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Treatment of Hepatitis C Virus Infection: Is It Time for the Internist to Take the Reins?Treatment of Hepatitis C Virus Infection

Shyam Kottilil, MD, PhD; Mary Wright, MD, MPH; Michael A. Polis, MD, MPH; and Henry Masur, MD
[+] Article, Author, and Disclosure Information

From the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, and National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, Maryland.

Financial Support: By the intramural program of the National Institutes of Health Clinical Center and National Institute of Allergy and Infectious Diseases.

Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0741.

Corresponding Author: Henry Masur, MD, Critical Care Medicine Department, National Institutes of Health Clinical Center, 10 Center Drive, Room 2C145, Bethesda, MD 20892.

Current Author Addresses: Dr. Kottilil: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 10/11N204, Bethesda, MD 20892.

Dr. Wright: Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8 West Drive, MSC 2665, Building 15B1, Room 0204, Bethesda, MD 20892.

Dr. Polis: Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 1118, 6700B Rockledge Drive, Bethesda, MD 20892.

Dr. Masur: Critical Care Medicine Department, National Institutes of Health Clinical Center, 10 Center Drive, Room 2C145, Bethesda, MD 20892.

Author Contributions: Conception and design: S. Kottilil, M.A. Polis, H. Masur.

Analysis and interpretation of the data: S. Kottilil, M.A. Polis, H. Masur.

Drafting of the article: S. Kottilil, M. Wright, M.A. Polis, H. Masur.

Critical revision of the article for important intellectual content: S. Kottilil, M. Wright, M.A. Polis, H. Masur.

Final approval of the article: S. Kottilil, M.A. Polis, H. Masur.

Provision of study materials or patients: S. Kottilil.

Statistical expertise: S. Kottilil.

Obtaining of funding: S. Kottilil, H. Masur.

Administrative, technical, or logistic support: S. Kottilil, H. Masur.

Collection and assembly of data: S. Kottilil.

Ann Intern Med. 2014;161(6):443-444. doi:10.7326/M14-0741
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Treatment of hepatitis C virus infection has entered a new era in which the cure of individual patients is eminently feasible and community-wide eradication is conceivable. This commentary evaluates the role of internists in initiating and managing treatment of this condition.

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Yet another issue for which internists will be held accountable?
Posted on September 17, 2014
Michael P. Carson, MD
Jersey Shore University Medical Center
Conflict of Interest: None Declared
This comment is to generate thought, not simply be contrarian. I have my clinical niche and certainly encourage other internists to aggressively pursue their interests including HCV. I enjoy the opportunities to quarterback for complex cases. My concern, to use one example, is that private insurers, Medicare, ACO and PCMH initiatives expect internists to act as data clerks for every aspect of care for patients with a diabetes code in the EMR. We're faulted when the patient has an endocrinologist who already addresses the many DM checkboxes but doesn't use my EMR, and are penalized by the NCQA certification program when I don't allocate staff to call the ophthalmologist who didn't bother to send me a letter documenting the eye exam. An initiative such as "the time is now" for us to treat HCV must be accompanied by a plan for a comprehensive system based infrastructure supported by the companies claiming to be responsible for patient well being, not just a way for us to get more patients into our office slots and increase the preapproval paperwork burden for our staff. If this issue will overwhelm SUBspecialists, then practicing internists should be supported as we are expected to handle many more issues during an office visit.
HCV exuberance. Rational or irrational?
Posted on September 19, 2014
D.Venes, MD
Staff Physician, Pelican Bay State Prison
Conflict of Interest: None Declared
The authors state, "For the first time since the identification of hepatitis C virus (HCV) ... communitywide eradication of HCV infection seems possible." However, direct-acting antivirals (DAAs) have never been shown to prevent either cirrhosis of the liver nor hepatocellular carcinoma. Even if DAAs are effective in preventing these crucial complications of chronic hepatitis C, the prevalence of both cirrhosis and liver cancer is already rising, and is likely to rise continuously for decades to come. Internists may assume some responsibility for antiviral administration and for monitoring of drug side effects, but the potentially lethal complications of chronic hepatitis C will likely need specialty input for the remainder of our professional lives.
Posted on October 15, 2014
Neeral L. Shah, MD, Virginia Kelly, RN, Stephen H. Caldwell, MD
University of Virginia
Conflict of Interest: None Declared
The opinion expressed by Kottilil [1] raises issues regarding the future of Hepatitis C (HCV) therapy. As they cite, over 230 million persons are likely infected with HCV. The number of people found to be infected with HCV will grow with the updated recommendations from the U.S Preventative Services Task Force.[2] Treatment regimens have traditionally been wrought with side effects and dose adjustments. In the age of interferon free regimens, patients tolerate the therapy without many complications.
We agree with the authors’ opinion that internists, subspecialists, and public health authorities will need to work in cooperation to treat this population. While some patients may benefit from a Hepatologist referral, we also agree that identification on the front line to properly triage these people will be essential to success.. [3]
Hepatologists have been the primary providers in treating HCV up to this point in time. The American Association for the Study of Liver Diseases (AASLD) has partnered with the Infectious Disease Society of America (IDSA) to develop a website for up to date guidelines to direct HCV therapy (hcvguidelines.org) as therapy is rapidly evolving. Further, specialty societies are creating educational materials geared towards the first line providers to support efforts in HCV eradication. Internists are an integral part of the identification of HCV patients, and coordinated efforts with the specialists that have a long history of treating this disease will be essential. While it might be the right time for internists to take the reins, we think it is important that they have the right specialist alongside to help guide these treatment plans. Importantly, guidance on expanding the pool of care providers should derive from those experienced in surmounting the hurdles of providing such care and dealing with both mild chronic and advanced liver disease and potentially fatal liver disease.
1. Kottilil, S., et al., Treatment of hepatitis C virus infection: is it time for the internist to take the reins? Ann Intern Med, 2014. 161(6): p. 443-4.
2. Moyer, V.A. and U.S.P.S.T. Force, Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med, 2013. 159(5): p. 349-57.
3. Mitruka, K., et al., Expanding primary care capacity to treat hepatitis C virus infection through an evidence-based care model--Arizona and Utah, 2012-2014. MMWR Morb Mortal Wkly Rep, 2014. 63(18): p. 393-8.

Authors' Response to Comments
Posted on November 12, 2014
Shyam Kottilil MD PhD (1), Mary Wright MD MPH (2), Michael A. Polis MD MPH (2)
(1)Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health; (2) Collaborative Clinical Research Branch, Division of Clinical Research, Nati
Conflict of Interest: None Declared
To the Editor:

Dr. Venes correctly states that “…direct acting agents (DAAs) have never been shown to prevent either cirrhosis or hepatocellular carcinoma…” Indeed, the long term effects of new drugs on the complications of Hepatitis C infection merit careful study to be certain that their apparent benefits are fully realized. The experience with virologic cure following interferon based therapies suggests that cure of HCV infection using DAAs will plausibly prevent such sequelae (1,2).

Dr. Venes also observes that, even if DAAs prevent complications, we will have to manage many patients in the current cohort of HCV-infected individuals who either do not access care, or who already have advanced liver disease. This is a correct observation, but an observation which underscores the need to treat as many patients with HCV infection as possible now so that we reduce progression of HCV-related liver disease to the greatest extent possible.

Drs. Shah and Caldwell and Ms. Kelly emphasize the importance of internists gaining knowledge and experience in HCV management, and collaborating with subspecialists. We wholeheartedly agree with this. Professional organizations are accelerating their efforts to have continuing medical education for providers with different experiential backgrounds and to provide guidance documents and tutorials that are up-to-date, focused, and practical. The guidance website (www.hcvguidelines.org) cited in our paper and by Dr. Shah and colleagues (and which two of us co-author) has had over 150,000 unique visitors since its inauguration January 29, 2014, and almost one million page views. Internists are highly skilled at working with subspecialists to provide excellent management for patients whose problems are beyond their expertise or scope of practice. Partnerships between primary care providers and subspecialists are vital for all aspects of medicine, including HCV management.

Dr. Carson points out with passion the plight of internists in the current era. All of us are required by payers and regulatory agencies to do more and more. The ability to support EMRs and to afford to pay staff that have the time to respond to these diverse demands is challenged by declining reimbursement. More importantly, such demands can rob us of the deep satisfaction of taking care of the whole patient. We do not mean to suggest that it is practical for every internist to become an expert in HCV …but internists can certainly identify infected patients, enhance their linkage to care, and cure a large fraction of infected patients.


1. Poynard T, McHutchison J, Manns M, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology. 2002b;122(5):1303-1313.
2. Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis c. J Hepatol. 2001;34(5):730-739.

Treatment of HCV infection by internist is like putting the cart before the horse
Posted on December 9, 2014
Shahid Habib MD, Thomas D Boyer MD
University of Arizona
Conflict of Interest: None Declared
With great interest we read the article “Treatment of Hepatitis C Virus Infection: Is It Time for the Internist to Take the Reins?”
The treatment of hepatitis C (HCV) has be left to hepatologists, gastroenterologist and to a lesser extent infectious disease physicians. The limited number of physicians treating HCV reflects the toxicity of the treatment and the understanding that the associated liver disease may require addition management. With the advent of effective and safe direct acting antiviral drugs (DAA) is it now time, as suggested by Kottilil et al. (1), that internists should become the primary providers for patients with HCV? We feel the article by Kottilil et al understated the complexity of these patients and their care should remain in the hands of the subspecialists.
The first step in treating the HCV patient is identifying the infection. Primary care physicians do a poor job of screening patients for HCV (2,3). In addition, they also do a poor job of identifying those with cirrhosis and screening for hepatocellular carcinoma (4). The authors mistakenly assume it is only patients with complicated disease who are at risk for complications. In fact it is the asymptomatic and unidentified cirrhotic who frequently presents with a large and untreatable.
The other major issue with the new treatments for HCV is cost. Some patients may require as little as 8 weeks of therapy whereas for others treatment may be as much as 48 weeks. The cost of cure may therefore vary from ~$75,000 to $400,000. Given these costs it is not surprising that some insurance companies, including medicaid, have established criteria of who and who will not be covered for treatment. To obtain approval for treatment requires significant time in collecting all of the required data and then communicating with the insurance company to obtain authorization for treatment. In practices that treat large number of HCV infected patients this process is streamlined but in a practice with a handful of HCV patients negotiating the insurance bureaucracy would prove difficult.
Kottilil et al. have underestimated the complexity of caring for and treating patients with HCV. They have focused on the infection and largely forgotten the liver. Despite the exciting development of new and nontoxic therapies, most HCV patients will be best served by referral to a subspecialist. The internist should focus on identifying these patients in their practice.
1. Shyam Kottilil, MD, PhD; Mary Wright, MD, MPH; Michael A. Polis, MD, MPH; and Henry Masur, MD. Treatment of Hepatitis C Virus Infection: Is It Time for the Internist to Take the Reins? Ann Intern Med. 2014;161(6):443-444. doi:10.7326/M14-0741
2. Jeanne M. Ferrante, MD; Dock G. Winston; Ping-Hsin Chen, PhD; Andrew N. de la Torre, MD. Family Physicians’ Knowledge and Screening of Chronic Hepatitis and Liver Cancer. Fam Med 2008;40(5):345-51.
3. Almario CV1, Vega M, Trooskin SB, Navarro VJ. Examining hepatitis C virus testing practices in primary care clinics. J Viral Hepat. 2012 Feb;19(2):e163-9. doi: 10.1111/j.1365-2893.2011.01539.x. Epub 2011 Nov 17.
4. Kanwal F1, Schnitzler MS, Bacon BR, Hoang T, Buchanan PM, Asch SM.Quality of care in patients with chronic hepatitis C virus infection: a cohort study. Ann Intern Med. 2010 Aug 17;153(4):231-9. doi: 10.7326/0003-4819-153-4-201008170-00005.
5. Wong CR1, Garcia RT, Trinh HN, Lam KD, Ha NB, Nguyen HA, Nguyen KK, Levitt BS, Nguyen MH. Adherence to screening for hepatocellular carcinoma among patients with cirrhosis or chronic hepatitis B in a community setting. Dig Dis Sci. 2009 Dec;54(12):2712-21. doi: 10.1007/s10620-009-1015-x. Epub 2009 Oct 30.
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