Infection
by the Hepatitis B virus causes the liver disease Hepatitis B, which can lead
to liver failure and cancer. A
simple vaccine can reduce chances of infection, but in places with widespread
poverty many people can’t afford the cost of a vaccine. Subsequently, in such places infection
rates remain consistently high leading to an estimated 240 million people
worldwide who are chronically infected and 686,000 people who die as a result
of Hepatitis B every year.[1] Due to the epidemic of chronically
infected Hepatitis B patients, antiviral drugs have been developed to help
prevent the onset of Hepatitis B. One
particular type of antiviral is called a nucleoside analogue. Such antivirals work by inhibiting
viral replication through the use of an alternative DNA subunit, which can be
incorporated into viral DNA and subsequently blocks a virus’ own replication
machinery.[2] Nucleoside analogues are exceedingly
useful therapies until mutations in the virus’ genetic material causes
resistance to the antivirals.
A
paper[3]
published in the journal Nature in July
of 2016 by Liu et al. details the usefulness of a specific nucleoside analogue,
Entecavir, for treatment of a chronic Hepatitis B infection. The researchers examined the
effectiveness of Entecavir treatment in participants who had never been treated
with a nucleoside analogue compared to those who had been treated with one, either
lamivudine (LAM) or adefovir dipivoxil (ADV). The study was conducted over 5 years on 89 individuals from
China who were infected with Hepatitis B for at least 6 months and were only
treated with Entecavir. Statistical
analysis was used to determine if Entecavir lead to viral remission as
associated with prior treatment with LAM, prior history of LAM-resistance,
prior history of partial virus resistance to ADV, and prior history of primary
treatment failure to ADV.
The
results of the study indicated that anyone who had never been treated with a
nucleoside analogue before exhibited complete viral remission with only a
minimal chance of developing resistance.
This is opposed to patients previously treated with a nucleoside
analogue, who still responded well to Entecavir but at a lower rate of
remission. The sample group was
further characterized by experience with LAM and ADV. Interestingly, individuals previously treated with LAM, with
or without developing resistance, were successfully treated for Hepatitis B, as
were ADV patients with partial resistance. However, ADV-experienced patients who had failed previous
treatment had a significantly reduced probability of achieving viral remission
when treated with Entecavir.
The
study by Liu et al. provides important support for reducing antiviral
resistance as a result of overuse. Chronic Hepatitis B can be effectively treated with
antivirals, like Entecavir, but for those who failed the first line treatment,
doctors should carefully choose the next course of therapy. By not just prescribing any antiviral when
someone has an infection, hopefully the current issue with widespread
antibiotic resistance can be avoided, or at least minimized, in regards to antivirals. The results of the paper strongly support
conscientious and judicious use of antiviral drugs.
The
treatment distinction suggested by Liu et al. for patients with different
histories is also indicative of the future of medicine. Previous means of treating a disease
involved a one-size fits all approach.
For example, the paper discusses how ADV was the primary means of
treatment for chronic Hepatitis B in China for the past decade. If a patient was diagnosed with Hepatitis
B, he or she was most likely given ADV without deliberation. However, as the results of the study
indicated, such an approach is not effective due to acquired resistance. Thus, it is important for those in the
healthcare profession to consider a patient’s personal history prior to
treatment in order to successfully treat an infection, instead of relying on a
generalized approach.
In order to facilitate the growth
of personalized medicine, basic research into the conditions affecting the
success of a particular treatment is necessary. Liu et al. provided important information on a specific
drug, but the study was limited by size, as acknowledged by the researchers. Future research should be more wide
spread, meaning more antivirals examined in a larger number of participants
with different conditions. Such
work would allow for the development of a comprehensive set of guidelines regarding
the use of antivirals. Analysis of
a large set of treatment results could be the beginning of a global initiative
for stemming antiviral resistance by providing personalized treatment.
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