thesis
Clinical and virological studies on α-interferon treatment of chronic hepatitis type B
- Publication date
- 16 June 1993
- Publisher
- The positive results of a-interferon (IFN) therapy have generated an important change in
the therapeutic approach of chronic hepatitis B patients. The studies presented in this
thesis are directed to the question how the efficacy of a-IFN therapy for chronic hepatitis
B could be improved (chapter 1). In particular we investigated whether patient selection,
modification of the treatment schedule and new virological assessments could contribute to
answer this question.
For optimal management of the HBV-infected patients it is important to defme indications
for new treatment modalities as a-IFN and liver transplantation. We followed a cohort of
98 patients with HBsAg-positive cirrhosis and determined which variables influenced the
survival (chapter 2). High age, the presence of ascites and a high serum bilirubin level
were indepently associated with a short duration survival. For the group with a
compensated cirrhosis HBeAg-negative patients exhibited a significantly better prognosis
than HBeAg-positive patients. In contrast we could not fmd a difference in survival in
decompensated patients with a different HBeAg status. These fmdings suggest that there is
an indication for antiviral therapy for patients with a compensated hepatitis B cirrhosis and
active viral replication (HBeAg positive) whereas liver transplantation appears the major
therapeutic option for patients with a decompensated chronic hepatitis B infection.
The standard course of a-IFN therapy for chronic hepatitis B lasts 16 weeks and leads in
about one third of the patients to cessation of virus replication. Intermittent a-IFN therapy
of 24 weeks duration and prolongation of treatment in patients who already exhibited a
partial response (HBV-DNA negative) could enhance the HBeAg serocvonversion rate
(chapter 3). Another modification of the standard a-IFN treatment is combination therapy
with zidovudine. In a randomized controlled study (chapter 4) we found that this
combination was not more effective than a-IFN monotherapy. In patients treated with the
combination of a-IFN and zidovudine side effects, in particular anemia and leucopenia,
were more prominent than in those treated with a-IFN and placebo. In chapter 5 the
benefit of a-IFN retreatment in chronic hepatitis B patients who previously failed to
respond was evaluated. A response (HBeAg seroconversion) to therapy occurred in 2 of
the 18 (11 %) investigated patients. This response rate may be comparable to the
spontaneous HBeAg seroconversion incidence and therefore the efficacy of a-IFN
retreatment in chronic hepatitis B appears limited. Variables with a known predictive
value towards response for initial a-IFN courses (e.g. the level of inflammatory acitvity)
did not influence the result of the retreatment.