Over years or decades, chronic hepatitis C virus (HCV)
infection can lead to serious liver disease including cirrhosis, hepatocellular
carcinoma (HCC) and end-stage liver failure. Up to 20% of people with chronic
hepatitis C develop cirrhosis within 20 years, and among these the risk of HCC
may reach 4%. Successful treatment of hepatitis C has the potential to slow or
halt liver disease progression and reduce the risk of long-term consequences
including liver cancer and liver-related death.
Jeffrey McCombs of the University
of Southern California in Los Angeles looked at the impact
of HCV viral load suppression with treatment on the risk of morbidity and
mortality among people living with chronic hepatitis C and receiving care through the US
Veterans Health Administration.
This observational cohort study included 128,769 eligible
patients in the Department of Veterans Affairs HCV Clinical Case Registry
during the period 1999-2010 (out of a pool of nearly 361,000) who had
detectable HCV RNA (>25 IU/ml) and available HCV genotype data. Almost all were men,
half were white, one-third were black and the average age was 52 years. Most
(79%) had HCV genotype 1, the most common type in the US and the hardest to
The primary outcomes considered were death and a
composite endpoint of compensated cirrhosis, decompensated cirrhosis, HCC or
Over a median follow-up period of six years, 24% of patients
in the analysis started hepatitis C treatment but only 16% of treated individuals – or just 4% overall – achieved undetectable viral load at some point after
Introducing a 'Hepatitis Debrief' on the final day of
the conference, Ronald Valdiserri, US Deputy Assistant Secretary for Health,
described the national HCV 'treatment cascade' in the US. According to a 2013
report by Scott Holmberg from the Centers for Disease Control and Prevention (CDC) and
colleagues, 50% of people with chronic hepatitis C (1.6 million out of an
estimated total of 3.2 million) have been diagnosed, 32 to 38% are referred to
care, 7 to 11% start treatment and only 5 to 6% are successfully treated.
In McCombs' study, achieving HCV viral suppression was
associated with a 27% reduced risk of liver-related adverse outcomes (adjusted hazard
ratio [HR] 0.73) and a 45% lower risk of death (adjusted HR 0.55).
Unadjusted mortality rates were 6.8 deaths per 1000 person-years for people who achieved undetectable viral load compared to 21.8 per 1000
person-years for those without viral suppression.
The researchers also found that people with HCV
genotype 2 had a significantly lower risk of liver-related events or death compared to those
with genotype 1 (adjusted HR 0.77 and 0.80, respectively). Conversely, people
with genotype 3 were at higher risk relative to those with genotype 1 (adjusted
HR 1.11 and 1.17, respectively).
Other significant risk factors for adverse outcomes or
death included male sex, white race, older age and prior hospital admission.
"Viral load suppression reduces risk of future liver
events by 27% and death by 45%", the researchers concluded. These
the first study using a large population of patients with a wide array of
disease progression and levels of fibrosis, "verifies earlier findings
that viral load reduction through treatment can significantly reduce the risk
of adverse patient outcomes".
As a limitation, this analysis looked at whether people had ever reached
undetectable viral load rather than sustained virological response (SVR) – the
accepted definition of a cure – but McCombs noted that fewer than 20% of
people who achieve undetectable HCV RNA are thought to relapse.
At a media overview on
the first day of the conference, AASLD president Gregory Fitz noted that while
only one-quarter of veterans received treatment, "if you did, you lived
longer and lived better". He noted that McCombs' results were based on
"old school treatment" using interferon-based therapy, and that
outcomes would likely be better using new direct-acting antiviral agents. But given
the continued risk of liver cancer, he stressed that one "can't just clear
the virus and think the story is over".