The Challenges of Caring for Newly Diagnosed Patients With HCV: Filling the Gap

Medscape Infectious Diseases

An Increasing Role for ID and Primary Care Clinicians?

Kaushal B. Shah, MD, Dawd S. Siraj, MD, MPH&TM

December 11, 2013

Hepatitis C Virus Infection

Hepatitis C virus (HCV) is an RNA virus causing major worldwide morbidity and mortality. If not diagnosed and treated early, HCV can have severe complications, including esophageal varices, liver cirrhosis with decompensation, and hepatocellular carcinoma. It is the leading indication for liver transplantation and a leading cause of hepatocellular carcinoma in the United States.^[1]

Since the discovery of HCV in 1989,^[2] remarkable progress has been made in its treatment. The newly approved direct-acting antiviral (DAA) protease inhibitor-based regimen has improved response rates, ushering in a new era in the management of patients with HCV. More effective, short course, and simpler regimens are expected in the near future. The recent update in the screening guidelines published by the US Preventive Services Task Force (USPSTF)^[3] is expected to increase the number of patients seeking care.

Epidemiology of HCV

HCV infects 170-200 million people around the globe, accounting for 3% of world's population. It is a much bigger problem compared with HIV, which has an overall prevalence of only about 34 million.^[4] In United States, approximately 3.2 million people are infected with HCV, and about two thirds are unaware of their diagnosis.^[5]

HCV is the most common chronic bloodborne pathogen in the United States. HCV antibody prevalence approaches 1.6%, and 78% of persons who test positive have detectable viremia.^[6]

Currently, 6 major genotypes and more than 80 subtypes have been identified worldwide.^[7] Genotype 1 is the most common type in the United States,^[8] where an estimated 16,000 new cases of HCV and 15,000 HCV-related deaths occur yearly.^[3]

HCV Screening and Diagnosis

Screening Guidelines

In the United States, the most important risk factor for HCV infection remains injection drug use. Other risk factors include past or current injection drug use, receipt of a blood transfusion before 1992, being born to an HCV-infected mother, incarceration, intranasal drug use, unregulated tattoos, and other unregulated percutaneous exposures. Previous guidelines recommended risk-based screening.

Unfortunately, as many as 45% of all HCV diagnosed patients report no known exposure risk.^[3] According to data from 1999 to 2008, about three fourths of patients in the United States living with HCV infection were born between 1945 and 1965, with a peak prevalence of 4.3% in persons aged 40-49 years.^[3,9] After conducting 2 systematic reviews of the evidence on HCV progression, complications, and available therapies, in June 2013, the USPSTF updated the screening guidelines by adding 1-time HCV screening of people born between 1945 and 1965.^[3]

With this change in the screening guideline, more than 800,000 people with chronic HCV will be identified.^[10] This will undoubtedly stress the already stretched field of HCV clinicians. By the end of 2007, only 21% of all estimated infected persons had received antiviral therapy. If this trend is not changed, it is projected that only 14.5% of liver-related deaths related to HCV during 2002-2030 would be prevented.^[11,12]

The reasons for these distressing statistics are multifactorial, with the lack of early screening with advanced disease at time of care and the limited number of specialists who treat patients with HCV being the main driving factors. The recently updated screening guideline is expected to improve this situation, but without a massive increase in HCV providers who will absorb the increased demand for care, its impact will be blunted.

Diagnostic Testing

For years, HCV treatment decisions have been based on stage of liver inflammation and fibrosis as determined by liver biopsy. Although considered the gold standard, liver biopsy is an invasive and expensive procedure that can be associated with morbidity and, rarely, mortality.^[13] Furthermore, this test is saddled by significant sampling error (30%-35%), poor and inadequate sampling, and inter- and intrareader variability of interpretation of results.^[13]

Noninvasive blood tests and ultrasonographic scanning of the liver are becoming increasingly precise in staging liver disease in patients with HCV.^[14] The US Food and Drug Administration (FDA) approved liver ultrasonographic elastography, the FibroScan® (Echosens, Paris, France), in mid-2013. In a recent meta-analysis, the sensitivity and specificity of FibroScan to detect fibrosis were 87% and 91%, respectively.^[15]

Paradigm Shift in Management of HCV

The main goal in the treatment of HCV is sustained virologic response (SVR). SVR is associated with a substantial (> 50%) reduction in risk for all-cause mortality^[16] and substantially lower rates of liver-related death and decompensated cirrhosis with ascites, variceal bleeding, encephalopathy, or impaired hepatic synthetic function.^[17]

In 2011, the first DAAs -- telaprevir and boceprevir -- were licensed in the United States for treatment of HCV genotype 1.^[18,19] The addition of DAAs to the management of HCV has improved the rates of SVR from 44% to 75%.^[20] Furthermore, approximately 20 new HCV treatments are undergoing phase 2 or phase 3 clinical trials.^[21] These new regimens have improved side-effect profiles and are expected to improve SVR rates and shorten the duration of therapy.

Increased Demand for HIV Care

Currently, clinical HCV care is primarily provided by hepatologists and gastroenterologists. When screening was limited and rates of SVR were low, most patients with HCV sought medical attention late in the disease process, when they required advanced specialist care. Moreover, the need for liver biopsy to stage disease has centered the care of patients with HCV among hepatologists. The changing guidelines for screening, the precision of noninvasive techniques for staging liver disease, and the approval of highly effective DAAs will probably change this paradigm gradually.

In the United States, there are approximately 14,000 practicing gastroenterologists.^[21] With no increase in fellowship positions, the surge in the HCV patient population will be an extraordinary burden on these already stretched HCV care providers. Furthermore, the multiple new drug combinations, complex drug/drug interactions and side-effect profiles, challenging socioeconomic issues, and comorbid conditions common in patients with HCV will require specialists who are familiar and comfortable with handling those complex issues.

There are many persuasive reasons for infectious diseases (ID) specialists to integrate HCV care into their practices. An estimated 15%-20% of patients with HIV are coinfected with HCV.^[22] In HIV practice, we formulate complex antiviral combinations, manage drug/drug interactions of fundamentally similar medications to the HCV regimen (protease inhibitors, nucleosides, non-nucleosides), interpret results of antiviral drug resistance testing, and devise salvage regimens. ID specialists care for patients with HIV who have complex social, financial, substance abuse, alcoholism, depression, and nonadherence issues that require sustained and involved long-term care. Experience with the same general principles would apply and serve us well if we gradually incorporate care of HCV-infected patients into our practice.

HCV, like HIV, is a public health issue that requires an integrated approach to care. The focus on risk factor identification, diagnosis, transmission prevention, education, and provision of access to care will require clinicians to work closely with public health systems. ID specialists can apply their expertise in this area to help patients with HCV and strengthen the public health system.

The needs and care of patients with HIV and HCV are similar, but at the same time, ID specialists must appreciate the differences and create working relationships with hepatologists, gastroenterologists, and transplant centers for more coordinated and effective care. This will foster a better transition of patient care when diagnostic and therapeutic services for such issues as variceal bleeding, ascites, hepatocellular carcinoma, or liver transplant are required.

With these issues in mind, the Infectious Diseases Society of America (IDSA) has created an HCV task force that is spearheading the training of ID physicians through increasing coverage at society meetings, preparing training webinars, and working on a curriculum for ID fellowship training in HCV patient care. In the long run, this will fill a crucial gap in the overall care of patients with HCV.^[23]

If HCV screening is implemented as recommended and the number of patients increases as anticipated, the addition of ID clinicians might not even be adequate to meet the demand. The reasons and rationale that justify the need for ID physicians could work as well for primary care physicians, internists, and family medicine specialists. With proper training, the fundamental changes on evaluation and management of HCV will make it possible for these primary care providers to be involved in direct care of patients with HCV.

Clinic Organization for HCV Care

Clinicians who are planning to add HCV care to their practices will need a clinic-wide plan to prepare for the increased patient load and work volume.^[24,25] Because staff resources and time are limited, healthcare providers will have to determine how best to allocate clinic resources and use support staff to maximize productivity without compromising the quality and safety of care. This is better handled if care is centered around a designated management team who will dedicate a portion of their time to HCV care.

Before offering the service and on an ongoing basis, the HCV management team should receive education on HCV and the current approved management of HCV. The complex drug/drug interaction profile, side effects, and dosing schedules make this education critical to providing quality standardized care. It would be advisable to prepare a manual or protocol to standardize knowledge and care among clinic staff.

Nurse practitioners, physician assistants, and pharmacists can be an integral part of the HCV management team. With proper supervision and education, they can play critical roles in the day-to-day care and follow-up of patients. Most of the issues that are brought by patients while undergoing HCV treatment can be addressed by these medical professionals, allowing physicians to use their time to evaluate new patients.

A New Era in HCV Care

A new era is dawning in HCV care. Multiple recent developments are playing a role in this change, including:

• Recent updates in the HCV screening guideline, which are expected to bring an unprecedented number of new patients;

• The approval of the FibroScan® and refinement of biochemical tests to noninvasively stage liver disease; and

• The approval of shorter, safer, more effective, and possibly all-oral DAA-based HCV treatment regimens.

As a result of these changes, not only we will see an increased number of patients who will be seeking care, but most will be at the early stage of their disease, further reducing the need for highly specialized tests and care. To meet this increased demand, more HCV care providers will be required in the near future. Considering their expertise in comprehensive HIV care, we believe that ID physicians are the ideal candidates to fill this critical gap. Collaborative training with hepatologists, modification of ID fellowship training to include HCV patient care, and multimedia continuous training of ID physicians by IDSA and the HCV task force should continue to pave the way for the new era.

References

1. Sanyal AJ; Governing Board the Public Policy, Clinical Practice, Manpower Committees of the AASLD. The Institute of Medicine report on viral hepatitis: a call to action. Hepatology. 2010;51:727-728.

2. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359-362.

3. Moyer VA; US Preventive Services Task Force. Screening for hepatitis C virus infection in adults: US Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2013;159:349-357.

4. Marinho RT, Barreira DP. Hepatitis C, stigma and cure. World J Gastroenterol. 2013;19:6703-6709.

5. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705-714.

6. US Preventive Services Task Force. Screening for hepatitis C virus infection in adults. September 13, 2013.http://effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1698 Accessed November 30, 2013.

7. Bunchorntavakul C, Chavalitdhamrong D, Tanwandee T. Hepatitis C genotype 6: a concise review and response-guided therapy proposal. World J Hepatol. 2013;5:496-504.

8. Manos MM, Shvachko VA, Murphy RC, Arduino JM, Shire NJ. Distribution of hepatitis C virus genotypes in a diverse US integrated health care population. J Med Virol. 2012;84:1744-1750.

9. Smith BD, Morgan RL, Beckett GA, et al; Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61(RR-4):1-32.

10. Rein DB, Smith BD, Wittenborn JS, et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in US primary care settings. Ann Intern Med. 2012;156:263-270.

11. Volk ML. Antiviral therapy for hepatitis C: why are so few patients being treated? J Antimicrob Chemother. 2010;65:1327-1329.

12. Godofsky E. Why should infectious disease physicians care for the hepatitis C-infected patient? Infect Dis Clin North Am. 2012;26:839-847.

13. Patel K, Friedrich-Rust M, Lurie Y. FibroSURE and FibroScan in relation to treatment response in chronic hepatitis C virus. World J Gastroenterol. 2011;17:4581-4589.

14. Poynard T, Imbert-Bismut F, Munteanu M, Ratziu V. FibroTest-FibroSURE: towards a universal biomarker of liver fibrosis? Expert Rev Mol Diagn. 2005;5:15-21.

15. Talwalkar JA, Kurtz DM, Schoenleber SJ, West CP, Montori VM. Ultrasound-based transient elastography for the detection of hepaticfibrosis: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2007;5:1214-1220.

16. Backus LI, Boothroyd DB, Phillips BR, Belperio P, Halloran J, Mole LA. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol. 2011;9:509.e.1-516.e.1.

17. Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335-1374.

18. Jacobson IM, McHutchison JG, Dusheiko G, et al; ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405-2416.

19. Poordad F, McCone J Jr, Bacon BR, et al; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-1206.

20. Asselah T, Marcellin P. Direct acting antivirals for the treatment of chronic hepatitis C: one pill a day for tomorrow. Liver Int. 2012;32 Suppl 1:88-102.

21. Elta GH. GI training: where are we headed? Am J Gastroenterol. 2011;106:395-397.

22. Koziel MJ, Peters MG. Viral hepatitis and HIV infection. N Engl J Med. 2007;356:1445-1454.

23. McGovern BH. Hepatitis C virus and the infectious disease physician: a perfect match. Clin Infect Dis. 2012;55:414-417.

24. Levine CD, Nordenson NJ. Chapter 1: getting ready for direct-acting antiviral (DAA) therapy. In: HCV Care and Guidance. eHandbook. http://lmt.projectsinknowledge.com/2037/ Accessed November 30, 2013.

25. Infectious Diseases Society of America. Hepatitis C curriculum. http://www.idsociety.org/HCV_Curriculum/ Accessed November 23, 2013.

Source

 

Rapid Hepatitis C Virus Testing: An Innovative Pilot Study for Testing and Linking High Risk Populations from a Mobile Healthcare Clinic

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

1756. Rapid Hepatitis C Virus Testing: An Innovative Pilot Study for Testing and Linking High Risk Populations from a Mobile Healthcare Clinic

Session: Poster Abstract Session: Viral Infections; Pathogenesis and Epidemiology

Saturday, October 5, 2013

Room: The Moscone Center: Poster Hall C

Posters IDSA.2013.#41989.Morano.pdf (1.4 MB)

Background: After recent release of effective HCV treatments, CDC guidelines aim to increase HCV testing and linkage to treatment for certain high-risk populations. This approach has not, however, been empirically tested using rapid HCV testing strategies.

Methods: An innovative rapid HCV testing campaign was deployed from a mobile medical clinic (MMC) in New Haven, CT using routine medical intake information. Clients could select rapid versus traditional phlebotomy testing.  Traditional testing included phlebotomy for other medical co-morbidities, including syphilis, hepatitis B, and chronic medical conditions.  Independent correlates of: 1) type of HCV testing strategy; and 2) reactive HCV antibody results were assessed. Linkage to HCV care was defined as completing one follow-up clinical visit in person with confirmatory HCV testing.

Results: All of 190 clients approached from March 2012 to March 2013 accepted HCV testing; 154 (81.1%) chose rapid HCV testing. Overall, 17 (8.9%) were HCV+, with 13 (8.4%) in the rapid and 4 (11.1%) in the traditional group.  Generally, participants were mean age 35.9 years, previously incarcerated (51.1%), had >15 lifetime sexual partners (81.6%), were US-born (84.7%), had used illicit drugs (75.3%), and previously tattooed (64.2%).  Of the 60 (31.6%) people who inject drugs (PWID), only 9 (15.0%) were within the “baby boomer” cohort.

Independent correlates of choosing rapid HCV testing over phlebotomy were non-PWID (AOR 25.0; p=0.027) and less than 15 lifetime sexual partners (marginal effect 0.17; p=0.003). Independent correlates of being HCV+ were being non-Hispanic White (AOR 15.2; p=0.002), reported sex with a known HCV+ partner (AOR 33.0; p<0.001), and increasing age (AOR 1.08; p=0.003). Among the 17 HCV+ patients, only 7 (53.8%) were within the “baby boomer” cohort, and 12 (70.6%) were successfully linked to HCV care.  

Conclusion: The majority of individuals prefer rapid HCV testing, yet higher risk individuals opted for traditional phlebotomy testing, perhaps to identify other comorbid conditions. Rapid testing, however, identified the majority of new HCV infections, using an innovative MMC model which successfully engaged individuals who might otherwise not have been tested in traditional healthcare settings. Risk-based testing thus necessarily augments the “baby boomer” HCV screening age category.

Jamie Morano, MD, MPH¹, Alexei Zelenev, PhD², Andrea Lombard, RN, BSN, MPH, CIC³, Britton Gibson, MPH², Ruthanne Marcus, MPH⁴ and Frederick Altice, MD⁵, (1)Department of Infectious Diseases, Yale University School of Medicine, Yale Clinical Research, Yale University AIDS Program, Center for Interdisciplinary Research on AIDS, New Haven, CT, (2)Yale University School of Medicine, Yale University AIDS Program, New Haven, CT, (3)Viral Hepatitis Section, Connecticut Department of Public Health, Hartford, CT, (4)Yale Clinical Research, Yale University AIDS Program, Yale School of Public Health, New Haven, CT, (5)Yale University School of Medicine, Yale School of Public Health, Director, Yale University AIDS Program, Yale Clinical and Community Research, Yale Center for Interdisciplinary Research on AIDS, New Haven, CT

Disclosures:

J. Morano, Vertex Pharmaceuticals Circle of Care Hepatitis C Grant: Grant Investigator, Research grant and Research support

A. Zelenev, None

A. Lombard, None

B. Gibson, Vertex Pharmaceuticals: Collaborator, Salary

R. Marcus, None

F. Altice, Vertex Pharmaceuticals Circle of Care Hepatitis C Grant: Investigator, Research grant and Supporting Mobile Clinic Work for HCV Testing; No Drug Support Given

Source

Transmission of Hepatitis C Virus from an Organ Donor with Undetectable Viremia by Nucleic Acid Testing

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

630. Transmission of Hepatitis C Virus from an Organ Donor with Undetectable Viremia by Nucleic Acid Testing

Session: Oral Abstract Session: Infections in Transplantations and Immunocompromised

Friday, October 4, 2013: 9:30 AM

Room: The Moscone Center: 220-226

Background: Nucleic acid testing (NAT) is used for screening hepatitis C virus (HCV) infection among solid organ donors. On March 9, 2012 two organ recipients were reported to the Centers for Disease Control and Prevention with newly diagnosed HCV infections on routine post-transplant screening. Despite active injection drug use (IDU), the donor had undetectable HCV by polymerase chain reaction (PCR) testing. A public health investigation was initiated to determine the sources of HCV transmission.

Methods: The following donor and recipient specimens were tested by RNA quantitative PCR for HCV: donor’s serum, donor splenocytes from organ recovery; and recipients’ pre-and post-transplant serum. HCV genomic sequencing and quasispecies analysis were used to measure relatedness of HCV. Medical records were reviewed and recipients were interviewed for HCV-related risk factors. Epidemiologic investigations into source of transmission included assessment of healthcare exposures. 

Results: HCV RNA was undetectable by PCR and anti-HCV was negative by enzyme immunoassay on donor serum, but HCV genotype 2b was isolated from donor splenocytes procured at organ recovery, 4 days after serum collection. HCV genotype 2b was newly isolated by PCR in the left kidney recipient (day 9 post-transplant) and the heart recipient (day 30 post-transplant); two other recipients had chronic HCV infection before transplant. Quasispecies analysis showed close relatedness between HCV strains from the left kidney and heart recipients, indicating a common source; comparison to the donor’s HCV strains is ongoing. The donor’s IDU and recent plasma transfusion were identified as HCV-related risks. Trace-back of transfused units is ongoing; no other sources have been identified.

Conclusion: We report the first known transmission of HCV infection from an organ donor with negative screening by NAT, indicating very recent donor infection. These findings highlight the importance of communicating transmission risk to recipients, despite the most sensitive available donor screening. Donor-derived transmission of HCV and standardized recipient follow-up testing should be considered in recipients of organs procured from donors with behavioral risks for blood-borne pathogens.

Anil Suryaprasad, MD¹, Susan N. Hocevar, MD², Lauren Torso, MPH³, Jan Drobeniuc, MD, PhD¹, Yury Khudyakov, PhD¹, David Pegues, MD, FIDSA, FSHEA⁴, Matthew J. Kuehnert, MD, FIDSA² and Emily Blumberg, MD, FIDSA⁵, (1)Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, (2)Division of Healthcare Quality and Promotion, Office of Blood, Organ, and Other Tissue Safety, Centers for Disease Control and Prevention, Atlanta, GA, (3)Pennsylvania Department of Health, Harrisburg, PA, (4)University of Pennsylvania Health System, Philadelphia, PA, (5)Medicine, University of Pennsylvania Health System, Philadelphia, PA

Disclosures:

A. Suryaprasad, None

S. N. Hocevar, None

L. Torso, None

J. Drobeniuc, None

Y. Khudyakov, None

D. Pegues, None

M. J. Kuehnert, None

E. Blumberg, None

Source

FDA Approves First Genotyping Test for Patients with Hepatitis C Virus

FDA NEWS RELEASE

For Immediate Release: June 20, 2013
Media Inquiries: Susan Laine 301-796-5349, susan.laine@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA approves first genotyping test for patients with hepatitis C virus

The U.S. Food and Drug Administration today approved a test that identifies the genotypeof hepatitis C virus (HCV) that apatientis carrying. The Abbott RealTime HCV Genotype II, which can differentiate genotypes 1, 1a, 1b, 2, 3, 4, and 5,using a sample of an infected patient’s blood plasma or serum, will aid health care professionals in determining the appropriate approach to treatment.   Because the various HCV genotypes respond differently to available drug therapies, knowing the type of HCV a person is infected with can result in better patient outcomes.

“Tests such as this one can help physicians gain an understanding of a patient’s HCV status,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in FDA’s Center for Devices and Radiological Health. “Along with other clinical factors, the particular type of HCV is an important consideration in aiding health care professionals in determining if and when to initiate treatment and the appropriate type of treatment.”

According to the Centers for Disease Control and Prevention, HCV is the most common chronic blood-borne infection in the United States and the leading cause of liver transplants. About 3.2 million people in the United States have a chronic HCV infection and approximately 15,000 people die from the effects of the virus each year. Seventy-five to 85 percent of people infected with HCV are not able to fight off the virus on their own and develop a chronic HCV infection that requires treatment. Untreated chronic HCV infections may lead to liver cancer, severe liver damage and liver failure.

HCV is transmitted through blood and other bodily fluids. Injection drug users who share needles are at the highest risk for HCV infection. Health care workers stuck by needles that have been used on HCV-infected patients and children born to HCV-infected mothers are also at risk.

The Abbott RealTime HCV Genotype II is approved for individuals known to be chronically infected with HCV. It is not approved for use as a diagnostic test or as a screening test for the presence of HCV genetic material in blood, blood products or tissue donors. It has not been evaluated in newborns or pediatric patients, or in patients with compromised immune systems, such as people with AIDS.

The FDA based its approval of the Abbott RealTime HCV Genotype II, in part, on the assessment of the test's accuracy in differentiating specific HCV viral genotypes compared to a validated genesequencing method.  The FDA also reviewed data from investigators demonstrating the relationship between HCV genotype and effectiveness of drug therapy.

The Abbott RealTime HCV Genotype II test is manufactured by Abbott Molecular Inc.,
in Des Plaines, Ill.

For more information:

• FDA: Medical Devices¹
• FDA: Office of In Vitro Diagnostic Device Evaluation and Safety²:
• CDC: Hepatitis C Information for Health Professionals
  ³
• Testing Recommendations for Chronic Hepatitis C Virus Infection Among Persons Born During 1945-1965⁴
• VA: National Hepatitis C Program⁵
• NIH: What I need to know about Hepatitis C (simple text)  ⁶
• NIH: Chronic Hepatitis C: Current Disease Management⁷
• NLM: Hepatitis C - Interactive Tutorial  ⁸

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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Rapid Progress and Effective Cures Usher New Era for Hepatitis C

Released:5/29/2013 4:55 PM EDT
Source Newsroom:Saint Louis University Medical Center

Adrian Di Bisceglie, M.D., chair of internal medicine and co-director of the Liver Center at Saint Louis University, urges baby boomers to learn about the risk factors for hepatitis C and talk with their physicians about screening for the virus.

Newswise — In 1989, researchers first identified the hepatitis C virus, a health threat that had been worrying doctors as they noticed patients with unexplained liver damage occurring after receiving blood transfusions. The discovery of the potentially debilitating and deadly virus sparked several decades of productive research. Researchers made unusually rapid progress, in medical research terms, and developed therapies that had success in eliminating the virus, at least in some patients. Then, in 2011, two new drugs were brought to market that changed the landscape in a dramatic way, offering a cure for many more who suffer from a chronic form of the illness.

Currently, we estimate that 4 million people in the U.S. are infected with the virus, and at least 10,000 people in this country will die from its complications each year. Symptoms of hepatitis C can be quite variable and often only develop at the most advanced stages of liver disease, years after the virus was contracted. For this reason, it is believed that roughly 60 percent of those who have the virus are unaware of it. Patients who have a chronic infection can develop inflammation of the liver, leading to fibrosis and cirrhosis, as well as other complications that may result in liver cancer and death.

While hepatitis C is sometimes compared to HIV, and, indeed both are blood-borne, the viruses behave differently. For example, hepatitis C is not frequently spread through sexual contact. It is more likely to be transmitted from a needle stick, blood transfusion or organ transplant received before 1992, recreational drug use, or from mother to infant.

(In fact, reducing hepatitis C transmission by blood donation has been a success story of its own. In the mid-1960’s, approximately one in 10 transfusions was associated with hepatitis, initially referred to as non-A, non-B hepatitis, but now known as hepatitis C. Now, thanks to an all-volunteer blood donor system, as well as questionnaires that weed out donations from those with high risk behavior, and the routine testing of donated blood for various biomarkers of hepatitis, the risk is virtually nonexistent at one in five million.)

Today, we see hepatitis C patients from all walks of life. We see captains of industry who may have contracted the virus in their youth and healthcare workers who received accidental needle sticks on the job or even young people who acquired it from their mothers at birth. Because they may only begin to show symptoms decades later, it’s often impossible to pinpoint the exact way the virus was contracted.

However, there is an inexpensive and accurate blood test for hepatitis C. Liver disease specialists advocate that those at risk ask their doctor to be tested. In particular, the CDC now recommends that all baby boomers -- those born between 1945 and 1965 -- be screened. Doctors also urge those with risk factors such as a blood transfusion prior to 1992, a history of injection drug use and abnormal liver enzymes counts be tested.

With parallel clinical trials successfully concluding in recent years, two effective new drugs, Merck’s boceprevir and Vertex’s telaprevir, were FDA approved in 2011 to treat the virus. Added to the existing treatment regimen of peginterferon and ribavirin, these new medicines can cure nearly 80 percent of those with the disease.

Though the new treatments still require the use of peginterferon, which frequently causes taxing side effects, we’ve turned a corner. The new drugs lower the average treatment time from 1 year to 6 months. More antiviral drugs against hepatitis C are in the pipeline, and their use may eventually eliminate the need for interferon altogether.

But, right now, we can tell patients with hepatitis C that treatment time is expected to be much less than a year, is far more likely to cure them, and is likely to add years to their lives. The opportunity to halt progressive liver damage is a chance to save those with the virus from debilitating fatigue, cancer and death.

Physicians now can recommend testing to patients with the knowledge that we have effective medicines to treat the virus if we find it. These new medicines are revolutionizing the care of those with hepatitis C. It’s critical that those at risk be screened so the illness can be treated.

Adrian Di Bisceglie, M.D. is chair of the department of internal medicine and co-director of the Liver Center at Saint Louis University. He also served as Liver Diseases Section Chief at the National Institutes of Health where he supervised research in viral hepatitis and was among the first to use interferon when the illness simply was known as non-A, non-B hepatitis. Throughout the search for a cure for hepatitis C, Di Bisceglie led numerous research studies and recently co-authored a New England Journal of Medicine paper on the successful telaprevir clinical trial.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.

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Only half of those with HCV complete confirmatory RNA test

May 7, 2013

Nearly 50% of people who have ever had hepatitis C virus have received a follow-up RNA test to confirm whether they are still infected, according to new research by the CDC.

“The majority of people who have HCV do not even know they have HCV,” John Ward, MD, director of the CDC’s Division of Viral Hepatitis, said during a media briefing. “People must complete the two-step testing process to accurately identify current infection, so that they can receive the treatment they need. These data give us an idea of the gap between those who are and those who are not receiving the second follow-up test, showing us that we have a substantial challenge in front of us.”

The researchers evaluated surveillance data from eight sites in the United States, obtained from 2005 to 2011. They compared the number of people with a positive HCV antibody test with the number of people with a positive HCV RNA test. They examined the numbers by birth cohort, surveillance site and number of deaths. They also calculated the rates of newly reported HCV infection in 2011.

There were 217,755 people with newly reported HCV, and among those, 107,209 (49.2%) only had a positive antibody test and 110,546 (50.8%) had a positive RNA test. In both groups, people born from 1945 to 1965 comprised most new infections. Across all of the sites, the rate of persons with newly reported HCV infection was 84.7 per 100,000 population.

“HCV affects about 3 million Americans, most of whom are baby boomers,” CDC Director Thomas Frieden, MD, MPH, said during the media briefing. “The bottom line is that if you were born from 1945 to 1965, get tested, and if that test is positive, have follow-up testing. You may not remember everything that happened in the ’60s and ’70s, but your liver does.”

According to Frieden, about half of the people infected with HCV will go on to have serious liver problems and about one-third may die of complications from their infections. HCV also is the leading cause of liver cancer, which is the fastest growing cause of cancer-related death in the United States, he said. If baby boomers are tested and receive care, about 120,000 deaths can be prevented.

The CDC recommends that testing for HCV begins with a rapid or laboratory-conducted assay for HCV antibody. A reactive result should be followed up with nucleic acid testing for HCV RNA.

For more information:

CDC. MMWR. 2013;62(early release):1-5.

CDC. MMWR. 2013;62(early release):1-4.

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The Diagnosis and Treatment of Hepatitis C: A Technical Landscape

Opportunities to Revolutionise Care in Developing Countries

This report provides an overview on the current state of play and a framework for action with regards to hepatitis C diagnostics and treatment in resource-poor settings.

SUMMARY AND STATEMENT OF PRIORITY

Hepatitis C (HCV) has been a silent killer among people living in low- and middle-income countries. Factors including lack of epidemiologic data, poorly tolerated treatment with low success rates, and cost and complexity of care have all contributed to a vicious cycle of neglect that has allowed a growing epidemic of HCV to blossom unchecked.

But recent advances in both diagnosis and treatment, as well as new data on prevalence in low- and middle-income countries, provides an unprecedented opportunity to take the lead in turning back the growing tide of HCV and dramatically improve the wellbeing of people infected with HCV. New all-oral regimens offer the potential of being robust, well-tolerated and pan-genotypic.

Thus, not only improving cure rates, but also simplifying diagnosis and management requirements. Advances in and scale up of molecular testing in low-resource environments facilitates diagnosis and monitoring of HCV.

Taken together, these new tools open the door to managing this deadly coinfection in low- and middle-income countries. The simplified package of care may also enable decentralization of diagnosis and treatment as well as pave the way for eventual task-shifting to less specialized cadres of health workers. However, several key interventions are required in order to spark this revolution in HCV care:

• Proactive normative guidelines at the WHO and at country level are needed
• Regular screening of patients at high risk for HCV, including those infected with HIV, is critical
• Access to appropriate diagnostics, including molecular tests, is of utmost importance and can be facilitated by utilizing the same platforms currently being rolled out for HIV
• Prices of both interferon-based therapy as well as new all-oral therapy must be appropriate to facilitate scale up in low- and middle-income countries, and biosimilar and generic competition is required in order to reach a fair price.
• Access to new oral therapies depends not only on price but also on registering of these new medications in key countries, as well as the WHO or other normative bodies signaling their importance by inclusion in the model Essential Medicines List.

There is no time like the present to rapidly address this hidden and ignored epidemic. The benefits of new tools and data will not be realised without key market interventions as well as prioritisation of this disease at the WHO and at country level. But if the choice is made to invest now in the tools needed to fight HCV in low- and middle-income countries, the potential benefits are vast.

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POSTER PRESENTATION OF THIS WORK FROM EASL

REPORT AS PDF IN ENGLISH

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Rapid Tests Accurate in First-Line HCV Screening

^{Courtesy US. Dept of Veterans Affairs}

By: JENNIE SMITH, Family Practice News Digital Network

FROM ANNALS OF INTERNAL MEDICINE

Vitals

Major Finding: Blood-based point-of-care tests for hepatitis C virus have the highest sensitivity for screening at 98.9%, with specificity ranging from 99.5% for whole blood and 99.7% for serum or plasma.

Data Source: A meta-analysis of 18 studies that evaluated the accuracy of one or more tests.

Disclosures: Ms. Shivkumar and colleagues’ study was supported by grants from the Canadian Institutes of Health Research. None of the authors declared conflicts of interest.

Rapid diagnostic and point-of-care tests for hepatitis C virus are accurate enough to be used in first-line HCV screening worldwide, according to results from the first systematic review of evidence on such tests.

Blood-based point-of-care tests (POCTs) had better sensitivity and specificity overall than did blood-based rapid diagnostic tests (RDTs), Sushmita Shivkumar of McGill University, Montreal, Quebec, and her colleagues reported Oct. 15 in Annals of Internal Medicine.

POCTs do not require sample processing or refrigeration, and have a shelf life of 6 months or more. Rapid diagnostic tests, or RDTs, require refrigeration and sample processing. Manufactured by a variety of firms under various marketing names, all the tests can detect HCV infection in under 30 minutes, with many taking less than 5 minutes, according to the investigators, who conducted a meta-analysis of 18 studies evaluating the accuracy of one or more RDT or POCT, compared with standard assays (Ann. Intern. Med. 2012;157:558-566).

Ms. Shivkumar and her colleagues found blood-based POCTs (using serum, plasma, or whole blood) to be the most accurate of the tests evaluated in the included studies, showing 98.9% sensitivity with a 95% confidence interval [CI] of 94.5% to 99.8% for whole blood and 96.8% to 99.6% for serum or plasma). RDTs of serum or plasma had 98.4% sensitivity (95% CI 88.9% to 99.8%). Specificity was highest in POCTs of serum or plasma at 99.7% (95% CI, 99.3% to 99.9%), followed by POCTs of whole blood at 99.5% (95% CI, 97.5% to 99.9%), RDTs of serum or plasma at 98.6% (95% CI, 94.9% to 99.6%). POCTs for oral fluids had a sensitivity of 97.1% (95% CI, 94.7% to 98.4%) and specificity of 98.2% (95% CI, 92.2% to 99.6%).

POCTs and RDTs cannot distinguish between acute and chronic HCV infections, which is one of the reasons that public health organizations continue to favor conventional assays. The Food and Drug Administration currently approves the use of a single POCT for HCV, and for use only in nontraditional settings; in the United Kingdom and Canada such tests have not yet been approved.

However, by being fast, accurate, and cheaper than conventional tests, the rapid diagnostic and point-of-care tests offer "great potential for expanded first-line screening for hepatitis C infection and demonstrate the utility of blood-based singleton POCTs and of multiplex POCTs designed to provide integrated HIV and HCV screening of at-risk populations," Ms. Shivkumar and her associates wrote in their analysis. "Their rapid turnaround time limits loss to follow-up and facilitates early linkages."

The authors also concluded that their findings showed that the rapid and point-of-care tests could play a "substantial role" in expanded global screening initiatives for HCV.

The blood-based POCTs, besides being the most accurate, have the advantage of not requiring refrigeration, the investigators wrote. This feature is key in developing countries in Africa and Asia, where prevalence of HCV infection is highest.

Ms. Shivkumar and her colleagues noted several weaknesses in their meta-analysis, mostly related to the quality of studies included. Only three of the studies they evaluated were blinded, while four received industry funding; the conventional assays used as reference varied in the studies, and HCV genotype information was not collected in most.

The study was supported by grants from the Canadian Institutes of Health Research. None of the authors declared conflicts of interest.

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Tests Can Get More Into Treatment

Chronic hepatitis C virus (HCV) infection is a common worldwide problem. It is estimated that 170 million people are afflicted. Unfortunately, the majority of infected people remain undiagnosed. In many parts of the world, patients do not have access to medical personnel or diagnostic testing so that the diagnosis of HCV can be made. For patients that do have access, standard testing for HCV is cumbersome and expensive, adding to the diagnostic burden and diminishing the opportunity for diagnosis. Even in the United States, it is estimated that the majority of people infected with HCV have not been diagnosed. These factors have provided the impetus to develop less cumbersome and inexpensive tests for HCV, with the hope that they could be implemented throughout the world to increase the number of patients diagnosed with HCV.

Although there have been numerous studies examining individual diagnostic tests for HCV, there has not been an exhaustive review of both rapid and point-of-care screening tests for HCV. Ms. Shivkumar and her associates performed a literature review and meta-analysis of 18 studies worldwide that use the tests to screen for HCV in adults. They assessed the studies for diagnostic accuracy variables including sensitivity, specificity, likelihood rates (LRs) and diagnostic odds ratios (DORs) for available rapid and point-of-care diagnostic tests.

The assessment indicates that point-of-care tests of blood (serum, plasma, or whole blood) have the highest accuracy, followed by rapid diagnostic tests of serum or plasma and then by point-of-care diagnostic tests of oral fluids. However, all tests showed excellent sensitivity, specificity, likelihood rates and diagnostic odds ratios.

Strategies to improve the identification of patients infected with HCV are changing. In fact, the Centers for Disease Control and Prevention recently updated screening guidelines, recommending that screening change from ineffective risk-factor based screening to age-based screening. Testing strategies are also a source of potential improvement. This comprehensive global review suggests that rapid diagnostic and point-of-care tests are useful as initial screening tests for HCV. Although potential biases inherent in retrospective meta-analysis reviews are discussed, the quality of the analysis is excellent and the conclusions are valid.

These diagnostic test results are available rapidly in the field, and thus are available at the point of care. The tests are also relatively inexpensive and are easy to perform. With more effective therapies for HCV in development, broadening the ability to diagnose HCV worldwide is increasingly important. Integration of these tests into the diagnostic algorithm for HCV offers a more effective screening strategy with subsequent diagnosis of more people infected with HCV worldwide.

Dr. Steven L. Flamm is a professor of gastroenterology, hepatology, and surgery at Northwestern University, Chicago. He has no disclosures.

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New Hepatitis C Assay from Roche Provides Accurate and Rapid Results

10 Apr 2012

Due to the high rate of asymptomatic infections, clinical diagnosis of hepatitis C is difficult and screening assays are of major importance. An estimated 216,000 individuals are chronically infected with hepatitis C (HCV) in the UK, and HCV-related end stage liver disease and mortality continue to increase.

The new Roche Elecsys^® anti-HCV II assay is used to demonstrate the presence of antibodies against HCV during acute and chronic stages of disease, and after a passed infection. The assay provides 100% clinical sensitivity for all known genotypes, leading to early detection of infection, and patient-oriented decision making.

With high specificity in blood donors (99.84%) and samples from clinical routine, pregnant women and dialysis patients, use of the Elecsys anti-HCV II assay increases laboratory testing efficiencies. To optimize workflows and provide operational cost savings, the ready-to-use liquid reagents have a long onboard stability of 31 days on all Roche immunoassay platforms.

The new assay complements the Roche serology assay menu that includes assays for Hepatitis A, Hepatitis B, Hepatitis C, HIV, TORCH, Herpes, Syphilis and other infectious diseases.

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Hepatitis C assay important in patient diagnosis

The Roche Elecsys anti-HCV II assay provides 100% clinical sensitivity for all known genotypes

Edited by the Laboratorytalk editorial team Apr 6, 2012

Roche has extended its serology panel to include a new generation Elecsys anti-HCV II

With an estimated 216,000 individuals chronically infected in the UK (England 161,000, Northern Ireland 4,000, Scotland 39,000, Wales 12,000), hepatitis C (HCV) remains a major public health problem; and HCV-related end stage liver disease and mortality continue to increase1

The Health Protection Agency states that it is necessary to sustain and enhance efforts to raise awareness, prevent new infections, increase diagnosis, and treat more individuals with infection.

The new Roche Elecsys anti-HCV II assay can play an effective part in this strategy, as it is used to demonstrate the presence of antibodies against HCV during acute and chronic stages of disease, and after a passed infection.

Due to the high rate of asymptomatic infections, clinical diagnosis of hepatitis C is difficult and screening assays are of major importance.

The Roche Elecsys anti-HCV II assay provides 100% clinical sensitivity for all known genotypes, leading to early detection of infection and patient-oriented decision making.

With high specificity in blood donors (99.84%) and samples from clinical routine, pregnant women and dialysis patients, use of the Elecsys anti-HCV II assay increases laboratory testing efficiencies.

To optimise workflows and provide operational cost savings, the ready-to-use liquid reagents have a long onboard stability of 31 days on all Roche immunoassay platforms.

The new assay complements the Roche serology assay menu that includes assays for Hepatitis A, Hepatitis B, Hepatitis C, HIV, TORCH, Herpes, Syphilis and other infectious diseases.

Source

‘Faster, cheaper’ hepatitis C test designed

14 March 2012

CAIRO — The American University in Cairo said Wednesday that a team of its researchers has designed a faster and cheaper test for all types of hepatitis C, which it says affects about 10 million Egyptians.

The development “reduces the two-step testing proccet carried out over a number of days to a one-step process that takes less than an hour... at a fraction of the cost of traditional diagnostic protocols,” the university said.

The liquid chemistry test can diagnose hepatitis C using gold nanoparticles, it said.

“Our test is sensitive and inexpensive, and it does not need sophisticated equipment,” said Hassan Azzazy, professor of chemistry and head of the research team.

“Detecting HCV during the first six months raises the recovery rate to 90 percent. Little is done on the national level to combat the alarming prevalence of hepatitis C in Egypt,” said Azzazy.

The AUC said Egypt has about 10 million people who suffer from the hepatitis C virus (HCV), with the blood-borne pathogen infecting almost 500,000 in the country each year.

Worldwide, around 170 million people are estimated to be living with the chronic disease caused by the virus.

Unlike hepatitis A or B, most people infected with HCV cannot shake off the virus on their own because, when under attack by the immune system, it morphs into stronger variants.

The World Health Organisation estimates that three to four million people are newly infected with HCV each year.

The WHO says Egypt has one of the highest rates of hepatitis C prevalence in the world, putting the rate of infection in the country at 22 percent.

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Roche improves cutting-edge portfolio for early hepatitis C diagnosis and targeted treatment

Rotkreuz, 06 March 2012

Elecsys® anti-HCV II immunoassay from Roche receives CE mark

Roche now offers a fully updated state-of-the-art portfolio for the early detection of hepatitis C virus (HCV) infection and personalized disease management. The improved diagnostics and patient monitoring solution provides an one-stop shop for HCV testing with unprecedented performance in early infection and ease of use, allowing clinicians to work efficiently and to suit individual patient treatment.¹

Early detection of HCV infection is vital in order to provide consolidated care of acute and chronic infection, and adequate treatment of drug response monitoring are crucial to overall therapy success. Patients undergoing a peginterferon alfa-2a and ribavirin therapy can be monitored precisely by real-time PCR measurement.

With the novel Elecsys anti-HCV II immunoassay on cobas® e modules Health Care Professionals get a cutting-edge tool for the early qualitative detection of antibodies against HCV. The updated assay with CE mark approval delivers enhanced convenience, specificity, increased reliability and consistency for improved efficiency in screening patients and blood donors.¹

Following the identification of HCV antibodies, testing for HCV RNA, which is a crucial marker in the management of hepatitis C, confirms the infection and aids clinicians in predicting treatment response. In December 2011, Roche also received the CE mark for its HCV RNA qualitative and quantitative tests, which offer sensitive detection of HCV RNA and viral load measurement for predicting drug response on the COBAS® AmpliPrep/COBAS® TaqMan® fully automated platform.

As Personalized Healthcare has already begun to add true medical value for health professionals and patients, Roche’s novel portfolio underlines the clear shift from an ‘equal shares for all’ principle toward a target oriented and response-guided therapy approach. Out now, the updated portfolio of HCV testing and monitoring from Roche delivers a convenient set of tools to laboratories and clinicians to improve patient care.

About hepatitis C

World Health Organization figures show that around 200 million people globally are infected with HCV, which is particularly concentrated in the blood. Around 170 million people are chronic carriers of the virus, which can lead to cirrhosis, liver failure, and hepatocellular carcinoma.² Identifying HCV infection is difficult because there are often no symptoms. Most cases go undetected and there is currently no vaccine to prevent infection. Many countries are currently unable to screen blood donations for infections such as hepatitis C.³

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References

1)Esteban Juan et al (2012). Elecsys anti-HCV II: a sensitive and specific assay for diagnosing hepatitis C virus (HCV) infection. In: Hepatology, Vol. 6, N° 1; Zitzer Heike et al (2011). Clinically Relevant HCV RNA Viral Load Results Using a Sensitive, Quantitative Assay. 7th European Meeting on Molecular Diagnostics, October 12-14, 2011, Scheveningen, the Netherlands
2)World Health Organization. Hepatitis C. Fact sheet N°164. Retrieved from http://www.who.int/mediacentre/factsheets/fs164/en/ on February 19, 2012.
3)World Health Organization. Blood Safety and Availability. Fact sheet N°279. Retrieved from http://www.who.int/mediacentre/factsheets/fs279/en/index.html on February 19, 2012.

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