is not associated with accelerated progression of liver fibrosis in people
with hepatitis C virus (HCV) infection, according to US research published in the
online edition of the Journal of
Infectious Diseases. Factors linked with fibrosis progression were low
fibrosis stage at baseline and flares in alanine aminotransferase (ALT) levels.
The major strengths of the study were its large sample size and the fact that participants had at least two liver biopsy
results during follow-up, Dr Daniel S Fierer of Mount Sinai Hospital, New York, commented in an accompanying editorial.
HCV is a leading
cause of serious liver disease. The infection can cause progressive liver
fibrosis, cirrhosis, liver cancer and death. Effective therapies are now
available. However, these treatments are costly and it is therefore necessary
to prioritise the people in greatest need, especially those experiencing rapid
Abnormal fat deposits in the liver.
As the factors
associated with the progression of liver fibrosis in the context of HCV
infection are poorly understood, investigators from Cornell Medical College,
New York, designed a retrospective study to determine the rates and risk
factors for disease progression. The research involved 378 people with HCV infection who had two or more liver biopsies between 1997 and 2013. The
investigators analysed the effect of demographic, epidemiological and virologic
factors on progression of fibrosis.
Individuals had a
mean age of 48 years, 59% were male, 60% were white and 87% had infection with
HCV genotype 1. Approximately a third – 31% – had co-infection with HIV.
At the time of
first biopsy, 36% of people had mild (grade 1) liver inflammation, 57% had
moderate (grade 2) inflammation and 7% had severe (grade 3) inflammation.
Fibrosis was absent in 12% of people (stage 0), whereas 32% had stage 1
(mild) fibrosis, 39% had stage 2 (moderate) fibrosis and 16% had stage 3
Fibrosis stage 2
and above was associated with elevated inflammation at the time of the first
biopsy (OR = 9.00; 95% CI, 5.53-14.64, p < 0.001). Fatty liver disease
(steatosis) was present in the majority – 59% – of people and this was
associated with both higher fibrosis stage (OR= 2.39; 95% CI, 1.38-4.14, p =
0.002) and higher inflammation (OR = 4.07; 95% CI, 2.26-7.35, p < 0.001) at
A total of 558
consecutive biopsy pairs were available for analysis. Mean duration between
first and last biopsies was 7 years, and the mean period between adjacent
biopsies was 4 years.
57% of people advanced at least one biopsy stage, 16% progressed two stages and
7% developed cirrhosis.
for potential confounders, factors associated with fibrosis progression were
no/mild fibrosis at first biopsy (OR = 13.51; 95% CI, 7.44-24.53, p < 0.001)
and at least one ALT flare (200u/l threshold) during follow-up (OR = 2.64; 95%
CI, 1.30-5.36, p = 0.007).
progression rate from fibrosis stages 0 to 1 was highest – three times higher than the rate of
progression between stages 2 and 3.
at stage zero for an average of 2.55 years and at stage 2 for an average of
Analysis of the
subset of people who developed cirrhosis showed that progression occurred in
a mean of eight years of follow-up. Factors associated with progression were
genotype-3 infection (p = 0.04), ALT level (p < 0.001). Higher fibrosis
stage at first biopsy and lower baseline platelet count were both of borderline
“We did not
observe an association between fibrosis progression and HIV co-infection,”
comment the investigators. “This could potentially be explained by
well-controlled HIV viremia in co-infected patients.”
The authors also point out that their findings call into question the
assumption that fibrosis progresses at a steady, or linear, rate, and
they conclude, “we
found varying stage-specific progression rates in patients with chronic
In an accompanying
editorial, Daniel S Fierer of Mount Sinai Hospital, New York, said that
understanding factors associated with fibrosis progression in people with HCV infection was “a crucial medical issue.” However, he was not convinced
that all people with HIV/HCV co-infection even in the modern antiretroviral era have a
risk of fibrosis progression. Citing his own research in
HIV-positive gay men who acquired HCV via sexual transmission, he noted
of these people experienced rapid fibrosis progression, suggesting
that the acquisition of HCV after HIV is more harmful to the liver than
evidence is that they rapidly progress to having moderate levels of
and some of those with the most immunocompromise experience further
progression to cirrhosis,” writes Fierer. Yet Zeremski and colleagues
report that progression from mild or no cirrhosis to moderate fibrosis
was the most frequently-observed form of progression in their study,
suggesting that what Fierer and colleagues are observing is a common
pattern regardless of HIV status, and that Fierer's cohort are
distinctive more for having well-established dates of HCV infection than
for their previous HIV infection.