Accepted Manuscript Screening, Diagnosis, Treatment, and Management of Hepatitis C: A Novel, Comprehensive, Online Resource Center for Primary Care Providers and Specialists Edward Lebovics, MD, FACP, AGAF, FACG Klara Czobor PII:
S0002-9343(14)00888-2
DOI:
10.1016/j.amjmed.2014.10.004
Reference:
AJM 12699
To appear in:
The American Journal of Medicine
Please cite this article as: Lebovics E, Czobor K, Screening, Diagnosis, Treatment, and Management of Hepatitis C: A Novel, Comprehensive, Online Resource Center for Primary Care Providers and Specialists, The American Journal of Medicine (2014), doi: 10.1016/j.amjmed.2014.10.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Screening, Diagnosis, Treatment, and Management of Hepatitis C: A Novel, Comprehensive, Online Resource Center for Primary Care Providers and Specialists
a
RI PT
Authors: Edward Lebovics, MD, FACP, AGAF, FACG,a Klara Czoborb
Sarah C. Upham Division of Gastroenterology & Hepatobiliary Diseases, New York Medical College,
Valhalla, New York, NY; bKlast Consulting, Inc. New York, NY.
SC
ABSTRACT
Current initiatives focusing on hepatitis C (HCV) screening and diagnosis, together with the advent of
M AN U
oral interferon (IFN)-free treatment regimens have prompted Elsevier Multimedia Publishing and the American Journal of Medicine (AJM) to develop a novel, comprehensive, online Resource Center dedicated to providing both primary care providers and specialists with the latest information on the screening, diagnosis, treatment, and management of HCV. To date, only 25% of infected patients have been diagnosed and only 5% cured. With the Centers for Disease Control and Prevention (CDC) and the US Prevention Services Task Force (USPSTF) recommendation of one-time screening for all individuals
TE D
born between 1945 and 1965, and the availability of safe and effective therapy, it is anticipated that primary care providers and community practices will become increasingly responsible for the screening, diagnosis, and management of infected patients, as well as providing access to care by specialists when needed. The AJM Hepatitis C Resource Center site will have two major channels; one channel tailored to
EP
specifically address the needs of internal medicine physicians and other primary care providers, and one channel tailored to address the needs of specialists including hepatologists, gastroenterologists, and
AC C
infectious disease specialists. Systematic surveys of these clinician audiences are being conducted by Elsevier to assess educational gaps, and ensure that the content of each channel of the Resource Center satisfies the needs of the intended audiences. In a recent Elsevier survey of primary care physicians (PCPs) who had screened and/or participated in the care of patients with HCV within 6 months of participating in the survey, 60% of PCPs stated that they were not very confident or only somewhat confident about screening patients for chronic HCV infection. A recent Elsevier survey of specialists revealed low levels of satisfaction with the treatment options available in 2013, with “no therapy” being selected for up to 38% of patients. This survey also showed that experience with newly-approved options for HCV including IFN-free regimens is currently limited, but the likelihood that a variety of
ACCEPTED MANUSCRIPT
patient types will be treated with these options is high. This provides an impetus for educational opportunities focusing on optimizing treatments for the different HCV genotypes and for patients with comorbidities. Further results of the PCP and specialist surveys will be published on the Resource Center. Each channel of the Resource Center will be comprised of a variety of specific communication
RI PT
elements, which are open to sponsorship, and include roundtable panel discussions, case studies, and direct links to relevant original research, review articles, and guidelines. All Resource Center
components are peer-reviewed for publication on the Resource Center by the AJM Editorial Office and the Resource Center Guest Editor, Edward Lebovics, MD. The AJM Hepatitis C Resource Center will be
SC
accessible from the AJM online home page (http://www.amjmed.com) and will be launched
immediately prior to the American Association for the Study of Liver Diseases (AASLD) Liver Meeting to
M AN U
be held from November 7 to 11, 2014 in Boston, Massachusetts.
MANUSCRIPT INTRODUCTION
Of an estimated 4.1 million persons infected with hepatitis C (HCV) in the United States (US), approximately 3.2 million have a chronic infection.(1) Chronic infection is the hallmark of HCV, and is defined as a persistence of the virus for greater than 6 months after the initial infection.(2) While 25% to
TE D
30% of patients acutely infected with HCV may develop jaundice, abdominal pain, or more commonly, nonspecific flu-like symptoms such as fatigue, muscles aches, and nausea, the majority of acutely infected patients are asymptomatic.(3) Up to 80% of people infected with HCV will develop chronic disease.(2) Chronic HCV infection is often asymptomatic for decades, and individuals harboring the virus
EP
may go unnoticed unless tested or discovered incidentally such as during an investigation of elevated aminotransferases.(2) To date, only 25% of infected patients have been diagnosed and only 5% cured.(4)
AC C
HCV RNA can be detected as early as 7 days after exposure, but the antibody to HCV (anti-HCV Ab) may not be present until 6 to 8 weeks after exposure.(5) Chronic hepatitis C is diagnosed when HCV RNA is present 6 months after exposure.(5) A patient with a chronic HCV infection may also present was nonspecific symptoms such as nausea, anorexia, and fatigue or signs of cirrhosis upon examination.(2) Cirrhosis, the end-stage outcome of fibrosis progression, may take an average of 30 years to develop in HCV-infected individuals.(6) Progressive liver fibrosis is an important consequence of chronic HCV infection, with resultant cirrhosis that may lead to liver failure (decompensation) and hepatocellular carcinoma (HCC).(2) HCV is the leading cause of HCC, and the most common indication for liver transplantation in the United States.(7,
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8) It is likely that more cases of HCC, decompensated cirrhosis, and liver transplants due to HCV, will be observed in the coming years.(9) Unfortunately, HCV-associated mortality is on the rise in the US and currently exceeds that for HIV.(10) It has been estimated that in 2012, the healthcare cost of HCV was $6.5 billion, and it has been predicted that the cost will peak at $9.1 billion in 2024.(11) While the high
RI PT
health burden of HCV largely relates to the development of advanced liver disease, additional disease burden and costs are generated by extrahepatic manifestations of HCV infection including
cryoglobulinemic vasculitis, lymphoproliferative disorders, renal disease, and rheumatoid-like polyarthritis.(12)
SC
IMPORTANCE OF RISK-BASED AND BIRTH-COHORT-BASED SCREENING FOR HEPATITIS C
Of all the people in the US living with HCV, an estimated 76% are adults born during 1945 to 1965: a
M AN U
generation known as the Baby Boomers.(13) These individuals may have been exposed to HCV before universal precautions were implemented, and they may not recall or report risk factors to their primary care providers.(7, 13, 14) A sizeable percentage of Baby Boomers are unaware of their infection status, and given that this population has likely been infected for several decades, it’s not surprising that HCVassociated morbidity and mortality are on the increase in the US.(13)
Routine risk-based HCV testing is recommended by many organizations including the Centers for Disease
TE D
Control and Prevention (CDC), the American Association for the Study of Liver Diseases (AASLD), and the American College of Gastroenterology for individuals with risk factors such as the following:(15) Injection drug use
•
Having received clotting factor concentrates produced before 1987
•
Being on chronic hemodialysis
•
Having persistently abnormal alanine aminotransferase levels
•
Being a recipient of donated blood from a person who tested positive for HCV
• •
AC C
•
EP
•
Having received a blood transfusion or organ transplant before July 1992 Having HIV
Men who have sex with men (MSM)
However, clinician reluctance to ask about risk factors, or patient unawareness or reluctance to disclose risk behaviors, limit the use of risk-based screening strategies.(15) To increase the possibility of more timely care and treatment, the CDC is actively supporting initiatives to simplify testing, improve provider and patient awareness, and expand recommendations for HCV screening beyond risk-based strategies.(15) Both the CDC and the US Prevention Services Task Force (USPSTF) currently recommend
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that risk-based screening should be augmented with a one-time screening for people born between 1945 and 1965.(7, 14) This birth-cohort approach targets individuals with the highest prevalence of HCV infection and also removes any behavioral stigma from screening.(7, 14) The USPSTF has specifically assigned a Grade B to two recommendations: screening for HCV infection in persons at high risk for
RI PT
infection, and one-time HCV screening for adults born between 1945 and 1965.(14) A USPSTF Grade B designation expands access to clinical preventive services.(14) In line with the recommendations issued by the CDC and the USPSTF, Governor Andrew M. Cuomo of New York State recently signed into law a new Section 2171 of the Public Health Law that requires the offering of a hepatitis C screening test to
SC
every individual born between 1945 and 1965 receiving inpatient hospital care or primary care.(16) This new law has been enacted to increase HCV testing in New York State and ensure timely diagnosis and
M AN U
linkage to care.(16)
IMPLICATIONS OF INCREASED SCREENING FOR HEPATITIS C AND THE USE OF NOVEL THERAPIES Implementation of risk-based and birth-cohort-based HCV screening recommendations are expected to increase demand for testing to detect current HCV infection.(15) In addition, all-oral, IFN-free therapeutic regimens for chronic HCV infection are becoming a reality, and they appear to be more
TE D
tolerable, more effective, shorter in duration, and simpler to administer than IFN-based therapies.(15) However, primary care providers can have misconceptions about whom to screen, the risk of progression of liver disease, and the available therapies.(17, 18) Also at issue is a lack of providers who can and are willing to treat HCV, and a lack of comprehensive educational resources to provide the
EP
latest information on the screening, diagnosis, treatment, and management of HCV.(19) The possible training of community-based healthcare providers to screen, diagnose, treat, manage, or appropriately refer HCV, especially with the advent of more efficacious and tolerable therapeutic regimens, may
AC C
eventually become a key approach to broadening access to effective care.(15) Community-based health centers often have advantages of being culturally appropriate and accessible to patients in both urban and rural areas.(15)
Unfortunately, among patients who are recognized as being positive for anti-HCV Ab, it is estimated that fewer than half are receiving adequate care, which may be related to a variety of misconceptions about HCV and its treatment on behalf of the patient and the provider.(20) Both primary care providers and specialists need to be provided with the latest information on the screening, diagnosis, treatment, and management of HCV. In a recent survey conducted by Elsevier Multimedia publishing, of primary care
ACCEPTED MANUSCRIPT
physicians (PCPs) who had screened and/or participated in the care of patients with HCV within 6 months of participating in the survey, 60% of PCPs stated that they were not very confident or only somewhat confident about screening patients for chronic HCV infection (Elsevier Multimedia Publishing, Personal Communication). In addition, the survey revealed that PCP confidence in initiating treatment in
RI PT
patients newly diagnosed with chronic hepatitis C infection and no comorbidities was low; only 21% and 16-22% of PCPs stated that they were more than somewhat confident in initiating IFN-based and the newer oral-based therapies, respectively (Elsevier Multimedia Publishing, Personal Communication). Interestingly, a recent survey of specialists including hepatologists, gastroenterologists, and infectious
SC
disease specialists, also conducted by Elsevier Multimedia Publishing, revealed low levels of satisfaction with the treatment options available in 2013, with “no therapy” being selected for up to 38% of patients (Elsevier Multimedia Publishing, Personal Communication). This survey also showed that while
M AN U
experience with newly-approved options for HCV, including IFN-free regimens, is currently limited, the likelihood that a variety of patient types will be treated with these options is high, which provides an impetus for educational opportunities focusing on optimizing treatments for the different HCV genotypes and for patients with comorbidities (Elsevier Multimedia Publishing, Personal Communication). As new all-oral regimens enter the market, clinicians need to be made constantly aware of regimen success rates in patients with advanced liver disease or difficult-to-treat HCV
TE D
genotypes, and how to monitor and manage treatment-related toxicities, and address the extent of clinically-relevant viral resistance and duration of therapy. A NOVEL COMPREHENSIVRE ONLINE HEPATITIS C RESOURCE CENTER FOR BOTH PRIMARY CARE
EP
PROVIDERS AND SPECIALISTS
Current initiatives focusing on HCV screening and diagnosis, together with the advent of oral-based
AC C
therapies and IFN-free treatment regimens have prompted Elsevier Multimedia Publishing and the American Journal of Medicine (AJM) to develop a novel, comprehensive, online Resource Center dedicated to providing both primary care providers and specialists with the latest information on the screening, diagnosis, treatment, and management of HCV. For example, while faced with the daunting task of screening all individuals born between 1945 and 1965, clinicians should be aware that a simplified HCV testing sequence has been proposed by the CDC to meet this demand.(21) This sequence involves initial testing for anti-HCV Ab, followed by an FDA-approved nucleic acid testing assay for the detection of HCV RNA in those patients who are reactive for anti-HCV Ab.(21) Rapid tests for anti-HCV Ab, such as OraQuick, are becoming available and may allow access to HCV testing in settings lacking
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laboratory-based diagnostic services.(22) It is important to note that despite the effectiveness and safety of newer oral HCV regimens, the cost of these regimens may introduce socioeconomic and ethical considerations into treatment decisions, especially in populations with limited resources. Questions regarding access to therapy, treatment prioritization, and the possible targeting of specific populations
RI PT
such us active injection users, need to be discussed in healthcare provider and public forums.
Primary care providers and specialists may have differing needs for education, and the AJM Hepatitis C Resource Center is geared toward satisfying the needs of the variety of clinician audiences who are currently and predicted to be intimately involved in the care of patients infected with HCV. The
SC
Resource Center site has two major channels; one channel tailored to specifically address the needs of internal medicine physicians and other primary care providers, and one channel tailored to address the
M AN U
needs of specialists including hepatologists, gastroenterologists, and infectious disease specialists. Elsevier Multimedia Publishing and AJM is further tailoring the content of each channel to meet specific educational needs by conducting and reviewing the results of systematic surveys geared toward primary care and specialist audiences. Results of these surveys will be published on the Resource Center. Each channel of the Resource Center will be comprised of a variety of specific communication elements including roundtable panel discussions, case studies, and direct links to relevant original research, and
TE D
review articles. While links to appropriate HCV treatment guidelines,(23-25) which are constantly being updated and are valuable resources for providers, will also be provided on the Resource Center, expert opinion pieces can be helpful when guidelines become outdated, and should be considered as a means to provide guidance in a rapidly changing field. All Resource Center components are peer-reviewed for
EP
publication on the Resource Center by the AJM Editorial Office and the Resource Center Guest Editor; Edward Lebovics, MD, FACP, AGAF, FACG, FAASLD, Upham Professor of Gastroenterology, Director,
AC C
Sarah C. Upham Division of Gastroenterology & Hepatobiliary Diseases, New York Medical College, Valhalla, New York. The AJM Hepatitis C Resource Center will be accessible from the AJM online home page (http://www.amjmed.com) and will be launched immediately prior to the AASLD Liver Meeting to be held from November 7 to 11, 2014 in Boston, Massachusetts. CONCLUSION
The hope for the future is that screening in conjunction with all-oral treatment regimens will reduce barriers to care and allow treatment within primary care and community sites for many HCV-infected patients. The guidance of specialists and cooperative practice partnerships to ensure appropriate
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referral will help this vision become a reality. The AJM Hepatitis C Resource Center serves as an initial step in a long, ambitious, and ultimately rewarding journey.
7.
8.
9.
10. 11. 12.
13. 14. 15. 16.
17. 18.
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5. 6.
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4.
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3.
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2.
Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Annals of internal medicine. 2006;144(10):705-14. Huffman MM, Mounsey AL. Hepatitis C for primary care physicians. Journal of the American Board of Family Medicine : JABFM. 2014;27(2):284-91. Kamal SM. Acute hepatitis C: a systematic review. The American journal of gastroenterology. 2008;103(5):1283-97; quiz 98. Holmberg SD, Spradling PR, Moorman AC, Denniston MM. Hepatitis C in the United States. The New England journal of medicine. 2013;368(20):1859-61. Thomas DL, Seeff LB. Natural history of hepatitis C. Clinics in liver disease. 2005;9(3):383-98, vi. Poynard T, Ratziu V, Benmanov Y, et al. Fibrosis in patients with chronic hepatitis C: detection and significance. Seminars in liver disease. 2000;20(1):47-55. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports / Centers for Disease Control. 2012;61(RR-4):1-32. Di Bisceglie AM, Lyra AC, Schwartz M, et al. Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status. The American journal of gastroenterology. 2003;98(9):2060-3. Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting future complications of chronic hepatitis C in the United States. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003;9(4):331-8. Ly KN, Xing J, Klevens RM, et al. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Annals of internal medicine. 2012;156(4):271-8. Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57(6):2164-70. Jacobson IM, Cacoub P, Dal Maso L, et al. Manifestations of chronic hepatitis C virus infection beyond the liver. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2010;8(12):1017-29. Ward JW. The epidemiology of chronic hepatitis C and one-time hepatitis C virus testing of persons born during 1945 to 1965 in the United States. Clinics in liver disease. 2013;17(1):1-11. Moyer VA, USPSTF. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Annals of internal medicine. 2013;159(5):349-57. Afdhal NH, Zeuzem S, Schooley RT, et al. The new paradigm of hepatitis C therapy: integration of oral therapies into best practices. Journal of viral hepatitis. 2013;20(11):745-60. Shah NR. NYS HCV Testing Law: Dear Colleague letter. 2013; Available from: https://www.health.ny.gov/diseases/communicable/hepatitis/hepatitis_c/rapid_antibody_testing /docs/2013-11-18_dcl_hepc_testing.pdf. Zickmund SL, Brown KE, Bielefeldt K. A systematic review of provider knowledge of hepatitis C: is it enough for a complex disease? Digestive diseases and sciences. 2007;52(10):2550-6. Shehab TM, Sonnad SS, Lok AS. Management of hepatitis C patients by primary care physicians in the USA: results of a national survey. Journal of viral hepatitis. 2001;8(5):377-83.
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1.
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REFERENCES
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24.
25.
RI PT
SC
23.
M AN U
22.
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21.
EP
20.
Volk ML. Antiviral therapy for hepatitis C: why are so few patients being treated? The Journal of antimicrobial chemotherapy. 2010;65(7):1327-9. Fishbein DA, Lo Y, Reinus JF, et al. Factors associated with successful referral for clinical care of drug users with chronic hepatitis C who have or are at risk for HIV infection. Journal of acquired immune deficiency syndromes. 2004;37(3):1367-75. Centers for Disease Control & Prevention. Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morbidity and mortality weekly report. 2013;62(18):362-5. Smith BD, Teshale E, Jewett A, et al. Performance of premarket rapid hepatitis C virus antibody assays in 4 national human immunodeficiency virus behavioral surveillance system sites. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2011;53(8):780-6. AASLD, IDSA, IAS-USA. Recommendations for testing, managing, and treating hepatitis C. 2014; Available from: http://www.hcvguidelines.org. World Health Organization. Guidelines for the screening, care, and treatment of persons with hepatitis C infection. 2014; Available from: http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1. EASL Recommendations on treatment of hepatitis C. 2014; Available from: http://files.easl.eu/easl-recommendations-on-treatment-of-hepatitis-C.pdf.
AC C
19.
S0002-9343(14)00888-2
DOI:
10.1016/j.amjmed.2014.10.004
Reference:
AJM 12699
To appear in:
The American Journal of Medicine
Please cite this article as: Lebovics E, Czobor K, Screening, Diagnosis, Treatment, and Management of Hepatitis C: A Novel, Comprehensive, Online Resource Center for Primary Care Providers and Specialists, The American Journal of Medicine (2014), doi: 10.1016/j.amjmed.2014.10.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Screening, Diagnosis, Treatment, and Management of Hepatitis C: A Novel, Comprehensive, Online Resource Center for Primary Care Providers and Specialists
a
RI PT
Authors: Edward Lebovics, MD, FACP, AGAF, FACG,a Klara Czoborb
Sarah C. Upham Division of Gastroenterology & Hepatobiliary Diseases, New York Medical College,
Valhalla, New York, NY; bKlast Consulting, Inc. New York, NY.
SC
ABSTRACT
Current initiatives focusing on hepatitis C (HCV) screening and diagnosis, together with the advent of
M AN U
oral interferon (IFN)-free treatment regimens have prompted Elsevier Multimedia Publishing and the American Journal of Medicine (AJM) to develop a novel, comprehensive, online Resource Center dedicated to providing both primary care providers and specialists with the latest information on the screening, diagnosis, treatment, and management of HCV. To date, only 25% of infected patients have been diagnosed and only 5% cured. With the Centers for Disease Control and Prevention (CDC) and the US Prevention Services Task Force (USPSTF) recommendation of one-time screening for all individuals
TE D
born between 1945 and 1965, and the availability of safe and effective therapy, it is anticipated that primary care providers and community practices will become increasingly responsible for the screening, diagnosis, and management of infected patients, as well as providing access to care by specialists when needed. The AJM Hepatitis C Resource Center site will have two major channels; one channel tailored to
EP
specifically address the needs of internal medicine physicians and other primary care providers, and one channel tailored to address the needs of specialists including hepatologists, gastroenterologists, and
AC C
infectious disease specialists. Systematic surveys of these clinician audiences are being conducted by Elsevier to assess educational gaps, and ensure that the content of each channel of the Resource Center satisfies the needs of the intended audiences. In a recent Elsevier survey of primary care physicians (PCPs) who had screened and/or participated in the care of patients with HCV within 6 months of participating in the survey, 60% of PCPs stated that they were not very confident or only somewhat confident about screening patients for chronic HCV infection. A recent Elsevier survey of specialists revealed low levels of satisfaction with the treatment options available in 2013, with “no therapy” being selected for up to 38% of patients. This survey also showed that experience with newly-approved options for HCV including IFN-free regimens is currently limited, but the likelihood that a variety of
ACCEPTED MANUSCRIPT
patient types will be treated with these options is high. This provides an impetus for educational opportunities focusing on optimizing treatments for the different HCV genotypes and for patients with comorbidities. Further results of the PCP and specialist surveys will be published on the Resource Center. Each channel of the Resource Center will be comprised of a variety of specific communication
RI PT
elements, which are open to sponsorship, and include roundtable panel discussions, case studies, and direct links to relevant original research, review articles, and guidelines. All Resource Center
components are peer-reviewed for publication on the Resource Center by the AJM Editorial Office and the Resource Center Guest Editor, Edward Lebovics, MD. The AJM Hepatitis C Resource Center will be
SC
accessible from the AJM online home page (http://www.amjmed.com) and will be launched
immediately prior to the American Association for the Study of Liver Diseases (AASLD) Liver Meeting to
M AN U
be held from November 7 to 11, 2014 in Boston, Massachusetts.
MANUSCRIPT INTRODUCTION
Of an estimated 4.1 million persons infected with hepatitis C (HCV) in the United States (US), approximately 3.2 million have a chronic infection.(1) Chronic infection is the hallmark of HCV, and is defined as a persistence of the virus for greater than 6 months after the initial infection.(2) While 25% to
TE D
30% of patients acutely infected with HCV may develop jaundice, abdominal pain, or more commonly, nonspecific flu-like symptoms such as fatigue, muscles aches, and nausea, the majority of acutely infected patients are asymptomatic.(3) Up to 80% of people infected with HCV will develop chronic disease.(2) Chronic HCV infection is often asymptomatic for decades, and individuals harboring the virus
EP
may go unnoticed unless tested or discovered incidentally such as during an investigation of elevated aminotransferases.(2) To date, only 25% of infected patients have been diagnosed and only 5% cured.(4)
AC C
HCV RNA can be detected as early as 7 days after exposure, but the antibody to HCV (anti-HCV Ab) may not be present until 6 to 8 weeks after exposure.(5) Chronic hepatitis C is diagnosed when HCV RNA is present 6 months after exposure.(5) A patient with a chronic HCV infection may also present was nonspecific symptoms such as nausea, anorexia, and fatigue or signs of cirrhosis upon examination.(2) Cirrhosis, the end-stage outcome of fibrosis progression, may take an average of 30 years to develop in HCV-infected individuals.(6) Progressive liver fibrosis is an important consequence of chronic HCV infection, with resultant cirrhosis that may lead to liver failure (decompensation) and hepatocellular carcinoma (HCC).(2) HCV is the leading cause of HCC, and the most common indication for liver transplantation in the United States.(7,
ACCEPTED MANUSCRIPT
8) It is likely that more cases of HCC, decompensated cirrhosis, and liver transplants due to HCV, will be observed in the coming years.(9) Unfortunately, HCV-associated mortality is on the rise in the US and currently exceeds that for HIV.(10) It has been estimated that in 2012, the healthcare cost of HCV was $6.5 billion, and it has been predicted that the cost will peak at $9.1 billion in 2024.(11) While the high
RI PT
health burden of HCV largely relates to the development of advanced liver disease, additional disease burden and costs are generated by extrahepatic manifestations of HCV infection including
cryoglobulinemic vasculitis, lymphoproliferative disorders, renal disease, and rheumatoid-like polyarthritis.(12)
SC
IMPORTANCE OF RISK-BASED AND BIRTH-COHORT-BASED SCREENING FOR HEPATITIS C
Of all the people in the US living with HCV, an estimated 76% are adults born during 1945 to 1965: a
M AN U
generation known as the Baby Boomers.(13) These individuals may have been exposed to HCV before universal precautions were implemented, and they may not recall or report risk factors to their primary care providers.(7, 13, 14) A sizeable percentage of Baby Boomers are unaware of their infection status, and given that this population has likely been infected for several decades, it’s not surprising that HCVassociated morbidity and mortality are on the increase in the US.(13)
Routine risk-based HCV testing is recommended by many organizations including the Centers for Disease
TE D
Control and Prevention (CDC), the American Association for the Study of Liver Diseases (AASLD), and the American College of Gastroenterology for individuals with risk factors such as the following:(15) Injection drug use
•
Having received clotting factor concentrates produced before 1987
•
Being on chronic hemodialysis
•
Having persistently abnormal alanine aminotransferase levels
•
Being a recipient of donated blood from a person who tested positive for HCV
• •
AC C
•
EP
•
Having received a blood transfusion or organ transplant before July 1992 Having HIV
Men who have sex with men (MSM)
However, clinician reluctance to ask about risk factors, or patient unawareness or reluctance to disclose risk behaviors, limit the use of risk-based screening strategies.(15) To increase the possibility of more timely care and treatment, the CDC is actively supporting initiatives to simplify testing, improve provider and patient awareness, and expand recommendations for HCV screening beyond risk-based strategies.(15) Both the CDC and the US Prevention Services Task Force (USPSTF) currently recommend
ACCEPTED MANUSCRIPT
that risk-based screening should be augmented with a one-time screening for people born between 1945 and 1965.(7, 14) This birth-cohort approach targets individuals with the highest prevalence of HCV infection and also removes any behavioral stigma from screening.(7, 14) The USPSTF has specifically assigned a Grade B to two recommendations: screening for HCV infection in persons at high risk for
RI PT
infection, and one-time HCV screening for adults born between 1945 and 1965.(14) A USPSTF Grade B designation expands access to clinical preventive services.(14) In line with the recommendations issued by the CDC and the USPSTF, Governor Andrew M. Cuomo of New York State recently signed into law a new Section 2171 of the Public Health Law that requires the offering of a hepatitis C screening test to
SC
every individual born between 1945 and 1965 receiving inpatient hospital care or primary care.(16) This new law has been enacted to increase HCV testing in New York State and ensure timely diagnosis and
M AN U
linkage to care.(16)
IMPLICATIONS OF INCREASED SCREENING FOR HEPATITIS C AND THE USE OF NOVEL THERAPIES Implementation of risk-based and birth-cohort-based HCV screening recommendations are expected to increase demand for testing to detect current HCV infection.(15) In addition, all-oral, IFN-free therapeutic regimens for chronic HCV infection are becoming a reality, and they appear to be more
TE D
tolerable, more effective, shorter in duration, and simpler to administer than IFN-based therapies.(15) However, primary care providers can have misconceptions about whom to screen, the risk of progression of liver disease, and the available therapies.(17, 18) Also at issue is a lack of providers who can and are willing to treat HCV, and a lack of comprehensive educational resources to provide the
EP
latest information on the screening, diagnosis, treatment, and management of HCV.(19) The possible training of community-based healthcare providers to screen, diagnose, treat, manage, or appropriately refer HCV, especially with the advent of more efficacious and tolerable therapeutic regimens, may
AC C
eventually become a key approach to broadening access to effective care.(15) Community-based health centers often have advantages of being culturally appropriate and accessible to patients in both urban and rural areas.(15)
Unfortunately, among patients who are recognized as being positive for anti-HCV Ab, it is estimated that fewer than half are receiving adequate care, which may be related to a variety of misconceptions about HCV and its treatment on behalf of the patient and the provider.(20) Both primary care providers and specialists need to be provided with the latest information on the screening, diagnosis, treatment, and management of HCV. In a recent survey conducted by Elsevier Multimedia publishing, of primary care
ACCEPTED MANUSCRIPT
physicians (PCPs) who had screened and/or participated in the care of patients with HCV within 6 months of participating in the survey, 60% of PCPs stated that they were not very confident or only somewhat confident about screening patients for chronic HCV infection (Elsevier Multimedia Publishing, Personal Communication). In addition, the survey revealed that PCP confidence in initiating treatment in
RI PT
patients newly diagnosed with chronic hepatitis C infection and no comorbidities was low; only 21% and 16-22% of PCPs stated that they were more than somewhat confident in initiating IFN-based and the newer oral-based therapies, respectively (Elsevier Multimedia Publishing, Personal Communication). Interestingly, a recent survey of specialists including hepatologists, gastroenterologists, and infectious
SC
disease specialists, also conducted by Elsevier Multimedia Publishing, revealed low levels of satisfaction with the treatment options available in 2013, with “no therapy” being selected for up to 38% of patients (Elsevier Multimedia Publishing, Personal Communication). This survey also showed that while
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experience with newly-approved options for HCV, including IFN-free regimens, is currently limited, the likelihood that a variety of patient types will be treated with these options is high, which provides an impetus for educational opportunities focusing on optimizing treatments for the different HCV genotypes and for patients with comorbidities (Elsevier Multimedia Publishing, Personal Communication). As new all-oral regimens enter the market, clinicians need to be made constantly aware of regimen success rates in patients with advanced liver disease or difficult-to-treat HCV
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genotypes, and how to monitor and manage treatment-related toxicities, and address the extent of clinically-relevant viral resistance and duration of therapy. A NOVEL COMPREHENSIVRE ONLINE HEPATITIS C RESOURCE CENTER FOR BOTH PRIMARY CARE
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PROVIDERS AND SPECIALISTS
Current initiatives focusing on HCV screening and diagnosis, together with the advent of oral-based
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therapies and IFN-free treatment regimens have prompted Elsevier Multimedia Publishing and the American Journal of Medicine (AJM) to develop a novel, comprehensive, online Resource Center dedicated to providing both primary care providers and specialists with the latest information on the screening, diagnosis, treatment, and management of HCV. For example, while faced with the daunting task of screening all individuals born between 1945 and 1965, clinicians should be aware that a simplified HCV testing sequence has been proposed by the CDC to meet this demand.(21) This sequence involves initial testing for anti-HCV Ab, followed by an FDA-approved nucleic acid testing assay for the detection of HCV RNA in those patients who are reactive for anti-HCV Ab.(21) Rapid tests for anti-HCV Ab, such as OraQuick, are becoming available and may allow access to HCV testing in settings lacking
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laboratory-based diagnostic services.(22) It is important to note that despite the effectiveness and safety of newer oral HCV regimens, the cost of these regimens may introduce socioeconomic and ethical considerations into treatment decisions, especially in populations with limited resources. Questions regarding access to therapy, treatment prioritization, and the possible targeting of specific populations
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such us active injection users, need to be discussed in healthcare provider and public forums.
Primary care providers and specialists may have differing needs for education, and the AJM Hepatitis C Resource Center is geared toward satisfying the needs of the variety of clinician audiences who are currently and predicted to be intimately involved in the care of patients infected with HCV. The
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Resource Center site has two major channels; one channel tailored to specifically address the needs of internal medicine physicians and other primary care providers, and one channel tailored to address the
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needs of specialists including hepatologists, gastroenterologists, and infectious disease specialists. Elsevier Multimedia Publishing and AJM is further tailoring the content of each channel to meet specific educational needs by conducting and reviewing the results of systematic surveys geared toward primary care and specialist audiences. Results of these surveys will be published on the Resource Center. Each channel of the Resource Center will be comprised of a variety of specific communication elements including roundtable panel discussions, case studies, and direct links to relevant original research, and
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review articles. While links to appropriate HCV treatment guidelines,(23-25) which are constantly being updated and are valuable resources for providers, will also be provided on the Resource Center, expert opinion pieces can be helpful when guidelines become outdated, and should be considered as a means to provide guidance in a rapidly changing field. All Resource Center components are peer-reviewed for
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publication on the Resource Center by the AJM Editorial Office and the Resource Center Guest Editor; Edward Lebovics, MD, FACP, AGAF, FACG, FAASLD, Upham Professor of Gastroenterology, Director,
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Sarah C. Upham Division of Gastroenterology & Hepatobiliary Diseases, New York Medical College, Valhalla, New York. The AJM Hepatitis C Resource Center will be accessible from the AJM online home page (http://www.amjmed.com) and will be launched immediately prior to the AASLD Liver Meeting to be held from November 7 to 11, 2014 in Boston, Massachusetts. CONCLUSION
The hope for the future is that screening in conjunction with all-oral treatment regimens will reduce barriers to care and allow treatment within primary care and community sites for many HCV-infected patients. The guidance of specialists and cooperative practice partnerships to ensure appropriate
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referral will help this vision become a reality. The AJM Hepatitis C Resource Center serves as an initial step in a long, ambitious, and ultimately rewarding journey.
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Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Annals of internal medicine. 2006;144(10):705-14. Huffman MM, Mounsey AL. Hepatitis C for primary care physicians. Journal of the American Board of Family Medicine : JABFM. 2014;27(2):284-91. Kamal SM. Acute hepatitis C: a systematic review. The American journal of gastroenterology. 2008;103(5):1283-97; quiz 98. Holmberg SD, Spradling PR, Moorman AC, Denniston MM. Hepatitis C in the United States. The New England journal of medicine. 2013;368(20):1859-61. Thomas DL, Seeff LB. Natural history of hepatitis C. Clinics in liver disease. 2005;9(3):383-98, vi. Poynard T, Ratziu V, Benmanov Y, et al. Fibrosis in patients with chronic hepatitis C: detection and significance. Seminars in liver disease. 2000;20(1):47-55. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports / Centers for Disease Control. 2012;61(RR-4):1-32. Di Bisceglie AM, Lyra AC, Schwartz M, et al. Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status. The American journal of gastroenterology. 2003;98(9):2060-3. Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting future complications of chronic hepatitis C in the United States. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003;9(4):331-8. Ly KN, Xing J, Klevens RM, et al. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Annals of internal medicine. 2012;156(4):271-8. Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57(6):2164-70. Jacobson IM, Cacoub P, Dal Maso L, et al. Manifestations of chronic hepatitis C virus infection beyond the liver. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2010;8(12):1017-29. Ward JW. The epidemiology of chronic hepatitis C and one-time hepatitis C virus testing of persons born during 1945 to 1965 in the United States. Clinics in liver disease. 2013;17(1):1-11. Moyer VA, USPSTF. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Annals of internal medicine. 2013;159(5):349-57. Afdhal NH, Zeuzem S, Schooley RT, et al. The new paradigm of hepatitis C therapy: integration of oral therapies into best practices. Journal of viral hepatitis. 2013;20(11):745-60. Shah NR. NYS HCV Testing Law: Dear Colleague letter. 2013; Available from: https://www.health.ny.gov/diseases/communicable/hepatitis/hepatitis_c/rapid_antibody_testing /docs/2013-11-18_dcl_hepc_testing.pdf. Zickmund SL, Brown KE, Bielefeldt K. A systematic review of provider knowledge of hepatitis C: is it enough for a complex disease? Digestive diseases and sciences. 2007;52(10):2550-6. Shehab TM, Sonnad SS, Lok AS. Management of hepatitis C patients by primary care physicians in the USA: results of a national survey. Journal of viral hepatitis. 2001;8(5):377-83.
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