meta analysis about hbv -some search result from pubmed

medline

1: Am J Public Health  2002 Oct;92(10):1619-28

Chinese herbal medicine and interferon in the treatment of chronic hepatitis B:
a meta-analysis of randomized, controlled trials.

McCulloch M, Broffman M, Gao J, Colford JM Jr.

Pine Street Clinic, San Anselmo, CA, USA.

OBJECTIVES: This meta-analysis was conducted to examine the effectiveness of
Chinese herbal medicine (either alone or with interferon alfa) in treating
chronic hepatitis B. METHODS: We searched the TCMLARS, AMED, CISCOM, EMBASE,
MEDLINE, and Cochrane Collaboration databases and then hand-searched the
articles' bibliographies. RESULTS: Chinese herbal medicine significantly
increased seroreversion of HBsAg and was equivalent to interferon alfa in
seroreversion of HBeAg and hepatitis B virus (HBV) DNA; Chinese herbal medicine
combined with interferon alfa significantly increased seroreversion of HBsAg,
HBeAg, and HBV DNA. The Chinese herbal medicine active component bufotoxin
combined with interferon alfa significantly increased HBeAg and HBV DNA
seroreversion. The Chinese herbal medicine active component kurorinone was
equivalent to interferon alfa in seroreversion of HBeAg and HBV DNA.
CONCLUSIONS: Although the quality of existing studies was poor, these data
suggest that further trials of Chinese Herbal Medicine and interferon in chronic
hepatitis B infection are justified.

Publication Types:
Meta-Analysis

PMID: 12356611 [PubMed - indexed for MEDLINE]



2: J Gastroenterol Hepatol  2002 Apr;17(4):406-8

Management of patients with chronic hepatitis B.

Liaw YF.

Liver Research Unit, Chang Gung University Memorial Hospital, 199 Tung Hwa North
Road, Taipei, Taiwan. [email protected]

Better understanding of hepatitis B virus (HBV) replication and the natural
history and immunopathogenesis of chronic hepatitis B, together with the
introduction of effective agents with different mechanisms of action, is the
basis for better therapeutic strategies against chronic hepatitis B. Substantial
experience has now been accumulated in the use of some of these drugs, and an
Asia-Pacific Consensus has been reached on indications for their use. The goals
of therapy and aspects of general management will be reviewed here. Among
currently available drugs, alpha-interferon therapy gives a response rate
(hepatitis B e antigen (HBeAg) seroconversion) of 30-40% compared with 10-20% in
matched controls, but patients with lower alanine aminotransferase (ALT), higher
HBV-DNA, and immunosuppressed patients have a poorer response, and
alpha-interferon can be dangerous in cirrhosis. Meta-analysis of four controlled
trials also suggests that thymosin-alpha1 is effective, but more studies are
needed. Lamivudine has been most extensively studied. It is effective in terms
of HBV-DNA loss, ALT normalization, HBeAg seroconversion, and improvement in
histology, as well as being well tolerated. After 1 year of treatment, HBeAg
seroconversion rate increased with higher pretherapy ALT levels, suggesting that
patients with stronger endogenous antiviral defenses to kill hepatocytes
harboring covalently closed circular DNA have a better response to direct
antiviral effects. Lamivudine is also beneficial in HBeAg negative chronic
hepatitis B, and patients with decompensated cirrhosis and HBV replication.
However, genotypic-resistant tyrosine-methionine-aspartate-aspartate (YMDD)
mutations start to emerge after 9-10 months of lamivudine therapy, and their
incidence increases more quickly than the HBeAg seroconversion rate durating
prolonged therapy. Thus the benefits of long-term lamivudine must be balanced
against concern about YMDD mutations, and the durability of treatment response.
There are encouraging preliminary results for adefovir dipivoxil, entecavir,
emtricitabine, clevudine and other nucleoside/nucleotide analogs in the early
stages of appraisal; entecavir and adefovir dipivoxil appear effective in
patients with YMDD mutants. Further development of new drugs and new strategies,
such as combination or sequential therapy, may help to better achieve the goals
of treatment for chronic hepatitis B in the new century. Copyright 2002
Blackwell Publishing Asia Pty Ltd

Publication Types:
Review
Review, Tutorial

PMID: 11982720 [PubMed - indexed for MEDLINE]


4: Aliment Pharmacol Ther  2001 Dec;15(12):1899-905

The efficacy of thymosin in the treatment of chronic hepatitis B virus
infection: a meta-analysis.

Chan HL, Tang JL, Tam W, Sung JJ.

Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese
University of Hong Kong, Hong Kong.

BACKGROUND: Trials of thymosin treatment in chronic hepatitis B virus infection
have been small and the results have been inconsistent. AIM: To conduct a
meta-analysis to evaluate the efficacy of thymosin treatment in chronic
hepatitis B virus infection. METHODS: Randomized controlled trials comparing
thymosin for over 24 weeks vs. placebo (or usual care) in the treatment of
chronic hepatitis B virus infection were identified through MEDLINE, EMBASE and
the Cochrane Register of Clinical Trials. Biochemical (normalization of
transaminases) and virological (loss of hepatitis B virus DNA and hepatitis B e
antigen) responses were analysed using the intention-to-treat method. The odds
ratio was used to measure the magnitude of the efficacy. RESULTS: Five trials
(353 patients) were identified. The odds ratio (95% confidence interval) of the
virological response of thymosin over placebo at the end of treatment, 6 months
post-treatment and 12 months post-treatment were 0.56 (0.2-1.52), 1.67
(0.83-3.37) and 2.67 (1.25-5.68), respectively. There was an increasing trend of
the virological response with time since the cessation of thymosin treatment
(P=0.02). There was no difference in the biochemical response between the
thymosin and placebo groups at the end of treatment, 6 months post-treatment and
12 months post-treatment. CONCLUSIONS: Thymosin is effective in suppressing
viral replication in chronic hepatitis B virus infection, but the effect is
delayed until 12 months after the cessation of treatment.

Publication Types:
Meta-Analysis

PMID: 11736720 [PubMed - indexed for MEDLINE]

8: Int J Clin Pharmacol Ther  2001 Jan;39(1):4-11

Antiviral drugs in chronic hepatitis B: review and meta-analysis.

Malaguarnera M, Restuccia S, Ferlito L, Mazzoleni G, Giugno I, Pistone G.

Department of Internal Medicine and Geriatrics, University of Catania, Italy.

Many researchers have attempted to identify the drugs capable of acting on the
viral replication cycle and maintaining clinical remission in chronic hepatitis
B. We evaluated the efficacy of antiviral drugs in chronic hepatitis B, by
examination of 20 controlled and non-controlled trials conducted between 1985
and 1996. In chronic hepatitis B, adenine arabinoside and its monophosphate did
not achieve satisfactory results, even though combination therapy with cortisone
seemed to achieve very good results (remission rates ranging from 45% to 66% in
patients treated). Lamivudine did not seem to furnish lasting effects in chronic
hepatitis B, because many patients relapse after suspension of the treatment due
to the appearance of HBV variants resistant to the drug. Contrasting results
were observed with famciclovir. Treatment of chronic hepatitis B, with this drug
seemed capable of reducing HBV-DNA serum levels by a mean of 50% compared to
pretreatment values, with normal alanine aminotransferase levels in about 30% of
treated patients. Ganciclovir treatment of chronic hepatitis B seemed to furnish
good, but transient, results. Even if no antiviral drug represented a valid
alternative to interferon, antivirals may become the drugs of choice in chronic
hepatitis B, because they are aimed at the etiology of disease.

Publication Types:
Meta-Analysis
Review
Review, Tutorial

PMID: 11204937 [PubMed - indexed for MEDLINE]



9: J Gastroenterol Hepatol  2000 May;15 Suppl:E46-52

Use of immunomodulatory therapy (other than interferon) for the treatment of
chronic hepatitis B virus infection.

Lau GK.

University Department of Medicine, Queen Mary Hospital, Hong Kong SAR, China.
[email protected]

Chronic hepatitis B virus (HBV) infection is a major health threat in Asia. In
order to design a better therapeutic regimen, the underlying mechanism of HBV
viral persistence must be understood. Immunological studies have found that
impaired HBV virus-specific T cell reactivity is the major cause of chronic
infection, whereas strong and multispecific T cell responses to HBV are
associated with long-term control, but not elimination of the virus.
Furthermore, in the serological clearance of hepatitis B surface antigen (HBsAg)
in allogeneic haematopoietic cell transplantation, HBsAg seroconversion is
associated with activation of the donor's hepatitis B core antigen-specific CD4+
T lymphocytes. This suggests that the donor's hepatitis B core antigen-specific
CD4+ T cells provide 'intermolecular T cell help' for the HBsAg seroconversion.
These findings are relevant to the future development of therapeutic vaccines or
DNA vaccine as immunotherapy for chronic hepatitis B. Apart from
interferon-alpha, thymosin alpha1 (Talpha1) has been investigated for treatment
of chronic hepatitis B. Meta-analysis of 4 randomized controlled studies
investigating the safety and efficacy of Talpha1 monotherapy for the treatment
of chronic hepatitis B showed that 6 months treatment with Talpha1 (1.6 mg twice
weekly) almost doubles the sustained response rate (36%) compared with controls
(19%; P=0.04). However, more specific immunological approaches are being
developed; notably, hepatitis B core antigen-based therapeutic vaccine was found
to induce T cell proliferative responses in chronically infected hepatitis B
patients to the T helper epitope included in the construct. However, the
cytokine profile observed suggested the induction of a T helper 0/T helper 2
CD4+ T cell response rather than T helper 1 response. Thus, its combination with
interferon-gamma or interleukin-12, which might reverse the CD4+T cell response,
should be considered. In the future, it is likely that different types of
combination therapy may have to be tailor-made for chronic HBV infection with
different virological and immunological profiles and different degrees of liver
damage.

Publication Types:
Review
Review, Academic

PMID: 10921382 [PubMed - indexed for MEDLINE]



10: Acta Gastroenterol Belg  1998 Apr-Jun;61(2):219-23

Interferon: a meta-analysis of published studies in pediatric chronic hepatitis
B.

Vajro P, Migliaro F, Fontanella A, Orso G.

Department of Pediatrics, University of Naples Federico II, Italy.

Perinatally infected Asian children respond poorly to interferon (IFN) therapy.
In contrast, IFN therapy seems to be more effective in Caucasian children who
presumably acquired HBV infection later in life. We reviewed seven controlled
studies of IFN treatment in children with chronic hepatitis B living in western
countries (216 treated, and 200 untreated children). Before treatment all
patients were HBeAg and HBV-DNA +ve, with a biopsy proven chronic hepatitis B.
Ages ranged 1 to 16 years (mean age 7 years). Most patients were Caucasian.
Protocols which have been adopted may schematically be divided into protocols
which have used high doses of IFN (7.5 to 10 MU/sqm/TIW), and protocols which
have used low doses of IFN (3 to 6 MU/sqm/TIW), with a short (3 to 6 months) or
a long duration of treatment (12 months). The percentage of treated patients
who, at the end of treatment, lost HBV-DNA (that in most studies corresponded
also to HBeAg serum conversion) averages 20 to 58% (mean 35.5%) that is much
higher than that observed in controls (range 8-17%; mean 11.4%). A better trend
is probably observed only in patients who received the treatment for a longer
period of time. At the end of treatment, low percentages of patients lost BsAg
(range 0-4%; mean 1.1%): again higher doses tend to be more effective than lower
doses. In some studies IFN has been shown to significantly accelerate the
termination of viral replication. Data on longer term outcome of IFN treatment
in Caucasian children are scarce and confirm results obtained at short and at
medium-term FU either in horizontally either in perinatally infected children.
Results from few randomized controlled trials of interferon therapy with
prednisone priming in Chinese and Caucasian children were comparable to results
obtained without prednisone. In one study steroid priming did not potentiate the
effect of IFN, however it existed a tendency of prednisone to improve HBeAg
clearance in patients with normal aspartate aminotransferase, and alanine
aminotransferase activity lesser than 100 u/l. In most studies, factors
positively influencing response rates of IFN treatment are represented by severe
inflammation in the basal liver biopsy, high basal levels of serum transaminase,
low basal levels of serum HBV-DNA. Vertical transmission may be considered a
factor adversely affecting the response to IFN treatment both in Chinese and
Caucasian population. In general in most controlled studies, the majority of
responders have shown a significant reduction in hepatic inflammation and
transaminase normalization. Children have a low risk of developing severe
IFN-induced side effects. Adverse reactions and worsening of health-related
quality of life were tolerable and did not seem to be a limiting factor for IFN
therapy in young candidates.

Publication Types:
Meta-Analysis

PMID: 9658614 [PubMed - indexed for MEDLINE]



11: Int J Cancer  1998 Jan 30;75(3):347-54

A meta-analysis of epidemiological studies on the combined effect of hepatitis B
and C virus infections in causing hepatocellular carcinoma.

Donato F, Boffetta P, Puoti M.

Cattedra di Igiene, Universita di Brescia, Italy. [email protected]

The aim of the study was to assess whether co-infection by hepatitis-B virus
(HBV) and hepatitis-C virus (HCV) is associated with a higher risk of developing
hepatocellular carcinoma (HCC) than each infection alone. A meta-analysis of
data published up to June 1997 was performed. HBsAg and anti-HCV antibodies or
HCV RNA (anti-HCV/HCV RNA) were considered as serological markers of current HBV
and HCV infection respectively. A total of 32 case-control studies were suitable
for a quantitative overview. The summary odds ratios (OR) were 13.7 for HBsAg
positivity and 11.5 for anti-HCV/HCV RNA positivity. The OR for anti-HCV was
lower among studies using second- or third-generation anti-HCV or HCV RNA (OR,
8.2) with respect to studies with first-generation anti-HCV test (OR, 19.1).
When combining data from the studies with second- or third-generation anti-HCV
or HCV RNA, the OR for HBsAg positivity and anti-HCV/HCV RNA negativity was 22.5
(95% confidence interval (CI), 19.5-26.0), the OR for anti-HCV/HCV RNA
positivity and HBsAg negativity was 17.3 (95% CI, 13.9-21.6), and the OR for
both markers positivity was 165 (95% CI: 81.2-374, based on 191 cases and 8
controls exposed). A synergism was found between HBV and HCV infections, the OR
for co-infection being greater than the sum and lower than the product of those
for each infection alone. The interaction was therefore negative according to
the multiplicative model, providing epidemiological evidence both of an
independent effect and of interference between the 2 viruses in the carcinogenic
process.

Publication Types:
Meta-Analysis

PMID: 9455792 [PubMed - indexed for MEDLINE]



12: Vaccine  1997 Oct;15(15):1624-30

Ten-year neonatal hepatitis B vaccination program, The Netherlands, 1982-1992:
protective efficacy and long-term immunogenicity.

del Canho R, Grosheide PM, Mazel JA, Heijtink RA, Hop WC, Gerards LJ, de Gast
GC, Fetter WP, Zwijneberg J, Schalm SW.

Department of Internal Medicine II, University Hospital Dijkzigt, Rotterdam,
Netherlands.

From 1982 to 1989, 705 infants born to HBsAg-positive mothers entered the Dutch
neonatal hepatitis B vaccination program and received passive-active hepatitis B
immunization in three randomized controlled trials testing variations in time of
starting active vaccination, dose and type of vaccine, and number of hepatitis B
immunoglobulin (HBIg) injections. A meta-analysis of individual patient data of
the three randomized trials was performed to determine which independent host
and vaccination related factors influence protective efficacy and long-term
immunogenicity, and to assess whether hepatitis B vaccination concomitant with
standard DKTP vaccination provides optimal protection. Statistical methodology
included multivariate logistic regression analysis. Eight infants (1.1%), all
born to HBeAg-positive mothers, became HBsAg carriers within the first year of
life. The protective efficacy rate (PER) of passive-active immunization at 12
months follow-up was 92% for the total group of children from 114 HBeAg-positive
mothers with no significant differences between children starting active
immunization at birth or at 3 months of age, between infants starting at 3
months of age receiving one or two doses of HBIg or between those receiving
plasma derived or recombinant vaccine. The only factor that affected the PER
significantly was the level of maternal HBV DNA; PER was 100% if maternal HBV
DNA was < 150 pg ml-1 and 68% for HBV DNA levels > 150 pg ml-1. After 5 years of
follow-up, the group that started active immunization at birth had significantly
more infants with loss of seroprotection (anti-HBs levels < 10 IU l-1, 15%) than
the corresponding group starting at 3 months of age (anti-HBs < 10 IU l-2, 2%).
One of 35 children with loss of seroprotection at 2 years became a HBsAg carrier
in the fifth year of follow-up. This meta-analysis shows that the protective
efficacy of passive-active hepatitis B vaccination is mainly influenced by
material HBV DNA levels, and independent of the time of starting active
vaccination at birth or at 3 months of age; long-term immunity was enhanced by
starting active vaccination concomitant with DKTP vaccination. These findings
allow incorporation of hepatitis B vaccine into the standard infant immunization
programs for countries with a passive-active immunization strategy for the
control of hepatitis B. Additional measures are needed to protect neonates of
highly viremic women.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 9364693 [PubMed - indexed for MEDLINE]



13: Ann Med Interne (Paris)  1997;148(3):198-204

Treatment of glomerulonephritis in microscopic polyangiitis and Churg-Strauss
syndrome. Indications of plasma exchanges, Meta-analysis of 2 randomized studies
on 140 patients, 32 with glomerulonephritis.

Guillevin L, Cevallos R, Durand-Gasselin B, Lhote F, Jarrousse B, Callard P.

Hopital Avicenne, University of Paris, France.

Although plasma exchanges (PE) have no added benefit in the treatment of
vasculitides of the polyarteritis nodosa (PAN) group with steroids (CS) +/-
cyclophosphamide (CY), this has not been demonstrated in patients presenting
with glomerulonephritis (GN). We therefore reanalyzed the records of microscopic
polyangiitis (MPA) or Churg-Strauss syndrome (CSS) patients presenting with GN.
PATIENTS AND METHODS: Patients were included consecutively in 2 randomized
trials: a) comparing CS vs CS + PE (n = 78) and b) comparing CS + pulse CY +/-
PE in PAN and CSS with factors of poor prognosis (n = 62); 9-12 PE/patient were
performed. RESULTS: 32 patients, 18 men and 14 women, presented with GN, 28 MPA
and 4 CSS, mean age 53.2 +/- 17 years. Clinical/biological manifestations before
treatment were comparable in both groups: weight loss 84.4%, fever 62.5%,
mononeuritis multiplex 62.5%, purpura 28.1%, GI tract involvement 43.8%,
arthritis 37.5%, asthma 12.5%, CNS manifestations 9.4%; cardiac involvement
9.4%; mean creatininemia was 303 +/- 286 mumol/l, proteinuria > 0.5 g/l or 1g/d
was found in every case, microscopic hematuria in 20/32 patients, leukocyturia
in 12/32. Eight out of/16 were ANCA-positive, ELISA detected anti-MPO antibodies
in 5 and anti-PR3 in 3. HBV infection was never observed. After 1 year of
treatment, creatininemia decreased from 374.4 +/- 352 to 290 +/- 352 mumol/l in
the PE group and from 287 +/- 292 to 170 +/- 67 in the non PE group (NS). Six
patients of the PE group and 2 of the non-PE group were dialyzed at onset of
treatment. Four of the 6 PE patients and 1 of the 2 not treated with PE were off
dialysis 1 year later. In addition 1 patient from the PE group developed a flare
with renal failure and required chronic dialysis. The 5-year survival was higher
in the PE group (4 deaths/19) than in the non PE group (7/13). The survival
curve was 74% in the PE group vs 54% in the non-PE group (NS). CONCLUSION: This
study confirms that PE have no added benefit in the treatment of GN in MPA and
CSS.

Publication Types:
Review
Review, Tutorial

PMID: 9255326 [PubMed - indexed for MEDLINE]



14: Epidemiol Infect  1996 Oct;117(2):313-25

Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas.

Edmunds WJ, Medley GF, Nokes DJ, O'Callaghan CJ, Whittle HC, Hall AJ.

Department of Biological Sciences, University of Warwick, Coventry, UK.

This paper uses meta-analysis of published data and a deterministic mathematical
model of hepatitis B virus (HBV) transmission to describe the patterns of HBV
infection in high endemicity areas. We describe the association between the
prevalence of carriers and a simple measure of the rate of infection, the age at
which half the population have been infected (A50), and assess the contribution
of horizontal and perinatal transmission to this association. We found that the
two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar
prevalences of carriers and values of A50, and that there is a negative
nonlinear relationship between A50 and the prevalence of carriers in high
endemicity areas (Spearman's Rank, P = 0.0086). We quantified the risk of
perinatal transmission and the age-dependent of infection to allow a comparison
between the main hyper-endemic areas. East Asia was found to have higher
prevalences of HBeAg positive mothers and a greater risk of perinatal
transmission from HBeAg positive mothers than sub-Saharan Africa, though the
differences were not statistically significant. However, the two areas have
similar magnitudes and age-dependent rates of horizontal transmission. Results
of a simple compartmental model suggest that similar rates of horizontal
transmission are sufficient to generate the similar patterns between A50 and the
prevalences of carriers. Interrupting horizontal transmission by mass
immunization is expected to have a significant, nonlinear impact on the rate of
acquisition of new carriers.

Publication Types:
Meta-Analysis

PMID: 8870629 [PubMed - indexed for MEDLINE]



15: Clin Infect Dis  1996 Jul;23(1):131-7

Interferon-alpha therapy for chronic hepatitis B in children: a meta-analysis.

Torre D, Tambini R.

Division of Infectious Diseases, Regional Hospital, Varese, Italy.

A meta-analysis of six randomized clinical trials involving 240 children with
chronic hepatitis B treated with recombinant interferon-alpha (IFN-alpha) was
performed. IFN-alpha treatment was effective in blocking viral replication.
Clearance of hepatitis B virus (HBV) DNA from sera occurred in 44 of 127 treated
patients (P < .00001), and clearance of hepatitis B e antigen (HBeAg) occurred
in seven of 74 treated patients (P = .099). IFN-alpha normalized serum levels of
alanine aminotransferase (ALT) in 33 of 85 treated patients (P = .017). At the
end of the follow-up period, viral replication was still reduced in
IFN-alpha-treated patients, HBV DNA clearance occurred in 36 of 126 patients (P
= .014), and HBeAg clearance occurred in 29 of 126 patients (P = .026).
Regarding these virological and biochemical endpoints, we found that prolonged
therapy (> 6 months) was associated with a better response, whereas high dosages
of IFN-alpha were not. These findings could be biased by limited follow-up.
Children with high ALT levels had a better response. However, these randomized
clinical trials had some methodological flaws, including the lack of information
on histologic response to IFN-alpha treatment by pediatric patients and the
absence of "hard outcomes" (such as survival or development of cirrhosis or
hepatocellular carcinoma).

Publication Types:
Meta-Analysis

PMID: 8816142 [PubMed - indexed for MEDLINE]



16: J Hepatol  1994 Oct;21(4):646-55

The treatment effect of alpha interferon in chronic hepatitis B is independent
of pre-treatment variables. Results based on individual patient data from 10
clinical controlled trials. European Concerted Action on Viral Hepatitis
(Eurohep).

Krogsgaard K, Bindslev N, Christensen E, Craxi A, Schlichting P, Schalm S,
Carreno V, Trepo C, Gerken G, Thomas HC, et al.

Department of Infectious Diseases, Rigshospitalet, University of Copenhagen,
Denmark.

Alpha interferon induces HBeAg seroconversion in about one third of treated
patients and has become an established treatment of chronic hepatitis B. A
number of smaller studies have suggested that response to treatment is more
likely to occur in patients with higher levels of transaminases, with recent
(adult) onset, a history of acute hepatitis, low levels of HBV DNA and in
heterosexual males. The aim of this European co-operative study was to estimate
the effect of alpha interferon more accurately and to evaluate the influence of
host pre-treatment variables on the effect of interferon. Individual data were
collected from 751 patients from 10 controlled clinical trials on alpha
interferon (lymphoblastoid or recombinant) treatment for chronic hepatitis B.
Alpha interferon was administered to 496 patients, while 255 were untreated
controls. Individual patient data were analysed by survival analysis (log rank
test and Cox regression analysis), stratified by trial, with the disappearance
of HBeAg as the major endpoint. The results showed that the HBeAg disappearance
rate with or without interferon treatment was higher in patients with high
aminotransferase levels, with a history of acute hepatitis and in male
heterosexual patients disregarding HIV status. If HIV-positive patients were
excluded, the effect of sexual orientation was not significant. Therapy with
alpha interferon increased the a priori HBeAg disappearance rate by a factor of
1.76; the relative treatment effect of alpha interferon was independent of the
tested pretreatment host variables, but dependent on the total (intended)
interferon dose (low dose < or = 200 MU/m2 increased HBeAg disappearance by a
factor 1.37; medium/high dose > or = 200 MU/m2 increased HBeAg disappearance by
a factor 2.05). In conclusion, this meta-analysis suggests that the effect of
alpha interferon is less than previously assumed and independent of pretreatment
host variables tested. It confirms the higher therapeutic benefit of a total
dose exceeding 200 MU/m2 and of selection of patients based on disease activity
and immune reactivity. Although all patient seem to have the same relative
benefit, the absolute benefit of alpha interferon treatment seems to be greatest
in patients with high transaminase levels and with a history of acute hepatitis.

Publication Types:
Meta-Analysis

PMID: 7814812 [PubMed - indexed for MEDLINE]



17: Ann Intern Med  1993 Aug 15;119(4):312-23

Comment in:
ACP J Club. 1994 Jan-Feb;120 Suppl 1:12

Effect of alpha-interferon treatment in patients with hepatitis B e
antigen-positive chronic hepatitis B. A meta-analysis.

Wong DK, Cheung AM, O'Rourke K, Naylor CD, Detsky AS, Heathcote J.

Toronto Hospital, Ontario.

PURPOSE: To determine whether alpha-interferon is effective in terminating viral
replication and in eradicating the carrier state in patients with chronic
hepatitis B virus (HBV) infection. DATA SOURCES: Randomized controlled studies
published in the English literature between January 1966 and June 1992 were
identified through a MEDLINE computer search. STUDY SELECTION: Fifteen
randomized controlled studies with a total of 837 adult chronic HBV carriers who
were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen
(HBeAg) were identified. Studies were included if patients were treated for at
least 3 months and followed for at least 6 months after cessation of therapy.
RESULTS: Overall, the loss of HBsAg occurred 6% more often in interferon-treated
patients than the natural seroconversion seen in controls (7.8% compared with
1.8%, P = 0.001), and the loss of viral replication occurred approximately 20%
more often in treated patients than in controls (33% compared with 12% for loss
of HBeAg and 37% compared with 17% for the loss of HBV DNA, P = 0.0001) if
patients received interferon for 3 to 6 months and were followed for 6 to 12
months. Interferon also had a significant treatment effect on the development of
antibodies to HBsAg (anti-HBs), antibodies to HBeAg (anti-HBe), and on the
normalization of alanine aminotransferase levels. CONCLUSIONS: Alpha-interferon
is effective in terminating viral replication and in eradicating the carrier
state in patients with chronic HBV infection who are HBeAg positive when these
patients are treated for 3 to 6 months and followed for 6 to 12 months after
cessation of therapy. Follow-up studies are required to determine whether
interferon reduces the risk for developing cirrhosis or hepatocellular
carcinoma.

Publication Types:
Meta-Analysis

PMID: 8328741 [PubMed - indexed for MEDLINE]



18: J Hepatol  1993 Jun;18(2):154-62

Interferon treatment in patients with chronic hepatitis B: a meta-analysis of
the published literature.

Tine F, Liberati A, Craxi A, Almasio P, Pagliaro L.

Clinica Medica R, Ospedale V. Cervello, Palermo, Italy.

The randomised clinical trials testing the effectiveness of interferon treatment
on Chronic Hepatitis B patients were reviewed by means of meta-analysis.
Twenty-two trials, published between 1987 and 1990, have identified where 1290
adult patients had been studied. Overall, interferon increased the rates of
serum HBV-DNA clearance and amino-transferases normalization about 3 times at
one year. However, when an analysis of internal consistency, clinical relevance
and methodology of these studies was made, the trials were not sufficient to
confirm the clinical effectiveness of the treatment since they had been planned
for short-term assessment based on biochemical and viral end points alone. The
link of these end points to other outcomes of more obvious clinical relevance
(i.e. evolution to cirrhosis or deterioration of cirrhosis, death) is, in fact,
questionable and thus the value of a meta-analysis based on currently available
trials is uncertain as a source for practical guidelines. We conclude that the
effectiveness of interferon in patients with chronic hepatitis B has yet to be
confirmed by long-term prospective studies which assess the outcome by
clinically meaningful end points such as cirrhosis, liver failure, or death.

Publication Types:
Meta-Analysis

PMID: 7691924 [PubMed - indexed for MEDLINE]



19: J Hepatol  1993;17 Suppl 3:S42-6

To treat or not to treat? The judicious use of interferon-alpha-2a for the
treatment of chronic hepatitis B.

Ryff JC.

Department of International Clinical Research, F. Hoffmann-LaRoche Ltd., Basel,
Switzerland.

Based on results from extensive clinical research, interferon-alpha-2a
(IFN-alpha-2a, Roferon-A, F. Hoffmann-LaRoche Ltd., Switzerland) and other
interferons have been registered for the treatment of chronic active hepatitis
B. The officially recommended dose regimen is 4.5 MIU (or 2.5 MIU/m2) thrice
weekly for 6 months. To present guidelines for the optimization of treatment for
individual patients, 3 major controlled trials from our worldwide research
program with a total of 416 patients were reviewed in a meta-analysis. Before
deciding whether to treat or not, the history, prognosis and chances of
treatment success for a given patient must be carefully assessed. Liver
histology and repeated quantitative measurements of markers for viral
replication (HBV-DNA, HBeAg) and biochemical markers for liver disease such as
ALT are valuable indicators. After the decision to treat, monthly quantitative
measurements of these markers make it possible to monitor therapeutic success.
Depending on the course they run, treatment can continue unchanged, be adjusted
in dose or duration until a full response is achieved, or be terminated early in
case of evidence of non-response.

Publication Types:
Meta-Analysis

PMID: 8509638 [PubMed - indexed for MEDLINE]

zws

very good!
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