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Editorial Board: Emmet
B. Keeffe, MD (Chair); M. Eric Gershwin, MD; Ira S. Goldman, MD; John L.
Gollan, MD, PhD; Kris V. Kowdley, MD; Paul Martin, MD; Marion G. Peters, MD |
Clinical Study Highlights in Hepatitis C
39th
Annual Meeting of the European Association for the Study of the Liver
Peginterferons in chronic hepatitis C (CHC)
Peginterferon α-2a
plus ribavirin improves quality of life. C. O'Brien and
colleagues reported the effect of a sustained virological response (SVR) on
health-related quality of life (HRQL) in 514 patients with CHC and persistently
normal alanine aminotransferase (PNALT) levels randomized to
receive peginterferon alfa-2a 180 µg/week plus ribavirin 800
mg/day for 24 or 48 weeks versus no treatment. The SVR rate with 48 weeks of combination therapy was 52%. Responders
had significantly better Short Form 36 (SF-36) Health Survey and Fatigue Severity
Scale (FSS) scores than nonresponders and untreated controls.
The differences between responders and nonresponders were significant in the
following SF-36 domains: general health, pain index, role physical, social
function, vitality and physical component scores, and also for the FSS. These
results suggest that current treatment guidelines might be expanded to include
treatment of CHC patients with PNALT levels. (C. O'Brien et al. J Hepatol 2004;39:499)
Peginterferon alfa-2b plus ribavirin is effective for treatment of recurrent HCV
infection after liver transplantation. S.
Lorenzini and colleagues reported the results of an open-label observational
study in which 18 patients experiencing recurrent HCV infection after liver
transplantation were treated with peginterferon alfa-2b (80 µg/week)
and ribavirin (600 mg/day). All
patients with an end of treatment response (6/18; 33%) obtained an SVR after 6
months of follow-up. The SVR rate was higher in naïve patients (3/7; 43%) than
in previous nonresponders (3/11; 27%). Numerous adverse events occurred,
including decompensation in cirrhotic patients, anemia and neutropenia. Adverse
events were effectively managed by dose reduction and/or growth factor therapy.
(S. Lorenzini et
al. J Hepatol 2004;39:489)
Lower incidence of hemolytic anemia with
viramidine versus ribavirin. R.
Gish and colleagues reported a clinical trial in which 180 patients were randomized to
receive peginterferon alfa-2a
180 µg/week in combination with oral viramidine 400 mg (n=47), 600 mg (n=43), 800 mg (n=45) administered bid
or ribavirin 1000/1200 mg/day (n=45). No significant difference was found between viramidine
(800-1600 mg/day) and ribavirin in the proportion of patients achieving undetectable HCV RNA or a
≥2 log decrease in viral load following 24 weeks of treatment.
Significantly fewer patients with anemia were seen in the viramidine versus the
ribavirin arm (2% versus 24%). Other adverse events were similar among the
treatment groups. (R.
Gish et al. J Hepatol 2004;39:479)
Human immunodeficiency virus
(HIV)/HCV coinfection
High SVR rate with peginterferon alfa-2a
plus ribavirin therapy in coinfected patients (APRICOT Study). F.J. Torriani and colleagues reported
the final 72-week results on the efficacy of peginterferon alfa-2a plus
ribavirin in 868 coinfected subjects randomized to
48 weeks of treatment with interferon
alfa-2a (3 MIU tiw) plus ribavirin 800 mg/day, peginterferon alfa-2a 180
µg/week plus placebo, or peginterferon alfa-2a 180
µg/week plus ribavirin. SVR rates were 40%, 20% and 12% in patients
receiving peginterferon alfa-2a plus ribavirin, peginterferon alfa-2a plus placebo and interferon alfa-2a plus ribavirin, respectively (P<0.0001 for
peginterferon alfa-2a plus ribavirin versus either comparator; P=0.008 for peginterferon
alfa-2a plus placebo versus interferon alfa-2a plus ribavirin). The percentage of patients with undetectable
HCV RNA at both end-of-treatment and end-of-follow-up underscored the importance of adding ribavirin to
interferon-based regimens to prevent relapse
in this population. The observed SVR of 40% supports the
use of peginterferon alfa-2a plus ribavirin for treatment of HCV
in coinfected patients. (F.J.
Torriani et al. J Hepatol 2004;39:92)
Coinfected patients with an EVR have a good
chance for SVR. M. Rodriguez-Torres and colleagues examined the
predictive value of an EVR by analyzing data from 289
coinfected patients randomized to 48 weeks of peginterferon alfa-2a
180 µg/week plus ribavirin 800 mg/day in the APRICOT study.
An EVR was present in 204 patients (71%), of whom 114 (56%)
achieved an SVR. 46% (50/110 patients) and 70% (59/84 patients) with genotype 1
and 2/3, respectively, with an EVR achieved an SVR.
The investigators concluded that coinfected patients without an EVR are
highly unlikely to develop an SVR, and thus treatment
with peginterferon alfa-2a plus ribavirin may
be discontinued, resulting in decreased adverse events and a savings in
healthcare resources. These results are similar to those previously reported
for patients with HCV infection without HIV infection. (M.
Rodriguez-Torres et al. J Hepatol 2004;39:507)
Early virologic response
Prolonged
peginterferon alfa-2a plus ribavirin is a better approach for patients without
an EVR. J.M. Sánchez-Tapias and colleagues
reported a clinical study comparing SVR rates in treatment-naïve patients
randomized to 48 (n=165) and 72 (n=161) weeks of peginterferon alfa-2a 180
µg/week and ribavirin 800 mg/day therapy after failing to achieve a rapid
virologic response at week 4 of combination therapy. For patients who were HCV
RNA-positive at week 4, SVR rates at the end of a 24-week follow-up were
significantly higher for those with a longer treatment duration (45% versus 32%
at 48 and 72 weeks). Extended treatment also significantly reduced the risk of
relapse and was especially beneficial in genotype 1 patients, but did not
increase the incidence of side effects, including neutropenia and
thrombocytopenia. (J.M. Sánchez Tapias et al. J Hepatol 2004;39:509)
EVR can predict SVR in patients receiving
peginterferon alfa-2a plus ribavirin. P.J.
Pockros and colleagues reported a clinical trial designed to determine whether
an EVR at week 12 of peginterferon alfa-2a 180 µg/week plus ribavirin 800
mg/day combination therapy has high negative predictive value for achieving an
SVR in patients with PNALT levels. The overall SVR rates were 39% (64/212) and
52% (109/210) in patients treated for 24 and 48 weeks, respectively (P<0.001
at 24 weeks). Among patients treated for 48 weeks, those with an EVR at week 12
were more likely to achieve an SVR than those without an EVR. Patients with CHC
may be suitable for treatment with peginterferon plus ribavirin irrespective of
ALT activity. (P.J. Pockros et al. J Hepatol 2004;39:503)
Single-dose 24-hour interferon-sensitivity
test predicts SVR. P. Ferenci and colleagues reported a
prospective phase III clinical trial designed to determine whether a
single-dose interferon-sensitivity test predicts SVR following treatment with
peginterferon alfa-2a 180 µg/week and ribavirin 1000/1200 mg/day and either
amantidine 100 mg bid or placebo in patients infected with genotype 1. The
24-hour virologic response test was found of value in predicting SVR; the
best outcome was observed for patients showing ≥1.4 log decrease
in HCV RNA. This testing may be useful in identifying patients
requiring a longer duration of combination therapy. (P.
Ferenci et
al. J Hepatol
2004;39:476)
STUDIES ON NATURAL HISTORY
Control of HIV viral load slows progression of liver fibrosis. N Bräu and colleagues studied the
effect of a reduction in HIV viral load achieved through antiretroviral therapy
on the fibrosis progression rates in 685 consecutive HCV-infected patients,
which included 297 HIV (+) and 388 HIV (-) patients. No difference in fibrosis
progression rates was seen between HIV/HCV-coinfected patients and
HCV-monoinfected patients. In the HIV/HCV-coinfected patients, the fibrosis
progression rate was strongly correlated with log10 HIV RNA levels,
but only weakly with CD4+ cell count. Undetectable HIV load was associated with
a slower fibrosis progression rate compared to any detectable HIV load. (N Bräu
et al. J Hepatol 2004;39:91)
Natural history of ascites and
prognostic factors for survival in cirrhotic patients.
LIVER TRANSPLANTATION
HCV recurrence is a severe event in
living donor liver transplantation. M Garcia-Retortillo and colleagues studied prognostic
factors associated with severe HCV recurrence (defined as the presence of
cirrhosis on liver biopsy and/or clinical decompensation) in 117 consecutive
HCV-infected patients undergoing liver transplantation. Severe HCV recurrence
occurred in 17 (18%) of 95 patients receiving a cadaveric organ compared to 9
(41%) of 22 patients receiving a liver from a living donor. Living donor liver
transplantation was independently associated with severe HCV recurrence. The
aggressive HCV liver disease recurrence seen in living donor liver recipients
may compromise graft and patient survival. (M Garcia-Retortillo et al. J Hepatol 2004;39:2)
DIAGNOSIS
C-reactive protein (CRP) is a highly
specific marker of alcoholic hepatitis. G Vanbiervliet and colleagues studied the diagnostic
accuracy of CRP in 102 alcoholics negative for HBsAg and anti-HCV. The level of
CRP increased significantly with the severity of acute alcoholic hepatitis and
with the presence of inflammation in the areas of fibrosis (p<0.001). For
threshold values of 15 and 25 mg/L of CRP, specificities of 89% and 97%,
respectively, were observed. The 25 mg/L threshold yielded a diagnostic
accuracy of 77.4%. Determination of CRP will allow the avoidance of liver
biopsy in some alcoholics with severe alcoholic hepatitis before treatment with
corticosteroids. (G Vanbiervliet et al. J Hepatol 2004;39:81)
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