For patients with hepatitis C virus (HCV) mono-infection, baseline
fibrosis stage is strongly predictive of the medium-term risk of serious liver
disease and death, investigators from the United States report in the online
edition of Clinical Infectious Diseases.
After five years of follow-up, over a third of patients with F4 stage liver
fibrosis at baseline had developed hepatic decompensation or liver cancer. This
compared to a progression rate of just 2% among patients with F0/F1 stage
disease at baseline.
“We observed significant progression to liver failure and death among
patients with advanced liver fibrosis or cirrhosis in the absence of successful
treatment,” write the authors. “Our results emphasise that effective treatment
is urgently needed in these groups of patients.”
Patients with HCV infection are at risk of developing liver fibrosis and
cirrhosis, leading to hepatic decompensation, liver cancer and early death.
Curative oral HCV therapy has recently become available. Current US guidelines recommend
that patients with liver cirrhosis or advanced fibrosis have the highest
priority for therapy, followed by individuals with less advanced fibrosis who
have co-infections or co-morbidities.
Modern HCV therapy is expensive and access to some regimens is limited
according to disease stage. Real-world evidence is needed to inform ongoing
debates about which patients should be prioritised for therapy. Investigators
from the Chronic Hepatitis Cohort Study (CHeCS) therefore designed a study
describing rates of progression of liver disease and all-cause mortality over
five years among 2,799 patients with HCV mono-infection according to their
baseline liver fibrosis stage (Metavir F0/1 – F4).
Fibrosis stage was determined by liver biopsy. The risk of progression
to serious liver disease in the absence of effective therapy after one, two and
five years of follow-up was reported.
Patients were biopsied between 2001-2012. At baseline 11% were at stage
F0, 26% at F1, 30% at F2, 18% at F3 and 15% at F4. The overall mean age at
baseline was 51 years. However, this differed according to fibrosis stage (F0/1
= 48 years vs. F4 = 53 years, p < 0.001). The proportion of males increased
as fibrosis stage advanced (53% in F0/1 vs. 69% in F4). As expected for the US,
over two-thirds of patients had genotype 1 infection.
During follow-up, 54% of patients received HCV therapy and 24% had two
or more attempted courses of treatment.
The risk of serious liver disease doubled with each increase in baseline
fibrosis stage. No patient with F0/F1 stage progressed to liver cancer. In
contrast, progression rates among patients with F4 disease were 9% to liver
cancer, 27% developed decompensated liver disease, 5% had a liver transplant
and approximately a quarter had died by the end of follow-up.
The one-year risk of liver cancer increased from 0.1% for patients with
baseline F0/1 fibrosis, to 1.6% for individuals with stage F4 fibrosis at
baseline. Two-year incidence of liver cancer was 0.3% for those with stage F2
at the start of the study and 6% for individuals with baseline F4 fibrosis.
Patients with baseline F4 fibrosis experienced the highest five-year rate of
decompensated liver disease (34% vs. 19% F3 vs. 4% F2 vs. 2% F1/0). Incidence
of decompensation was similar over five years between patients with F0/1 and F2
stage fibrosis at baseline.
Five years after biopsy, all cause mortality rates were 32% in stage F4,
14% in stage F3, 7% in F2 and 7% in F1/0.
The strongest factors associated with the development of decompensated
liver disease or liver cancer were baseline fibrosis stage F3 (aHR = 4.2) or F4
(aHR = 7.2) and a platelet count below normal (aHR = 3.45).
“This natural history study provides ‘real-world’ data about the
probability, time to and risk factors for HCV-related morbidity and mortality,”
conclude the investigators. “These timely data can help evidence-based decision
making by clinicians and policy makers about HCV management, and can help
inform the debate regarding the comparative benefits and harm of treating HCV
patients at the time of diagnosis versus waiting to treat only those patients
who show early signs of progression of liver disease (e.g. F2) or other
manifestations of infection.”