Should all individuals be screened for Hepatitis C?

The hepatitis C virus (HCV) is largely curable:

“In clinical trials, antiviral therapy with pegylated interferon and ribavirin (PEG-IFN
R) has resulted in a sustained viral response (SVR) (that is, cure) of HCV infection in 46% of patients infected with genotype 1 (which infects 70% and 90% of chronically infected white and African American persons in the United States, respectively) and as many as 81% of those infected with genotypes 2 or 3.”  (See these studies)

Nevertheless, approximately 4.1 million Americans are antibodypositive for hepatitis C virus (HCV), and approximately 75% of them are chronically infected.

Why do so few people get screened for HCV?  The CDC limits HCV screening largely to persons with a history of injection-drug use, hemodialysis, or elevated alanine aminotransferase levels.  Because screening is targeted and few people get tested, only 25% to 50% of patients with chronic hepatitis C are aware of their infection.

Would more widespread HCV screening be more cost effective?

This is the question a paper by Rein et al. (2012) attempts to answer.  The authors examine whether screening all adults born between 1945 and 1965 would be a cost-effective way to improve patient health.  HCV prevalence is highest for these cohorts.  The authors find that the answer to the question is ‘yes’.  Cost per case identified was $2874.  Based on historical treatment costs and expected health improvements, the authors found that that the incremental cost effectiviness ratio (ICER) was $15,700 per quality-adjusted life-year (QALY).  Adding antiviral therapy in addition to the standard pegylated interferon and ribavirin (PEG+IFN+
R) treatment had a higher ICER of $35,700.

The remainder of the post describes the methods Rein and co-authors use to make these estimates.

Methodology – Baseline Statistics

The authors use a Markov chain Monte Carlo simulation to model the prevalence of hepatitis C antibody stratified by age sex race/ethnicity, and history of injection drug use, and the natural history of chronic hepatitis. The authors modeled chronic HCV infection “…modeled chronic HCV infection based on Meta-Analysis of Histologic Data in Viral Hepatitis (METAVIR) scale units [Bedossa and Poynard]. We stratified annual disease progression by age at infection, sex, and alcohol consumption history and determined disease progression at model initiation by using historical HCV incidence data and published observations of annual progression in METAVIR units.” [see Thomas andd Seeff, Poynard, Bedossa and Opolon]

To define the model cohorts, the authors used data from the National Health and Nutrition Examination Survey (NHANES) for the year 2001 to 2006. The cohort was stratified into 40 mutually exclusive groups stratified by age, race/ethnicity, history of injection drug use, and prescription drug coverage. The authors “…further
stratified these cohorts into those with and those without antibody to HCV and divided those with antibodies into those with chronic (75%) and those with cleared (25%) infections.” [See Armstrong et al.]

Baseline mortality was determined using Census life tables.

Methodology – Treatment Scenarios

The authors examined four scenarios:

1. no screening or treatment;
2. risk-based screening, in which 18.5% (1% per year over the next 20 years) of persons unaware of their chronic infection were screened and offered PEG-IFN
   R treatment if identified;
3. birth-cohort screening in which all people born from 1945 through 1965 and unaware of their HCV antibody status were offered 1-time HCV antibody screening during their 2006 primary care visit, then were offered PEG-IFN
   R treatment if identified; and
4. an identical birth-cohort screening scenario in which patients with genotype 1 disease who initiated treatment received direct-acting antiviral (DAA) treatment in addition to standard therapy and patients with genotypes 2 and 3 received PEG-IFN
   R. Screening occurred once to identify prevalent cases.

The model also captures the likelihood people would refuse screening if offered (91%), the number of individuals who tested positive who would receive results (90%) and the share of patients with prescription drug coverage (87.6%).  Other barriers to treatments include contraindications (e.g., substance abuse, depression, uncontrolled diabetes or autoimmune disorders) or outright refusal of treatment (8.5%).  Overall, the authors assume that 40.8% of HCV positive patients would accept testing if offered.

Sustained viral response rates (SVR) were estimated to be 0.33 for genotypes 1 and 4 and 0.69 for genotypes 2/3. [See Antonucci et al., Dudley et al., and Thomson et al.].  The SVR for direct-acting antiviral (DAA) treatment plus standard therapy to 0.54 for patients with genotype 1.

Treatment costs of adding DAA to standard treatment were estimated using a report from NORC.  Prices of services were calculated based on the Medicare fee scheduel.  Additional costs include productivity losses from missed time at work. Using work estimating the QALY’s lost for people suffering from HCV, utility losses were also taken into account.

Sources (Main article)

• Rein DB, Smith BD, Wittenborn JS, Lesesne SB, Wagner LD, Roblin DW, Patel N, Ward JW, Weinbaum CM. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med. 2012 Feb 21;156(4):263-70. Epub 2011 Nov 4.

Sources (References)

• Antonucci G, Longo MA, Angeletti C, Vairo F, Oliva A, Comandini UV, Tocci G, Boumis E, Noto P, Solmone MC, Capobianchi MR, Girardi E. The effect of age on response to therapy with peginterferon alpha plus ribavirin in a cohort of patients with chronic HCV hepatitis including subjects older than 65 yr. Am J Gastroenterol. 2007 Jul;102(7):1383-91. Epub 2007 Mar 31.
• Armstrong GL, Alter MJ, McQuillan GM, Margolis HS. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology. 2000 Mar;31(3):777-82.
• Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996 Aug;24(2):289-93.
• Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM; PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004 Mar 2;140(5):346-55.
• Nainan OV, Alter MJ, Kruszon-Moran D, Gao FX, Xia G, McQuillan G, Margolis HS. Hepatitis C virus genotypes and viral concentrations in participants of a general population survey in the United States. Gastroenterology. 2006 Aug;131(2):478-84.
• Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997 Mar 22;349(9055):825-32.
• Rein DB, Wittenborn JS. The Cost-Effectiveness of Birth Cohort and Universal Hepatitis C Antibody Screening in U.S. Primary Care Settings. RTI International, September 2011.
• T Dudley, K O’Donnell, G Haydon, and D Mutimer. Disappointing results of combination therapy for HCV? Gut. 2006 September; 55(9): 1362–1363.
• Thomas DL, Seeff LB. Natural history of hepatitis C. Clin Liver Dis. 2005 Aug;9(3):383-98, vi.
• Thomson BJ, Kwong G, Ratib S, Sweeting M, Ryder SD, De Angelis D, Grieve R, Irving WL; Trent HCV Study Group. Response rates to combination therapy for chronic HCV infection in a clinical setting and derivation of probability tables for individual patient management. J Viral Hepat. 2008 Apr;15(4):271-8. Epub 2007 Dec 11.