December 11, 2013

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.


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