As well as increasing the risk of death from liver disease, chronic hepatitis C virus infection
increased the risk of death from circulatory and kidney disease as well as
several non-liver-related cancers, investigators report in the August 15th
edition of the Journal of Infectious
Researchers in Taiwan compared mortality
rates between three groups of people: those who had never been infected with
hepatitis C virus (HCV); individuals who had antibodies to hepatitis C but who
had cleared the infection; and people with chronic hepatitis C infection, indicated
by detectable levels of virus.
Mortality rates were similar for the first
two groups. However, people with chronic hepatitis C infection
were significantly more likely to die of liver disease and a number of other
“We found that anti-HCV seropositives with
detectable HCV RNA had an increased risk of dying from all causes of death,
whereas the risk for anti-HCV seropositives with negative HCV RNA was similar to
the risk for anti-HCV seronegatives,” write the investigators.
The study’s findings underline the
importance of detecting and treating chronic hepatitis C virus infection. New
guidance was recently issued in the US recommending routine screening for people born between 1945 and 1965, the age group that has the highest
hepatitis C prevalence.
There are an estimated 170 million
hepatitis C virus infections worldwide. The prevalence of infections in richer
countries is around 1% and is twice that level in resource-limited settings.
It is well recognised that infection with
hepatitis C increases the risk of death from liver disease, including cirrhosis
and liver cancer. There is some evidence that the infection also increases the
risk of death from non-liver-related causes.
However, hepatitis C can be cured with
antiviral therapy and previous research has suggested that this can reduce the
risk of death from both liver disease and other causes. The studies showing
this have been limited by their size or duration of follow-up. Investigators in
Taiwan therefore wanted to establish a clearer understanding of the
relationship between chronic hepatitis C virus infection and mortality.
They analysed data gathered
during the prospective Risk Evaluation of Viral Load and Associated Liver
Disease/Cancer (REVEAL) study.
Individuals who were uninfected with
hepatitis B virus were recruited to this study between 1991 and 1992 and were
followed until the end of 2008.
They were tested for the presence of
hepatitis C antibodies and hepatitis C RNA.
A total of 1095 participants had antibodies to
hepatitis C and 69% of these individuals had detectable virus.
Overall, people who were hepatitis C
virus-positive were significantly more likely to die of liver-related causes
(HR = 12.48; 95% CI, 9.34-16.66) as well as non-liver related causes (HR =
1.38; 95% CI, 1.15-1.16).
These non-liver-related causes included circulatory
diseases (HR = 1.50; 95% CI, 1.10-2.03), kidney disease (HR = 2.77; 95% CI,
1.49-5.15) and several cancers, including cancer of the esophagus (HR = 4.08;
95% CI, 1.38-12.08), prostate cancer (HR = 4.19; 95% CI, 1.18-14.94) and
thyroid cancer (HR = 8.22; 95% CI, 1.36-49.66).
The investigators then looked at the
relationship between ongoing hepatitis C virus replication and mortality risk.
After 18 years of follow-up, 0.3% of
hepatitis C-negative participants had died of liver disease. The mortality rate for
people who had cleared hepatitis C virus infection was non-significantly
higher at 1.6%. In contrast, 10% of participants with chronic infection died of
“There was no case that died from chronic
liver diseases and cirrhosis among participants seropositive for anti-HCV with
undetectable serum HCV RNA,” note the authors.
A similar relationship between chronic
hepatitis C virus and increased mortality was apparent when the investigators
looked at non-liver-related caused of death.
In all, 3% of hepatitis C-negative participants
died of cardiovascular disease, as did 3.5% of those who had cleared hepatitis C
and 5% of people with ongoing viral replication, a significant difference (p
A detectable hepatitis C viral load was
also associated with an increased risk of death from kidney disease (p <
“There was no death from chronic liver
disease and cirrhosis, esophagus cancer, prostate cancer, and thyroid cancer
among anti-HCV seropositives with undetectable serum HCV RNA at study entry,”
emphasise the investigators. “The consistent findings suggest active infection
(seropositive for HCV RNA) rather than prior infection (seropositive for
anti-HCV) is more important in predicting the long-term risk of mortality from
They therefore believe that hepatitis C
screening programmes should include tests for both antibodies to the infection
and hepatitis C RNA. “Anti-HCV seropositives, particularly those with
detectable HCV RNA, should be encouraged to modify health behaviors, including
weight reduction, tobacco cessation, or eating a balanced diet, in order to
decrease the risk of cancers, circulatory diseases, and renal disease.”
The author of an editorial accompanying the
study highlighted recent data showing that hepatitis C is now a more important
cause of death in the US than HIV. “Now is the time for chronic HCV infections
to be taken more seriously as an important public health problem.”
However, separate US research published in
the online edition of the Journal of
Infectious Diseases suggests that the pace of liver disease associated with
chronic hepatitis C virus infection is slow. A total of 384 people were
monitored 15 years after they were diagnosed and an estimated 25 years since
they were first infected with hepatitis C.
Liver biopsies showed that 33% had no liver fibrosis, 52% had only mild
fibrosis, 12% had intermediate fibrosis and only 2% had cirrhosis.
The investigators were encouraged by these
results, which they believe could inform hepatitis C treatment strategies: “It
is probable that those who have shown no or little fibrosis progression over 25
years will have a nonprogressive or slowly progressive course that will provide
time for more effective and safer therapies to emerge and induce sustained virologic
responses that appear tantamount to a cure.”