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http://www.hivandhepatitis.com/hep_c/news/050203a.html
Extending Peginterferon Plus Ribavirin Therapy to 72 Weeks in Late Responders
with Genotype 1 Chronic HCV Can Produce a Sustained Virologic Response
Most HCV-infected individuals in the US have genotype 1 HCV, which is the most
difficult genotype to treat successfully. In patients with HCV genotype 1, the
sustained virologic response (SVR) to 48 weeks of treatment with peginterferon
plus ribavirin (the current standard of care) is about 42%.
Study results suggest that one primary factor in SVR is rapid hepatitis C virus
(HCV) RNA clearance, which ranges from 75% for patients who clear in 12 weeks to
only 32% for those who lose HCV RNA at week 24.
Some researchers propose that extending therapy in patients who cleared HCV RNA
between weeks 12 and 24 (i.e., late responders) could increase SVR.
In a Letter to the Editor of the current issue of Hepatology (May 2003),
researchers at the Liver Clinic, Gastroenterology Institute, in Kaplan, Israel
describe results of a small study in nine patients:
"We selected 9 patients with chronic hepatitis C who were infected with genotype
1 in treatment with pegylated interferon alfa-2b plus ribavirin who cleared HCV
RNA between weeks 12 and 24 for therapy prolonged to 72 weeks. Three were men
and 6 were women, with a median age of 41 ± 14.57 years. All patients had
elevated alanine aminotransferase levels, positive HCV RNA, and a liver
examination showing chronic hepatitis.
"Patients were treated with a mean dose of 1.0 microgram/kg of peginterferon
alfa-2b once weekly (PEG-Intron) plus 800 mg/d of ribavirin (Rebetol). HCV RNA
was analyzed by using a quantitative, real-time, reverse-transcriptase
polymerase chain reaction technique with a lower limit of detection of 100 IU/L.
"Eight patients completed therapy and 6 months of follow-up. One patient stopped
therapy at week 48 because of thyroid alterations. Table 1 shows patient
characteristics and changes in HCV-RNA levels from baseline to week 12. .
Table 1. Baseline Characteristics of the 9 Patients Treated and HCV-RNA
Changes in Logs From Baseline to Week 12 and HCV-RNA Decline From Baseline to
Week 12
Case
Sex
Age (y)
Histology
ALT (UI/L)
HCV-RNA (UI/mL) Logs Baseline
HCV-RNA (UI/mL) Logs Week 12
HCV-RNA Decline Logs Between Baseline and Week 12
1
M
41
Moderate CAH
75
5.97
2.04
-3.93
2
M
36
Moderate CAH
186
5.40
3.00
-2.40
3
F
35
Mild CAH
95
6.23
2.68
-3.55
4
F
63
Moderate CAH
90
5.84
2.04
-3.80
5
F
61
Moderate CAH
83
6.61
3.38
-3.23
6
M
30
Moderate CAH
97
6.18
2.92
-3.31
7
F
52
Moderate CAH
104
6.23
2.81
-3.36
8
F
20
Moderate CAH
89
5.48
2.30
-3.18
9
F
52
Moderate CAH
78
5.47
2.18
-3.29
Abbreviations: ALT, alanine aminotransferase; CAH, chronic active
hepatitis.
"In all patients, HCV RNA was positive at week 12 of therapy but undetectable at
week 24 and throughout the 72 weeks of therapy. At week 24 of follow-up, 7
patients maintained an SVR and one relapsed (case 3).
"This study, with a small number of patients, showed that prolonged combination
therapy with peginterferon and ribavirin is very useful in late virologic
responders because it increases SVR. HCV-RNA determination has an important role
not only in the decision to stop therapy but also in better adjusting therapy.
"Currently, nonresponders can be detected by a quantitative HCV-RNA test at week
12, showing a decline of less than 2 logs in HCV-RNA concentrations. In these
patients, combination therapy should be stopped because the probabilities of a
sustained response are almost nil. In patients who achieve an early virologic
response, the probabilities of achieving an SVR were 80% for those who cleared
HCV RNA at week 12 and sooner, and 40% for those who achieved a 2-log reduction
in HCV-RNA concentrations but still remained HCV-RNA positive as a recent review
of multicenter studies has shown.
"All of our patients had a 2-log decline but remained HCV-RNA positive at week
12 and, taking into account the previous results, their probabilities of
achieving an SVR are lower than those patients who were HCV-RNA negative at week
12. In this subgroup of patients, with a slower decline in HCV-RNA levels,
usually genotype 1 patients with high baseline viral levels, continuing therapy
to 72 weeks could be the best way to ensure an SVR with acceptable tolerability
and safety.
"In summary, extending therapy with peginterferon alfa plus ribavirin to 72
weeks for late virologic responders may induce a higher SVR. These results merit
further prospective, randomized, controlled studies, using the optimal doses of
peginterferon and ribavirin for longer duration versus the current standard
48-week therapy in this subset of patients."
05/02/03
Reference
M Buti and others (Liver Clinic, Gastroenterology Institute, Kaplan, Israel).
Extending combination therapy with peginterferon alfa-2b plus ribavirin for
genotype 1 chronic hepatitis C late responders: A report of 9 cases. Letter to
the Editor. Hepatology 37 (5):1226. May 2003.
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