Can Cirrhotics Achieve a Histologic Response?
Study Design: 271 patients with cirrhosis or bridging fibrosis
were randomly assigned to receive subcutaneous treatment with 3 million
units of interferon alfa-2a three times weekly (88 patients), 90 µg
of peginterferon alfa-2a once weekly (96), or 180 µg of peginterferon
alfa-2a once weekly (87). Treatment lasted 48 weeks and was followed by
a 24-week follow-up period. Study assessed efficacy by measuring HCV RNA
and alanine aminotransferase and by evaluating liver-biopsy specimens.
A histologic response was defined as a decrease of at least 2 points on
the 22-point Histological Activity Index.
Most of the 271 patients enrolled had cirrhosis at base line. As is common
with other trials in patients with liver disease,2,3 nearly one third
of the patients did not return for second biopsies. Among the 184 patients
with paired liver biopsies, the proportion who had a histologic response
was lower among the patients assigned to receive unmodified interferon
(31 percent) than among those assigned to 90 µg of peginterferon
alfa-2a (44 percent [P=0.22]) and those assigned to 180 µg (54 percent
[P=0.02]) (Table 3). A histologic response correlated with a sustained
virologic response; among the patients with a virologic response at week
72, 80 percent of those assigned to receive interferon alfa-2a also had
a histologic response, as did 100 percent of those assigned to 90 µg
of peginterferon alfa-2a and 88 percent of those assigned to the 180-µg
dose. The virologic response was similar among patients with bridging
fibrosis or cirrhosis. A histologic response was seen in 26 percent, 33
percent, and 35 percent, respectively, of patients who did not have a
sustained virologic response. The histologic response also correlated
with the biochemical response at week 72: 40 percent, 79 percent, and
82 percent of the patients who had a biochemical response to interferon
alfa-2a or peginterferon alfa-2a at 90 µg or 180 µg, respectively,
also had a histologic response.
The rates of sustained virologic response (the response at week 72) were
8 percent, 15 percent, and 30 percent in patients assigned to unmodified
interferon alfa-2a, 90 µg of peginterferon alfa-2a, and 180 µg
of peginterferon alfa-2a, respectively (P=0.001 for the comparison between
180 µg of peginterferon alfa-2a and interferon alfa-2a [Table 3]).
A response to therapy at week 12 predicted a sustained response; at week
12, all of the 26 patients who had a sustained response to 180 µg
of peginterferon alfa-2a had had a decrease in viral load by a factor
of at least 100 as compared with base line, and 23 of them had had undetectable