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Complete eradication of HBV from host hepatocytes cannot be achieved with currently available agents because of the persistence of HBV covalently closed circular DNA. The main goal of treatment for chronic HBV infection, therefore, is to halt the progression of liver inflammation to fibrosis, cirrhosis, or HCC. Because these outcomes typically do not occur until decades after active infection, surrogate outcomes are used as measures of therapeutic efficacy and success. Several independent studies have shown that undetectable levels of HBV DNA, both spontaneous and treatment induced, as well as clearance of HBeAg and HBsAg, are associated with a lower risk of cirrhosis, HCC, and death.[13-15] Therefore, the major endpoints of treatment are a reduction of HBV DNA to undetectable levels (virologic response), a loss of HBeAg with or without the appearance of antibodies to HBeAg (serologic response), a reduction of ALT to levels considered normal (biochemical response), and a reduction in liver necroinflammation with or without an improvement of liver histology. Various studies have consistently shown that viral suppression with nucleos(t)ide analogues may reduce but does not eliminate the risk of HCC, particularly in patients with cirrhosis, and that the risk of HCC remains elevated in patients achieving viral suppression when compared with patients with truly inactive disease.[16-20] Loss of HBsAg from serum, accompanied by the appearance of anti-HBs, is currently, therefore, considered the optimal surrogate endpoint, although it is rarely achieved.[21,22] In addition, several studies have demonstrated that long-term therapy with nucleos(t)ide analogues is associated with reduction of liver fibrosis and reversal of cirrhosis in the large majority of patients, including those with advanced fibrosis or cirrhosis at baseline.[23-29] Improvement in liver histology is, therefore, also an appropriate goal of long-term HBV therapy.
For more information from inPractice on HBV viral replication, click here.