Prediction of Response to Immune Modifying Therapy for Patients with Chronic Hepatitis B using Hepatitis B Surface Antigen Levels

The treatment of chronic hepatitis B has greatly improved with the introduction of potent nucleos(t)ide analogues with a high barrier to resistance and peginterferon. The advantages and limitations of both treatment options should be considered when a patient has an indication to initiate antiviral therapy. Nucleos(t)ide analogues can be prescribed to all patients in whom treatment is indicated and offer easy daily oral dosing, are well tolerated and able to maintain suppression of viral replication for prolonged periods of time. However, a sustained off-treatment response is unlikely. A sustained response is more likely to be achieved in a subgroup of patients with a finite course of peginterferon therapy. Furthermore, sustained responders to peginterferon experience a strong degree of serum hepatitis B surface antigen (HBsAg) decline resulting in a higher rate of HBsAg clearance. Both peginterferon and nucleos(t)ide analogues can be given as first-line treatment option for chronic hepatitis B. However, peginterferon should only be considered for patients with a high chance of response because of the considerable side effects associated with this agent. Predictors of response at baseline, such as hepatitis B virus (HBV) genotype, alanine aminotransferase and HBV DNA levels, aid in selecting patients for peginterferon therapy, especially in hepatitis B e antigen (HBeAg-)positive disease. Furthermore, on-treatment viral markers, in particular quantitative HBV DNA and HBsAg, allow the identification of patients who are unlikely to benefit from peginterferon early during the treatment course, thereby avoiding unnecessary treatment. Patients who are not eligible for peginterferon or who have a low probability of response to peginterferon based on baseline or on-treatment factors should be advised to initiate or switch to nucleos(t)ide analogue therap

The Role of Interferon in Hepatitis B Therapy

Despite the introduction of new nucleos(t)ide analogues in recent years, peginterferon is still recommended as a potential first-line treatment option by current practice guidelines for the management of chronic hepatitis B. Peginterferon offers the advantage of higher sustained off-treatment response rates compared to nucleos(t)ide analogues because of its immunomodulatory effects. Sustained transition to the inactive hepatitis B surface antigen (HBsAg) carrier state can be achieved in about 30% of hepatitis B e antigen (HBeAg)–positive patients and 20% of HBeAg-negative patients. Recent studies have focused on identification of pretreatment and on-treatment factors that allow the selection of patients who are likely to achieve a sustained response to peginterferon therapy in order to avoid the side-effects and costs associated with unnecessary treatment. Future studies need to address whether specific virologic benchmarks can guide individualized decisions concerning therapy continuation and whether peginterferon combined with new potent nucleos(t)ide analogues improves treatment outcomes

Review article: chronic hepatitis B - anti-viral or immunomodulatory therapy?

P>Background First-line treatment options for chronic hepatitis B (CHB) consist of nucleos(t)ide analogues with a high barrier to resistance (entecavir and tenofovir) or the immunomodulatory agent peginterferon (PEG-IFN). The optimal choice for individual patients remains controversial. Aim To review treatment options for CHB, with a focus on deciding between prolonged nucleos(t)ide analogue therapy or a finite course of PEG-IFN. Methods A comprehensive literature search was undertaken. Results Long-lasting, treatment-maintained suppression of hepatitis B virus (HBV) DNA without resistance is achievable in most patients by entecavir or tenofovir. A sustained off-treatment response is, however, unlikely and long-term therapy must be anticipated. PEG-IFN offers a higher rate of sustained response in a subgroup of patients, but is frequently complicated by side effects. Pre-treatment predictors of response, including HBV genotype, alanine aminotransferase and HBV DNA levels, aid in selecting patients for PEG-IFN therapy. Furthermore, on-treatment markers such as quantitative hepatitis B surface antigen may be applied to identify nonresponders early during the PEG-IFN treatment course, thereby preventing unnecessary treatment. Conclusions Both nucleos(t)ide analogues and PEG-IFN can be prescribed as first-line treatment options for CHB. However, PEG-IFN should only be considered for patients with a high chance of response based on pre-treatment and on-treatment factors