All people with
chronic hepatitis C virus (HCV) infection should start therapy with direct-acting antivirals, research
published in the online edition of Clinical
Infectious Diseases suggests. Investigators from the United States found
that individuals with moderate fibrosis had an increased risk of mortality, and
that there was no accurate way of predicting disease progression of fibrosis
from mild to moderate.
“Although
increased mortality was evident among individuals with severe
fibrosis/cirrhosis, we observed some increased risk of mortality, even among
those with moderate fibrosis,” comment the authors. “These findings, and our
inability to identify with sufficiently high prognostic accuracy individuals
who would transition from a lower mortality risk state (minimal liver disease)
to a higher mortality risk state (moderate to severe liver disease), may not
support withholding HCV treatment until that transition occurs.”
An estimated 3
million individuals in the United States have chronic HCV infection. If
left untreated, the infection significantly increases the risk of liver-related
death and also several cancers.
Curative therapy
using direct-acting antivirals is now available. However, because of its high cost,
access is often limited to patients with at least moderate fibrosis. Guidelines
from the American Association for the Study of Liver Diseases (AASLD) and
Infectious Diseases Society of America (IDSA), however, recommend treatment for almost
all individuals with chronic infection. Denial of therapy to people with mild
fibrosis is justified by the assumption that this has no significant medical
consequences and that disease progression can be accurately and reliably
predicted.
Investigators from
the ALIVE study in Baltimore wanted to see if this was indeed the case. They
therefore designed an observational study involving 964 people with chronic
HCV infection and a history of injecting drug use who received follow-up before
effective treatment became available. Fibrosis was regularly assessed using
liver stiffness testing. The relationship between fibrosis stage and mortality was
calculated and the investigators explored whether individual or combinations of
risk factors could predict fibrosis progression.
No/mild fibrosis
was a liver-stiffness score below 8; moderate fibrosis a score between 8-12.3;
and severe fibrosis a score above 12.3.
Median age at
baseline was 49 years. Most study participants were male (72%) and African
American (87%). Over half (52%) were current injecting drug users and 14%
abused alcohol. The median duration of injecting was 28 years. A third had co-infection with HIV, 52% of whom were taking antiretroviral therapy.
Individuals were
followed for a median of 5.9 years (follow-up was between 2006 and 2014) after first
liver stiffness measurement. During this time, there were 155 deaths, an
overall mortality rate of 3.06 deaths per 100 person-years. Mortality was
highest among people with severe fibrosis (6.21 deaths per 100 person-years),
but was still significantly elevated (trend, p < 0.001) among people with
moderate fibrosis (3.59 per 100 person-years) compared to those with no/mild
fibrosis (2.21 per 100 person-years).
After taking into
account socio-demographic factors, substance use and HIV status, both all-cause
and non-accidental mortality were elevated, the later significantly, among
people with moderate fibrosis (aHR: 1.42; 95% CI 0.96-2.11; aHR: 1.66; 95%
CI: 1.06-2.59, respectively).
Factors associated
with disease progression were being overweight and a HIV viral load above
10,000 copies/ml. But their sensitivity for predicting progression from
mild/moderate fibrosis was only 32%.
A one-year change
in liver stiffness was also associated with progression to moderate fibrosis.
For people with no/mild fibrosis at baseline, each one point increase in
liver stiffness increased the risk of progression over 40-fold (aHR: 41,3; 95%
CI3.15-542.3). However, this had only fair predictive accuracy (72%).
“We observed
increased mortality among persons with severe and moderate fibrosis and
transitions to moderate fibrosis could not be predicted with high accuracy,”
conclude the authors. “These data support the AASLD/IDSA guidelines for
treatment of all persons with chronic HCV infection and not support withholding
treatment from those with mild disease.”