People with hepatitis C who achieve sustained
virological response to treatment had lower liver-related morbidity and
mortality rates compared to people who were not successfully treated,
according to research presented at the 2016 AASLD Liver Meeting in November.
Over years or decades chronic hepatitis C virus (HCV)
infection can lead to severe liver damage including cirrhosis, hepatocellular
carcinoma (HCC) and hepatic decompensation or liver failure. Successful
hepatitis C treatment can slow or halt liver disease progression, but people
who start treatment after they have already developed cirrhosis remain at risk
for HCC and end-stage liver disease.
Sofie Hallager of Copenhagen University Hospital and
colleagues assessed liver-related morbidity and mortality among people with hepatitis C who have cirrhosis in Denmark, and looked at how these were affected by
sustained virological response, defined as continued undetectable HCV RNA at 24
weeks after the end of treatment (SVR24).
An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
A disease or infection affecting the brain.
A non-invasive test, used instead of a biopsy, to measure the stiffness
or elasticity of the liver using an ultrasound probe.
Stretched veins which may burst and cause severe bleeding; a complication of cirrhosis.
This analysis included 1032 adults with chronic hepatitis C in the Danish Database for Hepatitis B and C (DANHEP) and national
health registries from January 2002 to the end of December 2013. A
majority (69%) were men and the median age was 52 years. Most had HCV genotypes
1 (43%) or 3 (37%).
A total of 550 people underwent treatment, of whom
232 (42%) achieved SVR24 and 275 were non-responders. People with HCV genotype
1 were less likely to be cured. The study period ended before all-oral
direct-acting antiviral therapy was available, so most were presumably treated
with interferon-based therapy; first-generation HCV protease inhibitors used
with interferon/ribavirin were available in the final years.
Cirrhosis was determined based on liver biopsy
(fibrosis stage F4), FibroScan
transient elastography (> 17 kPa) or clinical signs including ascites
(abdominal fluid accumulation), spontaneous bacterial peritonitis (abdominal
infection), bleeding varices (enlarged veins) in the oesophagus and hepatic
encephalopathy (brain impairment). At baseline 21% had decompensated cirrhosis
and 4% had liver cancer.
Looking at all people together, cumulative HCC
incidence at five years was 9.2%. The overall HCC incidence rate was 2.51 per
100 person-years. HCC was more common among heavy alcohol users and people with
HCV genotype 3.
The cumulative incidence of decompensation at five
years was 14.3% and the incidence rate was 3.44 per 100 person-years. Alcohol
use was the only significant risk factor for decompensation. In their abstract
the study authors reported that just over 10% developed ascites, about 8% had
bleeding varices, about 3% had hepatic encephalopathy and just over 1%
developed bacterial peritonitis.
Nearly a third of people died during follow-up, for
an all-cause mortality rate of 7.33 per 100 person-years for the whole cohort.
Looking at the effect of sustained response, HCC,
decompensation and death rates were lower for people who achieved SVR24
compared to those who were not cured.
After adjusting for confounding factors, the five-year
cumulative incidence of HCC was 5.4% in the SVR24 group versus 13.3% in the
non-SVR group. Incidence rates were 0.9 versus 3.6 per 100 person-years,
respectively, for an incidence rate ratio of 0.37.
For decompensation, five-year cumulative incidence was
4.8% in the SVR24 group versus 17.1% in the non-SVR group. Incidence rates were
0.8 versus 4.0 per 100 person-years, for an incidence rate ratio of 0.24.
All-cause mortality rates were 2.2 per 100
person-years in the SVR24 group versus 6.7 per 100 person-years in the non-SVR
group, for an incidence rate ratio of 0.66.
"Liver-related morbidity and mortality [were]
high among patients with chronic hepatitis C and cirrhosis in Denmark,"
the researchers concluded. "SVR24 was associated with reduced morbidity
and mortality." These findings, they added, underscore the "urgent
need to cure patients with chronic hepatitis C."
A related study also
presented at The Liver Meeting showed that the risk of HCC fell by 80% among people in British Columbia, Canada, who
were cured of hepatitis C compared to those without sustained response. Another
analysis from Spain found that successful hepatitis C treatment moderately reduced the likelihood of portal
hypertension, or high blood
pressure in the portal vein due to scar tissue in the liver, which can lead to
symptoms of decompensation. However, people who already had advanced cirrhosis
before treatment saw less benefit, emphasising the importance of treating