Abstract
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.
Highlights
Chronic Hepatitis B is a major cause worldwide of liver cirrhosis, hepatocellular carcinoma and liver related mortality
Due to the significant issues with resistance encountered with lamivudine, adefovir and telbivudine, only the 3rd generation Nucleotide analogues (NA’s), entecavir and Tenofovir disoproxil fumarate (TDF) are recommended as first line choices for CHB
Cessation of NA therapy is not recommended in HBeAg negative patients according to EASL or AASLD guidelines except for situations where HBsAg is cleared
Summary
Chronic Hepatitis B remains a major global problem with approximately 240 million people chronically infected and an estimated 600,000 people dying each year from the disease [1]. Reduction of the complications of chronic HBV infection, namely cirrhosis, decompensated liver disease, hepatocellular carcinoma and liver related death are the main goals of treatment of HBV. Sustained viral suppression is a necessary step in achieving reduction in the risks of complications in CHB even though a cure of the disease is currently not possible due to the persistence of cccDNA in the nucleus of infected liver cells and integration of the viral genome into that of the host. There are 2 major categories of therapeutic agents available; immunodulatory agents ie Interferon and anti-viral agents which include a number of oral nucleos(t)ide analogues
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