After being cured of hepatitis C, markers of liver fibrosis
do not continue to decline one year beyond cure, a study of women living with
HIV and hepatitis C in the United States has found. The results challenge the
assumption that most people with hepatitis C can expect to experience a
long-term improvement in liver health after hepatitis C cure and highlight the
need for ongoing monitoring of liver fibrosis after hepatitis C, say the study
investigators.
Studies in people with hepatitis C alone have shown evidence
of short-term improvements in liver fibrosis (liver tissue becoming scarred and
hardened) after they are cured of hepatitis C. However, there is less evidence
on fibrosis regression in people with HIV and hepatitis C.
The Women’s Interagency HIV Study (WIHS) has been recruiting
and following women with HIV since 1994 and monitors participants every six
months. To investigate the evolution of liver fibrosis in women who undergo
hepatitis C treatment, WIHS investigators identified 116 women with HIV and
hepatitis C in the cohort who had been treated with direct-acting antivirals
for hepatitis C and had at least one pre-treatment visit within two years of
starting treatment or a visit no more than a year prior to treatment (the
peri-treatment visit) and at least one post-treatment visit within two years of
completing treatment.
Glossary
- regression
Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.
One hundred and three had pre-treatment data, 116 had
peri-treatment data, 115 had a post-treatment visit within one year and 107 had
a post-treatment visit within two years of completing treatment.
The study population was predominantly Black (68%) and the
median CD4 count was above 500. Around 90% were taking antiretroviral
treatment, three quarters had an undetectable viral load, and integrase
inhibitor use increased so that by two years after completing hepatitis C
treatment, 57% of participants were taking an integrase inhibitor.
The investigators calculated an Enhanced Liver Fibrosis
score by measuring levels of three biomarkers of liver protein growth and
remodelling. When levels of these proteins are high, liver injury and
inflammation are causing fibrosis. The investigators also calculated the APRI
and FIB-4 scores for fibrosis using liver enzyme and platelet measurements, to
check whether the trajectory of measurements was similar for each scoring
method.
Compared to the pre-treatment period, liver fibrosis values
were lower in the peri-treatment and post-treatment periods. The median ELF
value declined from borderline moderate-to-severe fibrosis in the pre-treatment
period, to moderate fibrosis at subsequent visits. Median APRI and FIB-4 values
declined between periods, but remained in the mild and moderate ranges,
respectively.
When comparing changes in liver fibrosis scores in the six
months after treatment and from six months to two years after treatment, the
investigators found that whereas scores fell sharply in the six months after
completing treatment (-7% on the ELF score, 50% on APRI and 15% on FIB-4),
changes in the subsequent follow-up period were negligible (-0.5% on the ELF
score, -1.6% on APRI and -3% on FIB-4). The reduction in score in the six-month
to two-year period was only statistically significant for the FIB-4 score.
The researchers say that longer-term studies are needed to
evaluate whether liver fibrosis in people with HIV continues to decline in
severity or hits a plateau in the years after hepatitis C is cured. “Continued
monitoring of liver fibrosis and interventions to mitigate its progression in
people with HIV after HCV cure remain essential,” the researchers conclude.