Issue: 2008 > July-August > special report

Treatment of chronic hepatitis B virus infection - Dutch national guidelines

E.H.C.J. Buster, K.J. van Erpecum, S.W. Schalm, H.L. Zaaijer, J.T. Brouwer, H.C. Gelderblom, R.J. de Knegt, C. Minke Bakker, H.W. Reesink, H.L.A. Janssen


The development of this guideline was initiated and
coordinated by the Netherlands Association of
Gastroenterologists and Hepatologists (Nederlandse
Vereniging van Maag-Darm-Leverartsen). The aim is the
establishment of national standards in the evaluation and
antiviral treatment of patients with chronic hepatitis B virus (HBV) infection. This includes recommendations on the initial evaluation of patients, choice and duration of antiviral therapy, follow-up after antiviral therapy and monitoring of patients not currently requiring antiviral therapy.
The initial evaluation of chronic HBV-infected patients should include testing of liver biochemistry, virus serology and abdominal imaging. In patients without cirrhosis, antiviral treatment is recommended for those with a serum HBV DNA of at least 1.0 x 10,sup>5</sup> c/ml (&#8805;2.0 x 10<sup>4</sup> IU/ml) in combination with: a) elevation of serum alanine aminotransferase (ALAT) level above twice the upper limit of normal during at least three months, and/or b) histological evidence of porto-portal septa or interface hepatitis on liver histology. In patients with cirrhosis, antiviral treatment is recommended if serum HBV DNA is 1.0 x 10<sup>4</sup> c/ml (&#8805;2.0 x 10<sup>3</sup> IU/ml) or higher, independent of ALAT levels or histological findings. If the patient has decompensated cirrhosis, antiviral treatment is recommended if serum HBV DNA is 1000 c/ml
(&#8805;200 IU/ml) or higher.
Patients who do not have an indication for antiviral treatment should be monitored because there is a risk of (re)activation of disease activity. Monitoring every three to six months is recommended for HBeAg-positive and HBeAg-negative patients with high viraemia (HBV DNA &#8805;1.0 x 10<sup>5</sup> c/ml or &#8805;2.0 x 10<sup>4</sup> IU/ml) and normal ALAT levels. For patients with serum HBV DNA below 1.0 x 10<sup>5</sup> c/ml (<2.0 x 10<sup>4</sup> IU/ml) the recommended frequency of monitoring is every three to six months for HBeAg-positive patients and every six to 12 months for HBeAg-negative patients.
Peginterferon (PEG-IF N) therapy should be considered as initial therapy in both HBeAg-positive and HBeAg-negative patients without contraindications for treatment with this drug because of the higher chance of achieving sustained response compared with nucleos(t)ide analogue therapy.
In patients starting nucleos(t)ide analogue therapy, the
use of lamivudine is not preferred if long-term antiviral
treatment is expected due to the high risk of antiviral
resistance against this drug. Of the currently licensed
nucleos(t)ide analogues, entecavir has the lowest risk of
antiviral resistance (compared with lamivudine, adefovir
and telbivudine), while suppression of viral replication
seems most profound with either entecavir or telbivudine.
The recommended duration of treatment with PEG-IF N
is one year for both HBeAg-positive and HBeAg-negative
patients. In HBeAg-positive patents, nucleos(t)ide
analogue therapy should at least be continued until HBeAg seroconversion and a decline in HBV DNA to below 400 c/ml (80 IU/ml) has been achieved and maintained for six months during therapy. Whether nucleos(t)ide analogue therapy can be safely discontinued in HBeAg-negative patients is unknown; usually prolonged or indefinite antiviral treatment is necessary.
Patients receiving PEG-IF N should be monitored once a
month, while three monthly monitoring suffices for those
receiving nucleos(t)ide analogues. Genotypic analysis of
the HBV polymerase is indicated if an increase in serum
HBV DNA of at least 1 log10 c/ml (IU/ml) compared with
the nadir value is observed during nucleos(t)ide analogue therapy. Antiviral therapy should be changed as soon as possible in case of confirmed genotypic resistance. Adding a second antiviral agent seems beneficial over switching to another agent.
With the availability of multiple new antiviral drugs for the treatment of chronic hepatitis B, effective treatment is now possible for more patients and for longer periods. However, the complexity of HBV therapy has also increased. Nowadays, virtually all chronic HBV-infected patients can be effectively managed, either by inducing sustained off-treatment response or by maintaining an on-treatment response.