Liver
Fibrosis Common in HIV+ People without Viral Hepatitis
SUMMARY
Non-invasive blood tests indicate that people with HIV
have a significant risk of liver fibrosis progression
even if they do not have hepatitis B or C coinfection. |
By
Liz Highleyman
As effective antiretroviral
therapy has dramatically reduced the risk of death due
to AIDS-defining opportunistic illnesses, liver disease has
become an increasingly common cause of morbidity and mortality
among people with HIV.
In
many cases liver fibrosis -- which can progress to liver cirrhosis
or cancer -- is caused by coinfection with hepatitis
B or C. Less is known about
the incidence of liver fibrosis and its progression and risk
factors in people with HIV alone.
As
reported in the May
1, 2011, issue of Clinical Infectious Diseases,
Monia Mendeni and colleagues looked at the evolution and predictors
of liver fibrosis in HIV positive people without hepatitis
B or C, as determined by 2 non-invasive biomarker indices,
FIB-4 and APRI.
FIB-4
is calculated based on alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) levels, platelet count, and
patient age. APRI uses the AST-to-platelet ratio. These non-invasive
tests are not as reliable as liver biopsy for detecting and
staging fibrosis, but they are safer, less expensive, and
easier to repeat to assess changes over time.
This
prospective observational study included 1112 HIV patients
who started highly active antiretroviral therapy (HAART) at
2 large Italian referral centers between 1996 and 2006. The
study -- Hepatotoxicity of Different Kinds of Antiretrovirals
-- was initially designed to look at liver toxicity associated
with HIV drugs.
About 60% of participants were men and the mean age was 38
years. The median CD4 cell count was 201 cells/mm3, indicating
that half had serious immune suppression. Nearly 60% were
on boosted protease inhibitor-based HAART, with most of the
remainder taking NNRTIs. About 25% used "d-drugs"
-- didanosine (ddI;
Videx), stavudine
(d4T; Zerit), or zalcitabine (ddC; Hivid) -- which have
been linked to liver toxicity.
Participants were tested for liver function, HIV RNA levels,
and CD4 T-cell counts every 3 months. The average follow-up
duration was 2249 days (about 6 years). FIB-4 and APRI scores
fell into 3 classes, based on standard cut-off values, corresponding
to absent or minimal fibrosis, moderate fibrosis, and advanced
or severe fibrosis.
The researchers looked at concordance or agreement between
FIB-4 and APRI scores, and used Cox regression analysis to
analyze predictors of transition between fibrosis classes.
Patients who started out with class 3 scores at baseline were
excluded from the progression analysis.
Results
 |
The
concordance between FIB-4 and APRI was found to be "moderate"
(kappa 0.57). |
|
Among
1074 patients with FIB-4 class 1 or 2 at baseline, the
incidence of transition to a higher class was 24%, or
0.064 per person-year of follow-up. |
|
Among
1079 people with APRI class 1 or 2 at baseline, the incidence
of transition to a higher class was greater at 31%, or
0.099 per person-year. |
|
The
incidence of transition to a FIB-4 score > 3.25 or
APRI > 1.5 -- indicating advanced fibrosis -- was 6%
(0.013 per person-year) and 8% (0.018 per person-year),
respectively. |
|
45%
of patients according to FIB-4 and 52% according to APRI
reverted back to lower fibrosis classes, with no further
worsening. |
|
In a multivariate analysis, having HIV viral load <
500 copies/mL predicted lower risk of transition to a
higher fibrosis class according to both FIB-4 and APRI,
while higher CD4 count was protective only according to
FIB-4. |
|
There
was a trend toward protection in patients who continued
ART with no interruptions. |
|
Additional
risk factors for fibrosis progression were age >40
years, male sex, history of injection drug use, higher
degree of fibrosis at baseline, higher baseline gamma-glutamyl
transpeptidase level, and use of "d-drugs." |
|
Risk
factors were similar for transition to FIB-4 > 3.25
and APRI > 1.5. |
Based
on these findings, the researchers concluded, "our results
suggest a possible benefit associated with earlier HAART initiation,
provided that the effectiveness of HAART is sustained and
treatment with [d-drugs] is avoided."
The
concordance study showed "moderate agreement" between
FIB-4 and APRI, they elaborated in their discussion. "FIB-4
considers patient age and ALT level, whereas APRI does not,
which produced different results with the predefined cut-off
values. In particular, several patients who were in class
1 according to FIB-4 were in class 2 according to APRI. Therefore,
APRI seemed to be stricter than FIB-4, but the clinical meaningfulness
of this finding is questionable. In fact, both FIB-4 and APRI
were shown to have the highest positive predictive value only
for the most severe stages of liver fibrosis."
"The
effect of HAART as first-line treatment (including either
an NNRTI or a [boosted] PI) and the trend toward significant
protection in patients who continued [combination] ART without
any interruption provided consistent results," they added.
"Overall, the positive impact of the control of HIV infection
suggests that early initiation of HAART may provide an opportunity
to prevent liver fibrosis progression."
Investigator
affiliations: Institute of Infectious and Tropical Diseases,
University of Brescia, Brescia, Italy; Spedali Civili di Brescia,
Brescia, Italy; Institute of Infectious Diseases, Policlinico
di Bari, Bari, Italy.
5/3/11
Reference
M
Mendeni, E Foca, D Gotti, et al. Evaluation of Liver Fibrosis:
Concordance Analysis between Noninvasive Scores (APRI and
FIB-4) Evolution and Predictors in a Cohort of HIV-Infected
Patients without Hepatitis C and B Infection. Clinical
Infectious Diseases 52(9):1164-1173 (free
full text). May 1, 2011.
