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Sustained virological response to hepatitis C treatment reduces mortality, liver cancer and liver transplants
Liz Highleyman, 2014-11-10 09:00:00
People who achieve
sustained virological response (SVR) when treated with interferon-based therapy
for hepatitis C have a lower risk of death, are less likely to develop liver
cancer and need fewer liver transplants than those who were treated but not cured,
according to results from a meta-analysis of more than 34,000 patients
presented Sunday at the American Association for the Study of Liver
Diseases (AASLD) Liver Meeting in Boston.
While more research is
needed to confirm these findings, benefits are likely to be even greater for
hepatitis C patients treated with interferon-free direct-acting antivirals (DAAs),
which produce higher cure rates generally above 90%.
Previous studies have
shown that SVR - or continued undetectable HCV viral load after completion of
treatment - reduces the risk of hepatocellular carcinoma (HCC), liver
transplantation, liver-related death and all-cause mortality, but results have
been inconsistent and many of these studies have been small.
To learn more about
how SVR affects long-term outcomes, Andrew Hill from the University of
Liverpool and colleagues performed a meta-analysis of data from 34,563 people treated for chronic hepatitis C. Combined
data were used to calculate 5-year risk of all-cause mortality, HCC and liver
transplantation. They also looked at rates of HCV re-infection after treatment.
The cost-effectiveness of hepatitis C treatment depends not on achieving
undetectable HCV RNA per se - although this would reduce the risk of onward
transmission - but rather on reducing the occurrence of liver cancer, need for
liver transplantation and all-cause mortality.
searched the MEDLINE and EMBASE databases for studies comparing outcomes among
treated hepatitis C patients with SVR at 24 weeks post-treatment (SVR24) versus
those who were not cured. Typically, the regimen used was pegylated interferon
plus ribavirin - the old standard of care before the advent of direct-acting
antivirals. (SVR12 is now considered to be a cure in studies of DAAs.)
looked at people with HCV monoinfection overall, HCV monoinfected patients with
liver cirrhosis and HIV/HCV coinfected individuals. Although they attempted to
compare results from univariate and multivariate analysis to control for
confounding factors, multivariate data often were not available.
The analysis of
all-cause mortality included 18 studies of HCV monoinfected people, with a
total of 29,269 participants and an average follow-up period of 4.6 years.
There were nine studies of HCV monoinfected patients with cirrhosis, with a
total of 2,734 participants and an average follow-up of 6.6 years. Finally,
there were five HIV/HCV coinfection studies, with a total of 2,560 participants
and an average follow-up of 5.1 years.
Looking at a subset of
studies with multivariate and univariate data, risk of death due to any cause
fell by 71% for HCV monoinfected people who achieved SVR in univariate
analyses, or 62% in multivariate analyses, relative to those without SVR. Among
HCV monoinfected patients with cirrhosis, all-cause mortality dropped by 73% in
univariate analyses and by 84% in multivariate analyses. Among HIV/HCV
coinfected people, risk reductions were 75% and 73%, respectively.
The 5-year risk of all-cause death
was 4.5% among HCV monoinfected people who achieved SVR, compared to 10.5%
among those without SVR. Among HCV monoinfected patients with cirrhosis,
mortality rates were 3.6% with SVR versus 11.3% without SVR. Among coinfected
patients, mortality rates were 1.3% with SVR versus 10.0% without SVR.
The analysis of liver
cancer included 21 studies of HCV monoinfected people, with a total of 12,496 participants
and an average follow-up period of 6.1 years. There were 18 studies of HCV
monoinfected people with cirrhosis, with a total of 4,987 participants and an
average follow-up of 6.6 years. There were three HIV/HCV coinfection studies,
with a total of 2,085 participants and an average follow-up of 4.7 years.
The 5-year risk of developing
HCC was 2.9% among HCV monoinfected people who achieved SVR, compared to 9.3%
among those without SVR. Among cirrhotic HCV monoinfected patients, HCC rates
were 5.3% with SVR versus 13.9% without SVR. Among coinfected patients, rates
were 0.9% with SVR versus 10.0% without SVR.
Looking at liver transplants, the analysis included just one study of HCV monoinfected people, with a
total of 108 participants and an average follow-up period of 4.2 years. There
were two studies of HCV monoinfected cirrhotic people, with a total of 1,046 participants
and an average follow-up of 7.7 years. Finally, there were 2 HIV/HCV
coinfection studies, with a total of 2,039 participants and a follow-up of 4.9
Here, 0% of HCV monoinfected people with SVR needed a liver transplant,
compared with 2.2% of those who were not cured. Among HCV monoinfected
cirrhotics, transplant rates were 0.2% with SVR, rising to 7.3% without SVR.
Among coinfected people, transplant rates were 0.6% and 2.7%, respectively.
Turning to re-infection after achieving SVR, Hill said there was a 'marked
difference' across the three populations analysed. Reinfection was rare, at
0.9%, among people considered low-risk (24 studies, 6,046 participants, 4.1 years average follow-up). The
re-infection rate rose to 8.2% in a higher-risk group of prisoners and people
who inject drugs (16 studies, 1,203 participants, 5.0 years
average follow-up). But the re-infection rate was much higher, at 23.6%, among
HIV/HCV coinfected people (10 studies, 1,106 participants, 3.1 years average follow-up).
Hill noted that many of the coinfected patients were men who have sex
with men. Starting around the year 2000, outbreaks of apparently sexually
transmitted HCV infection have been widely reported among HIV-positive gay and
bisexual men in cities in Europe, the US and Australia. He said this analysis
could not provide details about specific risk factors, but the highest
re-infection rate was seen among coinfected people who also injected drugs.
With regard to the limitations of this meta-analysis, Hill noted that
people with SVR and those who are not cured may differ in baseline
characteristics, so more multivariate data are needed. He also stressed that
these findings are from studies of interferon-based treatment, and long-term
outcome data are not yet available for people treated with direct-acting
In this analysis of data from 34,563 patients treated for hepatitis C,
achieving SVR was associated with 62-84% reductions in all-cause mortality,
68-79% reductions in the risk of developing HCC and a 90% reduction in liver
transplantation, the researchers summarised.
However, they added, "there was a significant risk of subsequent
re-infection after SVR in some studies, which could reverse these benefits of