Andrew H Talal

Weill Cornell Medical College, New York, New York, United States

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Publications (108)790.99 Total impact

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    ABSTRACT: Although interferon (IFN)-α is known to exert immunomodulatory and antiproliferative effects on dendritic cells (DCs) through induction of protein-coding IFN-stimulated genes (ISGs), little is known about IFN-α-regulated miRNAs in DCs. Since several miRNAs are involved in regulating DC functions, it is important to investigate whether IFN-α's effects on DCs are mediated through miRNAs as well. In this study, we examined miRNA expression patterns in myeloid DCs (mDCs) and plasmacytoid DCs after exposing them to IFN-α. We report that IFN-α downregulates miR-221 in both DC subsets via inhibition of STAT3. We validated proapoptotic proteins BCL2L11 and CDKN1C as miR-221 targets suggesting that IFN-α can induce DC apoptosis via miR-221 downregulation. In addition, we validated another miR-221 target, SOCS1, which is known to be a negative regulator of JAK/STAT signaling. Consistent with this, miR-221 overexpression in mDCs enhanced the secretion of proinflammatory cytokines IL-6 and TNF-α. In peripheral blood mononuclear cells (PBMCs) of HIV-1/HCV co-infected individuals undergoing IFN-α-based treatment the baseline miR-221 expression was lower in non-responders compared with responders; and miR-221 expression directly correlated with DC frequency and IL-6/TNF-α secretion. In addition to PBMCs, we isolated total liver cells and kupffer cells from HCV-infected individuals and individuals with alcoholic cirrhosis. We found that both total liver cells and kupffer cells from HCV-infected individuals had significantly higher miR-221 levels compared with individuals with cirrhosis. Overall, we demonstrate that IFN-α exerts both antiproliferative and immunomodulatory effects on mDCs via miR-221 downregulation; and IFN-miR-221 axis can play important role in HCV pathogenesis and treatment.
    Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 06/2015; DOI:10.1089/jir.2014.0211 · 2.00 Impact Factor
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    ABSTRACT: Some drugs that are actively taken up into the liver exhibit greater than dose proportional increases in plasma exposure, although human liver-to-plasma concentration ratios have rarely been evaluated. Understanding these relationships has implications for drug concentrations at the target site, for certain classes of compounds such as direct-acting antivirals targeted towards hepatitis C virus . Treatment-experienced, chronic HCV non-cirrhotic patients (N=3) received vaniprevir (600 mg or 300 mg bid) on days 1-3 and (600 mg or 300 mg single dose) on day 4. Core needle biopsy was performed at 6 or 12 hours post-dose on day 4. Blood samples were collected pre-dose on days 1 and 4, and for 24 hours post-dose on day 4. The primary study objective was the hepatic concentration of vaniprevir at 6 and 12 hours post-dose. Vaniprevir plasma pharmacokinetic parameters increased in a greater than dose-proportional manner between the 300-mg and 600-mg doses, with ~5-fold increases in AUC0-12 and Cmax associated with a 2-fold increase in dose (AUC0-12, 10.6 µM/h to 59.5 µM/h; Cmax, 2.60 µM to 13.5 µM). In the 300-mg- and 600-mg-dose groups, mean liver concentrations of vaniprevir were 84.6 µM and 169 µM at 6 hours post-dose, and 29.4 µM and 53.7 µM at 12 hours post-dose. Liver concentrations were higher than plasma with liver-to-plasma concentration ratios of ~20-280. These data confirm higher vaniprevir concentrations in human liver compared with plasma and demonstrate that measurement of human liver drug concentration using needle biopsy is feasible.
    Antiviral therapy 04/2015; DOI:10.3851/IMP2958 · 3.02 Impact Factor
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    ABSTRACT: We assessed peripheral and liver CXCL10 levels in 15 patients treated with telaprevir/pegylated-interferon/ribavirin. Peripheral CXCL10 peaked (mean 3.1+1.9-fold) between treatment hour 6 and day 2, while intrahepatic CXCL10 mRNA peaked (mean 1.3+0.54-fold) at hour 10 or day 4. Peripheral CXCL10 levels were higher at treatment hour 10 (p=0.032) and day 2 (p=0.009) in patients with undetectable virus two weeks post-treatment initiation. Treatment hour 10 (p=0.023) and peak (p=0.034) intrahepatic CXCL10 levels were also higher in these patients. CXCL10 did not distinguish treatment responders from nonresponders. In conclusion, CXCL10 identified very rapid virological response in patients treated with a direct-acting antiviral. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:
    The Journal of Infectious Diseases 12/2014; 211(11). DOI:10.1093/infdis/jiu807 · 6.00 Impact Factor
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    ABSTRACT: Unlabelled: Understanding hepatitis C virus (HCV) replication has been limited by access to serial samples of liver, the primary site of viral replication. Our understanding of how HCV replicates and develops drug-resistant variants in the liver is limited. We studied 15 patients chronically infected with genotype 1 HCV treated with telaprevir (TVR)/pegylated-interferon alpha/ribavirin. Hepatic fine needle aspiration was performed before treatment and at hour 10, days 4 and 15, and week 8 after initiation of antiviral therapy. We measured viral kinetics, resistance patterns, TVR concentrations, and host transcription profiles. All patients completed all protocol-defined procedures that were generally well tolerated. First-phase HCV decline (baseline/treatment day 4) was significantly slower in liver than in plasma (slope plasma: -0.29; liver, -0.009; P < 0.001), whereas second-phase decline (posttreatment days 4-15) did not differ between the two body compartments (-0.11 and -0.15, respectively; P = 0.1). TVR-resistant variants were detected in plasma, but not in liver (where only wild-type virus was detected). Based upon nonstructural protein 3 sequence analysis, no compartmentalization of viral populations was observed between plasma and liver compartments. Gene expression profiling revealed strong tissue-specific expression signatures. Human intrahepatic TVR concentration, measured for the first time, was lower, compared to plasma, on a gram per milliliter basis. We found moderate heterogeneity between HCV RNA levels from different intrahepatic sites, indicating differences in hepatic microenvironments. Conclusion: These data support an integrated model for HCV replication wherein the host hepatic milieu and innate immunity control the level of viral replication, and the early antiviral response observed in the plasma is predominantly driven by inhibition of hepatic high-level HCV replication sites.
    Hepatology 12/2014; 60(6). DOI:10.1002/hep.27202 · 11.06 Impact Factor
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    ABSTRACT: HIV-1/HCV co-infection is a significant health problem. Highly active antiretroviral treatment (HAART) against HIV-1 has proved to be fairly successful. On the other hand, direct acting antiviral drugs against HCV have improved cure rates but high cost and development of drug resistance are important concerns. Therefore PEGylated interferon (PEG-IFN) and ribavirin (RBV) still remain essential components of HCV treatment, and identification of host factors that predict IFN/RBV treatment response is necessary for effective clinical management of HCV infection. Impaired dendritic cell (DC) and T cell responses are associated with HCV persistence. It has been shown that IFN/RBV treatment enhances HCV-specific T cell functions and it is likely that functional restoration of DCs is the underlying cause. To test this hypothesis, we utilized an antibody cocktail (consisting of DC maturation, adhesion and other surface markers) to perform comprehensive phenotypic characterization of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in a cohort of HIV-1/HCV co-infected individuals undergoing IFN/RBV treatment. Our results show that pre-treatment frequencies of mDCs are lower in non-responders (NRs) compared to responders (SVRs) and healthy controls. Although, the treatment was able to restore the frequency of mDCs in NRs, it downregulated the frequency of CCR7(+), CD54(+) and CD62L(+) mDCs. Pre-treatment frequencies of pDCs were lower in NRs and decreased further upon treatment. Compared to SVRs, NRs exhibited higher ratio of PD-L1(+)/CD86(+) pDCs prior to treatment; and this ratio remained high even after treatment. These findings demonstrate that enumeration and phenotypic assessment of DCs before/during therapy can help predict the treatment outcome. We also show that before treatment, PBMCs from SVRs secrete higher amounts of IFN-γ compared to controls and NRs. Upon genotyping IFNL3 polymorphisms rs12979860, rs4803217 and ss469415590, we found rs12979860 to be a better predictor of treatment outcome. Collectively, our study led to identification of important correlates of IFN/RBV treatment response in HIV-1/HCV co-infected individuals.
    10/2014; 5. DOI:10.4172/2155-9899.1000271
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    ABSTRACT: Objective The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. Design We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. Results Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. Conclusions Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.
    Gut 09/2014; 64(10). DOI:10.1136/gutjnl-2014-306997 · 14.66 Impact Factor
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    ABSTRACT: Background Noninvasive markers of liver fibrosis have not been extensively studied in patients with chronic hepatitis B virus (HBV) infection. Our aim was to evaluate the capacity of FibroSURE, one of the two noninvasive fibrosis indices commercially available in the United States, to identify HBV infected patients with moderate to severe fibrosis. Methods Forty-five patients who underwent liver biopsy at a single tertiary care center were prospectively enrolled and had FibroSURE performed within an average interval of 11 days of the biopsy. Results Of the 45 patients, 40% were Asian, 40% were African American, and 13% were Caucasian; 27% were co-infected with HIV and 67% had no or mild fibrosis. We found FibroSURE to have moderate capacity to discriminate between patients with moderate to high fibrosis and those with no to mild fibrosis (area under receiver operating characteristic [AUROC] curve = 0.77; 95% confidence interval [CI] [0.61, 0.92]). When we combined the fibrosis score determined by FibroSURE with aspartate aminotransferase (AST) measurements and HIV co-infection status, the discriminatory ability significantly improved reaching an AUROC of 0.90 (95% CI [0.80, 1.00]). FibroSURE also had a good ability to differentiate patients with no or mild from those with moderate to high inflammation (AUROC = 0.83; 95% CI [0.71, 0.95]). Conclusions FibroSURE in combination with AST levels has an excellent capacity to identify moderate to high fibrosis stages in chronic HBV-infected patients. These data suggest that FibroSURE may be a useful substitute for liver biopsy in chronic HBV infection.
    BMC Gastroenterology 07/2014; 14(1):118. DOI:10.1186/1471-230X-14-118 · 2.37 Impact Factor
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    ABSTRACT: Although persons who inject drugs have high prevalence of hepatitis C virus (HCV) infection, few receive treatment mostly because of lack of knowledge about the infection and its treatment. We assessed the level of HCV-related knowledge and willingness to participate in HCV treatment among methadone-maintained patients. A 30-item survey covering HCV-related knowledge and willingness to engage in HCV-related education and treatment was developed and completed by 320 methadone-maintained patients. Respondents' mean age was 53 ± 8.7 years, 59.5% were male, 55.1% were African American, and 38.3% were Hispanic. The mean duration of methadone maintenance was 7 ± 6.7 years. In the preceding 6 months, 6.9% of patients reported injection drug use, whereas 37.3% used noninjection drugs. Hepatitis C virus seropositivity was self-reported by 46.3% of patients. The majority of patients (78%) expressed willingness to participate in HCV-related education and to receive HCV treatment. Most patients (54.7%) correctly answered 5 or more of 7 questions assessing HCV knowledge. Hepatitis C virus-seropositive individuals and prior attendees at HCV-related educational activities demonstrated a higher level of HCV-related knowledge (P < 0.001 and P = 0.002, respectively). Younger patients (P = 0.014), those willing to attend an HCV-related educational activity (P < 0.001), and those with higher-HCV-related knowledge (P = 0.029) were more accepting of HCV treatment. Fear of medication-related side effects was the most common reason for treatment avoidance. The majority of patients reported willingness to receive HCV-related education and treatment. Treatment willingness was significantly associated with previous attendance at an HCV educational activity and a higher level of HCV-related knowledge.
    Journal of Addiction Medicine 05/2014; 8(4). DOI:10.1097/ADM.0000000000000041 · 1.76 Impact Factor
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    ABSTRACT: No method with low morbidity presently exists for obtaining serial hepatic gene expression measurements in humans. While hepatic fine needle aspiration (FNA) has lower morbidity than core needle biopsy, applicability is limited due to blood contamination, which confounds quantification of gene expression changes. The aim of this study was to validate FNA for assessment of hepatic gene expression. Liver needle biopsies and FNA procedures were simultaneously performed on 17 patients with chronic hepatitis C virus infection with an additional FNA procedure 1 week later. Nine patients had mild/moderate fibrosis and eight advanced fibrosis. Gene expression profiling was performed using Affymetrix microarrays and TaqMan qPCR; pathway analysis was performed using Ingenuity. We developed a novel strategy that applies liver-enriched normalization genes to determine the percentage of liver in the FNA sample, which enables accurate gene expression measurements overcoming biases derived from blood contamination. We obtained almost identical gene expression results (ρ = 0.99, P < 0.0001) comparing needle biopsy and FNA samples for 21 preselected genes. Gene expression results were also validated in dogs. These data suggest that liver FNA is a reliable method for serial hepatic tissue sampling with potential utility for a variety of preclinical and clinical applications.
    Journal of Viral Hepatitis 01/2014; 22(1). DOI:10.1111/jvh.12213 · 3.91 Impact Factor
  • Marija Zeremski · Anthony D Martinez · Andrew H Talal
    Clinical Infectious Diseases 12/2013; 58(6). DOI:10.1093/cid/cit804 · 8.89 Impact Factor
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    ABSTRACT: Despite a high prevalence of hepatitis C virus (HCV) infection, the vast majority of persons who inject drugs (PWID) have not engaged in HCV care due to a large number of obstacles. Education about the infection among both PWID and providers remains an important challenge as does discrimination faced by PWID in conventional health care settings. Many providers also remain hesitant to prescribe antiviral therapy due to concerns about adherence and relapse to drug use resulting in reinfection. Presently, however, as a result of improvements in treatment efficacy combined with professional society and government endorsement of HCV treatment for PWID, a pressing need exists to develop strategies to engage these individuals into HCV care. In this article, we propose several strategies that can be pursued in an attempt to engage PWID into HCV management. We advocate that multidisciplinary approaches that utilize health care practitioners from a wide range of specialties, as well as co-localization of medical services, are strategies likely to result in increased numbers of PWID entering into HCV management. Pursuit of HCV therapy after stabilization through drug treatment is an additional strategy likely to increase PWID engagement into HCV care. The full impact of direct acting antivirals for HCV will only be realized if innovative approaches are pursued to engage all HCV infected individuals into treatment.
    World Journal of Gastroenterology 11/2013; 19(44):7846-7851. DOI:10.3748/wjg.v19.i44.7846 · 2.37 Impact Factor
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    ABSTRACT: Resolution of chronic hepatitis C is considered when serum HCV RNA becomes repeatedly undetectable and liver enzymes normalize. However, long-term persistence of HCV following therapy with pegylated interferon-α/ribavirin (PegIFN/R) was reported when more sensitive assays and testing of serial plasma, lymphoid cells (PBMC) and/or liver biopsies was applied. Our aim was to reassess plasma and PBMCs collected during and after standard PegIFN/R therapy from individuals who became HCV RNA nonreactive by clinical testing. Of particular interest was to determine if HCV genome and its replication remain detectable during ongoing treatment with PegIFN/R when evaluated by more sensitive detection approaches. Plasma acquired before (n = 11), during (n = 25) and up to 12-88 weeks post-treatment (n = 20) from 9 patients and PBMC (n = 23) from 3 of them were reanalyzed for HCV RNA with sensitivity <2 IU/mL. Clone sequencing of the HCV 5'-untranslated region from plasma and PBMCs was done in 2 patients. HCV RNA was detected in 17/25 (68%) plasma and 8/10 (80%) PBMC samples collected from 8 of 9 patients during therapy, although only 5.4% plasma samples were positive by clinical assays. Among post-treatment HCV RNA-negative plasma samples, 9 of 20 (45.3%) were HCV reactive for up to 59 weeks post-treatment. Molecularly evident replication was found in 6/12 (50%) among PBMC reactive for virus RNA positive strand collected during or after treatment. Pre-treatment point mutations persisted in plasma and/or PBMC throughout therapy and follow-up. Therefore, HCV is not completely cleared during ongoing administration of PegIFN/R otherwise capable of ceasing progression of CHC and virus commonly persists at levels not detectable by the current clinical testing. The findings suggest the need for continued evaluation even after patients achieve undetectable HCV RNA post-treatment.
    PLoS ONE 11/2013; 8(11):e80078. DOI:10.1371/journal.pone.0080078 · 3.23 Impact Factor
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    ABSTRACT: Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.
    Journal of Viral Hepatitis 11/2013; 20(11):745-60. DOI:10.1111/jvh.12173 · 3.91 Impact Factor
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    Alimentary Pharmacology & Therapeutics 09/2013; 38(5):554-5. DOI:10.1111/apt.12424 · 5.73 Impact Factor
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    ABSTRACT: BACKGROUND: Depression and fatigue are common in chronic hepatitis C (CHC). OBJECTIVE: We report clinical predictors of these conditions in patients seen in a university clinic. METHODS: A total of 167 CHC patients completed the Patient Health Questionnaire-9 (PHQ-9) and Fatigue Severity Scale (FSS). Major depressive disorder (MDD) suggested by PHQ-9 was confirmed by clinical interview. FSS scores ≥41 were considered clinically significant fatigue. Logistic and multiple regression models were employed for analysis. RESULTS: Thirty-three percent of patients had MDD and 52% had clinically significant fatigue. Sixty-one percent were HIV-infected, among whom both MDD and clinically significant fatigue were significantly less prevalent (OR = 0.47 and 0.46, respectively). MDD was least common in patients without a history of IV drug use (OR = 0.28), and highest in methadone users (OR = 3.57). Compared with methadone users, patients with no history of IV drug use and former IV drug users had less severe fatigue (coefficients = -31.0, -34.0, respectively). Lack of a history of hepatitis treatment was also associated with less severe fatigue (coefficient= -7.6). CONCLUSION: Our study confirms high prevalence of fatigue and depression in CHC. HIV-positivity was associated with lower rates of MDD and clinically significant fatigue, arguably due to support systems for people living with HIV. Higher rates of depression in methadone users might be due to intrinsically higher rates of psychopathology in this group. Being on hepatitis treatment was associated with higher rates of fatigue, probably due to the adverse effects of interferon. Our findings emphasize the importance of routine screening and evaluation of depression and fatigue in CHC populations.
    Psychosomatics 06/2013; 54(5). DOI:10.1016/j.psym.2013.02.009 · 1.86 Impact Factor
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    ABSTRACT: Resistance mutations to HCV NS3 protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant STAT-C resistance mutations in the population we analyzed HCV genome sequences from 507 treatment-naïve HCV genotype 1 infected patients from the US, Germany and Switzerland. Phylogenetic sequence analysis and viral load data were used to identify the possible spread of replication competent, drug resistant viral strains in the population and to infer the consequences of these mutations upon viral replication in vivo. Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir, the NS5B polymerase inhibitor AG-021
  • Journal of Hepatology 04/2013; 58:S195-S196. DOI:10.1016/S0168-8278(13)60479-1 · 11.34 Impact Factor
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    Mohit Sehgal · Zafar K Khan · Andrew H Talal · Pooja Jain
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    ABSTRACT: Persistent infections with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are a major cause of morbidity and mortality worldwide. As sentinels of our immune system, dendritic cells (DCs) play a central role in initiating and regulating a potent antiviral immune response. Recent advances in our understanding of the role of DCs during HIV-1 and HCV infection have provided crucial insights into the mechanisms employed by these viruses to impair DC functions in order to evade an effective immune response against them. Modulation of the immunological synapse between DC and T-cell, as well as dysregulation of the crosstalk between DCs and natural killer (NK) cells, are emerging as two crucial mechanisms. This review focuses on understanding the interaction of HIV-1 and HCV with DCs not only to understand the immunopathogenesis of chronic HIV-1 and HCV infection, but also to explore the possibilities of DC-based immunotherapeutic approaches against them. Host genetic makeup is known to play major roles in infection outcome and rate of disease progression, as well as response to anti-viral therapy in both HIV-1 and HCV-infected individuals. Therefore, we highlight the genetic variations that can potentially affect DC functions, especially in the setting of chronic viral infection. Altogether, we address if DCs' potential as critical effectors of antiviral immune response could indeed be utilized to combat chronic infection with HIV-1 and HCV.
    Virology: Research and Treatment 02/2013; 4:1-25. DOI:10.4137/VRT.S11046
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    ABSTRACT: Background: Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States and will become an increasing source of morbidity and mortality with aging of the infected population. Our objective was to develop decision analytic models to explore the cost-effectiveness of screening in populations with varying prevalence of HCV and risks for fibrosis progression. Methods: We developed a Markov state transition model to examine screening of an asymptomatic community-based population in the United States. The base case was an ethnically and gender-mixed adult population with no prior knowledge of HCV status. Interventions were screening followed by guideline-based treatment, or no screening. Effectiveness was measured in quality-adjusted life-years (QALYs), and costs were measured in 2011 US dollars. Results: In the base case (US population, 49% male, 78% white, 13% African American, and 9% Hispanic, mean age, 46 years), screening followed by guideline-based treatment (using boceprevir as the direct-acting antiviral agent) of those with chronic HCV infection costs $47 276 per QALY. The overall HCV prevalence in the United States is reported to be 1.3%-1.9%, but prevalence varies markedly among patients with different numbers and types of risk factors. The marginal cost-effectiveness ratio (mCER) of screening decreases as prevalence increases. Below a prevalence of 0.84%, the mCER is greater than the generally accepted societal willingness-to-pay threshold of $50 000 per QALY and thus is not considered highly cost-effective. Conclusions: Targeted screening is cost-effective when prevalence of HCV exceeds 0.84%. Prospective evaluation of a screening tool is warranted and should include comparisons with other screening strategies.
    Clinical Infectious Diseases 02/2013; 56(10). DOI:10.1093/cid/cit069 · 8.89 Impact Factor
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    A H Talal · J Lafleur · R Hoop · P Pandya · P Martin · I Jacobson · J Han · E J Korner
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    ABSTRACT: Chronic hepatitis C (HCV) treatment with pegylated-interferon (PEG-IFN)/ribavirin (RBV) is often limited by preexisting medical, psychiatric and psychosocial contraindications. However, limited data exist in general patient populations. To evaluate the percentage of HCV-infected patients in the general US population who may have contraindications to PEG-IFN/RBV. The General Electric (GE) Centricity dataset was used to screen the US population between 2004 and 2009 for HCV infection and contraindications to PEG-IFN/RBV. HCV diagnosis and contraindications were identified using ICD-9-CM codes or laboratory values. Only patients with an encounter 180 days prior to HCV diagnosis were included. Demographic differences were calculated using Pearson's chi-squared test. Frequencies and percentages for absolute and relative contraindications to PEG-IFN and/or RBV were determined and proportions and rates/1000 person-months were calculated. A total of 15 561 021 patients were screened, and 45 690 (0.3%) were HCV-positive and were evaluated. Those with contraindications were significantly younger, female, White, not currently married and receiving Medicare or Medicaid coverage (all P < 0.0001). 17.3% had at least one contraindication to PEG-IFN/RBV (5.5 events/1000 person-months); bipolar disorder (6.5%), anaemia (Hgb < 10 g/dL; 5.9%), pregnancy (1.9%) and neutropenia (neutrophils <750 cells/mm3; 1.2%) were most frequently cited. Approximately, 17% of HCV-infected patients in the general US population had at least one contraindication to PEG-IFN/RBV. Most contraindications were relative and potentially modifiable. Clinical assessment of contraindications as relative and/or modifiable should be considered and used to determine if patients could benefit from current PEG-IFN–containing triple therapy or future PEG-IFN– or RBV-free regimens.
    Alimentary Pharmacology & Therapeutics 01/2013; 37(4). DOI:10.1111/apt.12200 · 5.73 Impact Factor

Publication Stats

3k Citations
790.99 Total Impact Points


  • 2002–2014
    • Weill Cornell Medical College
      • • Division of Gastroenterology and Hepatology
      • • Center for the Study of Hepatitis C
      • • Department of Medicine
      New York, New York, United States
  • 2013
    • University at Buffalo, The State University of New York
      Buffalo, New York, United States
  • 2008–2011
    • The Rockefeller University
      • Laboratory of Virology and Infectious Disease
      New York City, NY, United States
  • 2001–2011
    • Cornell University
      • Department of Medicine
      Итак, New York, United States
  • 2004–2007
    • Columbia University
      New York, New York, United States
  • 1998
    • Walter Reed Army Institute of Research
      Silver Spring, Maryland, United States