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Hepatitis: HELP
Articles by David R. Nelson
Based on 89 articles published since 2008
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Between 2008 and 2019, D. R. Nelson wrote the following 89 articles about Hepatitis.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline HCV Council--critical appraisal of data: recommendations for clinical practice in a rapidly evolving therapeutic landscape. 2016

Reau, Nancy / Fried, Michael W / Nelson, David R / Brown, Robert S / Everson, Gregory T / Gordon, Stuart C / Jacobson, Ira M / Lim, Joseph K / Pockros, Paul J / Reddy, K Rajender / Sherman, Kenneth E. ·Rush University Medical Center, Chicago, IL, USA. · University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · University of Florida, Gainesville, FL, USA. · Weill Cornell Medical College, New York, NY, USA. · University of Colorado, Aurora, CO, USA. · Henry Ford Medical Center, Detroit, MI, USA. · Yale University School of Medicine, New Haven, CT, USA. · Scripps Translational Science Institute, La Jolla, CA, USA. · University of Pennsylvania, Philadelphia, PA, USA. · University of Cincinnati College of Medicine, Cincinnati, OH, USA. ·Liver Int · Pubmed #26509462.

ABSTRACT: BACKGROUND & AIMS: HCV Council 2014, like its predecessor HCV Council 2011, assembled leading clinicians and researchers in the field of hepatitis C to critically evaluate current data regarding best practices for managing patients with chronic hepatitis C virus (HCV). METHODS: Clinical practice statements were developed that reflect the areas of potential controversy with high clinical impact. Faculty members were responsible for reviewing the literature to support or reject these statements. After a review and comprehensive discussion of the data, the HCV Council faculty voted on the nature of the evidence and the level of support for each statement. RESULTS: The results of the detailed analysis with expert opinion are summarized in this article. CONCLUSION: Numerous questions regarding optimal management of certain populations and clinical scenarios remain unanswered. The discussion in the article provides a summary of evidenced-based expert opinion that may help guide clinicians as additional information is developed.

2 Guideline Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-α-based regimens. 2014

Muir, A J / Gong, L / Johnson, S G / Lee, M T M / Williams, M S / Klein, T E / Caudle, K E / Nelson, D R / Anonymous3100771. ·Division of Gastroenterology, Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA. · Department of Genetics, Stanford University, Palo Alto, California, USA. · 1] Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, Colorado, USA [2] Clinical Pharmacy Services, Kaiser Permanente Colorado, Denver, Colorado, USA. · 1] Laboratory for International Alliance on Genomic Research, RIKEN Center for Genomic Medicine, Yokohama, Japan [2] National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan [3] School of Chinese Medicine, China Medical University, Taichung, Taiwan. · Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania, USA. · Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. · Department of Medicine, University of Florida, Gainesville, Florida, USA. ·Clin Pharmacol Ther · Pubmed #24096968.

ABSTRACT: Pegylated interferon-α (PEG-IFN-α or PEG-IFN 2a and 2b)- and ribavirin (RBV)-based regimens are the mainstay for treatment of hepatitis C virus (HCV) genotype 1. IFNL3 (IL28B) genotype is the strongest baseline predictor of response to PEG-IFN-α and RBV therapy in previously untreated patients and can be used by patients and clinicians as part of the shared decision-making process for initiating treatment for HCV infection. We provide information regarding the clinical use of PEG-IFN-α- and RBV-containing regimens based on IFNL3 genotype.

3 Guideline An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. 2011

Ghany, Marc G / Nelson, David R / Strader, Doris B / Thomas, David L / Seeff, Leonard B / Anonymous4170704. ·Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1800, USA. marcg@intra.niddk.nih.gov ·Hepatology · Pubmed #21898493.

ABSTRACT: -- No abstract --

4 Editorial Public-Private Partnership: Targeting Real-World Data for Hepatitis C Direct-Acting Antivirals. 2017

Mishra, Poonam / Florian, Jeffry / Peter, Joy / Vainorius, Monika / Fried, Michael W / Nelson, David R / Birnkrant, Debra. ·US Food and Drug Administration, Silver Spring, Maryland. · University of Florida, Gainesville, Florida. · University of North Carolina, Chapel Hill, North Carolina. ·Gastroenterology · Pubmed #28757271.

ABSTRACT: -- No abstract --

5 Editorial Hepatitis C drug development at a crossroads. 2009

Nelson, David R. · ·Hepatology · Pubmed #19787813.

ABSTRACT: -- No abstract --

6 Review Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges. 2019

Baumert, Thomas F / Berg, Thomas / Lim, Joseph K / Nelson, David R. ·INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Pôle Hépato-digestif, Institut Hospitalo-Universitaire, Nouvel Hôpital Civil, Strasbourg, France. Electronic address: Thomas.Baumert@unistra.fr. · Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany. · Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, Connecticut. · Department of Medicine, University of Florida, Gainesville, Florida. Electronic address: nelsodr@ufl.edu. ·Gastroenterology · Pubmed #30342035.

ABSTRACT: Chronic infection with hepatitis C virus is a major cause of liver disease and hepatocellular carcinoma worldwide. After the discovery of hepatitis C virus 3 decades ago, the identification of the structure of the viral proteins, combined with high-throughput replicon models, enabled the discovery and development of direct-acting antivirals. These agents have revolutionized patient care, with cure rates of more than 90%. We review the status of direct-acting antiviral therapies for hepatitis C virus infection and discuss remaining challenges. We highlight licensed compounds, discuss the potential to shorten therapy even further, and review different options for treatment failure and resistance. We also provide an overview of clinical experience with generic agents and evidence for their efficacy. Finally, we discuss the need for new drugs and outline promising targets for future therapies.

7 Review Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - A pooled analysis. 2017

Poordad, Fred / Nelson, David R / Feld, Jordan J / Fried, Michael W / Wedemeyer, Heiner / Larsen, Lois / Cohen, Daniel E / Cohen, Eric / Mobashery, Niloufar / Tatsch, Fernando / Foster, Graham R. ·The Texas Liver Institute/University of Texas Health, San Antonio, TX, USA. Electronic address: poordad@txliver.com. · Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. · Toronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada. · University of North Carolina (UNC) Liver Center, UNC School of Medicine, Chapel Hill, NC, USA. · Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. · AbbVie Inc., North Chicago, IL, USA. · Blizard Institute of Cell and Molecular Science, Queen Mary University London, London, UK. ·J Hepatol · Pubmed #28645740.

ABSTRACT: BACKGROUND & AIMS: Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r±DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis. METHODS: Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r±ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r+DSV±RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported. RESULTS: In 1,066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% confidence interval [CI]: 4.1-6.8) and 2.2% (95% CI: 1.4-3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7-2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2). CONCLUSIONS: This pooled analysis in 1,066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r±DSV±RBV in this population. These results support the use of OBV/PTV/r±DSV±RBV in this high-priority population. Lay summary: This pooled safety analysis in 1,066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was similar to previously reported rates in untreated patients.

8 Review Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review. 2017

Falade-Nwulia, Oluwaseun / Suarez-Cuervo, Catalina / Nelson, David R / Fried, Michael W / Segal, Jodi B / Sulkowski, Mark S. ·From Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Florida, Gainesville, Florida; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. ·Ann Intern Med · Pubmed #28319996.

ABSTRACT: Background: Rapid improvements in hepatitis C virus (HCV) therapy have led to the approval of multiple oral direct-acting antiviral (DAA) regimens by the U.S. Food and Drug Administration (FDA) for treatment of chronic HCV infection. Purpose: To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection. Data Sources: MEDLINE and EMBASE from inception through 1 November 2016. Study Selection: 42 English-language studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs. Data Extraction: Two investigators abstracted data on study design, patient characteristics, and virologic and safety outcomes sequentially and assessed quality independently. Data Synthesis: Six DAA regimens showed high sustained virologic response (SVR) rates (>95%) in patients with HCV genotype 1 infection without cirrhosis, including those with HIV co-infection. Effective treatments for HCV genotype 3 infection are limited (2 DAA regimens). Patients with hepatic decompensation, particularly those with Child-Turcotte-Pugh class C disease, had lower SVR rates (78% to 87%) than other populations. The addition of ribavirin was associated with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were low (<10% in the general population); regimens that included ribavirin had more mild or moderate adverse events than those without. Limitations: Twenty-three studies had moderate risk of bias (10 were open-label single-group trials, 11 had limited information on concealment of the allocation scheme, and 5 had selective outcome reporting). All but 1 of the studies were industry-funded. Heterogeneity of interventions precluded pooling. Conclusion: Multiple oral DAA regimens show high rates of safety, tolerability, and efficacy for treatment of HCV genotype 1 infection, particularly among persons without cirrhosis. Primary Funding Source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42014009711).

9 Review Hepatitis C virus: how to provide the best treatment with what I have. 2016

Nelson, David R / Peter, Joy. ·Department of Medicine, University of Florida, Gainesville, FL, USA. · Liver Research Program, University of Florida, Gainesville, FL, USA. ·Liver Int · Pubmed #26725898.

ABSTRACT: The therapeutic landscape for the treatment of chronic hepatitis C virus infection has been rapidly evolving, and by 2016 there will be six approved, all-oral regimens for use in patients in the USA and most of Western Europe. However, as many as patient populations will have limited access to new direct acting antiviral regimens, patients and physicians are often faced with the challenge of selecting the best regimen available, as opposed to the optimal treatment. In this paper, the challenges and opportunities in developing a high cure regimen for different patient populations will be discussed and highlighted through case-based scenarios.

10 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.

11 Review Optimal interferon-free therapy in treatment-experienced chronic hepatitis C patients. 2015

Peter, Joy / Nelson, David R. ·Department of Medicine, Division of Gastroenterology and Hepatology, University of Florida, Gainesville, FL, USA. ·Liver Int · Pubmed #25529089.

ABSTRACT: Over the past year, interferon (IFN) free dosing regimens have become available to treat chronic hepatitis C. Offering high rates of sustained virological response (SVR), short treatment and improved tolerability, IFN-free treatment now represents the paradigm for both treatment-naïve and -experienced patients. Patients with prior treatment failure, in particular those with cirrhosis, still represent some of the most difficult to treat, but the availability of multiple agents that can interrupt several steps of the HCV lifecycle affords providers and patients with options that can be combined and individually tailored to each patient's unique needs to obtain high rates of SVR.

12 Review Direct-acting antiviral agents and the path to interferon independence. 2014

Schmidt, Warren N / Nelson, David R / Pawlotsky, Jean-Michel / Sherman, Kenneth E / Thomas, David L / Chung, Raymond T. ·Department of Internal Medicine and Research Service, Veterans Affairs Medical Center, Iowa City, Iowa; Roy G. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa. Electronic address: warren-schmidt@uiowa.edu. · University of Florida, Section of Hepatobiliary Disease, Gainesville, Florida. · National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France; INSERM U955, Créteil, France. · University of Cincinnati, College of Medicine, Division of Digestive Diseases, Hepatology Section, Cincinnati, Ohio. · Johns Hopkins Medical Institution, Baltimore, Maryland. · GI Division and Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. ·Clin Gastroenterol Hepatol · Pubmed #23872239.

ABSTRACT: Chronic infection with hepatitis C virus (HCV) is a major global health problem; there are approximately 120 to 130 million chronic infections worldwide. Since the discovery of HCV 24 years ago, there has been a relentless effort to develop successful antiviral therapies. Studies of interferon-α-based therapies have helped define treatment parameters, and these treatment strategies have cured a substantial percentage of patients. However, interferon-α must be injected; there are problems with tolerability, adherence, and incomplete response in a large percentage of patients. New drug candidates designed to target the virus or the host have recently been introduced at an unprecedented pace. In phase I-III studies, these agents have exceeded expectations and achieved rates of response previously not thought possible. We are, therefore, entering a new era of therapy for HCV infection and interferon independence.

13 Review New therapeutic strategies in HCV: second-generation protease inhibitors. 2013

Clark, Virginia C / Peter, Joy A / Nelson, David R. ·University of Florida, FL, USA. ·Liver Int · Pubmed #23286850.

ABSTRACT: Telaprevir and boceprevir are the first direct-acting antiviral agents approved for use in HCV treatment and represent a significant advance in HCV therapy. However, these first-generation drugs also have significant limitations related to thrice-daily dosing, clinically challenging side-effect profiles, low barriers to resistance and a lack of pan-genotype activity. A second wave of protease inhibitors are in phase II and III trials and promise to provide a drug regimen with a better dosing schedule and improved tolerance. These second-wave protease inhibitors will probably be approved in combination with PEG-IFN and Ribavirin (RBV), as well as future all-oral regimens. The true second-generation protease inhibitors are in earlier stages of development and efficacy data are anxiously awaited as they may provide pan-genotypic antiviral activity and a high genetic barrier to resistance.

14 Review The role of ribavirin in direct acting antiviral drug regimens for chronic hepatitis C. 2012

Clark, Virginia / Nelson, David R. ·University of Florida, College of Medicine, Gainesville, FL 32610, USA. ·Liver Int · Pubmed #22212579.

ABSTRACT: Despite years of clinical use and extensive research efforts, the mechanism of action of ribavirin (RBV) is not well understood. Although it has only a mild, transient antiviral effect on HCV replication when administered as monotherapy, when combined with interferon, RBV improves sustained virological response (SVR) rates by approximately 25-30%. Proposed mechanisms of action for RBV against HCV include (1) a direct effect against the HCV RNA dependent RNA polymerase; (2) induction of misincorporation of nucleotides leading to lethal mutagenesis; (3) depletion of intracellular pools via inhibition of inosine monophosphate dehydrogenase; (4) alteration in the cytokine balance between a Th2 profile (anti-inflammatory) to a Th1 profile (pro-inflammatory); and (5) potentiating the effect of interferon via up-regulation of genes involved in interferon signalling. Given the lack of a clear understanding of RBV mechanism of action, it has been challenging to confidently position this drug with new direct antiviral agents (DAA). However, early clinical studies provide strong evidence for a benefit of RBV in combination with DAAs for both IFN containing and sparing regimens. The addition of RBV reduces viral breakthroughs and/or relapses, at least when drugs with low to moderate genetic barriers to resistance are paired together. This is particularly true in patients harbouring HCV subtype 1a. Ongoing studies are now addressing the utility of RBV in nucleoside containing DAA regimens, which offer both potent antiviral activity as well as a high genetic barrier to resistance. It is remarkable that the age-old question of the role of RBV in the future of HCV therapy remains as real today as it was two decades ago.

15 Review The role of triple therapy with protease inhibitors in hepatitis C virus genotype 1 naïve patients. 2011

Nelson, David R. ·Clinical and Translational Science Institute, University of Florida, FL 32610, USA. nelsodr@ufl.edu ·Liver Int · Pubmed #21205138.

ABSTRACT: With the introduction of direct-acting oral antiviral agents we are on the verge of a new era that will transform the treatment landscape. This review discusses recent developments in drug discovery for hepatitis C protease inhibitors. First generation protease inhibitors will offer higher sustained viral response rates in naïve populations when combined with standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new challenges in viral resistance and increased adverse events.

16 Review Hepatitis B reactivation and rituximab in the oncology practice. 2010

Villadolid, Jeryl / Laplant, Kourtney D / Markham, Merry Jennifer / Nelson, David R / George, Thomas J. ·Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida 32610-0278, USA. ·Oncologist · Pubmed #20930099.

ABSTRACT: Rituximab use in hematology and oncology practice has significantly and positively improved the clinical outcomes in patients with a wide variety of B-cell lymphoproliferative disorders. However, emerging data reveal that there is a risk of viral hepatitis B reactivation in some patients treated with rituximab. Many of these cases result in treatment delays, inferior oncologic outcomes, increased morbidity, and more rarely fulminant hepatic decompensation and death. Indeed, the rituximab package insert and many clinical practice guidelines have been modified to reflect these concerns. The true incidence and mechanism of reactivation are still being elucidated. This article focuses on the current evidence that supports these recently revised clinical recommendations along with a review of the risk factors for reactivation, suggested monitoring, and preventative interventions.

17 Review New therapies in the management of hepatitis C virus. 2010

Michaels, Anthony J / Nelson, David R. ·Division of Hepatology and Liver Transplantation, Shands Hospital, University of Florida, Gainesville, Florida, USA. ·Curr Opin Gastroenterol · Pubmed #20224396.

ABSTRACT: PURPOSE OF REVIEW: The present review discusses recent developments in drug discovery for hepatitis C. We are on the verge of a new era with the introduction of direct acting oral agents that will transform the treatment landscape. Both healthcare providers and patients need to stay abreast of these changes that will influence decisions to treat. This article will discuss the most promising up-to-date hepatitis C virus antiviral therapies in clinical investigation as well as the associated clinical trial results. RECENT FINDINGS: First generation protease inhibitors will offer higher sustained viral response rates for both naive (70-80%) and treatment-experienced (40-50%) populations when added to standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new challenges with viral resistance and increased adverse events. SUMMARY: There are currently a number of drugs under investigation that target the enzymes involved in hepatitis C virus replication. Year 2011 should bring the approval of the first generation of protease inhibitors that will offer higher cure rates for genotype 1 patients and open the door for the eventual testing of interferon-free regimens.

18 Review Review article: the management of hepatocellular carcinoma. 2010

Cabrera, R / Nelson, D R. ·Section of Hepatobiliary Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department Of Medicine, University of Florida, Gainesville, FL 32610-0277, USA. cabrer@medicine.ufl.edu ·Aliment Pharmacol Ther · Pubmed #19925500.

ABSTRACT: BACKGROUND: Hepatocellular carcinoma is the leading cause of death in cirrhosis. A majority of patients present at an advanced stage with poor prognosis. AIM: To review the current screening, diagnosis and management strategies involved in hepatocellular carcinoma. METHODS: A literature search was performed using PubMed for publications with a predetermined search string to identify relevant studies. RESULTS: Hepatocellular carcinoma is dramatically increasing in incidence that is mostly attributed to chronic hepatitis C and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and its clinical phenotype diabetes and obesity. Cirrhosis is the major predisposing risk factor and its presence necessitates close surveillance for hepatocellular carcinoma with serial imaging studies. Hepatocellular carcinoma can be diagnosed by its unique radiological behaviour of arterial enhancement and washout on delayed images. The Barcelona Clinic Liver Cancer staging classification system is a clinically useful algorithm for the management of patients with hepatocellular carcinoma. The simultaneous presence of cirrhosis in the patients complicates their management and monitoring for cirrhosis-related complications is important. CONCLUSIONS: Early diagnosis and definitive treatment remains the key to long-term outcome. A multidisciplinary approach is critical to the successful management of hepatocellular carcinoma. Studies combining sorafenib with locoregional or other targeted molecular therapies are likely to improve responses and outcome.

19 Review Novel interferons for treatment of hepatitis C virus. 2009

Clark, Virginia / Nelson, David R. ·Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA. ·Clin Liver Dis · Pubmed #19628153.

ABSTRACT: The current standard of care for treatment of hepatitis C is pegylated interferon and ribavirin. Despite the large number of new oral agents under development, interferon will likely remain the backbone of future therapy. Interferon has unique antiviral and immunomodulatory properties, which have been critical in limiting resistance to protease inhibitors and improving efficacy. Hence, optimizing pharmacokinetics and promoting adherence to interferon dosing regimens will become even more critical as new regimens enter the clinical arena. This review highlights novel interferons under development that may offer therapeutic advantages over the formulations currently available.

20 Review Hepatitis C virus: a critical appraisal of approaches to therapy. 2009

Nelson, David R / Davis, Gary L / Jacobson, Ira / Everson, Gregory T / Fried, Michael W / Harrison, Stephen A / Hassanein, Tarek / Jensen, Donald M / Lindsay, Karen L / Terrault, Norah / Zein, Nizar. ·Hepatology and Liver Transplantation, University of Florida, Gainesville, Florida 32610, USA. nelsodr@medicine.ufl.edu ·Clin Gastroenterol Hepatol · Pubmed #19114127.

ABSTRACT: -- No abstract --

21 Review Ribavirin: current role in the optimal clinical management of chronic hepatitis C. 2009

Reddy, K Rajender / Nelson, David R / Zeuzem, Stefan. ·GI Division, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA. rajender.reddy@uphs.upenn.edu ·J Hepatol · Pubmed #19091439.

ABSTRACT: Ribavirin in combination with peginterferon alfa shows strong clinical efficacy against chronic hepatitis C, and is now established as the standard of care. However, the precise role of ribavirin is still being defined, suggesting that optimal ribavirin dose should be maintained over the whole treatment period. Ribavirin dosage varies by bodyweight for genotype 1 disease (1000mg/day in patients 75kg), whereas 800mg/day is sufficient to ensure optimal response in all genotype 2/3 patients. Similarly, genotype 1 patients benefit from 48 weeks of therapy, while 24 weeks is sufficient for genotype 2/3 disease. Recent data suggest treatment success is dependent on cumulative ribavirin exposure, as patients who receive <60% of the planned dose have lower response rates, regardless of whether reductions are from temporary interruptions or premature cessation of therapy. All patients should be monitored for hemolytic anemia, as early diagnosis allows management through small dose reductions and stepwise return to the target dose, maximizing cumulative exposure. Despite these recent advances in our knowledge, many questions remain, such as whether the role of ribavirin will change or even be eliminated as new therapies are developed.

22 Review Dynamic evolution of therapy for chronic hepatitis C: how will novel agents be incorporated into the standard of care? 2008

Zeuzem, Stefan / Nelson, David R / Marcellin, Patrick. ·JW Goethe University Hospital, Frankfurt, Germany. Zeuzem@em.uni-frankfurt.de ·Antivir Ther · Pubmed #18839776.

ABSTRACT: There is a need for improved treatment strategies and new therapeutic agents to increase cure rates in chronic hepatitis C virus (HCV) infection. Ongoing trials are aimed at optimizing sustained virological response rates with pegylated interferon (PEG-IFN) plus ribavirin. For a new agent to supplant the standard of care it must augment the strengths or compensate for the weaknesses of PEG-IFN plus ribavirin. To improve cure rates on its own, a new agent must not only suppress replication of the virus, but also clear infected hepatocytes. It is now clear that new anti-HCV agents will be used, at least initially, against a backbone of PEG-IFN plus ribavirin. A broad spectrum of agents is under investigation and it is hoped that these drugs will ultimately increase cure rates, reduce the required duration of therapy, improve tolerability and possibly simplify therapy. Reductions in serum HCV RNA ranging from 2 to 5 log10 IU/ml have been obtained in human trials with NS3/4A protease inhibitors and polymerase inhibitors. A minimum of additive reductions in serum HCV RNA levels have been observed when agents in these classes have been administered with PEG-IFN plus ribavirin in treatment-naive patients. Preliminary results in non-responders to IFN are less promising. Combinations of small molecules will be needed in order to produce sustained suppression of HCV replication in the absence of the standard of care, and such large clinical trials are several years away. The treatment paradigm for chronic hepatitis C continues to evolve and will eventually incorporate new drugs as they are approved.

23 Review Ribavirin considerations in treatment optimization. 2008

Dusheiko, Geoffrey / Nelson, David / Reddy, K Rajender. ·Royal Free Hospital, London, United Kingdom. ·Antivir Ther · Pubmed #18432160.

ABSTRACT: Ribavirin is a guanosine analogue that has little antiviral activity when used alone, but considerably enhances the efficacy of conventional and pegylated interferon in the treatment of hepatitis C virus (HCV). The precise mode of action of ribavirin is not fully understood; however, it is crucial for the achievement of high sustained virological response (SVR) rates by enhancing virological response and reducing relapse rates. Data from several studies have confirmed that higher initial doses of ribavirin lead to higher SVR rates. Furthermore, intensified ribavirin dosing might also improve SVR rates in 'difficult-to-cure' patients. It is also important to minimize ribavirin dose reductions to promote high SVR rates and to maintain ribavirin levels throughout treatment to prevent viral breakthrough and relapse. The pharmacokinetic profile of ribavirin reveals a long elimination half-life due to accumulation in the blood, such that its side-effect profile includes haemolytic anaemia. Therefore, finding the optimal ribavirin dose requires a balance between efficacy and its associated side effects to ensure improved patient outcomes. Here, we discuss how optimizing the ribavirin component of combined therapy for HCV is an essential part of treatment optimization.

24 Review Management of viral hepatitis in hematologic malignancies. 2008

Firpi, Roberto J / Nelson, David R. ·Division of Gastroenterology, Hepatology and Nutrition Section of Hepatobiliary Diseases and Liver Transplantation, University of Florida Gainesville, FL 32610-0214, USA. firpirj@medicine.ufl.edu ·Blood Rev · Pubmed #18343002.

ABSTRACT: Viral hepatitis is the third major cause of liver dysfunction in allogeneic transplant recipients and has become a significant concern in patients with hematological malignancies receiving chemotherapy. Thus, identification of patients at risk for viral hepatitis is very important when evaluating and treating hematological malignancies. Serologic screening for all patients should include anti-HCV, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) testing. Current therapies for hepatitis B (HBV) virus infection are aimed at viral suppression, while treatment for hepatitis C (HCV) virus can eradicate infection in many treated patients. To prevent HBV viral reactivation, prophylaxis with nucleoside analogues should be initiated for all HBsAg-positive patients. HCV infection appears to have little impact on short-term survival after bone marrow transplantation (BMT), but eventually can impact long-term survival due to progression of liver disease. In this review we will highlight the mechanisms of virus reactivation, clinical manifestations, and management strategies to minimize acute and chronic morbidity in this population.

25 Clinical Trial A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: Results from a large US multi-center observational study. 2018

Evon, Donna M / Stewart, Paul W / Amador, Jipcy / Serper, Marina / Lok, Anna S / Sterling, Richard K / Sarkar, Souvik / Golin, Carol E / Reeve, Bryce B / Nelson, David R / Reau, Nancy / Lim, Joseph K / Reddy, K Rajender / Di Bisceglie, Adrian M / Fried, Michael W. ·Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America. · Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America. · Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America. · Division of Gastroenterology, Hepatology & Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America. · Division of Gastroenterology and Hepatology, Department of Medicine, University of California Davis, Davis, California, United States of America. · Division of General Medicine and Clinical Epidemiology, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America. · Department of Health Behaviors, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America. · Department of Population Health Sciences, Duke University, Durham, North Carolina, United States of America. · Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, Florida, United States of America. · Department of Internal Medicine, Section of Hepatology, Rush University, Chicago, Illinois, United States of America. · Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut, United States of America. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, United States of America. ·PLoS One · Pubmed #30067745.

ABSTRACT: BACKGROUND: Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables. METHODS AND FINDINGS: PROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016-2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0-15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20-50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40-50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not. CONCLUSIONS: This large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication. TRIAL REGISTRATION: (Clinicaltrial.gov: NCT02601820).

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