Two-year interferon therapy with or without ribavirin in chronic delta hepatitis.
ABSTRACT The only beneficial agent for the treatment of chronic delta hepatitis (CDH) is interferon (IFN). However, there is no consensus on the best dosage or duration of IFN therapy. As ribavirin (RBV) increases the sustained response when added to IFN in chronic hepatitis C, probably because of its immunomodulatory effect, we aimed to investigate the efficacy of 2-year IFN treatment and whether RBV had any additive effect to IFN in CDH.
Patients (n = 31) with CDH were randomized with a 1:2 ratio as 10 patients (3 females/7 males, age 39 +/- 9) receiving IFN monotherapy (9 MU IFN-alpha2a three times weekly) and 21 patients (8 females/13 males, age 38 +/- 11) receiving IFN plus RBV for 2 years (IFN at the same dosage and RBV at 1000-1200 mg/day). Alanine transferase normalization and hepatitis delta virus (HDV) RNA negativity at the end of treatment and at the end of the follow-up period (at least 6 months following 2-year treatment) were primary endpoints of the study. In addition, virological response and biochemical response were determined separately.
Eight of 31 patients (25%) had cirrhosis in liver biopsies. Six patients from the IFN monotherapy group and 12 patients from the combination group had biochemical response. Five patients from the IFN monotherapy group and 11 patients from the combination group had virological response at the end of therapy. Two patients from the IFN group and five patients from the combination group had sustained biochemical response at the end of the follow-up period. Hepatitis B virus (HBV) activations with HBV DNA positivity were observed in two patients (one from the IFN monotherapy group, one from the combination group). Two patients (20%) in the IFN group and five patients (23.5%) in IFN plus RBV group remained as virological responders at the end of the follow-up period (P > 0.05). None of the patients with liver cirrhosis were responsive at the end of the follow-up period.
Almost 20% of the patients with CDH were responsive to 2-year IFN treatment at the end of the follow-up period and no additional effect of RBV was observed. Patients with advanced liver disease failed to respond to treatment.
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ABSTRACT: Dual and triple infections with hepatitis virus C (HCV), B (HBV) and D (HDV) frequently lead to severe liver damage. Hereby we describe a 38-year-old Caucasian male coinfected with HCV (genotype 3a), HBV [positive hepatitis B surface antigen (HbsAg) and antibody to hepatitis B core antigen; negative hepatitis B e antigen (HbeAg) and antibody to hepatitis B e antigen (anti-HBe)] and HDV. Laboratory diagnostics revealed increased liver enzymes and histological examination of the liver showed signs of fibrosis with moderate inflammation. On therapy with pegIFN-α2b and ribavirin HCV-RNA was undetectable at week 8. After week 24 the antiviral therapy was stopped because of a HBs-seroconversion, the loss of HbeAg and the detection of anti-HBe. Furthermore the HCV-RNA was negative. Six months after successful treatment of the triple-infection, HCV- and HDV-RNA and HbsAg remained negative and the liver enzymes had been completely normalized. In conclusion, pegylated-interferon plus ribavirin may be an effective therapy for HCV, HBV and HDV-coinfected patients.Clinics and practice. 05/2012; 2(3):e64.
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ABSTRACT: Approximately 5% of hepatitis B virus (HBV) carriers are coinfected with hepatitis D virus (HDV). HBV/HDV coinfection is a major cause of cirrhosis and end stage liver disease in chronic HBsAg carriers. The only approved therapy for chronic hepatitis delta is interferon alpha (IFN α) in either pegylated or conventional forms. Although higher doses and longer durations of IFN α therapy in HBV/HDV coinfected patients are currently applied, yet treatment response is low. We aimed to determine the efficacy of IFN α-2b therapy in patients with HBV/HDV coinfection. In this cross sectional study, 20 HBsAg carriers with positive Anti-HDVAb and RT-PCR for HDV RNA were recruited and treated for three year duration with 5 million units (MU) of IFN α-2b, three times weekly or one year with 5 MU of IFN α-2b daily. Sustained virological response (SVR) was defined as a negative qualitative HDV RT-PCR, 6 months after treatment cessation. Overall, 3 (15%) subjects achieved SVR, 10 cases (50%) relapsed after treatment cessation and 7 (35%) patients did not clear HDV during the treatment. HDV coinfection with HBV had very low response rate to high doses and long durations of IFN α-2b therapy.Hepatitis Monthly 03/2014; 14(3):e15729. · 1.80 Impact Factor
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ABSTRACT: The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years have heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus (HBV, HCV, and HDV). The introduction of direct acting antivirals (DDAs) for the treatment of HBV carriers has permitted the long-term use of these compounds for the continuous suppression of viral replication, whilst in the case of HCV in combination with the standard of care [SOC, pegylated interferon (PegIFN), and ribavirin] sustained virological responses (SVRs) have been achieved with increasing frequency. Progress in the case of HDV has been slow and lacking in significant breakthroughs.This paper aims to summarise the current state of play in treatment approaches for chonic viral hepatitis patients and future perspectives.Scientifica. 01/2012; 2012:478631.
The only beneficial agent for the treatment of chronic
delta hepatitis (CDH) is interferon (IFN). However, there is
no consensus on the best dosage or duration of IFN
therapy. As ribavirin (RBV) increases the sustained
response when added to IFN in chronic hepatitis C, prob-
ably because of its immunomodulatory effect, we aimed
to investigate the efficacy of 2-year IFN treatment and
whether RBV had any additive effect to IFN in CDH.
Methods: Patients (n=31) with CDH were randomized
with a 1:2 ratio as 10 patients (3 females/7 males, age
39 ±9) receiving IFN monotherapy (9 MU IFN-α2a three
times weekly) and 21 patients (8 females/13 males, age
38 ±11) receiving IFN plus RBV for 2 years (IFN at the
same dosage and RBV at 1000–1200 mg/day). Alanine
transferase normalization and hepatitis delta virus (HDV)
RNA negativity at the end of treatment and at the end of
the follow-up period (at least 6 months following 2-year
treatment) were primary endpoints of the study. In addi-
tion, virological response and biochemical response were
Results: Eight of 31 patients (25%) had cirrhosis in liver
biopsies. Six patients from the IFN monotherapy group
and 12 patients from the combination group had
biochemical response. Five patients from the IFN
monotherapy group and 11 patients from the combina-
tion group had virological response at the end of therapy.
Two patients from the IFN group and five patients from
the combination group had sustained biochemical
response at the end of the follow-up period. Hepatitis B
virus (HBV) activations with HBV DNA positivity were
observed in two patients (one from the IFN monotherapy
group, one from the combination group). Two patients
(20%) in the IFN group and five patients (23.5%) in IFN
plus RBV group remained as virological responders at the
end of the follow-up period (P>0.05). None of the
patients with liver cirrhosis were responsive at the end of
the follow-up period.
Conclusion: Almost 20% of the patients with CDH were
responsive to 2-year IFN treatment at the end of the
follow-up period and no additional effect of RBV was
observed. Patients with advanced liver disease failed to
respond to treatment.
Two-year interferon therapy with or without
ribavirin in chronic delta hepatitis
Fulya Gunsar1*, Ulus Salih Akarca1, Galip Ersoz1, Arzu Celebi Kobak1, Zeki Karasu1, Gul Yuce2, Tankut Ilter1
and Yucel Batur1
1Ege University Medical School Gastroenterology and 2Pathology Department, Izmir, Turkey
*Corresponding author: Tel: +90 232 3881969 143; Fax: +90 232 3745761; E-mail: email@example.com
Antiviral Therapy 10:721–726
Hepatitis delta virus (HDV) is a defective RNA virus
that needs the helper function of the hepatitis B virus
(HBV) for replication and infection [1,2]. Chronic
delta hepatitis (CDH) is the least frequent, but the
most severe, form of viral hepatitis, and leads to
cirrhosis in 30–70% of patients [2–4]. In some regions
of the world, such as south-eastern Turkey, more than
20% of the HBV carriers have HDV infection. It is esti-
mated that 15 million people are infected with HDV
worldwide . Of the compounds tested in various
pilot studies and randomized controlled trials, only
interferon-α (IFN-α) has been shown to have an effect
on CDH. However, treatment has only been effective in
a small number of patients – clearence of HDV RNA
has been documented in less than 10% of patients
treated with IFN [3–7]. Therefore, alternative thera-
peutic options are under investigation. Famciclovir,
acyclovir or lamivudine had no effect on CDH [2,4,8].
In other studies, ribavirin (RBV) monotherapy had no
effect on CDH [9,10]. RBV is a purine nucleoside
analogue that has been found to interfere with viral
messenger RNA synthesis and to inhibit the replication
of a wide range of RNA and DNA viruses in vivo and
in vitro [11–13]. RBV has also been shown to have
effects [11–13]. In chronic
hepatitis C (CHC), RBV monotherapy has not
achieved antiviral activity. However, IFN and RBV
combination therapy has increased efficacy in naive or
in IFN-resistant patients with CHC [14,15]. The ther-
apeutic contribution of RBV in treating CHC is attrib-
uted to its immunomodulatory properties, which
intensify the effect of IFN. Therefore, it might be
expected that RBV would increase the suboptimal ther-
apeutic effect of IFN in CDH, as the mechanisms of
liver injury in this disease are similar to those of CHC.
In addition, there is no consensus on the dosage or
© 2005 International Medical Press 1359-6535
duration of IFN treatment required to achieve an
optimal sustained virological response in CDH . The
duration of IFN therapy in most studies is 1 year [1,6].
It could be reasonable to treat patients for longer
(18–24 months), to prevent relapse. In this study, we
aimed to evaluate the efficacy of 2-year IFN
monotherapy in CDH and to compare this effect with
IFN plus RBV for the same duration.
Materials and methods
This is a single centre study. As patients with naive
delta hepatitis are scarce, all patients with CDH
admitted to the hospital during the 2-year period who
had not received any treatment and met the inclusion
criteria were included.
Patients were enrolled into the study according to the
inclusion and exclusion criteria shown in Box 1. The
study was performed in accordance with the Declaration
of Helsinki and the study protocol was approved by the
Ethics Committee of Ege University Medical School.
Informed consent was obtained from all patients.
Hepatitis serologies including hepatitis B surface
antigen (HBsAg), anti-HBs, HBeAg, anti-HBc
immunoglobulin G (IgG) and IgM were determined
by commercial assays (micro-particle enzyme
immunoassay, Abbott Laboratories, Abbott Park, IL,
USA). HBV DNA was tested by hybridization assay
(Digene Hybrid Capture system, Beltsville, MD, USA).
The lower limit of detection of this test is 5 pg/ml. Anti-
HDV levels were determined by micro-enzyme
immunoassay (Organon, Tecnica, Boxtel, the
Netherlands). HDV RNA was qualitatively tested by
in-house nested PCR . The sensitivity of the PCR
assays was approximately 1000 genomes for single
PCR and 1–10 genomes for nested PCR. Anti-HCV
was tested by enzyme immunoassay (Roche
Diagnostics, Branchburg, NJ, USA). Biochemical
and haematological factors were measured by
Liver ultrasound was performed for all patients. All
patients had liver biopsies before treatment. Knodell
scoring was used for histological assessment of the liver
biopsies by one pathologist (GY).
Schedule of therapy and follow-up
A random allocation rule was applied because of the
small size of the study population. Patients were
randomized into two groups with a 1:2 ratio.
One-third of the patients received IFN-α monotherapy
(9 MU IFN-α2a three times weekly); two-thirds were
treated with the same doses of IFN and RBV
During therapy, the patients came to an out-patient
clinic once a month. The patients filled in a diary
illustrating the use of drugs, and they brought the
empty boxes and syringes at each visit. Routine labora-
tory studies including alanine transferase (ALT), aspar-
tate transaminase, direct and indirect bilirubin,
prothrombin time and complete blood count were
performed for every visit. All side effects (for example
anaemia, flu-like symptoms, leukopaenia and low
platelet counts) were noted. If a patient had
neutropaenia (less than 1500/mm3) or thrombocy-
topaenia (less than 40 000/mm3), IFN therapy was
interrupted for 1 week, but if a patient had persistent
neutropaenia and thrombocytopaenia, IFN dosage was
reduced or granulocyte–macrophage colony-stimu-
lating factor (GM-CSF) was added to therapy. In addi-
tion, RBV dosage was reduced if haemoglobin
concentrations decreased to 10 g/dl or less. Serum was
tested for the presence of HDV RNA every 2 months
and for HBV every 6 months. HBV DNA was tested at
baseline and later in the study if activation of hepatitis
was suspected. After the treatment period patients were
followed up at 2-month intervals for at least
Biochemical response was defined as normalization of
ALT levels for at least two consecutive visits. HDV
RNA negativity, defined as the loss of serum HDV
RNA (detected by PCR) in two consecutive samples of
2 months apart, was accepted as a virological response.
Virological relapse for HDV was defined as the
F Gunsar et al.
© 2005 International Medical Press
Box 1. Inclusion and exclusion criteria for the study
1. Positive HBsAg with or without positive HBV DNA
2. Positive anti-delta antibody with positive HDV RNA
3. Increased ALT levels: 1.3–10 times the upper limit of normal
All these criteria should be met for at least the previous 6 months
1. Outside the age limit of 18–65
2. Any previous antiviral therapy
3. Coinfection with HCV or HIV
4. Decompensated liver disease (defined by a serum bilirubin level
over 2.5 times the upper limit of normal, a prothrombin time
prolonged by over 3 seconds and a serum albumin level less than
3 g/dl; or a history of ascites, variceal haemorrhage or hepatic
5. Evidence of autoimmune hepatitis or metabolic liver disease,
serious psychiatric disorders or severe systemic illness
6. White-blood-cell count less than 3000/mm3, absolute neutrophyl
count less than 1500/mm3, haemoglobin less than 10 g/dl, and
platelet count less than 100 000/mm3
reappearance of HDV RNA. HBV DNA positivity was
defined as HBV activation.
All data were analysed on an intention-to-treat basis.
The changes in ALT levels were studied by Wilcoxon’s
signed rank test. The clinical and laboratory character-
istics of the responders and non-responders were
assessed using the χ2or Fisher’s exact test.
A total of 48 newly admitted patients with delta hepatitis
were screened during the 2-year period. Thirty-one
patients were randomized to IFN monotherapy (10
patients) or IFN plus RBV (21 patients).
Demographic features and baseline characteristics of
patients are summarized in Table 1. Baseline character-
istics of the patients receiving IFN monotherapy and of
patients receiving IFN plus RBV were similar with
respect to age, gender, transaminase levels and liver
histology (P>0.05). All patients tested positive for
HBsAg and anti-HBe, and negative for HBV DNA.
Therapy results, drug dosages and basal fibrosis
scores and their relation to therapy response are
summarized in Table 2.
In the IFN monotherapy group, two patients
stopped IFN therapy [one due to decompensation of
liver disease (this patient had cirrhosis at baseline), the
other one due to intolerable side effects of IFN]. The
other 8 patients completed 2-year IFN therapy period.
IFN dose was reduced in four patients. One needed
GM-CSF for persistent leukopaenia.
In the combination therapy group, three patients
stopped IFN plus RBV therapy [one due to decompen-
sation of liver disease (this patient had cirrhosis at
baseline), two due to intolerable side effects of IFN].
One patient refused to continue the treatment at month
10, when he was positive for HDV RNA. Seventeen
patients completed 2 years of IFN plus RBV therapy.
IFN dosages were reduced in four patients. Three
patients needed to use GM-CSF factor for persistent
leukopaenia. In two patients, RBV dosages were
reduced because of anaemia.
The median follow-up period of the patients after
stopping the treatment was 10 months (range 8–20
In the IFN monotherapy group, virological response
was observed in five patients (50%) at the end of
therapy. All had biochemical response as well.
Virological response was achieved at a median of 12
months (range 10–20 months). Biochemical response
was observed in six patients at the end of therapy. ALT
became normal at a median 4th month of the treatment
(range 2–12 months) in these patients. The remaining
two patients who completed the 2-year therapy period
had persistently high ALT levels. Both of them
completed the study with the reduced dosages of IFN
(3 MU three times weekly). Three of the virological
responders had increased ALT levels during the follow-
up period [two with HDV reactivation at the fourth
and eighth month, one with HBV activation (HBV
DNA was 150 pg/ml) at the eighth month]. The
patients with relapses of HDV were still negative for
HBV DNA and positive for HBsAg. None of these
three patients developed hepatic decompensation. The
patient with HBV activation was treated with lamivu-
dine. IFN treatment was reinstituted in one of the
patients with HDV reactivation. Biochemical response
was observed in two patients at the end of the follow-
up period. These two patients (20%) remained as viro-
logical responders at the end of follow-up period (8th
and 10th month). Liver fibrosis scores and IFN dosages
of virological responders are summarized in Table 2.
In the IFN plus RBV group, virological response was
observed in 11 (52.3%) patients. Biochemical response
was observed in 12 patients. ALT normalization was
achieved at a median 11th month (range 3–24 months).
Virological response was observed at a median 18th
month (range 12–24). In seven patients, virological
response was achieved after the first year of the
therapy. During the follow-up period, five patients had
increased levels of ALT, four of them had relapses of
HDV during the sixth month following treatment, and
another patient had activation of HBV during the
fourth month following treatment and became positive
for HBV DNA (his HBV DNA was found as 50 pg/ml).
He was treated with lamivudine. These patients with
HDV reactivation were still negative for HBV DNA
Antiviral Therapy 10:6
Two-year therapy in chronic hepatitis D
Table 1. Baseline charecteristics of patients with IFN
monotherapy and IFN plus RBV therapy
CharacteristicIFN group IFN plus RBV group
HBsAg positivity, n
HBV DNA positivity, n
Anti HBe positivity, n
HDV RNA positivity, n
Fibrosis grade 3 or 4, n
*Mean ±SD. †Median (range). ALT, alanine transferase; AST, aspartate transami-
nase; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HDV, hepatitis
delta virus; IFN, interferon; RBV, ribavirin.
and positive for HBsAg. IFN therapy was reinstituted
in two of these patients. One patient did not continue
to participate in the study after the 2-year therapy
period. The other five (23.5%) patients remained as
virological responders at the end of follow-up (at the
10th, 16th, 20th and 22nd month) and these five
patients also had biochemical response. Liver fibrosis
scores and IFN dosages of virological responders are
summarized in Table 2. One of the virological respon-
ders became anti-HDV negative at the end of follow-up.
Eight of sixteen end-of-therapy responders cleared
the virus after the first year of treatment. We emphasize
that 1 year of IFN therapy was not sufficient in nearly
50% of patients with CDH.
There was no relation between the response and the
following parameters: basal ALT levels, the time for ALT
normalization or HDV negativity, or Knodell score of
liver biopsy. However, none of eight cirrhotic patients
and seven of 23 non-cirrhotic patients (30.4%)
responded to treatment (P=0.07). Three cirrhotic
patients (37.5%) and three non-cirrhotic patients (13%)
could not complete the 2-year treatment (P>0.05).
IFN dosage was not related to response rate. None
of the patients lost HBsAg during follow-up.
In this study, 2-year IFN-α2a treatment was used to
treat CDH, and the added contribution of RBV to this
regimen was investigated. Previous studies revealed
that higher IFN doses were more effective than lower
doses [3,6,17]. Therefore, a 9 MU three times weekly
dose of IFN was used in the study. Two of ten patients
(20%) from the IFN monotherapy group and five of 21
patients (23.8%) from the combination therapy group
remained as virological responders during follow-up of
at least 6 months. Eight of 16 patients who achieved a
virological response at the end of the treatment
attained virological response after the first year of
treatment. It is obvious that extension of IFN treatment
to 2 years almost doubles the response rate of 1-year
treatment. During the course of the treatment, five
patients were withdrawn from the study because of the
side effects of IFN, IFN dose was reduced in eight
patients, and RBV dose was reduced in two patients.
After the completion of treatment, relapses of HDV
were observed in seven of 16 responders and another
two patients became positive for HBV DNA. None of
the cirrhotic patients had a virological response during
Previous studies demonstrated that 1-year IFN-α
treatment can achieve a 10% response in patients with
delta hepatitis [1,4,6,17–20]. Yurdaydin et al. detected
sustained response in two of 15 patients who
completed 2-year IFN therapy, and they suggested that
extending the treatment to 2 years did not increase the
sustained response . However, comparing our
results with those seen in the literature (10% response
F Gunsar et al.
© 2005 International Medical Press
Table 2. Schedule of therapy and response rates in the two groups
Schedule of therapy and response ratesIFN group IFN plus RBV group
Drop out 24
Dosage reduction of IFN 4 (2 patients on 6 MU; 2 patients
4 (1 patient on 6MU; 3 patients
on 3 MU)
Usage of GM-CSF 13
Dosage reduction of ribavirinN/A2
Virological response at the EOT 5 (50%) 11 (52.3%)
IFN dosage in virological responders at the EOT3 patients on 9 MU; 2 patients
on 6 MU
8 patients on 9 MU; 1 patient
on 6 MU; 2 patients on 3 MU
Baseline liver fibrosis in the virological responders
at the EOT
1 patient with stage 0; 3 patients with
stage 3; 1 patient with stage 4
4 patients with stage 1; 6 patients
with stage 3; 1 patient with stage 4
Biochemical response at the EOT
6 (60%) 12 (57.1%)
Virological response at the end of the follow-up period2 (20%)5 (23.5%)
Biochemical response at the end of the follow-up period2 (20%) 5 (23.5%)
IFN dosages in the virological responders at the end of
the follow-up period
1 patient on 9 MU; 1 patient
on 6 MU
3 patients on 9 MU; 1 patient
on 6 MU; 1 patient on 3 MU
Baseline liver fibrosis in the virological responders at the
end of the follow-up period
2 patients with stage 32 patients with stage 3; 3 patients
with stage 1
EOT, end of treatment; GM-CSF, granulocyte–macrophage colony-stimulating factor; IFN, interferon; RBV, ribavirin.
with 1-year therapy), and considering the patients who
responded after the first year in our study (50% of
responders), 2-year treatment seems to be better than
1-year treatment [3,4]. Nevertheless, the most effective
dose of IFN in delta hepatitis is not clear. Patients who
were treated with 9 MU had a better response than
patients who were treated with 3 MU in other studies
[6,21]. However, there were responders among the
patients who received either full dose or reduced dose
of IFN in this study (Table 2). Future therapies trying
different doses of IFN in a larger population are
Data related to RBV treatment in delta hepatitis are
scanty. A few patients with delta hepatitis were treated
with RBV in two studies and no response was obtained
[9,10]. Similarly, RBV monotherapy in CHC has been
unsuccessful. However, it synergistically enhances the
effect of IFN against HCV [14,15]. RBV has an
immunomodulatory role in treating HCV infection.
Several studies have shown that RBV can mediate
immunomodulation by altering the type 1/type 2
cytokine bias in favour of type 1 during an immune
response [11,13]. A good response to RBV and IFN-α
was associated with activation of a HCV-specific T-cell
response during treatment . As the pathogenesis of
delta hepatitis, which is suggested to be immune medi-
ated, is similar to CHC , RBV can be expected to
increase the effectiveness of IFN in patients with delta
hepatitis. Our study is the first to evaluate and compare
the IFN plus RBV combination therapy with IFN
monotherapy in CDH. Unfortunately, the IFN plus
RBV combination did not offer an advantage over IFN
monotherapy. Kaymakoglu et al. investigated the IFN
and RBV therapy in 19 patients with CDH. The viro-
logical response rate of these patients was 21% at the
end of the follow-up period, which is similar to our
results. Furthermore, Kaymakoglu et al. showed that
RBV has no synergistic activity with IFN in treating
Responsiveness was not found to be related with
some pre-treatment and on-treatment factors such as
basal ALT level, the time for ALT normalization or
HDV negativity and basal Knodell score of liver biop-
sies. Rosina et al. could not find any clinical or
biochemical factor that can predict a response to IFN
therapy in CDH . However, a virological or
biochemical response cannot be achieved in IFN-
treated CDH patients with liver cirrhosis, suggesting
that advanced liver disease is a poor prognostic
predictor in IFN-based treatment of CDH. In advanced
liver disease, it is probable that the basal ALT level does
not have predictive value in determining the response
It is well established that HDV inhibits hepadnavirus
replication, both in the acute and chronic phase (24).
Therefore all the patients in this study were negative
for HBV DNA at the beginning of the study. Of
interest, two patients displayed HBV reactivation
during their follow-up period, although their HDV
RNA persisted to be negative. We propose that a
decrease over time of HDV activation caused the disap-
pearance of inhibition of HBV replication. Wu et al.
have described a similar pattern in patients from a
study carried out in Taiwan, characterized by
decreasing levels of HDV and reactivation of HBV with
moderately high ALT levels during the course of CDH
. Therefore, during the management of delta
hepatitis, HBV flare should be kept in mind.
In conclusion, IFN seems to be the only effective
agent against CDH among the current treatment regi-
mens. The duration of treatment should be at least 2
years. Further studies are required on whether
prolonged treatments beyond 2 years will increase the
response rate. The addition of RBV to IFN therapy has
no advantages over IFN monotherapy. As patients with
CDH have advanced liver disease, they are not able to
tolerate well the regular IFN dose that is used in
chronic hepatitis B. Therefore, early diagnosis and
treatment seem to be essential. After repressing the
delta virus, HBV may escape from its suppressor effect
and HBV flare can be observed. So, in light of the
suboptimal effects of IFN in treating CDH, more effec-
tive antiviral agents (affecting, for instance, HBV
cccDNA or delta antigen expression) are awaited.
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