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.
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
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.
A non-invasive test, used instead of a biopsy, to measure the stiffness
or elasticity of the liver using an ultrasound probe.
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.
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
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
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.