HCV Guideline Committee, July 2017
This guideline on treatment of chronic hepatitis C virus (HCV) infection was developed by the New York State (NYS) Department of Health (DOH) AIDS Institute (AI) to guide primary care providers and other practitioners in NYS in treating patients with chronic HCV infection. The guideline aims to achieve the following goals:
- Increase the number of NYS residents with chronic HCV infection treated for and cured of HCV.
- Increase compliance with the 2014 NYS public health law that requires HCV antibody screening be offered to every individual born between 1945 and 1965 who receives healthcare services from a physician, physician assistant, or nurse practitioner in a primary care or inpatient hospital setting.
- Reduce the growing burden of morbidity and mortality associated with chronic HCV infection.
- Integrate current evidence-based clinical recommendations into the HCV-related implementation strategies of the Ending the Epidemic (ETE) Initiative, which seeks to end the AIDS epidemic in NYS by the end of 2020.
The NYSDOH AI is publishing these guidelines at a critical time: 1) new treatments are available that can cure chronic HCV infection; 2) the burden of HCV disease is increasing in NYS [CDC 2016]; and 3) primary care providers and other clinical care practitioners in NYS are playing an essential role in screening for and diagnosing chronic HCV infection and in providing state-of-the-art therapy for their patients.
New Standard of Care for Treatment of Chronic HCV Infection
The availability of safe and effective regimens of oral direct-acting antivirals (DAAs) has revolutionized HCV care. New DAA agents and new combinations of agents continue to be tested and approved, and these efficacious combinations have replaced earlier treatments as the standard of care for curing chronic HCV infection. The DAA regimens make cure possible for many patients, but these patients must first be identified, engaged in care, offered appropriate screening for status of their HCV infection/disease, and have access to treatment.
The goal of HCV therapy is a sustained virologic response (SVR), which is defined as the absence of detectable HCV RNA at least 12 weeks after completion of therapy. An SVR is the equivalent of cure. DAA regimens have been associated with an SVR rate of more than 90% and have excellent tolerability in both treatment-naive and treatment-experienced patients with and without cirrhosis [Falade-Nwulia et al. 2017].
Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, et al. Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review. Ann Intern Med 2017;166(9):637-48. [PMID: 28319996]
Burden of HCV Disease
HCV Guideline Committee, updated February 2019
First isolated in 1989, HCV is the most common chronic blood-borne infection in the United States [Chen and Morgan 2006; Armstrong, et al. 2006], and research suggests that more than 50% of persons with HCV infection are unaware of their infection status [Denniston et al. 2012]. Injection drug use is associated with the highest risk of contracting HCV [Alter 1999, 2007]. Other key routes of HCV transmission include receipt of infected blood or organs (before 1992) or blood products (before 1987), mother-to-child transmission (also known as vertical transmission), sexual transmission, and needle sticks/exposure in healthcare settings [CDC 1998]. According to National Health and Nutrition Examination Study (NHANES) data, among patients participating from 2001 to 2008, the prevalence of HCV infection in persons aged >20 years was 1.3% in the United States. After adjusting for populations not sampled in the NHANES surveys, such as the incarcerated and homeless, the researchers estimated that 3.5 million people were living with chronic HCV infection in the United States [CDC 2013; Edlin et al. 2015]. Approximately 75% of reported cases were among persons born between 1945 and 1965 [Armstrong et al. 2006; Denniston et al. 2012; CDC 2013].
The Centers for Disease Control and Prevention (CDC) reported 162,863 cases of chronic HCV infection (past or present) nationwide in 2015 [Adams et al. 2016]. The number of reported cases in New York State (excluding New York City) and New York City for 2017 are provided in Box 1.
|Box 1: Acute and Chronic HCV Infection Cases* Reported in New York State and New York City|
|New York State** [NYSDOH 2018]||New York City [NYC DOHMH 2018]|
*Cases meeting the CDC case definition for acute or chronic (NYS) or chronic (NYC), confirmed or probable cases of HCV. There may be duplication of individuals both within and between the NYS and NYC HCV surveillance systems, and the total cases reported in Box 1 should not be interpreted as numbers of unique individuals reported with HCV.
Ensuring access to effective DAA treatment for all individuals with chronic HCV and curing chronic HCV infection in as many as 90% of patients will prevent substantial morbidity and mortality. Approximately 25% to 30% of persons with untreated chronic HCV infection will advance to cirrhosis within 20 to 30 years, with progression occurring more quickly in men, in patients who use alcohol, in those who acquire HCV infection after age 40, and in patients with HIV/HCV coinfection [Klevens et al. 2015; Younossi et al. 2015]. Of those with cirrhosis, >25% will develop end-stage liver disease or hepatocellular carcinoma (HCC), resulting in death if a liver transplant is not received [Klevens et al. 2012].
Chronic HCV infection drives the development of HCC by inducing fibrosis and cirrhosis [El-Serag 2012]. From 1999 through 2013, deaths from primary liver cancer in the United States increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer [Ryerson et al. 2016]. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Population modeling performed in 2011 posited that if new antiviral regimens consistently resulted in an 80% response rate, and if 50% of all HCV patients were treated, then, within 10 years, there would be a 15% reduction in cases of cirrhosis, a 30% reduction in cases of HCC, and 34% fewer deaths from liver disease, indicating the substantial effects that treatment would have in reducing liver disease morbidity [Rosen 2011].
In New York State (including New York City), the mortality rate associated with HCV increased from 4.0 per 100,000 population in 2001 to 5.5 per 100,000 population in 2015 [CDC 2016]. The HCV-related mortality rate in New York State surpassed the HIV-related mortality rate in 2012, indicating the severity of disease burden and the urgency for wider treatment availability.
Adams DA, Thomas KR, Jajosky RA, et al. Summary of Notifiable Infectious Diseases and Conditions – United States, 2014. MMWR Morb Mortal Wkly Rep 2016;63(54):1-152. [PMID: 27736829]
Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol 2007;13(17):2436-41. [PMID: 17552026]
Alter MJ. Hepatitis C virus infection in the United States. J Hepatol 1999;31 Suppl 1:88-91. [PMID: 10622567]
Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;144(10):705-14. [PMID: 16702586]
CDC. Multiple Cause of Death 1999-2015 on CDC WONDER Online Database. 2016 Dec. https://wonder.cdc.gov/mcd-icd10.html [accessed 2017 Dec 18]
CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR Recomm Rep 1998;47(Rr-19):1-39. [PMID: 9790221]
CDC. Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep 2013;62(18):362-5. [PMID: 23657112]
Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci 2006;3(2):47-52. [PMID: 16614742]
Denniston MM, Klevens RM, McQuillan GM, et al. Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001-2008. Hepatology 2012;55(6):1652-61. [PMID: 22213025]
Edlin BR, Eckhardt BJ, Shu MA, et al. Toward a more accurate estimate of the prevalence of hepatitis C in the United States. Hepatology 2015;62(5):1353-63. [PMID: 26171595]
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012;142(6):1264-73.e1. [PMID: 22537432]
Klevens M, Huang X, Yeo AE, et al. The Burden of Liver Disease Among Persons With Hepatitis C in the United States. CROI; 2015 Feb 23-25; Seattle, WA. http://www.croiconference.org/sessions/burden-liver-disease-among-persons-hepatitis-c-united-states
Klevens RM, Hu DJ, Jiles R, et al. Evolving epidemiology of hepatitis C virus in the United States. Clin Infect Dis 2012;55 Suppl 1:S3-9. [PMID: 22715211]
New York City Department of Health and Mental Hygiene (NYC DOHMH). September 2018.
New York State Department of Health (NYSDOH). Communicable Disease Electronic Surveillance System. 2018 Aug 2.
Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med 2011;364(25):2429-38. [PMID: 21696309]
Ryerson AB, Eheman CR, Altekruse SF, et al. Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer 2016;122(9):1312-37. [PMID: 26959385]
Younossi ZM, Otgonsuren M, Henry L, et al. Inpatient resource utilization, disease severity, mortality and insurance coverage for patients hospitalized for hepatitis C virus in the United States. J Viral Hepat 2015;22(2):137-45. [PMID: 24813350]
Role of NYS Primary Care Providers in Treatment of HCV
HCV Guideline Committee, updated July 2018
Primary care providers in New York State (NYS) are assuming a major role in the screening, diagnosis, treatment, and monitoring of patients with chronic HCV infection. When prescribing HCV antiviral therapy, clinical experience and appropriate continuing education are both important to ensure that HCV medications are prescribed safely and correctly and that all patients receive the highest quality of care.
This guideline covers screening, diagnosis, pretreatment assessment, treatment, and post-treatment monitoring for primary care providers treating patients with chronic HCV infection. In terms of HCV treatment, the guideline includes recommendations for initial HCV treatment in patients with and without cirrhosis and for retreatment in patients with and without cirrhosis who have failed previous DAA and non-DAA regimens.
As stated in these recommendations, care providers new to HCV treatment should consult with a liver disease specialist when treating patients with chronic HCV infection and any of the following conditions:
- Compensated and decompensated cirrhosis.
- Concurrent hepatobiliary conditions.
- Extrahepatic manifestations of HCV, including renal, dermatologic, and rheumatologic manifestations.
- Significant renal impairment (creatinine clearance <30 mL/min) and/or undergoing hemodialysis.
- Active hepatitis B (HBV) infection, defined as HBV surface antigen–positive and detectable HBV DNA.
- Retreatment after any DAA treatment failure.
Care providers should refer patients with chronic HCV infection and decompensated liver disease and patients who are pre- or post-transplant to a liver disease specialist. Depending on their level of experience and expertise, care providers may also want to refer patients who have coexisting conditions (including HIV) that require treatment with complex drug regimens to a liver disease specialist.
Development of this Guideline
HCV Guideline Committee, July 2017
This guideline was developed by the New York State (NYS) Department of Health (DOH) AIDS Institute (AI) Clinical Guidelines Program, which is a collaborative effort between the NYSDOH AI Office of the Medical Director and the Johns Hopkins University School of Medicine, Division of Infectious Diseases.
Established in 1986, the goal of the Clinical Guidelines Program is to develop and disseminate evidence-based, state-of-the-art clinical practice guidelines to improve the quality of care provided to people with HIV, HCV, and STIs and to improve drug user health and LGBT health throughout the State of New York. NYSDOH AI guidelines are developed by committees of clinical experts through a consensus-driven process.
The NYSDOH AI Hepatitis C Virus Infection Guideline Committee was charged with developing evidence-based clinical recommendations for primary care providers in NYS who treat patients with chronic HCV infection. The resulting recommendations are based on an extensive review of the medical literature and reflect consensus among this panel of HCV experts. Each recommendation is rated for strength and for quality of the evidence (see below). If recommendations are based on expert opinion, the rationale for the opinion is included. See About this Guideline for a full description of the development process, including evidence collection and recommendation development.
|AIDS Institute HIV Clinical Guidelines Program Recommendations Rating Scheme|
|Strength of Recommendation||Quality of Supporting Evidence|
|A = Strong||1 = At least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints|
|B = Moderate||2 = One or more well-designed, nonrandomized trial or observational cohort study with long-term clinical outcomes|
|C = Optional||3 = Expert opinion|
Related Materials and Resources
HCV Guideline 1/4-fold Pocket Guides:
Clinical Training from CEI
HCV Guideline Slide Set: Are you giving a talk on HCV? Share the NYSDOH AIDS Institute HCV guideline with your audience. The slide set presents information on the entire guideline (45 slides), but individual slides can be copied and pasted into your presentation. The content of individual slides cannot be changed.