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Effect of interferon-alpha and ribavirin therapy on
serum GB virus C/hepatitis G virus (GBV-C/HGV) RNA levels in
patients chronically infected with hepatitis C virus and
GBV-C/HGV.
Lau JY, Qian K, Detmer J, Collins ML, Orito E, Kolberg JA,
Urdea MS, Mizokami M, Davis GL
Department of Medicine, University of Florida, Gainesville
32610, USA.
J Infect Dis 1997 Aug;176(2):421-6
GB virus C/hepatitis G virus (GBV-C/HGV) is a newly
described virus associated with hepatitis in humans, and
GBV-C/HGV coinfection is common in patients chronically
infected with hepatitis C virus (HCV). To determine the
clinical impact of GBV-C/HGV infection in such patients and
the effect of interferon-alpha and ribavirin therapy on serum
GBV-C/HGV RNA levels, GBV-C/HGV RNA was detected and
quantitated in serum samples from 62 chronically infected HCV
patients by a combination of a qualitative nested reverse
transcription-polymerase chain reaction and a newly developed
quantitative branched DNA assay: 10 patients were positive for
serum GBV-/HGV RNA. There were no differences in the clinical,
biochemical, and histologic features of the patients with
GBV-C/HGV-HCV coinfection compared with those with HCV
infection alone. Interferon-alpha treatment caused a marked
but usually transient reduction in serum GBV-C/HGV RNA, and
ribavirin had, at most, a modest antiviral effect.
Interferon-ribavirin for chronic hepatitis C with
and without cirrhosis: analysis of individual patient data of
six controlled trials. Eurohep Study Group for Viral
Hepatitis.
Schalm SW, Weiland O, Hansen BE, Milella M, Lai MY, Hollander
A, Michielsen PP, Bellobuono A, Chemello L, Pastore G, Chen
DS, Brouwer JT
Department of Hepatogastroenterology and Biostatistics,
Erasmus University Hospital Rotterdam, Rotterdam, The
Netherlands.
Gastroenterology 1999 Aug;117(2):408-13
BACKGROUND & AIMS: The aim of this study was to compare
interferon (IFN)-ribavirin combination therapy with IFN
monotherapy in chronic hepatitis C with particular focus on
its efficacy in cirrhosis.
METHODS: A multivariate analysis of individual patient data
of all randomized controlled trials using an IFN-ribavirin
arm, reported between 1991 and March 1998, was performed.
Centers included 1 Asian and 5 European university-based
referral centers for liver disease. A total of 197 patients
with chronic hepatitis C received IFN-alpha (3 MU three times
weekly) and ribavirin (1-1.2 g daily) for 6 months, and 147
patients received IFN-alpha (3 MU three times weekly) for 6
months. Patients were characterized according to previous IFN
therapy, presence of cirrhosis, and genotype 1. Efficacy of
therapy was evaluated by assessing the sustained response rate
by logistic regression analysis.
RESULTS: Patients without cirrhosis treated with
IFN-ribavirin had a significantly higher sustained response
rate than those treated with IFN, approximately 3-fold for
previously untreated patients (IFN-ribavirin: genotype 1, 33%;
genotype 2/3, 65%; IFN: genotype 1, 8%; genotype 2/3, 24%). In
cirrhosis, sustained response rates with IFN-ribavirin
(previously untreated: genotype 1, 7%; genotype 2/3, 24%) were
also significantly higher than those with IFN (previously
untreated: genotype 1, 1%; genotype 2/3, 5%). Clinical
relevant superiority of combination therapy over IFN
monotherapy was also observed for relapse; the same trend was
observed for nonresponders. Tolerance for IFN-ribavirin was
similar for patients with or without cirrhosis.
CONCLUSIONS: Combination with ribavirin significantly
enhances the sustained response rate of IFN therapy in major
patient types (cirrhosis, genotype 1) with chronic hepatitis
C. Thus, IFN-ribavirin combination is likely to become the
antiviral therapy of choice for cirrhosis caused by hepatitis
C.
A randomized trial of ribavirin and
interferon-alpha vs. interferon-alpha alone in patients with
chronic hepatitis C who were non-responders to a previous
treatment. Multicenter Study Group under the coordination of
the Necker Hospital, Paris, France.
Pol S, Couzigou P, Bourliere M, Abergel A, Combis JM, Larrey
D, Tran A, Moussalli J, Poupon R, Berthelot P, Brechot C
Assistance Publique/Hopitaux de Paris, Necker, France.
J Hepatol 1999 Jul;31(1):1-7
BACKGROUND/AIM: Fifty percent of patients infected with
hepatitis C virus (HCV) show no response to alpha-interferon,
and no alternative therapy has thus far proven to be
effective. Therapeutic combination with ribavirin and
alpha-interferon has shown promising results in naive patients
and in relapsers, but based on limited series, it was reported
to be inefficient in non-responders. The aim of our study was
therefore to explore and compare, in a randomized trial, the
tolerance and potential efficacy of alpha-interferon alone
with a sequential combination of ribavirin and the same
alpha-interferon regimen in those patients.
METHODS: Sixty-four non-responder patients were randomized
in the alpha2b-interferon group (a 6-month course at a dosage
of 6 MU followed by a 6-month course of 3 MU three times
weekly subcutaneously) and 62 in the "combination" group
(sequential combination of the same alpha2b-interferon therapy
preceded by a 2-month course of ribavirin which was then
associated for 2 months with alpha2b-interferon at a daily
dosage of 1.0 or 1.2 g).
RESULTS: Treatment withdrawal was necessary for six
patients from the alpha-interferon and eight patients from the
combination group. Normalization of aminotransferase
activities was significantly more frequent after the 4-month
course of ribavirin with 2 months of interferon than after 2
months of interferon alone (52.8 vs. 26.2%, p<0.01), but
this difference was not maintained after ribavirin withdrawal.
Disappearance of serum HCV RNA (PCR) was significantly more
frequent at the end of treatment in the combination group
(24.5 vs. 7.7%, p=0.02), but did not differ 6 months after the
end of therapy (9.8 and 8.3%, respectively). The long-term
response was not associated with liver status (cirrhosis vs.
absence of cirrhosis) or genotype. Mean viremia was
significantly lower in long-term responders than in
non-responders or relapsers in both groups (p<0.001 for the
interferon group and p<0.05 for the combination group), but
the large extent of viral load precluded reliable prediction.
The pre- and post-treatment hepatitis activity index did not
differ between the two groups. While a crude histopathological
improvement in the hepatitis activity index for a given
patient was more frequently observed in the combination group
(69.2 vs. 35.9%, p<0.01), improvement as defined by a
decrease of at least 2 in the hepatitis activity index was
significant only for lobular necrosis and degeneration.
CONCLUSIONS: This study demonstrates the efficacy of the
combination of ribavirin/alpha-interferon in non-responders.
Indeed, (i) it is fairly tolerated; (ii) it increases the rate
of the initial biological response, and of the virological
response by decreasing breakthrough, though this benefit is
not sustained; and (iii) it induces a significant histological
improvement in necrosis. A simultaneous and prolonged
combination of ribavirin/alpha-interferon should be further
evaluated in non-responders.
Health-related quality of life in chronic hepatitis
C: impact of disease and treatment response. The
Interventional Therapy Group.
Ware JEJr, Bayliss MS, Mannocchia M, Davis GL
Health Assessment Lab, New England Medical Center, Boston,
MA, USA.
jware@qmetric.com
Hepatology 1999 Aug;30(2):550-5
Hepatitis C infects nearly 4 million Americans. Most have
chronic hepatitis C (CHC), which progresses to cirrhosis in
about 20% of patients. Interferon treatment leads to transient
responses in about 40% of patients and apparent eradication of
infection in 7% to 40% of patients. In this report, we
document the impact of CHC on health-related quality of life
(HQL), and changes in HQL among treatment responders. Three
hundred twenty-four CHC patients from 10 countries who had
relapsed after responding to interferon-alfa therapy were
randomized to monotherapy (IFN alfa-2b + placebo) or
combination therapy (IFN alfa-2b + ribavirin), treated for 24
weeks, and followed up for 24 weeks. HQL was assessed using
the Hepatitis Quality of Life Questionnaire (HQLQ), containing
the generic SF-36 Health Survey, three additional generic
scales, and two hepatitis-specific scales. Before treatment,
CHC patients were impaired in 5 of 8 SF-36 concepts (physical
functioning, role-physical, general health, vitality, and
social functioning) in comparison with matched population
norms. Sustained virological response (SVR) to treatment
yielded improvements on three generic scales (vitality, social
functioning, and health distress) and the CHC-specific health
distress scale. Overall response to treatment (SVR plus
histological improvement) yielded the same pattern of
improvements with additional gains in generic general health
and CHC-specific limitations. Successful treatment of CHC
improved HQL as measured by both CHC-specific and generic
measures of functional health and well being.
Combination therapy for chronic hepatitis C:
interferon and ribavirin.
Christie JM, Chapman RW
Department of Gastroenterology, John Radcliffe Hospital,
Oxford.
Hosp Med 1999 May;60(5):357-61
Hepatitis C virus (HCV) infection is one of the commonest
causes of liver cirrhosis and hepatocellular carcinoma. This
review deals with treatment of chronic HCV infection with a
combination of interferon and ribavirin. Recent trials have
shown that approximately 40% of patients will clear HCV with
combination treatment. This is an important advance in the
treatment of this serious viral infection.
Retreatment of non-responder or relapser chronic
hepatitis C patients with interferon plus ribavirin vs
interferon alone.
Milella M, Santantonio T, Pietromatera G, Maselli R, Casalino
C, Mariano N, Genchi C, Pastore G
Clinic of Infectious Diseases, University of Bari,
Italy.
Ital J Gastroenterol Hepatol 1999
Apr;31(3):211-5
BACKGROUND AND AIM: Interferon-alpha treatment of chronic
hepatitis C is beneficial in only 20-30% of patients. This
study evaluates if combination therapy with Interferon-alfa
plus ribavirin is effective in inducing a response in patients
who did not respond to, or relapsed after, a standard
Interferon-alfa treatment.
PATIENTS AND METHODS: A total of 88 patients, 49
non-responders and 39 relapsers to previous Interferon-alfa
therapy, were randomized to receive either natural
Interferon-alfa (6 MU t.i.w.) plus ribavirin (1000 mg/daily)
or natural Interferon-alfa alone (6 MU t.i.w.) for 6 months.
All were followed for 12 months after stopping therapy. Serum
aminotransferase levels were assessed monthly and HCV RNA was
evaluated by RT-PCR (Amplicor, Roche) at end of therapy and
the end of follow-up.
RESULTS: After treatment, a higher response rate defined as
return to normal of aminotransferases and absence of serum HCV
RNA was observed among patients treated with
Interferon-alfa-ribavirin: 4/28 (14%) vs 1/21 (5%)
non-responder patients and 9/19 (47%) vs 5/20 (25%) in the
relapsers group. At the end of follow-up, a sustained response
was found only in the combination treatment group: 4% and 32%
in non-responder and relapser patients, respectively.
CONCLUSIONS: Our results suggest that retreatment with
natural Interferon-alfa plus ribavirin is more effective than
Interferon-alfa alone in increasing the response rate in
patients with chronic hepatitis C who relapse after a previous
standard IFN treatment whereas it is less effective in
non-responder patients.
[Experience with combined interferon alpha-2b and
ribavirin in the therapy of chronic hepatitis C. Experience
with one-year therapy of 100 patients. Multicenter
study].
Feher J, Lengyel G, Balint T
Orszagos Belgyogyaszati Intezet, Budapest.
Orv Hetil 1999 May 30;140(22):1235-8
It has been established that the long term interferon
therapy in patients with chronic hepatitis C is able to
produce sustained remission only in about 20 per cent of the
cases. According to the newest data the combined interferon
and ribavirin therapy significantly increases the remission of
patients in naive, non-responder or relapsed cases. Clinical
remission was confirmed by enzyme activity of alaninamino
transferase (ALT) and HCV-RNA-PCR tests. In order to get exact
data of the remission rate and the symptom free period, a
prospective multicenter study has been introduced in Hungary.
Ten leading hepatologic units have been involved into the
trial. Till now the combined therapy with interferon-alfa-2b
(3 MU, three times a week) and ribavirin--(1000-1200 mg daily)
for one year has been finished in 100 cases with chronic
hepatitis C. The mean value of ALT activity decreased near to
the normal level, in 58 patients it was in the normal range.
Side effects with mild or moderate grades have been found in
31 cases. The interim report of this multicenter study confirm
the efficacy of this combined therapy in chronic hepatitis
C.
Changes in serum hepatitis C virus RNA in
interferon nonresponders retreated with interferon plus
ribavirin: a preliminary report.
Nyberg L, Albrecht J, Glue P, Gianelli G, Zambas D, Elliot M,
Conrad A, McHutchison J
Division of Gastroenterology/Hepatology, Scripps Clinic and
Research Foundation, La Jolla, California 92037, USA.
J Clin Gastroenterol 1999 Jun;28(4):313-6
Ribavirin, a nucleoside analogue, inhibits replication of
RNA and DNA viruses and may control hepatitis C virus (HCV)
infection through modulation of anti-inflammatory and
antiviral actions. Ribavirin monotherapy has no effect on
serum HCV RNA levels. In combination with interferon, this
agent appears to enhance the efficacy of interferon. The aim
of this study was to monitor serum HCV RNA levels early during
therapy with interferon and ribavirin compared with that
previously seen in the same patients during interferon
monotherapy. Five patients who previously showed no response
to therapy with interferon alfa 3 MU three times weekly for 6
months were retreated with the identical dose of interferon
alfa 2b in combination with oral ribavirin 1,000 mg/day. Serum
HCV RNA levels were monitored at baseline, week 4, week 8, and
week 12 of therapy by a quantitative multicycle polymerase
chain reaction assay. In the first 8 to 12 weeks, serum HCV
RNA levels showed a greater decrease in all patients when
retreated with combination therapy compared with interferon
alone. Mean (+/- SEM) serum HCV RNA levels for interferon
therapy alone were 3.3 +/- 0.95, 1.2 +/- 0.95, 1.6 +/- 1.2,
and 2.3 +/- 1.2 x 10(6) copies/ml at week 0, 4, 8, and 12,
respectively. This was compared with 3.3 +/- 0.83, 0.3 +/-
0.2, 0.03 +/- 0.02, and 0.15 +/- 0.14 x 10(6), respectively,
for the interferon and ribavirin group (p < 0.07 at week
8). Two of five patients had undetectable serum HCV RNA during
combination therapy. Combination therapy with interferon and
ribavirin in prior interferon nonresponders reduces serum HCV
RNA levels compared with interferon alone. This may suggest
some additional antiviral effect of ribavirin when given with
interferon.
Pilot study of triple antiviral therapy for chronic
hepatitis C in interferon alpha non-responders.
Brillanti S, Foli M, Di Tomaso M, Gramantieri L, Masci C,
Bolondi L
Department of Internal Medicine and Gastroenterology,
Policlinico S. Orsola, University of Bologna, Italy
sbrillanti@csi.com
Ital J Gastroenterol Hepatol 1999
Mar;31(2):130-4
BACKGROUND: No effective therapy exists for interferon
non-responding chronic hepatitis C patients.
AIMS: Pilot study evaluating the potential efficacy and
safety of triple antiviral therapy in interferon-alpha
non-responders.
PATIENTS AND METHODS: Twenty consecutive adult patients
with chronic hepatitis C who had failed to respond to a
6-month course of interferon alpha were randomly assigned to
receive a combination of interferon alpha + oral ribavirin
(double therapy), or the same combination + oral amantadine
(triple therapy), for 6 months.
RESULTS: By the end of therapy, normal alanine transaminase
(biochemical response) was obtained in 2 out of 10 patients on
double therapy but in 7 out of 10 on triple therapy (p <
0.05), and negative serum hepatitis C virus (HCV) RNA
(virological response) occurred in 1 out of 10 patients on
double therapy but in 7 out of 10 patients on triple therapy
(p < 0.01). Six months after therapy, biochemical response
was sustained in 1 (double therapy) and 4 patients (triple
therapy), respectively, and the virological response was
sustained in no patient on double therapy but in 3 patients on
triple therapy.
CONCLUSIONS: Triple antiviral therapy seems to be able to
induce biochemical and virological responses in interferon
alpha non-responders with chronic hepatitis C.
[Effectiveness of interferon, glycyrrhizin
combination therapy in patients with chronic hepatitis
C].
[Article in Japanese]
Abe Y, Ueda T, Kato T, Kohli Y
Second Department of Internal Medicine, Fukui Medical
School.
Nippon Rinsho 1994 Jul;52(7):1817-22
SNMC (stronger Neominophagen C), whose active component is
glycyrrhizin (a saponin extracted from licorice) has been
utilized to improve the liver function in Japan. To assess the
effectiveness of interferon (IFN), SNMC combination therapy in
patients, who did not respond to IFN therapy alone, we
investigate 28 patients with histology of CAH 2B at 12 weeks
after IFN administration. 15 patients received IFN alone
continuously (group A), and 13 patients received IFN with SNMC
(group B) for 12 weeks thereafter. Normalization of serum ALT
level was observed in 33.3% of group A and in 64.3% of group
B. Disappearance of serum HVC RNA was 13.3% in group A and
38.5% in group B. But these data were not significant
statistically. Histological improvement was not significant,
between group A and B by Knodel's HAI score, but reversal of
histological grade (Europe classification) was noted more
frequently in group B. A case of posttransfusion hepatitis
type C, exacerbated by IFN therapy is reported. HLA class I
antigen was strongly expressed in the liver tissue after
administration of IFN. In this case, potentiation of cellular
immunity was thought to be the cause of the exacerbation and
IFN, SNMC combination therapy was useful in improving liver
function.
Plasma selenium levels and risk of hepatocellular
carcinoma among men with chronic hepatitis virus
infection.
Yu MW, Horng IS, Hsu KH, Chiang YC, Liaw YF, Chen CJ
School of Public Health, College of Public Health, National
Taiwan University, Taipei.
Am J Epidemiol 1999 Aug 15;150(4):367-74
Both experimental and epidemiologic studies have linked a
low dietary intake of selenium with an increased risk of
cancer. The authors examined the association between plasma
selenium levels and risk of hepatocellular carcinoma (HCC)
among chronic carriers of hepatitis B and/or C virus in a
cohort of 7,342 men in Taiwan who were recruited by personal
interview and blood draw during 1988-1992. After these men
were followed up for an average of 5.3 years, selenium levels
in the stored plasma were measured by using hydride atomic
absorption spectrometry for 69 incident HCC cases who were
positive for hepatitis B surface antigen (HBsAg) and/or
antibodies against hepatitis C virus (mostly HBsAg positive)
and 139 matched, healthy controls who were HBsAg positive.
Mean selenium levels were significantly lower in the HCC cases
than in the HBsAg-positive controls (p = 0.01). Adjusted odds
ratios of HCC for subjects in increasing quintiles of plasma
selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively.
The inverse association between plasma selenium levels and HCC
was most striking among cigarette smokers and among subjects
with low plasma levels of retinol or various carotenoids.
There was no clear evidence for an interaction between
selenium and alpha-tocopherol in relation to HCC risk.
Two cases of hepatitis C treated with herbs and
supplements.
Stern E
J Altern Complement Med 1997 Spring;3(1):77-82
The treatment of two cases of hepatitis C using herbal
medicine and nutritional supplements is presented. The
selection of medicinals was based upon both biomedical
findings and traditional Chinese medical diagnosis. The text
describes the course of each patient's illness documented both
subjectively and objectively using blood values and
traditional Chinese medicine analysis as parameters.
Explanation and/or citations are given for each medicinal
used. Both patients improved during the course of treatment;
subjective signs and symptoms (especially fatigue) as well as
liver enzyme levels demonstrated improvement.
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