Nearly one-third of chronic hepatitis C patients with liver cirrhosis and
12% with advanced fibrosis progressed to decompensation within five years, and
23% and 11%, respectively, died, according to a study presented at the American
Association for the Study of Liver Diseases (AASLD) Liver Meeting last
month in Boston. These findings underscore the urgent need for treatment for
or decades, chronic hepatitis C virus (HCV) infection can progress to serious
liver disease including cirrhosis, hepatocellular carcinoma (HCC), liver
decompensation – when the liver can no longer carry out its vital functions –
and liver-related death.
treatment that leads to sustained virological response (SVR) can slow or halt
liver disease progression and may allow for some degree of recovery. When the
standard of care was interferon-based therapy – which lasted up to a year, caused
difficult side-effects and cured only about half of patients – treatment was
recommended only for people with evidence of progressive liver damage.
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.
- hepatocellular carcinoma (HCC)
Liver cancer. A long-term complication of chronic inflammation of the liver or cirrhosis.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
Stretched veins which may burst and cause severe bleeding; a complication of cirrhosis.
highly effective and well-tolerated interferon-free direct-acting antiviral
regimens are available, some experts have called for universal treatment. But
given the drugs' high cost, current guidelines state that people with advanced
liver disease should be prioritised, and many national health systems and private
insurers are limiting treatment to the sickest patients.
Moorman from the US Centers for Disease Control and Prevention (CDC) and colleagues
looked at liver disease progression to decompensation or HCC and all-cause
mortality among people in the Chronic Hepatitis Cohort Study. CHeCS is an ongoing observational study of more
than 14,000 people with hepatitis C at four integrated healthcare systems in Michigan, Pennsylvania, Hawaii and Oregon.
This analysis included 2839 chronic
hepatitis C patients with biopsy-confirmed fibrosis in the era prior to
direct-acting antivirals. Participants had liver biopsies performed during
2001-2012, before the onset of HCC or decompensation, and before receiving
hepatitis C treatment.
A majority of participants (about
60%) were men, two-thirds were white and the median age was just over 50 years;
more than 80% were in the highest-risk 1945-1965 birth cohort. Baseline
biopsies revealed that 1204 (42%) had absent or mild fibrosis (Metavir stage
F0-F1), 810 (29%) had moderate fibrosis (stage F2), 461 (16%) had advanced
fibrosis (stage F3) and 364 had cirrhosis (stage F4).
The researchers analysed the number
of cases of HCC, decompensation, liver transplantation and death due to all
causes over an average follow-up period of 5.5 years. Decompensation was defined
as the first occurrence of portal hypertension, ascites (abdominal fluid
accumulation), oesophageal varices (distended veins), hepatic encephalopathy
(brain impairment) or liver failure with hepato-renal syndrome.
Among people with cirrhosis at baseline,
29% experienced decompensation, 11% developed HCC, 5% underwent liver
transplantation and 23% died due to any cause. Among people with advanced
fibrosis, 12% experienced decompensation, 5% developed HCC, 2% had transplants
and 11% died. Among people with moderate fibrosis, the rates were lower: 4%,
1%, 1% and 6%, respectively.
Looking at treatment, 62% of participants
with cirrhosis, 72% with advanced fibrosis and 46% with moderate fibrosis were
ever treated after their baseline biopsy. Among the subset of participants with known
treatment outcomes, 47%, 55% and 75%, respectively, achieved sustained
Among people with cirrhosis, the risk
of decompensation was significantly lower among treated compared with untreated
patients – approximately 25% vs 50% at the maximum follow-up of seven years;
the risk of HCC was also significantly lower, about 7% vs 15%.
Among people with stage F3 fibrosis,
the difference in decompensation rates between treated and untreated patients
was also significant, 10% vs 25% at seven years. Fewer treated patients
developed HCC (approximately 4% vs 7%), but this
difference did not reach statistical significance.
There was no significant difference
in decompensation or HCC rates between treated and untreated patients with F2
fibrosis, but rates were low – under 4% for decompensation and under 2% for
HCC – in both groups.
In a multivariate analysis, people
with cirrhosis were about five times more likely to experience decompensation,
and those with F3 fibrosis were nearly three times more likely, compared to
those with F2 fibrosis. Low platelet count and elevated bilirubin at baseline
were also associated with a greater risk of decompensation, while receiving
treatment was associated with a 30% lower risk.
"We observed substantial liver
disease progression in a population-based observational cohort among patients
meeting liver disease stage criteria that now confer 'high' or 'highest'
recommendation for treatment," the researchers concluded.
These findings show that people with advanced fibrosis, in addition to
those with cirrhosis, are at substantial risk of liver-related complications and
should receive treatment. People with moderate fibrosis are at lower risk, but
still four out of 100 may progress to decompensation without treatment.