William F. Balistreri, MD

Disclosures

March 17, 2016

In This Article

Editor's Note: Based on presentations delivered at The Liver Meeting 2015—the 66th Annual Meeting of the American Association for the Study of Liver Diseases—this is the first of a three-part series on hepatitis C. Part 1 will review the prevalence, screening methods, and access and barriers to care. Subsequent parts will discuss treatment options and outcomes and will further clarify the nuances and limitations of currently available antiviral agents, the management of drug/drug interactions, and the emergence of resistance and its impact.

Introduction

Progress in the development, validation, and approval of an increasing variety of targeted therapeutic direct-acting antiviral (DAA) regimens for patients with chronic hepatitis C virus (HCV) infection has had a major impact on outcomes, as evidenced by research presented at The Liver Meeting 2015. The new DAA strategies, which have already obviated interferon, now have the potential to also eliminate the need for ribavirin and its attendant hematologic, teratogenic, and other side effects.

However, the burden of HCV will continue to be substantial unless aggressive screening and treatment policies are implemented. Thus, these revolutionary advances in the treatment of HCV have led to an enhanced focus on the "cascade of care" that is required to achieve optimal outcomes. This sequence involves screening and detection, disease staging, access to care, appropriate treatment triage, and medication adherence and monitoring.

Prevalence and Screening

The first step in creating a world without hepatitis C is recognition of the infection itself so that the sequence of care can be initiated. Estimates of the prevalence of hepatitis C, a clear understanding of who is most at risk for the disease, and a valid screening methodology will be required to develop effective treatment approaches.

The Cost of Making Hepatitis C a Rare Disease

Chhatwal and colleagues[1] provided an estimate of how many patients will require treatment in 2015 and beyond, as well as the long-term health outcomes under different treatment penetration rates. They used their previously published Hepatitis C Disease Burden Simulation Model to simulate the clinical management of HCV from 2001 onward, including risk-based screening until 2013 and the addition of birth-cohort screening afterward. They modeled antiviral treatment in different waves, starting with pegylated interferon/ribavirin until 2011 and followed by the launch of boceprevir/telaprevir in 2012, sofosbuvir/simeprevir in 2014, and oral DAA regimens in 2015.

They estimated that in 2015, 2 million noninstitutionalized patients would be chronically infected and viremic. Among these patients, 1.1 million would be aware of their HCV status and insured, and therefore potential DAA candidates. They concluded that at the current annual treatment capacity of 200,000 patients, it would take at least 10 years to treat the majority of patients. By 2025, the number of treatment candidates would decline to less than 50,000 patients.

Chhatwal and colleagues projected that despite DAA availability, 320,000 patients would die because of HCV, 32,000 patients would receive liver transplants, 202,000 would develop decompensated cirrhosis, and 156,000 would progress to hepatocellular carcinoma by 2050. Doubling the annual treatment capacity could avoid 8000 deaths, 700 transplants, and 4000 cases of hepatocellular carcinoma by 2050. Increasing early HCV treatment capacity is essential to decreasing disease burden, preventing progression to advanced liver disease, and improving health outcomes of patients with chronic hepatitis C in the United States.

Treating HCV infection during the early stages of fibrosis would improve health outcomes in a cost-effective manner. However, substantial aggregate costs will be incurred, and there will be implications for healthcare coverage policies and clinical decision-making.[2] The annual cost of HCV in 2010 was $7 billion (before DAA availability) and reached $18 billion in 2015.[3] Treatment cost was 78% of the total HCV cost in 2015. By 2022, the annual HCV treatment cost would drop below $1.8 billion, and by 2030, the availability of generic agents would bring the cost of treatment below $14 million. Because of the aging population, Medicare would bear the maximum cost burden (39% of the total) from 2017 onward. Under the current HCV management policies, it would cost $104 billion to make HCV a rare disease by 2040.

Pho and colleagues[4] estimated the economic value of providing treatment for HCV relative to other major interventions. They calculated the net monetary benefit of therapy provided for all individuals estimated to be infected with HCV in the United States, using a value of statistical life framework. Compared with no treatment, treating 2.7 million individuals with HCV would result in 9.5 million life-years gained at an incremental cost of $347 billion. The net monetary benefit of HCV treatment exceeds that of such interventions as influenza vaccinations at long-term facilities and shielding x-ray components.

The scope of benefit conferred by new HCV therapies is large, owing to the high mortality risk of HCV, the curative effect of therapy, and the size of the population infected. However, at current prices, the incremental cost of therapy represents a 3478-fold increase in nationwide spending on hepatitis C—more than 11% of all national health expenditures, and 11 times the annual budget of the National Institutes of Health.

Ward and Mermin[5] editorialized that the US public health implications of the impending simple, safe, and curative HCV therapies could be profound. In addition, an editorial in the Lancet further emphasized the unique opportunity to reduce the burden of HCV globally.[6] However, patients cannot benefit from a drug that they cannot afford, or if they are unaware of their disease.

Awareness of Hepatitis C Status

Large disparities exist in the awareness of HCV status, particularly among marginalized and seemingly low-risk groups.

Linthicum and colleagues[7] examined awareness of HCV status across racial, risk, and income groups in the United States by accessing data from five combined waves of the National Health and Nutrition Examination Survey (NHANES). Respondents who tested positive for anti-HCV or HCV RNA during 2003-2012 participated in a follow-up survey. Of these, 59% reported that they were already aware of their HCV status when informed of their positive HCV test results in NHANES.

Rates of prior HCV status awareness varied considerably; 71% of "baby boomers" (adults born between 1945 and 1965) reported prior awareness, compared with 28% of adults who were not in major risk groups. Thus, HCV screening practices before 2010 appear to have identified just over one half of total HCV cases in the noninstitutionalized US population.

With new therapies offering the potential of a cure, the development of effective HCV screening policies is of great importance.

Cirrhosis Among Patients With Hepatitis C

Udompap and colleagues[8] determined the prevalence of advanced cirrhosis in people with chronic hepatitis C infection in the United States. They used the NHANES data to identify participants with detectable serum HCV RNA and then assessed liver fibrosis using validated surrogate indicators (the aspartate aminotransferase/platelet ratio [APRI] and fibrosis-4 [FIB-4] scores). The prevalence of cirrhosis and fibrosis was determined among survey participants for three eras: 1988-1994, 1999-2006, and 2007-2012.

Among 52,644 adults, 1.4% had HCV. Despite a steady decline in the prevalence of HCV among the NHANES survey participants, the probability of cirrhosis rose steadily. On the basis of APRI scores, the estimated prevalence of cirrhosis (Ishak stage 5 or 6) climbed from 6.6% in the earliest era to 7.6% and 17% in the next two eras, respectively. The prevalence of advanced fibrosis (Ishak stage 4-6) on the basis of FIB-4 scores also rose steadily, from 8.6% to 10.1% and then 16.0%. These data project to a current estimate of 370,500 Americans with cirrhosis and 347,800 with advanced fibrosis.

In a logistic regression analysis, increasing age and increasing rates of diabetes mellitus among patients with HCV correlated with the rising prevalence of cirrhosis. Patients with HCV were often asymptomatic and unaware of their infection.

Therefore, these data further underscore the current recommendations for HCV screening in asymptomatic individuals and highlight the need for systematic assessment for liver fibrosis and comprehensive medical management in those with HCV infection. Although the national burden of HCV is declining, the rates of end-stage liver complications may increase without efforts to screen and initiate therapies that provide high rates of sustained virologic response.

Targeted Screening

Several presentations at The Liver Meeting 2015 discussed strategies and policies to identify individuals who are at highest risk for HCV infection and are therefore candidates for targeted screening. Current recommendations call for one-time screening of baby boomers. However, most new HCV infections occur among individuals who use intravenous drugs and share injecting equipment. People who inject drugs also have high rates of incarceration; this captive population offers an opportunity for screening and therapeutic intervention.

Stone and colleagues[9] assessed the potential prevention benefit of scaling up HCV detection and treatment for imprisoned patients. Their model suggests that DAA treatment among people who inject drugs could result in a 46% relative reduction in chronic HCV prevalence by 2030. A 70% relative reduction could be achieved by 2030 if 38% of HCV-infected people who inject drugs are treated during imprisonment. Scaling up HCV treatment rates in prison could provide important benefits and be a feasible strategy for undertaking widespread HCV treatment as a prevention strategy.

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