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Two
Studies Show Rapid Liver Fibrosis Progression in HIV-HCV Coinfected Patientsl Two recently published studies added further weight to the research
showing faster liver disease progression in people with HIV. Study
1 As
reported in the October 2007 issue of AIDS, researchers from Johns Hopkins
Medical School conducted a prospective study to assess the incidence of liver
fibrosis progression among HIV-HCV coinfected individuals, and whether HCV or
HIV treatment alters the course of progression. The
study cohort included 174 non-cirrhotic coinfected adults who had at least 2 liver
biopsies with a median interval of 2.9 years. About three-quarters were men, most
(86%) were African American, and the median age was 44 years. About
60% were receiving Biopsies
were scored by a single pathologist using the Ishak modified histological activity
index scoring system (range F0-F6). Significant fibrosis progression was defined
as an increase of at least 2 Ishak fibrosis units (stages) between the first and
second biopsies. Results ·
On
initial biopsy, 77% had absent or minimal fibrosis (stage F0-F1), while 9% had
moderate fibrosis (F2) and 11% had advanced fibrosis or cirrhosis (F3-F4). ·
48%
had no change in fibrosis scores between the first and second biopsies. ·
24%
experienced significant fibrosis progression (≥ 2 units) -- about twice
the rate in HCV monoinfected individuals -- and 22% had a 1 unit increase. ·
Among
progressors, the median fibrosis progression rate (FPR) was 0.83 units per year.
·
Factors
associated with HIV disease and its treatment (CD4 count, HIV viral load, type
or duration of HAART) and measures related to HCV disease (genotype, HCV viral
load) were not significantly different in progressors and non-progressors. ·
37
patients (21%) received anti-HCV treatment, but only 3 (2.7%) achieved sustained
virological response (SVR). ·
Overall,
fibrosis progression was not associated with anti-HCV treatment. ·
However,
the 3 patients who achieved SVR were non-progressors. ·
In
a multivariate analysis, the only factor associated with fibrosis progression
was an elevated (≥ 2.5 x upper limit of normal) serum AST level between
biopsies (odds ratio 3.4). “Over
a 3-year interval, significant fibrosis progression can occur in coinfected individuals
even if minimal disease was detected on initial biopsy,” the authors concluded.
“In this context, factors other than treatment for HIV or HCV modify the risk
of fibrosis progression.” It
is interesting that people who received anti-HCV therapy were as likely to experience
fibrosis progression as untreated individuals. This may be attributable to the
very low rate of sustained response, although some prior studies have indicated
that interferon-based therapy has a beneficial effect on fibrosis even in non-responders. Study
2 In
the second study, published in the November 2007 Journal of Viral Hepatitis,
French researchers studied fibrosis progression in HIV-HCV coinfected patients
who were not receiving anti-HCV therapy. They retrospectively analyzed data from
32 patients with 2 successive liver biopsies. The median interval between the
two biopsies was 49 months (range 24-80). About three-quarters (79%) were on antiretroviral
therapy at the time of the first biopsy and the mean CD4 cell count was 470 cells/mm3.
Results ·
On
the first biopsy, most patients had absent or minimal (stage F0-F1) fibrosis,
except for 2 with moderate (F2) fibrosis. ·
On
the second biopsy, the fibrosis stage distribution was as follows: o
F0:
0%; o
F1:
41%; o
F2:
34%; o
F3:
19%; o
F4:
6%. ·
The
mean fibrosis progression rate was 0.25 units per year. ·
9
patients (28%) were considered rapid progressors (progression by ≥ 2 units);
their FPR was 0.5 units per year. ·
There
was no association between fibrosis progression and patient age, alcohol consumption,
CD4 cell count, HIV viral load, HCV genotype, or ALT or AST levels. ·
Analysis
of the treatment received between the 2 biopsies did not find any correlation
between fibrosis progression and any specific drugs. ·
15
patients (45%) started anti-HCV therapy based on the results of the second biopsy.
In
conclusion, the authors wrote, “Liver fibrosis in HIV-HCV coinfected patients
should be evaluated at least every 3 years, as 9 of 32 (28%) of our patients progressed
by at least 2 fibrosis points despite a high CD4 cell count.” They
added that development of non-invasive methods of fibrosis evaluation should allow
for more frequent monitoring. 11/02/07 References
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