Weekend Reading: Current options for treating HCV genotypes 1-4

Weekend Reading: State-of-the-Art Decision Making in HCV Genotypes 1-4 

Good afternoon folks, when a new learning activity is launched with basic information about HCV this blog offers a quick summary and links to the presentation. 

A new Web-based CME presented by IAS–USAAn Intensive Workshop on Evolving Strategies in Viral Hepatitis Management, aired this month in Atlanta, GA. 

Although this learning activity is clinical in nature and directed at physicians, anyone living with HCV and considering treatment has an opportunity to learn more about disease management, testing, methods used to assess fibrosis, current options for treating HCV genotypes 1-4, and more. 

Participants can listen to an audio, or view a slide-set along with the webcast. I highly recommend watching the webcast, it offers an index for navigating through the program. 

Links
1- Begin by clicking, here
2- Under "An Intensive Workshop on Evolving Strategies in Viral Hepatitis Management" 
Click on a subject.
3- Decide to either listen or watch the webcast, when clicking on the latter a new page will launch, click on “I have read these instructions and understand them,” at the bottom of the page to begin the activity.



Index 
Learning Objectives
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Enjoyable, easy listening. 
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Kenneth E. Sherman, MD, PhD

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Kenneth E. Sherman, MD, PhD

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Michael S. Saag, MD

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Source - IAS–USAAn Intensive Workshop on Evolving Strategies in Viral Hepatitis Management


CDC Hepatitis Updates - HCV Testing Makes Public Health Sense



CDC Hepatitis Updates - HCV Testing Makes Public Health Sense

Centers for Disease Control and Prevention (CDC) sent this bulletin at 03/27/2015 11:18 AM EDT

Viral Hepatitis Updates from CDC

HCV Testing Makes Public Health Sense
In response to Is widespread screening for hepatitis C justified?, Drs. Jonathan Mermin and John W. Ward of CDC wanted to set the record straight on a number of key points including “the CDC and USPSTF recommendations for one-time testing of persons born during 1945-1965 are based on sound evidence that HCV testing linked to care is beneficial for patients, cost effective, and with the potential of averting over 120,000 deaths from HCV.”
http://www.bmj.com/content/350/bmj.g7809/rr-11

WHO issues its first hepatitis B treatment guidelines
WHO issued its first-ever guidance for the treatment of chronic hepatitis B. Worldwide, some 240 million people have chronic hepatitis B virus with the highest rates of infection in Africa and Asia. People with chronic hepatitis B infection are at increased risk of dying from cirrhosis and liver cancer. Key recommendations include: the use of a few simple non-invasive tests to assess the stage of liver disease to help identify who needs treatment; prioritizing treatment for those with cirrhosis - the most advanced stage of liver disease; the use of two safe and highly effective medicines for the treatment of chronic hepatitis B; and regular monitoring using simple tests for early detection of liver cancer, to assess whether treatment is working, and if treatment can be stopped.
http://apps.who.int/iris/bitstream/10665/154590/1/9789241549059_eng.pdf?ua=1&ua=1

New Hepatitis C & Injection Drug Use Fact Sheet
CDC has developed a fact sheet on Hepatitis C and injection drug use. The fact sheet includes an overview of hepatitis C including symptoms, testing, transmission, prevention, treatment, and reinfection.
http://www.cdc.gov/hepatitis/HCV/PDFs/FactSheet-PWID.pdf

FDA Safety Alert
Hepatitis C Treatments Containing Sofosbuvir in Combination With Another Direct Acting Antiviral Drug: Drug Safety Communication - Serious Slowing of Heart Rate When Used With Antiarrhythmic Drug Amiodarone
http://www.fda.gov/Safety/MedWatch/SafetyInformation/
SafetyAlertsforHumanMedicalProducts/ucm439662.htm

Depression rather than liver impairment reduces quality of life in patients with hepatitis C

Revista Brasileira de Psiquiatria
Print version ISSN 1516-4446
Rev. Bras. Psiquiatr. vol.37 no.1 São Paulo Jan./Mar. 2015
http://dx.doi.org/10.1590/1516-4446-2014-1446

ORIGINAL ARTICLES

Depression rather than liver impairment reduces quality of life in patients with hepatitis C


Luciana D. Silva12, Cláudia C. da Cunha1, Luciana R. da Cunha1, Renato F. Araújo1, Vanessa M. Barcelos1, Penélope L. Menta1, Fernando S. Neves3, Rosangela Teixeira12, Gifone A. Rocha4, Eliane D. Gontijo5
1Viral Hepatitis Outpatient Clinic, Instituto Alfa de Gastroenterologia, School of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte - MG - Brazil
2Department of Internal Medicine, School of Medicine, UFMG, Belo Horizonte - MG - Brazil
3Department of Mental Health, School of Medicine, UFMG, Belo Horizonte - MG - Brazil
4Laboratory of Research in Bacteriology, School of Medicine, UFMG, Belo Horizonte - MG - Brazil
5Department of Preventive and Social Medicine, School of Medicine, UFMG, Belo Horizonte - MG - Brazil

Abstract, introduction, and discussion only provided below, for full text article please click here

ABSTRACT
Objective:
Patients with chronic hepatitis C (CHC) have a poorer quality of life than those with other chronic liver diseases. However, some of the factors that determine health-related quality of life (HRQOL) in these patients, such as the degree of liver fibrosis, are still controversial. Therefore, the aim of the present study was to investigate the impact of CHC on HRQOL by conducting clinical, psychiatric, and sociodemographic evaluations.

Methods:
One hundred and twenty-four consecutive patients attending a referral center for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview, the Hamilton Depression Rating Scale, the Hospital Anxiety and Depression Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey. Multiple linear regression analyses were used to quantify independent associations between HRQOL and the clinical, psychiatric, and sociodemographic variables of interest.

Results:
Reduced HRQOL was independently associated with major depressive disorder (MDD) and with elevated levels of alanine aminotransferase, but was not associated with hepatic cirrhosis.

Conclusions:
MDD rather than the grade of liver fibrosis was strongly associated with HRQOL impairment in patients with CHC. These findings highlight that, in patients with CHC, the psychological effects of the disease deserve more attention and the implementation of integrated medical, psychiatric, and psychological care may be helpful.

Key words: Chronic hepatitis C; cirrhosis; health-related quality of life; major depressive disorder

Introduction
Approximately 170 million individuals are infected with the hepatitis C virus (HCV) worldwide.1 HCV is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC), and is responsible for more than 475,000 deaths around the world each year.1 The natural course of chronic hepatitis C infection (CHC) is slow and insidious; 50-80% of acutely infected individuals will progress to HCV chronic carrier status. Of these, 20% develop cirrhosis and its complications after 20 to 30 years of infection.2 In addition, HCV infection is associated with a series of extrahepatic manifestations, including depressive and anxiety symptoms, fatigue, and musculoskeletal/joint pain, which have been linked to reduced health-related quality of life (HRQOL).3

Issues linked to HRQOL have become remarkably important in the healthcare field.4 HRQOL is one dimension of broader quality of life that is more directly related to health, and it focuses on the patient's subjective evaluation of well-being, individual experiences, and values regarding the process of being sick.5 Evaluation of this parameter is essential, because it is known that the distress caused by a disease transcends target organ damage. Consequently, patients with a similar pattern of liver injury might have different degrees of suffering.

Although HRQOL is variably impaired in cirrhotic patients, the results of studies evaluating the impact of the degree of liver fibrosis on HRQOL are still controversial.6,7 Particularly in patients with CHC, scores indicative of poorer HRQOL have been identified even in the absence of clinically significant hepatic disease when compared with the scores of healthy individuals.8

Furthermore, the influence of viral load on HRQOL is unclear. Although it has been suggested that host factors are the major determinants of HRQOL in patients with CHC, some studies have shown that a sustained viral response improves HRQOL in patients receiving specific treatment for HCV.9
Despite the fact that CHC has a negative influence on all dimensions of HRQOL, including its physical, psychological, and social aspects,10 relevant issues should be raised, such as the translation of the results measured with generic or specific HRQOL instruments into clinical practice and, consequently, how these findings may influence clinical decision-making. Furthermore, regardless of the stage of liver disease, other potential predictors contribute to impaired HRQOL in patients with CHC, particularly psychiatric illness, which is common among these subjects.11 The interrelationship between liver function and psychiatric profile may be more multifaceted than suspected.11,12 Few prospective studies have assessed HRQOL in CHC patients using detailed clinical and psychiatric approaches in combination with semi-structured interviews for psychiatric diagnosis.13,14
Depressive symptoms have been extensively identified in adults with chronic health conditions,15 and correlate negatively with HRQOL. Patients with CHC have a high prevalence of depressive disorders,11,16 up to 70%, which is seven-fold higher than that found in the general population, independently of the degree of hepatic injury.8 As described above, CHC interferes not only with physical symptoms but also with psychological and social functioning.8

This study focuses on the integration of the patients' medical history, especially the evaluation of aspects beyond liver disease, while simultaneously measuring quality of life in the context of CHC. To this end, a multiprofessional and interdisciplinary approach was used to integrate the diverse health-related, psychological, and social aspects that are strongly linked to HRQOL. Expanding the assessment of these patients enables us to not only enhance knowledge about hepatitis C and other liver diseases, but also to recognize other medical issues, such as comorbid psychiatric difficulties, which, as a whole, may significantly influence the HRQOL of patients with chronic diseases,17 such as CHC.

Therefore, the aim of this study was to investigate whether variables related to sociodemographic characteristics, degree of liver impairment, clinical comorbidities, and psychiatric illnesses - especially depressive disorders - are independently associated with HRQOL in patients with CHC. We hypothesized that depressive symptoms might be significantly associated with reduced HRQOL in HCV-infected patients, regardless of the presence of clinically significant hepatic disease.

Discussion Only - Full text article, click here
In the present study, depressive disorder had a deeper impact on the HRQOL of patients with CHC than did the severity of liver disease. These results confirm that depressive symptoms have a negative influence on quality of life in individuals with chronic infection, as observed elsewhere.8,28,29 Additionally, our results demonstrated that not only the presence of MDD but also the severity of depressive disorder was associated with lower scores in all SF-36 domains, as well as in the physical component summary. It should be emphasized that the SF-36 domain scores and summary component scores were analyzed in combination. Several studies have demonstrated that the SF-36 summary component scores are not independent, i.e., the PCS and MCS may be partially measuring the same constructs.26 Therefore, the PCS/MCS scoring method imprecisely summarizes the scores of the SF-36 domains, and must be carefully analyzed and interpreted in combination with the domain scores.26

In health care, an alternative manner of assessing the HRQOL of patients would be to use instruments that are targeted at specific aspects of a particular disease. These disease-specific questionnaires are designed to identify disease-specific domains with high specificity and sensitivity.30 In addition to hepatic disease severity, other factors that influence CHC patients' HRQOL should be recognized. The administration of an instrument able to detect small changes in quality of life may increase identification of HRQOL-related issues. Among them, the diagnosis of psychological factors, such as depressive symptoms and anxiety, should be emphasized. Moreover, this process also permits physicians to make changes in patient management. In the present study, when a specific instrument was used to evaluate HRQOL in patients with CHC, MDD was strongly associated with poorer HRQOL, independently of the stage of liver disease.31 Altogether, these findings highlight the significance of psychiatric issues in HRQOL impairment in CHC patients.

The high prevalence of MDD (30.6%) observed in the present study is consistent with the results of previous investigations using structured psychiatric interviews in CHC patients.14 However, the pathogenesis of HCV-related psychiatric symptoms has not been completely clarified. Several lines of evidence have demonstrated that the virus is able to cross the blood-brain barrier. Recently, studies focusing on the analysis of quasispecies have allowed the identification of HCV-RNA in brain tissue.32 Otherwise, the role played by the host's immune response (especially cytokine-related effects) on psychiatric disorders in CHC should not be disregarded.33

In addition to depression, CHC has been shown to be associated with other psychiatric comorbidities that may themselves contribute to a poorer HRQOL.4,16,34 Despite the results of multivariate analyses in this study, the influence of anxiety disorder influence on the HRQOL of patients with CHC should not be ignored. The prevalence of anxiety disorders in patients with CHC has been shown to be as high as that of clinical depression.13,16 Some authors have explained that these elevated levels of psychiatric morbidity are related to coping with stigma and prejudice during the disease process.35 Overall, these life experiences and feelings may be responsible for increased rates of anxiety and contribute to the negative impact of chronic diseases, such as CHC, on HRQOL.36 Additionally, in this study, alcohol abuse was another psychiatric comorbidity associated with a reduction in the scores of two domains of the SF-36. This negative impact of alcohol use on HRQOL is consistent with previous studies.37

To the best of our knowledge, this is the first study to demonstrate an association between lower scores on the Functional Capacity domain of the SF-36 and HTN in patients with CHC. The high (35.5%) prevalence of HTN may be explained by the older age of the study population. Ethnicity and dietary and cultural habits should also be considered.

In agreement with previous studies, none of the SF-36 scores correlated with presence of cirrhosis, presence of necroinflammatory activity, or viral load.8,10,38 However, in contrast to previous investigations,10,38 higher ALT concentrations in this study were associated with decreased SF-36 scores in five domains and in two summary components. As CHC has been associated with several extrahepatic manifestations,3 one may speculate that elevated ALT concentrations might be associated with the activation of a systemic host immune response. This event might interfere with target organs beyond the liver, including the central nervous system.

Among the sociodemographic variables evaluated in the current study, family income and educational attainment were positively associated with three SF-36 domain scores. Helbling et al. showed that low income was the major factor associated with a reduced HRQOL among patients with CHC.10 In addition, previous investigations have demonstrated the positive influence of education on the HRQOL of patients with this disease.3,4

Of note, regarding host-related variables, it should be emphasized that the majority of studies assessing the HRQOL of patients affected by CHC have taken place in the context of routine medical care and did not use structured psychiatric interviews to confirm anxiety or mood disorders. Our subjects were patients of a university hospital; consequently, a close working relationship between clinicians, hepatologists, psychiatrists, and psychologists evaluating and treating these subjects was enhanced. An interdisciplinary and multiprofessional approach was developed for a better comprehension of CHC patients' clinical/psychiatric manifestations, with a particular focus on evaluating the deleterious effects of HCV that extend beyond liver disease.

The present study has some limitations. First, the subjects included were recruited from a referral center and, consequently, may not be representative of all patients with CHC. Second, although the SF-36 is considered to be the most appropriate generic instrument for HRQOL assessment in patients with chronic liver disease,22 some issues need to be evaluated. Independent of clinical/psychiatric illnesses, HCV infection alone has been shown to negatively impact HRQOL.8 Upon receiving a diagnosis of HCV, which is a contagious liver disease, these patients are faced with various challenges, such as adjusting to chronic comorbidity and coping with the stigma and the stress of social and familial relationships.35 In addition, individuals with CHC live with illness uncertainty, which may become a great psychological stressor for these subjects.39 Based on these aspects, use of the SF-36 instrument only may be insufficient for an appropriate evaluation of the HRQOL of patients with CHC, which is influenced by multiple complex factors. Furthermore, some studies point to the possibility of an overlap between HRQOL domains and psychiatric abnormalities, especially depressive symptoms. In the present study, the “depressive view” of depressed patients may have introduced bias in the interpretation of the SF-36 domain scores and summary component scores.40

In conclusion, we have clearly demonstrated that psychiatric disorders (particularly MDD) and active medical comorbidities, rather than the severity of liver disease, are the determinants of HRQOL impairment in patients with CHC. These findings highlight that the psychological effects of the disease on patients living with CHC deserve more attention, and that implementation of integrated medical, psychiatric, and psychological care may be helpful for patients with CHC.

Full text article, click here

Gilead’s Sovaldi® for HCV Genotype 2 Approved By Japan’s Ministry of Health, Labour and Welfare

Japan’s Ministry of Health, Labour and Welfare Approves Gilead’s Sovaldi® (sofosbuvir) for the Treatment of Genotype 2 Chronic Hepatitis C
Source News
Company Gilead Sciences, Positron
Date March 26, 2015

-- Sovaldi Part of First All-Oral Treatment Regimen for Genotype 2 Patients in Japan --

-- 96 Percent Cure Rates and Shortened, 12-Week Course of Therapy --

FOSTER CITY, Calif., Mar. 26, 2015 -- (BUSINESS WIRE) -- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Sovaldi® (sofosbuvir), a once-daily nucleotide analog polymerase inhibitor, for the suppression of viremia in patients with genotype 2 chronic hepatitis C virus (HCV) infection with or without compensated cirrhosis. Sovaldi is indicated for use in combination with ribavirin (RBV) for 12 weeks. Sovaldi (in combination with RBV) is the first all-oral, interferon-free treatment regimen for genotype 2 HCV infection. Sovaldi is also the first product to be marketed by Gilead in Japan.

“Today’s approval represents an important step forward in the management of hepatitis C in Japan, enabling genotype 2 infected patients the opportunity of a cure in 12 weeks with an all-oral regimen that eliminates the need for interferon,” said Masao Omata, MD, Yamanashi Prefectural Hospital Organization.

Primarily due to HCV, Japan has one of the highest rates of liver cancer of any industrialized country. Of the more than one million people chronically infected with HCV, 20-30 percent have the genotype 2 strain of the virus. Currently approved therapies in Japan for genotype 2 HCV infection involve 24-48 weeks of injections with pegylated interferon, which may not be suitable for many patients.

Sovaldi’s approval is supported by data from a Phase 3 clinical trial conducted in Japan (Study GS-US-334-0118) among treatment-naïve and treatment-experienced genotype 2 patients. Approval was based on 96 percent (n=135/140) of genotype 2 HCV-infected patients who received 12 weeks of an all-oral regimen of Sovaldi plus RBV 600–1,000 mg/day achieving a sustained virologic response 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV infection. The approval is also supported by SVR12 results from four international Phase 3 studies (FISSION, FUSION, POSITRON and VALENCE), which included genotype 2 HCV patients.

“There is a need in Japan for new HCV treatment options that are more effective and better tolerated and we have been pleased to partner with the medical community here in Japan to demonstrate the efficacy and safety of Sovaldi,” said Norbert Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “We look forward to making Sovaldi available in Japan as quickly as possible, while simultaneously continuing to work with the agency on its review of our second application for an all-oral sofosbuvir-based regimen for the treatment of genotype 1 HCV infection.”

Gilead filed a New Drug Application (NDA) in Japan for a single-tablet regimen of sofosbuvir and the NS5A inhibitor ledipasvir for the treatment of genotype 1 HCV infected patients on September 24, 2014. The ledipasvir/sofosbuvir single tablet regimen is an investigational product in Japan and its safety and efficacy have not yet been established.

IMPORTANT SAFETY INFORMATION

Use with potent P gp inducers: Drugs that are potent P-gp inducers in the intestine are expected to decrease sofosbuvir plasma concentration. Sovaldi is contraindicated in patients receiving the following substances: carbamazepine, phenytoin, rifampicin or St. John’s wort. Also, Sovaldi should be administered with care when coadministered with the following drugs: rifabutin, and phenobarbital.

Contraindications: Sovaldi is contraindicated in patients with severe renal function impairment (eGFR<30 mL/min/1.73m2) or patients with renal insufficiency requiring dialysis.

Anemia occurred in patients receiving Sovaldi in combination with ribavirin. Patients should be carefully observed and hemoglobin should be periodically monitored and appropriate measures should be taken including ribavirin dose adjusted according to the ribavirin package insert. If ribavirin is permanently discontinued, Sovaldi should also be discontinued.

Adverse reactions: In the Japanese Phase 3 clinical study, 61 of 140 (43.6 percent) patients experienced adverse reactions, including abnormal laboratory test values. The major adverse reactions were 21 anemia/hemoglobin decreased (15.0 percent), 7 headache (5.0 percent), 6 malaise (4.3 percent), 6 nausea (4.3 percent), and 6 pruritus (4.3 percent).

About Gilead

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that physicians and patients may not see advantages of Sovaldi over other therapies and may therefore be reluctant to prescribe the product, and the risk that payers may be reluctant to approve or provide reimbursement for the product. Further, the ledipasvir/sofosbuvir single tablet regimen may not be approved in Japan in the currently anticipated timelines or at all, and approval, if granted, may have significant limitations on its use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full Prescribing Information for Sovaldi and Harvoni is available at www.gilead.com .
Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc., or its related companies.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com , follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Gilead Sciences, Inc.
Investors:
Patrick O’Brien, +1 650-522-1936
Media:
Cara Miller, +1 650-522-1616
Seiko Noma, +81-3-6837-0790 (Japan)


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