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Hepatitis: HELP
Articles by Douglas T. Dieterich
Based on 81 articles published since 2010
(Why 81 articles?)

Between 2010 and 2020, Douglas Dieterich wrote the following 81 articles about Hepatitis.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Directly acting antivirals for hepatitis C virus arrive in HIV/hepatitis C virus co-infected patients: from 'mind the gap' to 'where's the gap?'. 2016

Childs, Kate / Taylor, Chris / Dieterich, Douglas / Agarwal, Kosh. ·aInstitute of Liver StudiesbDepartment of Sexual Health, King's College Hospital, London, UKcDivision of Liver Disease, Icahn School of Medicine, Mount Sinai Medical Centre New York, USA. ·AIDS · Pubmed #26836785.

ABSTRACT: In patients living with HIV infection with hepatitis C (HCV) is common. HIV/HCV co-infection results in more rapid liver fibrosis progression than HCV alone and end-stage liver disease is a major cause of morbidity and mortality in co-infected patients. Historically, treatment outcomes with interferon based therapy in this group have been poor but with the advent of directly acting antiviral (DAA) drugs for HCV, rates of cure have improved dramatically. This article reviews recent evidence on the treatment of HCV in co-infected patients including the efficacy of new regimens and information on drug-drug interactions between DAAs and antiretroviral therapy. We also discuss the relationship between the pathogenesis of HIV and HCV infections, the treatment of acute hepatitis C and the current debate regarding the cost-effectiveness and affordability of DAAs.

2 Editorial HCV vertical transmission in pregnancy: New horizons in the era of DAAs. 2015

Kanninen, Tomi T / Dieterich, Douglas / Asciutti, Stefania. ·Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY. · Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. · Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY. ·Hepatology · Pubmed #26238474.

ABSTRACT: -- No abstract --

3 Editorial Is screening baby boomers for HCV enough? A call to screen for hepatitis C virus in persons from countries of high endemicity. 2014

Asselah, Tarik / Perumalswami, Ponni V / Dieterich, Douglas. ·Centre de Recherche sur l'Inflammation (CRI), INSERM UMR 1149, Université Paris Diderot and Service d'Hépatologie, AP-HP Hôpital Beaujon, Clichy, Paris, France. ·Liver Int · Pubmed #24840955.

ABSTRACT: -- No abstract --

4 Editorial The end of the beginning for hepatitis C treatment. 2012

Dieterich, Douglas. · ·Hepatology · Pubmed #22174100.

ABSTRACT: -- No abstract --

5 Editorial Challenges and opportunities for hepatitis C drug development in HIV-hepatitis C virus-co-infected patients. 2011

Soriano, Vincent / Sherman, Kenneth E / Rockstroh, Juergen / Dieterich, Douglas / Back, David / Sulkowski, Mark / Peters, Marion. · ·AIDS · Pubmed #21866039.

ABSTRACT: The approval of the first direct-acting antivirals (DAAs) against the hepatitis C virus (HCV) has been eagerly expected for treating chronic hepatitis C in HIV individuals given that progression to cirrhosis and end-stage liver disease occurs faster in the co-infected population. The appropriate and judicious use of DAAs may provide cure to a large number of HIV-HCV patients. On the contrary, the widespread use of DAAs will occasionally be off-label or under unsatisfactory medical conditions, which may result in undesirable toxicities, drug interactions or selection of drug resistance in HCV. As a result of using first-generation DAAs in HIV-HCV-co-infected patients, a growing proportion of the remaining hepatitis C individuals will be those harboring non-HCV 1 genotypes or drug-resistant HCV variants. Over time, the largest reservoir of HCV genotype 1 patients will accumulate in resource-poor nations where access to hepatitis C therapy has been elusive and HIV treatment remains the primary health issue for the co-infected population.

6 Review Liver Disease in Human Immunodeficiency Virus Infection. 2019

Oikonomou, Katerina G / Tsai, Eugenia / Sarpel, Dost / Dieterich, Douglas T. ·Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA. Electronic address: katerina.oikonomou@mountsinai.org. · Icahn School of Medicine at Mount Sinai, 1 Gustav L. Levy Place, New York, NY 10029-6574, USA. ·Clin Liver Dis · Pubmed #30947879.

ABSTRACT: Liver disease in human immunodeficiency virus (HIV) remains a main cause of morbidity and mortality. Liver-related morbidity and mortality can be caused by multiple etiologic factors, including opportunistic infections, direct and indirect effects of antiretrovirals, direct and indirect effects of HIV, and viral hepatitides. These factors present with varied liver pathophysiologic mechanisms that lead to abnormalities in liver enzymes and synthetic function test, followed by distinct clinical presentations. This article elucidates the direct effects on HIV in the liver and explores the diagnostic and management challenges in patients with HIV in the era of highly active antiretroviral treatment.

7 Review Direct-acting antiviral treatment of acute hepatitis C virus infections. 2018

Misra, Suresh / Dieterich, Douglas T / Saberi, Behnam / Kushner, Tatyana. ·a Division of Liver Diseases, Department of Medicine , Icahn School of Medicine at Mount Sinai , New York , NY , USA. ·Expert Rev Anti Infect Ther · Pubmed #30067402.

ABSTRACT: INTRODUCTION: Hepatitis C contributes to significant morbidity and mortality worldwide. AHCV is defined as documented infection within 6 months of exposure. Treating acute hepatitis C virus (AHCV) with direct-acting antiviral agents in persons who inject drugs, HIV-positive men who have sex with men, and patients who acquire HCV nosocomially can contribute to the elimination of disease globally, preclude the morbidity and mortality of chronic disease, and prevent further transmission. Areas covered: In this review, we describe the epidemiology of AHCV, its natural history, the considerations involved in the decision of whether to treat AHCV, and the most current DAA therapy guidelines. PubMed was queried using key words and bibliographies were evaluated for relevant articles. Expert commentary: Despite the obvious benefits of AHCV treatment, clinical management is limited by the ability to identify asymptomatic cases and the absence of fully supported guidelines. However, clinical research is advancing and identifying specific regimens, decreasing treatment durations, and creating strategies to target at risk groups and screen for AHCV.

8 Review Direct-acting antiviral treatment for patients with hepatocellular carcinoma. 2018

Kushner, Tatyana / Dieterich, Douglas / Saberi, Behnam. ·Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA. ·Curr Opin Gastroenterol · Pubmed #29517502.

ABSTRACT: PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) affects a significant portion of patients with hepatitis C. The use of direct-acting antiviral (DAA) agents has transformed the disease outcomes in this patient group. RECENT FINDINGS: Hepatitis C virus (HCV) response to DAAs can be affected by the presence of HCC, whereas DAA therapy may affect the risk of HCC recurrence in patients with a history of HCC. SUMMARY: Emerging data are demonstrating lower sustained virologic response (SVR) rates in patients with HCC compared with patients without HCC. Conflicting studies have also suggested that rates of HCC recurrence in patients with a history of HCC can potentially be increased or decreased on DAA therapy. This review will provide a brief overview of these data and inform practitioners on important considerations to make when prescribing DAA therapy for patients with HCV and HCC.

9 Review American Gastroenterological Association Institute Technical Review on the Role of Elastography in Chronic Liver Diseases. 2017

Singh, Siddharth / Muir, Andrew J / Dieterich, Douglas T / Falck-Ytter, Yngve T. ·Division of Gastroenterology, University of California San Diego, La Jolla, California. · Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina. · Division of Liver Disease, Icahn School of Medicine, New York, New York. · Division of Gastroenterology and Hepatology, Cleveland VA Medical Center and University Hospitals, Case Western Reserve University, Cleveland, Ohio. ·Gastroenterology · Pubmed #28442120.

ABSTRACT: Chronic liver diseases (CLDs), due to chronic hepatitis C; hepatitis B; nonalcoholic fatty liver diseases (NAFLD); and alcoholic liver disease, are a leading cause of morbidity and mortality globally. Early identification of patients with cirrhosis at high risk of progression to liver-related complications may facilitate timely care and improve outcomes. With risks and misclassification associated with invasive tests, such as liver biopsy, noninvasive imaging modalities for liver fibrosis assessment have gained popularity. Therefore, the American Gastroenterological Association prioritized clinical guidelines on the role of elastography in CLDs, focusing on vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). To inform these clinical guidelines, the current technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for diagnostic accuracy studies. This technical review addresses focused questions related to: (1) comparative diagnostic performance of VCTE and MRE relative to nonproprietary, serum-based fibrosis markers for detection of cirrhosis in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), NAFLD, and alcoholic liver diseases; (2) performance of specific VCTE-defined liver stiffness cutoffs as a test replacement strategy (to replace liver biopsy) in making key decisions in the management of patients with CLDs; and (3) performance of specific VCTE-defined liver stiffness cutoffs as a triage test to identify patients with low likelihood of harboring high-risk esophageal varices (EVs) or having clinically significant portal hypertension (for presurgical risk stratification). This technical review does not address performance of other noninvasive modalities for assessing fibrosis (eg, acoustic radiation force pulse imaging or shear wave elastography) or steatosis (controlled attenuation parameter or magnetic resonance imaging-estimated proton density fat fraction).

10 Review Assessment of cost of innovation versus the value of health gains associated with treatment of chronic hepatitis C in the United States: The quality-adjusted cost of care. 2016

Younossi, Zobair M / Park, Haesuk / Dieterich, Douglas / Saab, Sammy / Ahmed, Aijaz / Gordon, Stuart C. ·aCenter For Liver Disease, Department of Medicine, Inova Fairfax Hospital bBetty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA cUniversity of Florida, Gainesville, FL dMount Sinai Medical Center, New York, NY eUniversity of California, Los Angeles, Los Angeles fStanford University, Standford, CA gHenry Ford Hospital, Detroit, MI. ·Medicine (Baltimore) · Pubmed #27741116.

ABSTRACT: BACKGROUND: New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs. AIM: The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States. DESIGN: A decision-analytic Markov model. DATA SOURCE: Published literature and clinical trial data. TIME HORIZON: Life Time. PERSPECTIVE: Third-party payer. INTERVENTION: This study compared four approved regimens in treatment-naïve genotype 1 chronic hepatitis C patients, including pegylated interferon and ribavirin (PR), first generation triple therapy (boceprevir + PR and telaprevir + PR), second generation triple therapy (sofosbuvir + PR and simeprevir + PR) and all-oral DAA regimens (ledipasvir/sofosbuvir and ombitasvir + paritaprevir/ritonavir + dasabuvir ± ribavirin). OUTCOME MEASURE: Quality-adjusted cost of care (QACC). QACC was defined as the increase in treatment cost minus the increase in the patient's quality-adjusted life years (QALYs) when valued at $50,000 per QALY. RESULTS: All-oral therapy improved the average sustained virologic response (SVR) rate to 96%, thereby offsetting the high drug acquisition cost of $85,714, which resulted in the highest benefit based on the efficiency frontier. Furthermore, while oral therapies increased HCV drug costs by $48,350, associated QALY gains decreased quality-adjusted cost of care by $14,120 compared to dual therapy. When the value of a QALY was varied from $100,000 to $300,000, the quality adjusted cost of care compared to dual therapy ranged from - $21,234 to - $107,861, - $89,007 to - $293,130, - $176,280 to - $500,599 for first generation triple, second generation triple, and all-oral therapies, respectively. Primary efficacy and safety measurements for drug regimens were sourced from clinical trials data rather than a real-world setting. Factors such as individual demographic characteristics, comorbidities and alcohol consumption of the individual patients treated may alter disease progression but were not captured in this analysis. CONCLUSION: New DAA treatments provide short-term and long-term clinical and economic value to society. PRIMARY FUNDING SOURCE: Gilead Sciences, Inc.

11 Review Management of Hepatitis C/HIV Coinfection in the Era of Highly Effective Hepatitis C Virus Direct-Acting Antiviral Therapy. 2016

Wyles, David L / Sulkowski, Mark S / Dieterich, Douglas. ·Divisions of Infectious Diseases, Department of Medicine, University of California, San Diego. · Johns Hopkins University School of Medicine, Baltimore, Maryland. · Division of Liver Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. ·Clin Infect Dis · Pubmed #27363438.

ABSTRACT: The increased life expectancy of persons infected with human immunodeficiency virus (HIV) treated with antiretroviral therapy (ART) has resulted in renewed attention to non-HIV-related diseases exacerbated by HIV infection. Coinfection with hepatitis C virus (HCV) is a particular area of concern, as the global prevalence has been estimated at 2.5-5 million people. In this article, we discuss the epidemiology of HCV infection and reinfection, HCV-related liver disease progression in the era of effective ART, and the efficacy of emerging HCV treatment strategies in persons with HIV/HCV coinfection. New data regarding treatment of persons with HIV/HCV coinfection suggest that HCV treatment should be a priority in those with HIV. Results from recent studies using all-oral HCV regimens have shown high rates of sustained virologic response in both clinical trials and real-world settings. A multidisciplinary approach to HCV treatment in those with HIV is recommended for optimal patient management. Following HCV cure, practitioners also need to be mindful of the risks for HCV reinfection and educate patients on protective measures.

12 Review Chronic hepatitis B and C infection in the United States: a review of current guidelines, disease burden and cost effectiveness of screening. 2016

Sarpel, Dost / Baichoo, Esha / Dieterich, Douglas T. ·a Division of Liver Diseases, Icahn School of Medicine at Mount Sinai , NY , New York , USA. ·Expert Rev Anti Infect Ther · Pubmed #27043049.

ABSTRACT: Chronic hepatitis B and C infection are the leading causes of hepatocellular carcinoma and liver related death in the world and in the United States respectively. Screening guidelines have been developed based on estimated prevalence determined by NHANES data. However, individuals with the most risk of chronic infection (incarcerated, homeless, immigrants, nursing home residents, and hospitalized persons) are underrepresented in this cohort leading to an underestimation of the true prevalence of chronic hepatitis B and C infection. This has led to recent updates in the screening guidelines. This review examines the change in the guidelines, the likely true seroprevalence of hepatitis B and C virus, as well as the burden of chronic infection in this population.

13 Review Direct-acting antiviral-based therapy for chronic hepatitis C virus in HIV-infected patients. 2015

Del Bello, David / Ita Nagy, Fanny / Hand, Jonathan / Khedemi, Rabea / Lécluse-Barth, Julien / Dieterich, Douglas / Piroth, Lionel. ·aInfectious Diseases Department, Mount Sinai Hospital, New York City, New York, USA bInfectious Diseases Department, University Hospital, Dijon, France cLiver Department, Mount Sinai Hospital, New York City, New York, USA. ·Curr Opin HIV AIDS · Pubmed #26248121.

ABSTRACT: PURPOSE OF REVIEW: The aim of this review was to detail the current therapies and treatments for chronic hepatitis C virus in coinfected patients, focusing on HCV antiviral agents currently used in practice today or scheduled to enter the open market soon. RECENT FINDINGS: Several direct-acting antiviral (DAA) combinations show high sustained virologic response (SVR) rates in HIV/HCV-coinfected patients, which are often close to those observed in HCV-monoinfected patients. Most recommendations regarding treatment stem from trials with coinfected patients. However, data are lacking for some aspects of HCV-treatment in coinfection, so extrapolations must be made from data obtained predominately from monoinfected patients. SUMMARY: HIV/HCV-coinfected patients, who, not too long ago, had inferior outcomes in capturing SVR, now enjoy similar fates as the monoinfected patients. They should thus be prioritized for treatment, since HCV and liver disease have become major causes of morbidity and mortality in this population. However, potential drug-drug interactions between antiretroviral agents and DAAs have to be systematically anticipated before initiating HCV therapy.

14 Review Development of sofosbuvir for the treatment of hepatitis C virus infection. 2015

Lawitz, Eric / Jacobson, Ira M / Nelson, David R / Zeuzem, Stefan / Sulkowski, Mark S / Esteban, Rafael / Brainard, Diana / McNally, John / Symonds, William T / McHutchison, John G / Dieterich, Douglas / Gane, Edward. ·Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas. · Icahn School of Medicine at Mount Sinai, New York, New York. · University of Florida, Gainesville, Florida. · Medical Center, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. · Johns Hopkins University School of Medicine, Baltimore, Maryland. · Hospital Universitario Val d'Hebron, Barcelona, Spain. · Gilead Sciences, Foster City, California. · Mount Sinai School of Medicine, New York, New York. · Auckland City Hospital, Auckland, New Zealand. ·Ann N Y Acad Sci · Pubmed #26235748.

ABSTRACT: The nucleotide analog NS5B polymerase inhibitor sofosbuvir was approved by the U.S. Food and Drug Administration (FDA) in December 2013 for the treatment of chronic hepatitis C virus (HCV) infection in combination with ribavirin or peginterferon and ribavirin. Sofosbuvir was developed to meet an urgent medical need for shorter, safer, simplified, more effective HCV treatment regimens and to reduce or eliminate the need for peginterferon. New treatment regimens were especially required for patient populations with limited treatment options, including patients who had failed prior HCV therapy, those with compensated and decompensated cirrhosis, and those who were either intolerant of or had contraindications to interferon. Sofosbuvir plus ribavirin for patients with genotype 2 or 3 HCV infection was the first approved all-oral treatment option. Sofosbuvir is also the backbone of the first regimen available for patients awaiting liver transplantation to prevent HCV recurrence, as well as the first oral interferon-free regimen for patients coinfected with HCV and HIV. This paper describes the development of sofosbuvir up to its original FDA approval.

15 Review A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update. 2015

Martin, Paul / Lau, Daryl T-Y / Nguyen, Mindie H / Janssen, Harry L A / Dieterich, Douglas T / Peters, Marion G / Jacobson, Ira M. ·Division of Hepatology, University of Miami School of Medicine, Miami, Florida. Electronic address: pmartin2@med.miami.edu. · Liver Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. · Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California. · Toronto Centre for Liver Diseases, University Health Network, Toronto, Canada. · Department of Medicine, Mount Sinai Medical Center, New York, New York. · Division of Gastroenterology, University of California, San Francisco, San Francisco, California. · Department of Medicine, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, New York. ·Clin Gastroenterol Hepatol · Pubmed #26188135.

ABSTRACT: Chronic hepatitis B (CHB) continues to be an important public health problem worldwide, including in the United States. An algorithm for managing CHB was developed by a panel of United States hepatologists in 2004 and subsequently updated in 2006 and 2008. Since 2008, additional data on long-term safety and efficacy of licensed therapies have become available and have better defined therapeutic options for CHB. The evidence indicates that potent antiviral therapy can lead to regression of extensive fibrosis or even cirrhosis, thus potentially altering the natural history of CHB. In addition, appropriate choice of antiviral agent can minimize the risk of resistance. This updated algorithm for managing CHB is based primarily on evidence from the scientific literature. Where data were lacking, the panel relied on clinical experience and consensus expert opinion. The primary aim of antiviral therapy for CHB is durable suppression of serum hepatitis B virus (HBV) DNA to low or undetectable levels. CHB patients who have HBV DNA >2000 IU/mL, elevated alanine aminotransferase level, and any degree of fibrosis should receive antiviral therapy regardless of their hepatitis B e antigen status. CHB patients with HBV DNA >2000 IU/mL and elevated alanine aminotransferase level but no evidence of fibrosis may also be considered for antiviral therapy. Approved antiviral therapies for CHB are interferon alfa-2b, peginterferon alfa-2a, lamivudine, adefovir, entecavir, telbivudine, and tenofovir, although the preferred first-line treatment choices are peginterferon alfa-2a, entecavir, and tenofovir. In determining choice of therapy, considerations include efficacy, safety, rate of resistance, method of administration, duration, and cost.

16 Review Pegylated-IFNα2a for HIV/hepatitis C virus coinfected patients: out with the old, in with the new. 2014

Bichoupan, Kian / Dieterich, Douglas T. ·Icahn School of Medicine , New York, NY , USA. ·Expert Opin Biol Ther · Pubmed #25104426.

ABSTRACT: INTRODUCTION: Liver disease is a major burden in patients co-infected with HIV and hepatitis C virus (HCV). From the time of its approval, pegylated-IFNα-2a (pegIFN-α2a) has played a major role in treatment of HCV in HIV/HCV co-infection. AREAS COVERED: This article briefly summarizes the epidemiology of HCV/HIV co-infection, the pharmacokinetic, and pharmacodynamic properties of pegIFN-α2a. Results from clinical trials investigating therapies containing pegIFN-α2a for HIV/HCV co-infected patients will be discussed with a focus on efficacy and safety. EXPERT OPINION: PegIFN-α2a has improved rates of sustained virologic response for co-infected patients. In combination with direct-acting antivirals (DAA), the disparity between mono- and co-infected patients is beginning to disappear. For the first time, IFN-free regimens are available in clinical practice. It is unlikely that pegIFN-α2a will continue to be a critical component in treatments for HCV in the general co-infected population.

17 Review HIV-hepatitis C virus co-infection in the era of direct-acting antivirals. 2014

Bichoupan, Kian / Dieterich, Douglas T / Martel-Laferrière, Valérie. ·Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA, kian.bichoupan@mssm.edu. ·Curr HIV/AIDS Rep · Pubmed #24996617.

ABSTRACT: Approximately one-third of patients infected with human immunodeficiency virus (HIV) are concomitantly infected with hepatitis C virus (HCV). As a result, liver disease remains a major source of morbidity and mortality in HIV patients. Prior to 2011, treatments of HCV lacked efficacy in clinical trials in HIV/HCV co-infected patients. Fortunately, several direct-acting antivirals (DAAs) have now entered clinical practice and others have reached advanced stages of clinical development. These therapies offer significant benefits such as improved rates of sustained virologic response (SVR), shortened durations of treatment, and compatibility with HIV antiretroviral therapies. Treatments such as sofosbuvir (SOF) have received approval for HIV/HCV co-infected patients. Moreover, interferon-free options exist for HIV/HCV co-infected patients who may be ineligible or intolerant of interferon. Despite these improvements, physicians must be aware of the differences between these DAAs, the patient characteristics that play a role on the effectiveness of these medications, and the drug-drug interactions these DAAs may have with existing HIV antiretroviral therapies. The aim of this review is to discuss the prevalence and incidence of HIV/HCV co-infection, critical factors related to patient evaluation, current treatment options, and new developments in the management of HIV/HCV co-infected patients.

18 Review Hepatitis C in HIV-infected patients: impact of direct-acting antivirals. 2014

Bichoupan, Kian / Dieterich, Douglas T. ·Icahn School of Medicine at the Mount Sinai School of Medicine, New York, USA. ·Drugs · Pubmed #24866024.

ABSTRACT: Approximately 30% of HIV-infected patients are co-infected with hepatitis C virus (HCV). After the release of highly active antiretroviral therapy, liver disease has become the leading cause of morbidity and mortality in HIV patients. Prior to 2011, HCV treatment with pegylated-interferon and ribavirin in HCV/HIV co-infected patients only allowed 14-38% of patients with HCV genotype 1 to achieve a sustained virologic response (SVR). Additionally, treatment was commonly discontinued as a result of adverse events. Recently, simeprevir and sofosbuvir have been approved by the US Food and Drug Administration (FDA) for HCV mono-infection. Sofosbuvir has been given FDA approval in co-infected patients offering unprecedented SVR rates and the potential for interferon-free therapy. HCV therapies that are in the pipeline offer improved treatment times, safety profiles, and rates of SVR. Despite these improvements, several new issues including adherence, drug-drug interactions with antiretroviral therapies, adverse events, resistance, and patient selection may complicate therapy. This article reviews the current status of direct-acting antivirals (DAA)-containing regimens for HIV/HCV co-infected patients in the USA. New results investigating telaprevir and boceprevir are also discussed as they are relevant for locations where new DAAs are not available. The impact future interferon-free therapies may have on co-infected patients is also discussed.

19 Review Treating HCV in HIV 2013: on the cusp of change. 2014

Martel-Laferrière, Valérie / Dieterich, Douglas T. ·Département de Microbiologie et Infectiologie, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada. ·Liver Int · Pubmed #24373079.

ABSTRACT: Treating hepatitis C virus (HCV) in HIV/HCV co-infected patients is a challenge. Even if the benefits of achieving a sustained virological response are clear, the rates achieved with the combination of pegylated-interferon and ribavirin are disappointing. The addition of direct acting antiviral agents (DAAs) to the treatment of hepatitis C is revolutionizing the treatment of HCV in mono-infected patients. Even if there have not been any agents approved for the treatment of co-infected patients, many studies specifically designed for this population are ongoing. This article reviews available data on the use of DAAs in co-infected patients and the challenges associated with these new drugs.

20 Review HIV/hepatitis C virus-coinfected patients and cirrhosis: how to diagnose it and what to do next? 2014

Martel-Laferrière, Valérie / Wong, Michael / Dieterich, Douglas T. ·Département de Microbiologie et Infectiologie, Centre Hospitalier de l'Université de Montréal, Quebec, Canada. ·Clin Infect Dis · Pubmed #24178247.

ABSTRACT: Liver disease, specifically cirrhosis, is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The diagnosis of early cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients may be challenging. The development of noninvasive methods for fibrosis assessment empowers the infectious disease specialist to diagnose advanced fibrosis or cirrhosis. Early diagnosis is essential to enroll patients in screening programs for esophageal varices and hepatocellular carcinoma. Cirrhosis may also modify decisions about treatment of both HIV and HCV, including vaccination, medications chosen, and referral for liver transplant.

21 Review Hepatitis C direct-acting antiviral agents: changing the paradigm of hepatitis C treatment in HIV-infected patients. 2014

Martel-Laferrière, Valérie / Bichoupan, Kian / Dieterich, Douglas T. ·Icahn School of Medicine at Mount Sinai, New York, NY. ·J Clin Gastroenterol · Pubmed #24172182.

ABSTRACT: Hepatitis C virus (HCV)-related liver disease is a major source of mortality in HIV-infected patients. Approximately one third of all patients with HIV are co-infected with HCV. Patients co-infected with HIV/HCV have shown lower rates of sustained virologic response with pegylated-interferon and weight-based ribavirin as well as more rapid progression of fibrosis than those with HCV mono-infection. Several direct-acting antiviral agents (DAAs), developed originally for HCV mono-infection, are being reevaluated for HIV/HCV co-infection. In addition, entirely new DAAs are being developed, including, interferon-free regimens with fewer side effects, allowing novel treatment opportunities for difficult-to-treat patients. In order for HCV DAAs to be successfully used in the HIV/HCV co-infected population several hurdles must be overcome, including adverse event management and drug-drug interactions. The aim of this review is to discuss the results of trials for new HCV therapies being developed for HIV/HCV co-infected patients and the impact of interferon-free regimens on treatment in the future.

22 Review Interferon-free regimens for hepatitis C: combine and conquer. 2014

Martel-Laferrière, Valérie / Bichoupan, Kian / Dieterich, Douglas T. ·Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10129, USA, valerie.martel-laferriere@umontreal.ca. ·BioDrugs · Pubmed #24170615.

ABSTRACT: Since the approval of the first direct-acting antiviral agents (DAAs), treatment for hepatitis C virus (HCV) has undergone significant transformation. A new milestone in the treatment of HCV, the approval of the first interferon-free regimens, could be achieved by the end of 2013. For patients with HCV who have absolute or relative contraindications to pegylated-interferon or have failed the currently available treatments, the arrival of new regimens will have a major impact on long-term outcomes. The combinations of DAAs in trials are numerous, and many have demonstrated sustained virologic response rates higher than 90 %. These improvements have also been observed in previous null responders and patients who failed telaprevir- or boceprevir-based regimens. Some specific subpopulations may not be perfectly served by interferon-free regimens, such as patients with genotypes 1a or 3 or cirrhosis, whereas others, such as HIV-infected patients or transplant patients, will definitively benefit from regimens with a lower burden of side effects. This paper reviews the interferon-free regimens currently in phase II or III for which sustained virologic response data are available and discusses the successes and potential pitfalls of these regimens.

23 Review Antiretroviral and anti-hepatitis C virus direct-acting antiviral-related hepatotoxicity. 2013

Han, Hyosun / Agarwal, Ritu / Martel-Laferriere, Valerie / Dieterich, Douglas T. ·Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, Annenberg 21-42, New York, NY 10029, USA. ·Clin Liver Dis · Pubmed #24099023.

ABSTRACT: Antiretroviral-related hepatotoxicity occurs commonly in patients with human immunodeficiency virus (HIV). Liver injury ranges from unconjugated hyperbilirubinemia and nodular regenerative hyperplasia to lactic acidosis and toxic hepatitis. Effective antiretroviral therapy has changed coinfected patients' primary morbidities and mortality to chronic liver disease rather than complications from HIV. Treatment for hepatitis C virus (HCV) is strongly encouraged early in all coinfected patients. However, drug-drug interactions must be considered to ensure safe and tolerable use alone or in combination with antiretroviral therapies. The first-generation and newer HCV direct-acting antivirals are promising in coinfected patients, with minimal side effects and hepatotoxicity.

24 Review The pharmacokinetic evaluation of boceprevir for treatment of hepatitis C virus. 2013

Shankar, Hari / Bichoupan, Kian / Dieterich, Douglas T. ·Icahn School of Medicine at Mount Sinai, Department of Liver Disease , 1468 Madison Ave, Annenberg Building, Room 21-42, New York, NY10029 , USA +1 212 831 8116 ; hari.shankar@mssm.edu. ·Expert Opin Drug Metab Toxicol · Pubmed #24079600.

ABSTRACT: INTRODUCTION: Boceprevir is an NS3/NS4A serine protease inhibitor that was approved for use in Hepatitis C virus (HCV) genotype 1 patients by the US Food and Drug Administration (FDA) in May 2011. The approval of this protease inhibitor marked a major paradigm shift in the treatment of HCV, as it was one of the first of many new small molecules specifically designed and approved for HCV. AREAS COVERED: In this article, the authors summarize boceprevir's pharmacokinetic and pharmacodynamic properties. In addition, they review Phase II and III trials of boceprevir as well as its clinical efficacy, dosing and safety. EXPERT OPINION: Boceprevir is a potent protease inhibitor for the treatment of genotype 1 HCV. It has a well-tolerated side-effect profile and increases the likelihood of SVR in naïve and previously treated patients. The impending release of newer more efficacious direct-acting antivirals may limit the use of boceprevir for patients infected with HCV.

25 Review Update on combinations of DAAs with and without pegylated-interferon and ribavirin: triple and quadruple therapy more than doubles SVR. 2013

Martel-Laferrière, Valérie / Dieterich, Douglas T. ·Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. valerie.martel-laferriere@mountsinai.org ·Clin Liver Dis · Pubmed #23177285.

ABSTRACT: Monotherapy is an ineffective way to treat hepatitis C and it leads to rapid development of resistance. An increasing number of drugs are currently being developed for the treatment of hepatitis C. This allows combination strategies that can overcome the development of resistance and improve sustained virologic response rates. This article focuses on the 2 main strategies in development: quadruple combination therapies, including pegylated-interferon and triple/quadruple pegylated-interferon free combination therapies. If the first combinations are leading to extremely high sustained virologic responses, the second ones offer hope that the era of pegylated-interferon will end soon.