Hepatitis C-related mortality continues to increase in the US

Deaths related to hepatitis C virus (HCV) infection continue to rise in the US despite the advent of highly effective interferon-free therapy, according to a CDC study presented on Saturday at IDWeek 2015 in San Diego, USA. While death certificate data indicate that hepatitis C is the most common infectious cause of death – exceeding HIV, hepatitis B and tuberculosis combined – HCV-related mortality is likely underestimated.

National estimates indicate that between 3 and 4 million people in the US are infected with HCV. Historically, most have been in the age cohort born between 1945 and 1965, but recent outbreaks among young people who inject drugs may shift this distribution.

Over years or decades, chronic HCV infection can lead to severe liver disease including cirrhosis, liver cancer and end-stage liver failure; hepatitis C is a leading indication for liver transplantation. Mortality due to hepatitis C has risen over the past decade, while deaths due to HIV have fallen and hepatitis B mortality remains low and stable. Experts estimate that only about half of people living with HCV have been diagnosed, and many do not become aware they have HCV until they develop advanced disease.

The development of direct-acting antiviral agents that can cure more than 90% of people with hepatitis C in three months or less without interferon has revolutionised treatment, but inadequate screening and the high cost of the new medications means most people are not yet benefiting from these advances.

Scott Holmberg of the Division of Viral Hepatitis at the US Centers for Disease Control and Prevention (CDC) and colleagues aimed to learn more about trends in hepatitis C mortality.

The researchers examined national multiple-cause-of-death (MCOD) records of all US death certificates from 2003 through 2013. They looked at ICD-10 diagnostic codes for hepatitis C and 60 other infectious diseases that are nationally reportable to the CDC. Deaths that had HCV and the other infections listed as ‘underlying conditions’ were divided by the US census population for each year.

Deaths with hepatitis C recorded on the death certificate increased from around 11,000 in 2003 to 19,358 in 2013, making it the most common infectious underlying condition. In contrast, deaths related to all the other reportable infectious diseases decreased from around 25,000 in 2003 to around 18,000 in 2013. 

After hepatitis C, the five most commonly listed infectious diseases were HIV, with 8831 deaths; Staphyloccus aureus (including MRSA), with 5136 deaths; hepatitis B, with 1871 deaths; tuberculosis, with 992 deaths; and Pneumococcal disease, with 885 deaths (4444 adult influenza deaths were not included in the top causes of death).

The analysis also looked at mortality rates among people in the Chronic Hepatitis Cohort Study (CHeCS) between 2007 and 2013. Unlike the larger national population, people in the CHeCS cohort were presumed to have adequate access to evolving hepatitis C care and treatment. To get a better idea of ‘hidden mortality’, the researchers also looked more closely at 1600 deaths of well-characterised CHeCS patients during 2006-2010.

Among the more than 12,000 people receiving care in the CHeCS cohort, the mortality rate doubled from about 2.3 per 100 person-years in 2007 to about 5.5 per 100 person-years in 2013.

Among the 1600 well-characterised CHeCS patients who died (mean age at death 59 years), only 19% had hepatitis C listed on their death certificates, even though more than 75% had evidence of liver disease before death. Applying this percentage to the entire population of people living with HCV, the researchers estimated that more than 75,000 deaths in 2013 may be attributable to hepatitis C.

“Deaths in chronic HCV-infected persons, even when grossly under-enumerated on death certificates, far outstrip deaths from 60 other infectious conditions reportable to CDC,” the investigators concluded. “Control of the ‘chronic’ and the ‘acute’ outbreaks will require a multipronged approach, with interventions along a testing-to-cure continuum of care.”

As Holmberg and colleagues reported in 2013, the hepatitis C cascade of care indicates that of the 3.2 million people estimated to be living with HCV in the US, 50% have had HCV antibody tests, 38% have received hepatitis C care, 23% have had HCV RNA tests (to diagnose active disease), 11% have received treatment and only 6% have achieved sustained virological response, considered to be a cure.

Antiviral therapy that cures hepatitis C can halt and even reverse liver disease progression, so expanded treatment should have an effect on mortality in the years to come.

Data from Gilead Sciences – which produces the best-selling interferon-free therapies sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir (Harvoni) – show that prescriptions for sofosbuvir-based regimens reached 470,000 in the second quarter of 2015, with more than half (about 270,000) in the US, just under 100,000 in Europe and just over 100,000 in developing countries.

Yet while the number of people receiving hepatitis C therapy is rising, barriers remain to achieving universal treatment. Due to the high cost of the new drugs, some private insurers and public payers are restricting access, for example by requiring that patients have advanced fibrosis, undergo a pre-treatment liver biopsy or FibroScan, abstain from alcohol and drugs for six months or be treated by specific specialists.

Beyond the cost of the drugs, other barriers include clinicians thinking hepatitis C is a benign chronic condition that doesn't require treatment, patient issues such as having other priorities, public ‘fatigue’ about infectious disease outbreaks and a reluctance to help people who inject drugs, and absence of a strong advocacy group.

Holmberg ended with a personal appeal to members of the Infectious Diseases Society of America – one of the professional organisations that sponsors IDWeek – to expand their knowledge about and treatment of this largest US infectious disease epidemic.