开更多
Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus(HCV)-monoinfected and human immunodeficiency virus(HIV)/HCV-coinfected pat...Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus(HCV)-monoinfected and human immunodeficiency virus(HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of noninvasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCVcoinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice.展开更多
The relation between the expression and activity of MMP-9 in C-reactive protein （CRP）-induced human THP-1 mononuclear cells and the activation of nuclear factor kappa-B （NF-κB） was studied to investigate the poss...The relation between the expression and activity of MMP-9 in C-reactive protein （CRP）-induced human THP-1 mononuclear cells and the activation of nuclear factor kappa-B （NF-κB） was studied to investigate the possible role of CRP in plaque destabilization. Human THP-1 cells were incubated in the presence of CRP at 0 （control group）, 25, 50 and 100 μg/mL （CRP groups） for 24 h. In PDTC （a specific NF-κB inhibitor） group, the cells were pre-treated with PDTC at 10 μmol/L and then with 100 μg/mL CRP. The conditioned media （CM） and human THP-1 cells in different groups were harvested. MMP-9 expression in CM and human THP-1 cells was measured by ELISA and Western blotting. MMP-9 activity was assessed by fluorogenic substrates. The expression of NF-κB inhibitor α （IκB-α） and NF-κB p65 was detected by Western blotting and ELISA respectively. The results showed that CRP increased the expression and activity of MMP-9 in a dose-dependent manner in the human THP-1 cells. Western blotting revealed that IiB-α expression was decreased in the cells with the concentrations of CRP and ELISA demonstrated that NF-κB p65 expression in the CRP-induced cells was increased. After pre-treatment of the cells with PDTC at 10 μmol/L, the decrease in IκB-α expression and the increase in NF-κB p65 expression in the CRP-induced cells were inhibited, and the expression and activity of MMP-9 were lowered too. It is concluded that increased expression and activity of MMP-9 in CRP-induced human THP-1 cells may be associated with activation of NF-κB. Down-regulation of the expression and activity of MMP-9 may be a new treatment alternative for plaque stabilization by inhibiting the NF-κB activation.展开更多
Hepatitis B virus(HBV), hepatitis C virus(HCV),and human immunodeficiency virus(HIV) affect many people in Asian countries, although there are geographic differences. Both HBV and HIV(HBV/HIV) and HCV/HIV co-infection...Hepatitis B virus(HBV), hepatitis C virus(HCV),and human immunodeficiency virus(HIV) affect many people in Asian countries, although there are geographic differences. Both HBV and HIV(HBV/HIV) and HCV/HIV co-infections are highly prevalent in Asia. Hetero- and homosexual, injection drug use, and geographic area are strong predictors of HBV, HCV, and HIV serostatus. In HBV endemic regions, the prevalence and genotype distribution of HBV/HIV coinfection is almost comparable with that in the general population. In Japan, where HBV has low endemicity, the prevalence of HBV/HIV co-infection is approximately 10-fold higher than that in the general population, and HBV Ae is the most common subgenotype among HIV infected individuals. Highly active antiretroviral therapy(HAART) is an effective treatment for HIV/Acquired Immune Deficiency Syndrome. Lamivudine, a component of HAART, is an effective treatment for HBV, HIV, and HBV/HIV co-infection; however, cost, emerging drug resistance, antiretroviral-associated liver toxicity and liver-related morbidity due to HCV progression are particular concerns. HCV/HIV co-infection may accelerate the clinical progression of both HCV and HIV. The high prevalence of HBV/HIV and HCV/HIV co-infections in Asia underscores the need to improve prevention and control measures, as fewer evidencebased prevention strategies are available(compared with Western countries). In this review, the most recent publications on the prevalence of HBV/HIV and HCV/HIV co-infections and related issues, such as therapy and problems in Asia, are updated and summarized.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
The Middle East and North Africa(MENA) region has endured several major events of infection parenteral transmission. Recent work has established the utility of using hepatitis C virus(HCV) as a proxy biomarker for ass...The Middle East and North Africa(MENA) region has endured several major events of infection parenteral transmission. Recent work has established the utility of using hepatitis C virus(HCV) as a proxy biomarker for assessing the epidemic potential for human immunodeficiency virus(HIV) parenteral transmission. In this review, we use data on the prevalence of HCV infection antibody(seroprevalence) among general population and high risk population groups to assess the potential for HIV parenteral transmission in MENA. Relatively low prevalence of HCV infection in the general population groups was reported in most MENA countries indicating that parenteral HIV transmission at endemic levels does not appear to be a cause for concern. Nonetheless, there could be opportunities for localized HIV outbreaks and transmission of other blood-borne infections in some settings such as healthcare facilities. Though there have been steady improvements in safety measures related to parenteral modes of transmission in the region, these improvements have not been uniform across all countries. More precautions, including infection control training programs, surveillance systems for nosocomial infections and wider coverage and evaluation of hepatitis B virus immunization programs need to be implemented to avoid the unnecessary spread of HIV, HCV, and other blood-borne pathogens along the parenteral modes of transmission.展开更多
文摘BACKGROUND The World Health Organization recommends testing all human immunodeficiency virus(HIV)patients for hepatitis C virus(HCV).In resource-constrained contexts with low-to-intermediate HCV prevalence among HIV patients,as in Cambodia,targeted testing is,in the short-term,potentially more feasible and cost-effective.AIM To develop a clinical prediction score(CPS)to risk-stratify HIV patients for HCV coinfection(HCV RNA detected),and derive a decision rule to guide prioritization of HCV testing in settings where‘testing all’is not feasible or unaffordable in the short term.METHODS We used data of a cross-sectional HCV diagnostic study in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh.Key populations were very rare in this cohort.Score development relied on the Spiegelhalter and Knill-Jones method.Predictors with an adjusted likelihood ratio≥1.5 or≤0.67 were retained,transformed to natural logarithms,and rounded to integers as score items.CPS performance was evaluated by the area-under-the-ROC curve(AUROC)with 95% confidence intervals(CI),and diagnostic accuracy at the different cut-offs.For the decision rule,HCV coinfection probability≥1% was agreed as test-threshold.RESULTS Among the 3045 enrolled HIV patients,106 had an HCV coinfection.Of the 11 candidate predictors(from history-taking,laboratory testing),seven had an adjusted likelihood ratio≥1.5 or≤0.67:≥50 years(+1 point),diabetes mellitus(+1),partner/household member with liver disease(+1),generalized pruritus(+1),platelets<200×10^(9)/L(+1),aspartate transaminase(AST)<30 IU/L(-1),AST-to-platelet ratio index(APRI)≥0.45(+1),and APRI<0.45(-1).The AUROC was 0.84(95%CI:0.80-0.89),indicating good discrimination of HCV/HIV coinfection and HIV mono-infection.The CPS result≥0 best fits the test-threshold(negative predictive value:99.2%,95%CI:98.8-99.6).Applying this threshold,30%(n=926)would be tested.Sixteen coinfections(15%)would have been missed,none with advanced fibrosis.CONCLUSION The CPS performed well in the derivation cohort,and bears potential for other contexts of low-to-intermediate prevalence and little onward risk of transmission(i.e.cohorts without major risk factors as injecting drug use,men having sex with men),and where available resources do not allow to test all HIV patients as recommended by WHO.However,the score requires external validation in other patient cohorts before any wider use can be considered.
基金Supported by Ministry of Economy and Competitiveness,Institute of Health Carlos,ISCIII:European fund for regional development(FEDER)Nos.RETICS RD 12/0028/0006 and RD16/0017/0003Ministry of Health,Social Services,and Equality,Nos.PNSD 2014/042 and PNSD 2015/027
文摘Alcohol use disorder(AUD) and hepatitis C virus(HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus(HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.
基金supported by grants from the Major Project Specialized for Infectious Diseases of the Chinese Health and Family Planning Commission[2014ZX10004002-004-002,2014ZX10004002-004-001]Young Talent Scholar Plan of Higher School in Hebei Province[BJ2017008]
文摘Objective Newly identified human rhinovirus C （HRV-C） and human bocavirus （HBoV） cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses.Methods A platform for culturing human airway epithelia in a three-dimensional （3D） pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction {PCR）. Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA.Results Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-2, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial （HAE） cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system.Conclusion Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.
文摘AIM To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus(HCV)/human immunodeficiency virus(HIV) co-infection in an urban HIV clinic.METHODS A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016.All patients included were receiving antiretroviral therapy(ART) with HIV RNA values of 100 copies/m L or fewer regardless of baseline HCV RNA level.The primary end point was a sustained virologic response of HCV at 12 wk(SVR12) after the end of therapy.RESULTS Of the 40 patients enrolled,55% were black,22.5% had been previously treated for HCV,and 25% hadcirrhosis.The patients were on a wide range of ART.Overall,39 patients(97.5%) had a SVR 12 after the end of therapy,including rates of 97.1% in patients with HCV genotype 1 a and 100% in those with HCV genotype 1 b.One patient with HCV genotype 3 a was included and achieved SVR12.Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis.Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn't reveal any resistance associated mutation in the NS5A or NS5B region.Interestingly,7(17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen.Two(5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy,which resolved after resuming the same ART regimen.No severe adverse events were observed and no patient discontinued treatment because of adverse events.The most common adverse events included headache(12.5%),fatigue(10%),and diarrhea(2.5%).CONCLUSION This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV,regardless of HCV baseline levels,HCV treatment history or cirrhosis condition.The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART.Occasional HIV virologic rebound occurred but later resolved without the need to change ART.
文摘Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share a common route of transmission so that about one third of HIV infected individuals show HCV coinfection. Highly active antiretroviral therapy has offered a longer and better life to infected patients. While has removed AIDS-related diseases from the list of most common causes of death their place has been taken by complications of HCV infection, such as cirrhosis, end stage liver disease and hepatocellular carcinoma (HCC). HIV/HCV co-infection requires complex management, especially when HCC is present. Co-infected patients with HCC undergo the same therapeutic protocol as their mono-infected counterparts, but special issues such as interaction between regimens, withdrawal of therapy and choice of immunosuppressive agents, demand a careful approach by specialists. All these issues are analyzed in this minireview.
文摘AIM:To document the epidemiologic patterns and risk factors of human immunodeficiency virus(HIV)and hepatitis C virus(HCV)infections in Mali in order to develop prevention means for both diseases.METHODS:Two prospective studies were conducted in Bamako in 2009 among 1000 pregnant women(i.e.,young women)who consulted six reference health centers,and in 2010,among 231 older women who attended general practice in two hospitals.Antibody tests and molecular analysis(performed only for HCV)were used to quantify the frequencies of both infections.The data were collected from patients recruited through a questionnaire.Transmission risk factors of both diseases were identified by univariate and multivariate analysis.RESULTS:HCV seroprevalence was 0.2% for young and 6.5% for older women.HIV prevalence was similar in both populations(4.1% vs 6.1%).In older women,the analysis of risk factors highlighted an association between HCV infection and episodes of hospitalization(P < 0.01).The study did not show an association between HIV infection and the variables such as hospitalization,transfusion,tattoo,dental care,and endoscopy.A significant decrease of HIV seroprevalence was detected in young women who used condoms for contraception more than for other purposes(P < 0.01).By contrast,HIV seroprevalence was significantly increased in young women using condoms mainly to prevent sexual infections rather than for contraception(P < 0.01).No HCV/HIV coinfection was detected in our study.CONCLUSION:Risk factors and epidemiologic data of HIV and HCV as well as the absence of co-infection strongly suggest epidemiological disparities between these diseases.
文摘Liver transplantation(LT)remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply.The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C(HCV)and hepatitis B(HBV)related liver disease and yet the number of patients waiting for LT continues to increase,driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcoholrelated liver disease.In addition,human immunodeficiency virus(HIV)infection,which was previously a contra-indication for LT,is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT.The rising demand for LT is projected to increase further in the future,thus driving the need to investigate potential means of expanding the pool of potential donors.One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive,HBV-positive,and HIVpositive donors.The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV,HBV or HIV infected recipients and in some cases uninfected recipients.
文摘Bouare et al found that hepatitis C virus (HCV) infection in Malian women is mainly transmitted through medical procedures with contaminated supplies, and that human immunodeficiency virus (HIV) transmission is predominantly sexual. The results of this study confirm those of a recent case-control study in New York and Oregon which demonstrated that healthcare exposures represent an important source of new HCV infections in United States. HCV seroprevalence was only 0.2% in pregnant, young Malian women, indicating that hygiene improved in healthcare facilities over time. Heterosexual transmission of HCV is exceptional, and can occur, from males to females, in extremely rare occasions in case of vaginal mucosal damage or less rarely through anal intercourse. The Malian study did not show an association between HIV infection and hospitalization, transfusion, tattoo, dental care. Transmission by needle-stick injury occurs in 0.9%-2.2% of exposures from HCV-infected subjects and in 0.1%-0.3% of exposures from HIV-infected in- dividuals. HCV is therefore more transmissible through percutaneous exposure.
文摘Human immunodeficiency virus(HIV)and hepatitis C virus(HCV)share the same transmission routes;therefore,coinfection is frequent.An estimated 5-10 million individuals alone in the western world are infected with both viruses.The majority of people acquire HCV by injection drug use and,to a lesser extent,through blood transfusion and blood products.Recently,there has been an increase in HCV infections among men who have sex with men.In the context of effective antiretroviral treatment,liver-related deaths are now more common than Acquired Immune Deficiency Syndromerelated deaths among HIV-HCV coinfected individuals.Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20%of chronically infected individuals.HCV treatment has rapidly changed with the development of new direct-acting antiviral agents;therefore,cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle.In this review,we focus on the epidemiology,diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.
文摘This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the on-going and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the Pub Med literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes.
基金The paper was support by a grant from the Ministry Youth Research of China,No.98-1-269
文摘AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.
文摘Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus(HCV)-monoinfected and human immunodeficiency virus(HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of noninvasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCVcoinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice.
文摘The relation between the expression and activity of MMP-9 in C-reactive protein （CRP）-induced human THP-1 mononuclear cells and the activation of nuclear factor kappa-B （NF-κB） was studied to investigate the possible role of CRP in plaque destabilization. Human THP-1 cells were incubated in the presence of CRP at 0 （control group）, 25, 50 and 100 μg/mL （CRP groups） for 24 h. In PDTC （a specific NF-κB inhibitor） group, the cells were pre-treated with PDTC at 10 μmol/L and then with 100 μg/mL CRP. The conditioned media （CM） and human THP-1 cells in different groups were harvested. MMP-9 expression in CM and human THP-1 cells was measured by ELISA and Western blotting. MMP-9 activity was assessed by fluorogenic substrates. The expression of NF-κB inhibitor α （IκB-α） and NF-κB p65 was detected by Western blotting and ELISA respectively. The results showed that CRP increased the expression and activity of MMP-9 in a dose-dependent manner in the human THP-1 cells. Western blotting revealed that IiB-α expression was decreased in the cells with the concentrations of CRP and ELISA demonstrated that NF-κB p65 expression in the CRP-induced cells was increased. After pre-treatment of the cells with PDTC at 10 μmol/L, the decrease in IκB-α expression and the increase in NF-κB p65 expression in the CRP-induced cells were inhibited, and the expression and activity of MMP-9 were lowered too. It is concluded that increased expression and activity of MMP-9 in CRP-induced human THP-1 cells may be associated with activation of NF-κB. Down-regulation of the expression and activity of MMP-9 may be a new treatment alternative for plaque stabilization by inhibiting the NF-κB activation.
基金Supported by The Japan Initiative for Global Research Network on Infectious Diseases(J-GRID)program from the Ministry of Education,Culture,Sports,Science and Technology,Japan
文摘Hepatitis B virus(HBV), hepatitis C virus(HCV),and human immunodeficiency virus(HIV) affect many people in Asian countries, although there are geographic differences. Both HBV and HIV(HBV/HIV) and HCV/HIV co-infections are highly prevalent in Asia. Hetero- and homosexual, injection drug use, and geographic area are strong predictors of HBV, HCV, and HIV serostatus. In HBV endemic regions, the prevalence and genotype distribution of HBV/HIV coinfection is almost comparable with that in the general population. In Japan, where HBV has low endemicity, the prevalence of HBV/HIV co-infection is approximately 10-fold higher than that in the general population, and HBV Ae is the most common subgenotype among HIV infected individuals. Highly active antiretroviral therapy(HAART) is an effective treatment for HIV/Acquired Immune Deficiency Syndrome. Lamivudine, a component of HAART, is an effective treatment for HBV, HIV, and HBV/HIV co-infection; however, cost, emerging drug resistance, antiretroviral-associated liver toxicity and liver-related morbidity due to HCV progression are particular concerns. HCV/HIV co-infection may accelerate the clinical progression of both HCV and HIV. The high prevalence of HBV/HIV and HCV/HIV co-infections in Asia underscores the need to improve prevention and control measures, as fewer evidencebased prevention strategies are available(compared with Western countries). In this review, the most recent publications on the prevalence of HBV/HIV and HCV/HIV co-infections and related issues, such as therapy and problems in Asia, are updated and summarized.
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 NPRP grant from the Qatar National Research Fund (a member of Qatar Foundation), No. NPRP 04-924-3-251the Biostatistics, Epidemiology, and Biomathematics Research Core at the Weill Cornell Medical College in Qatar
文摘The Middle East and North Africa(MENA) region has endured several major events of infection parenteral transmission. Recent work has established the utility of using hepatitis C virus(HCV) as a proxy biomarker for assessing the epidemic potential for human immunodeficiency virus(HIV) parenteral transmission. In this review, we use data on the prevalence of HCV infection antibody(seroprevalence) among general population and high risk population groups to assess the potential for HIV parenteral transmission in MENA. Relatively low prevalence of HCV infection in the general population groups was reported in most MENA countries indicating that parenteral HIV transmission at endemic levels does not appear to be a cause for concern. Nonetheless, there could be opportunities for localized HIV outbreaks and transmission of other blood-borne infections in some settings such as healthcare facilities. Though there have been steady improvements in safety measures related to parenteral modes of transmission in the region, these improvements have not been uniform across all countries. More precautions, including infection control training programs, surveillance systems for nosocomial infections and wider coverage and evaluation of hepatitis B virus immunization programs need to be implemented to avoid the unnecessary spread of HIV, HCV, and other blood-borne pathogens along the parenteral modes of transmission.
