Chronic Hepatitis B is a major cause worldwide of liver cirrhosis, hepatocellular carcinoma and liver related mortality. The ultimate goals of treatment are to reduce the risk of these complications and the endpoints used in clinical practice are viral suppression, ALT normalisation and histological regression of fibrosis as well as HBeAg seroconversion in patients who are HBeAg positive. The indications for treatment differ slightly in different regions however may still be conceptualised in terms of the phase of chronic hepatitis B Treatment options include a finite course of Peg IFN which has immunomodulatory as well as antiviral effects although its use may be limited by troublesome side effects and low efficacy in some patients. Recent advances in the use of quantitative HBsAg and HBeAg levels during Peg IFN treatment has provided some predictors of response and therefore the ability to individualise treatment courses to a degree, avoiding unnecessary prolongation of treatment where it is likely to be futile. The oral nucleoside/nucleotide analogues now available have high potency and very low rates of resistance however must be continued indefinitely in HBeAg negative patients and most HBeAg positive patients. Lifelong treatment raises issues of side effects such as renal and bone disease, compliance, and management during pregnancy. Research aimed at novel targets in the HBV life cycle or host immune response is ongoing. The ultimate goal of therapies for CHB remains HBsAg clearance which at present still occurs only in a minority of cases.

Therapeutic options for chronic hepatitis B have evolved over the past decade. The oral nucleoside analogue agents, Entecavir and Tenofovir, have high potency, very low rates of resistance and are well tolerated. They result in virological suppression and regression of fibrosis and reduce HCC in cirrhotic patients. They have a good safety profile however long term therapy is required in the majority of cases, especially in HBeAg negative CHB and monitoring of certain parameters eg renal function in Tenofovir remains necessary. Peg IFN is an alternative to oral NA’s and although it has a more significant side effect profile, and requires more intensive monitoring, its advantages are the finite duration of therapy and potential immunomodulatory effects. This makes it particularly suitable for women of childbearing age. Tailoring treatment to those with the best chance of response based on pre-treatment variables as well as on treatment measurement of quantitative HBsAg levels can further improve the utility of a course of Peg IFN and reduce unnecessary prolongation of treatment in those with very low chance of response. Future research will focus on identifying patients who can successfully stop NA therapy as well as on novel therapies or combinations of therapies that can target the HBV at various levels. Reliable and early HBsAg and cccDNA clearance and normalisation of the risks of cirrhosis and HCC remains the ultimate endpoint to which all therapies for CHB must strive.