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Hepatitis
Table 1: Summary of Available Medications for Management of Chronic Hepatitis B
Interferon Peginterferon Lamivudine Adefovir Entecavir Telbivudine Tenofovir
Alpha-2a Dipivoxil
Indication Consider for 1st-line Consider for 1st-line Not indicated as Not indicated as Indicated as Not recommended Indicated as
therapy if young, therapy if young, 1st-line therapy 1st-line therapy 1st-line therapy for as monotherapy 1st-line therapy
non-cirrhotic, high non-cirrhotic, high HBeAg-positive and given high rates of for HBeAg-
ALT, low HBV DNA, ALT, low HBV DNA, -negative disease resistance; resistance positive and
genotype A or B, genotype A or B is lower among -negative
although peginterferon responders within disease
alpha-2a is preferred 24 weeks
Route Subcutaneous Subcutaneous Oral Oral Oral Oral Oral
Treatment Defined Defined Undefined Undefined Undefined Undefined Undefined
course
Resistance None None 20% at 1 year None at 1 year <1% at 1 year 3–4% at 1 year None reported
70% at 5 years 29% at 5 years 1% at 5 years 25% at 2 years at 2 years
Side effects Significant Significant Minimal Potential Minimal Minimal Minimal
nephrotoxicity
Cost High High Low Intermediate High Intermediate Intermediate
ALT = alanine aminotransferase; HBeAg = hepatitis B e antigen; HBV = hepatitis B virus.
lack of antiviral drug resistance. However, the medication is delivered treatment as nearly all will relapse after stopping treatment.
29
In addition,
by injection and has a side effect profile that makes it difficult to after one year of treatment 14–32% of patients develop resistance; after
tolerate. In addition, its use is contraindicated in patients with five years the proportion who develop resistance is as high as 60–70%.
2
decompensated liver disease. Due to these high rates of antiviral resistance, lamivudine is no longer
considered first-line therapy for the treatment of CHB.
In a large clinical trial of patients with HBeAg-positive CHB,
monotherapy with peginterferon alpha-2a led to undetectable HBV Adefovir Dipivoxil
DNA in 25% and HBeAg seroconversion in 27% after 48 weeks of Treatment with adefovir, a nucleotide analogue, for one year in HBeAg-
treatment, with higher rates of HBeAg seroconversion seen after positive patients results in HBV DNA loss in 21% and HBeAg
longer follow-up.
22
Rate of HBsAg loss in two multicentre trials was 3% seroconversion in 12%, with a sustained response in 90%.
29,30
Among
at follow-up 24 weeks after treatment. Among patients with HBeAg- HBeAg-negative patients who need long-term therapy, 51% achieve HBV
negative CHB, peginterferon alpha-2a resulted in undetectable HBV DNA loss at one year.
31
Although rates of adefovir resistance are low at
DNA in 63% at the end of 48 weeks of treatment and 19% at follow-up one year, resistance has been reported to be as high as 29% after five
24 weeks after treatment.
23
HBsAg was lost in 3% after one year of years of treatment.
32
A main advantage of adefovir is its efficacy against
treatment. In both groups of patients, treatment with peginterferon lamivudine-resistant disease. However, with the recent approval of
alpha-2a was superior to lamivudine monotherapy. Furthermore, the tenofovir, which is structurally similar but has a higher potency and
addition of lamivudine to peginterferon alpha-2a did not improve the lower resistance, adefovir has become less preferred in the
rate of sustained response. Clinical trials of peginterferon alpha-2b management of CHB.
have reported similar results as those for alpha-2a; it is therefore an
option in countries where it is available.
24,25
Long-term follow-up of Entecavir
CHB patients treated with peginterferon has demonstrated high rates Entecavir is a nucleoside analogue that has potent antiviral activity.
of HBsAg clearance among individuals who experiencd virological Compared with lamivudine, one year of treatment in HBeAg-
response to the medication. HBsAg clearance rates among virological positive patients was associated with increased rates of HBV DNA
responders has been 30–71% for those with HBeAg-positive CHB and loss (67 versus 36%), normalisation of ALT and histological
35% for those with HBeAg-negative CHB.
26,27
improvement. HBeAg seroconversion was comparable for both
entecavir and lamivudine (21 versus 18%).
28
Similarly, in HBeAg-
Finally, HBV genotype is associated with response to peginterferon negative patients, treatment with entecavir compared with
alpha-2a, with genotypes A and B having more favourable treatment lamivudine led to higher HBV DNA loss (90 versus 72%) and
outcomes. Thus, peginterferon alpha-2a may be an appropriate first- increased histological improvement.
33
Unlike the nucleoside
line option for treatment of a young patient with genotype A or B analogues lamivudine and telbivudine, entecavir is associated with
disease and compensated liver disease, especially if a fixed course low antiviral resistance. In nucleoside-naïve patients, resistance is
without the risk of antiviral resistance is particularly attractive.
7
rare, at approximately 1% after five years; however, up to 50% of
lamivudine-refractory patients develop entecavir resistance after
Lamivudine five years.
34
Given its antiviral efficacy and low resistance profile
Lamivudine is a nucleotide analogue and was the first available oral among nucleoside-naïve patients, entecavir remains a preferred
therapy for HBV. Loss of HBV DNA after one year of lamivudine first-line treatment for CHB.
treatment is 36–44% among those with HBeAg-positive CHB and
60–73% among those with HBeAg-negative CHB.
2,22,27,28
However, only Telbivudine
50–80% of treated patients with HBeAg-positive disease have a durable Also a nucleoside analogue, telbuvudine has been demonstrated to
response, and patients with HBeAg-negative disease need indefinite have superior efficacy in treating CHB compared with lamivudine.
40 EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW
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