Coinfected People with Normal Liver Enzymes Respond Well to Interferon-based
positive people with normal levels of the liver enzyme alanine
aminotransferase (ALT) who received hepatitis C therapy using
pegylated interferon plus ribavirin responded as well as individuals
with elevated ALT, according to findings presented at the
XVIII International AIDS Conference (AIDS
2010) last month in Vienna.
of people with chronic hepatitis C virus
(HCV) infection will not progress to advanced liver disease such
carcinoma, but a larger proportion will develop some degree of liver
fibrosis, and research indicates that progression is more likely
among HIV/HCV coinfected
individuals than among those with HCV alone.
with signs of liver disease progression are typically advised to receive
treatment. Liver biopsy is the "gold standard" for determining
extent of liver damage, but elevated ALT -- a sign of liver inflammation
-- is also often considered an indicator of active disease progression
and need for treatment.
month's conference, Miguel Angel von Wichmann de Miguel from Hospital
de Donostia in San Miguel, Spain, and colleagues presented data from
an analysis of hepatitis C treatment in HIV/HCV coinfected patients
with persistently normal ALT, a group that has been less extensively
This single-arm, open-label, Phase 4 (post-market) study included 68
coinfected participants at multiple centers in Spain. Just over half
(35 people, or 52%) were classified as "case" patients with
normal ALT (at least 5 normal measurements over a 24-month period),
with the rest (33 people, or 49%) designated "control" patients
with elevated ALT (that is, the type of patients usually treated and
About three-quarters were men, the median age was 43 years, most (74%)
had hard-to-treat HCV genotypes 1 or 4, and just over half had high
baseline HCV viral load (? 800,000 IU/mL). Almost all (89%) were on
antiretroviral therapy (ART) with undetectable HIV viral load and the
median CD4 cell count was 461 cells/mm3.
All participants received 180
mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day
weight-adjusted ribavirin for 48 weeks, with a 24-week post-treatment
follow-up period to assess sustained virological response (SVR), or
continued undetectable HCV RNA.
The AIDS 2010 report included results at week 4 (rapid virological response,
or RVR) and week 12 (early virological response, or EVR); follow-up
is continuing to determine SVR rates.
of patients in the normal ALT group achieved RVR, or undetectable
HCV RNA at week 4 of therapy, compared with 33% in the elevated
ALT group, not a significant difference (P = 0.99).
rates, or at least a 2-log reduction in HCV RNA by week 12, diverged
a bit more -- 80% in the normal ALT and 96% in the elevated ALT
group -- but the difference did not reach statistical significance
(P = 0.10).
of complete EVR, or undetectable HCV RNA at week 12, were 52% and
68%, respectively, also not a significant difference.
levels decreased in both groups, but remained lower in the initially
normal ALT group.
were no significant differences between the 2 groups with regard
to safety profiles.
of patients in the normal ALT group and 45% in the elevated ALT
group experienced adverse events.
1 patient in each group required blood cell growth factors to manage
anemia or neutropenia.
patients in the normal ALT group compared with the elevated ALT
group (19% vs 40%, respectively) received interferon or ribavirin
dose adjustments or discontinued treatment due to adverse events,
but again this did not reach statistical significance (P = 0.25).
on these findings, the researchers concluded, "Response to peginterferon
alfa-2a plus ribavirin in HIV/HCV coinfected patients with persistently
normal ALT levels is comparable to those with elevated ALT levels."
Investigator affiliations: Hospital de Donostia, San Sebastian, Spain;
Hospital Universitario de Bellvitge, Barcelona, Spain; Hospital La Paz,
Madrid, Spain; Hospital de Cruces, Bilbao, Spain; Hospital La Princesa,
Madrid, Spain; Consorci Sanitari de Terrasa, Terrasa, Spain; Hospital
Clinic de Barcelona, Barcelona, Spain; Hospital General Universitario
de Alicante, Alicante, Spain; Hospital Santa Creu i Sant Pau, Barcelona,
Spain; Hospital Joan XXIII, Tarragona, Spain.
MA von Wichmann de Miguel, M Santin, J Gonzalez, and others (CONTRA).
Phase IV, open label study to evaluate peginterferon alpha-2a plus ribavirin
for treatment of chronic hepatitis C in HIV-infected patients with persistently
normal alanine aminotransferase. XVIII International AIDS Conference
(AIDS 2010). Vienna, July 18-23, 2010. (Abstract).