|
Treatment
of Patients with Advanced Hepatitis C with a Low Accelerating
Dosage Regimen of Peginterferon/Ribavirin Can Result in Favorable
Clinical Outcomes
Patients with advanced hepatitis C
virus (HCV) are at risk of death and are candidates for liver
transplantation. After transplantation, HCV recurs and may
rapidly progress to cirrhosis and graft loss. Treatment is
needed to prevent progression of disease and minimize HCV
recurrence after liver transplantation.
In
the present study, researchers at the Colorado School of Medicine
evaluated the effectiveness, tolerability, and outcome of
a low accelerating dose regimen (LADR) of antiviral therapy
with standard interferon and peginterferon/ribavirin in patients
with advanced HCV.
One
hundred twenty-four patients (male/female ratio 81:43; age
range 37-71 years; 70% genotype 1) were treated with LADR.
Sixty-three
percent had clinical complications of cirrhosis
(ascites, spontaneous bacterial peritonitis, varices, variceal
hemorrhage, and encephalopathy).
The
mean Child-Turcotte-Pugh (CTP) score was 7.4 +/- 2.3, and
the mean MELD score was 11.0 +/- 3.7. Fifty-six patients were
CTP class A, 45 were class B, and 23 were class C.
Results
·
Either
interferon
alfa-2b (Intron A 1.5 MU three times a week
[n = 119]) or peginterferon
alfa-2b (PegIntron 0.5 mcg/kg/wk [n = 5]) plus ribavirin (Rebetol
600 mg/d) was used initially; Peginterferon
alfa-2b (PegIntron) or peginterferon
alfa-2a (Pegasys initiated at 90 mcg/wk) plus ribavirin
(Rebetol or Copegus) was used in the
re-treatment of 15 patients.
·
Fifty-seven
patients (46%) were HCV RNA-negative at end of treatment response
(EOTR), and 67 (54%) were nonresponders.
·
Twenty-seven
patients (22%) achieved SVR with the initial course of treatment.
·
Thirty
patients recurred, for a relapse
rate of 53%.
·
Eleven
patients who relapsed were retreated,
3 with peginterferon/ribavirin and 8 with interferon/ribavirin,
and became HCV RNA-negative.
·
Three
of these 11 underwent transplantation,
and 2 have remained free of HCV after transplantation; the
other 8 relapsed again.
·
Twelve
nonresponders
were retreated with peginterferon/ribavirin; 1 (8%) of these
12 had sustained virological
response (SVR) and is stable in long-term follow-up.
·
Thus,
a total of 30 (24%) of the 124 patients remained HCV RNA-negative
in long-term follow-up after antiviral therapy.
·
Sixteen
patients discontinued treatment for side effects, and 51 were
virological nonresponders.
·
Eleven
of these 51 had less than 1 month of treatment either because
of urgent transplantation (n = 8) or dropout from therapy
(n = 3).
·
All
8 with urgent transplantation had recurrent hepatitis C.
·
The
remaining 40 discontinued therapy because of a lack of virological
response, but 25 of these 40 also experienced side effects.
In
conclusion, the authors write, “We treated 124 patients with
advanced hepatitis C with clinical or biochemical decompensation
using a LADR of interferon and ribavirin. Forty-six percent
cleared HCV RNA from blood on treatment, and 24% had sustained
clearance of HCV RNA. “
“Virological
response was highest in patients with non-1 genotypes, CTP
class A, and who achieved a full course of therapy. Eighty
percent of patients rendered HCV RNA-negative by LADR who
underwent liver transplantation remained free of HCV after
transplantation.”
“Our
experience suggests that antiviral therapy in patients with
advanced HCV may stabilize disease and reduce the risk of
post-transplantation recurrence.”
Section of Hepatology, Division of
Gastroenterology and Hepatology, Department of Medicine, University
of Colorado School of Medicine, 4200 East 9th Avenue, Denver,
CO, USA.
09/21/05
Reference
G
T Everson and others. Treatment of advanced hepatitis C
with a low accelerating dosage regimen of antiviral therapy.
Hepatology 42(2): 255-262. August 2005.
|
