People with HIV who were cured of hepatitis C experienced
greater reductions in liver stiffness if they were taking an antiretroviral
regimen that contained a non-nucleoside reverse transcriptase inhibitor (NNRTI),
Spanish researchers report in the Journal of Antimicrobial Chemotherapy.
Curing hepatitis C infection with direct-acting antiviral
treatment can result in improvements in liver health if liver damage is not too
advanced. Fibrosis, or scarring of liver tissue caused by an inflammatory
reaction to long-term hepatitis C infection, may be reduced after hepatitis C
is cured. Liver stiffness is a marker of fibrosis and can be measured by
passing sound waves through the liver using a non-invasive device (Fibroscan,
or transient elastography). A measurement above 14 kilopascals indicates severe
liver damage, or cirrhosis.
Measuring liver stiffness after hepatitis C has been cured
can identify people who remain at higher risk of liver complications.
A non-invasive test, used instead of a biopsy, to measure the stiffness
or elasticity of the liver using an ultrasound probe.
However, it is unclear if the choice of antiretroviral regimen has any effect on liver regeneration. Some antiretroviral drugs less frequently used nowadays have been associated with liver toxicity but the effects of modern antiretroviral therapy on liver regeneration are unknown.
Spanish researchers associated with the GEHEP multicentre
cohort wanted to investigate whether the choice of antiretroviral regimen
influenced liver regeneration after hepatitis C is cured in people with HIV.
They recruited 313 people with HIV on antiretroviral
treatment who had a liver stiffness measurement above 9.5kPa before starting
direct-acting antiviral treatment for hepatitis C and who were cured of
hepatitis C. People were eligible for inclusion in the study if their liver
stiffness was measured at the time of confirmatory testing for sustained
virologic response to direct-acting antiviral treatment, 12 weeks after
completion of treatment.
Of the 313 participants, 74 were treated with an
antiretroviral regimen that included an NNRTI (either rilpivirine or efavirenz)
and 239 were treated with a regimen containing two NRTIs and an integrase
inhibitor, or a protease inhibitor plus one or two NRTIs (some received a
boosted protease inhibitor and lamivudine).
NNRTI recipients had significantly lower alcohol
consumption, higher median CD4 counts (665 vs 527) and had a higher frequency
of undetectable viral load (95% vs 80%) than other participants but were
similar in age and gender.
The median liver stiffness measurement was 16.7 kPa in the
NNRTI group and 17.3 kPa in the non-NNRTI group, a non-significant difference.
Forty per cent of the NNRTI group and 34% of the non-NNRTI group had a liver
stiffness measurement below 14 kpA prior to direct-acting antiviral treatment.
After direct-acting antiviral treatment, people receiving an
NNRTI-based regimen had significantly greater reductions in liver stiffness
than people receiving other regimens (35% vs 29%, p=0.018).
A multivariate analysis controlling for age, sex, HCV
genotype 3 infection, NRTI backbone and propensity score, showed that NNRTI
treatment was the only factor apart from genotype 3 infection that had a
significant association with reduction in liver stiffness. The drugs used in
the NRTI backbone did not affect the degree of change in liver stiffness
However, a sub-analysis confined to the 200 people in the
study population with cirrhosis at baseline (liver stiffness above 14 kPA)
showed no significant advantage to NNRTI-containing treatment compared to other
regimens in achieving a liver stiffness reduction below 14 kPA. No other factor
was associated with improvement in liver stiffness in people with cirrhosis.
Thirty-five per cent of people with cirrhosis had experienced an improvement in
liver stiffness to a measurement below 14 kPa by the time of post-treatment
measurement. Forty-five per cent of people receiving an NNRTI experienced a
reduction in liver stiffness below 14 kPa, the highest proportion of any
sub-group, but this change did not reach statistical significance, possibly due
to the relatively low number of people taking NNRTIs in this population.
The researchers say that NNRTIs may speed up the process of
liver regeneration by encouraging apoptosis (programmed cell death). They
recommend further research in people with HIV to determine the long-term
impact of NNRTI treatment on liver stiffness after hepatitis C cure.