Benefits of long-term therapy with nucleos(t)ide analogues in treatment-naive patients with chronic hepatitis B

Objective: To assess the benefits of long-term nucleos(t)ide analogue (NA) therapy in reducing the severity and progression of liver disease in treatment-nave patients with chronic hepatitis B (CHB). Scope: As complications of CHB, such as hepatic decompensation and hepatocellular carcinoma (HCC), take a long time to develop in patients with less advanced disease, the long-term benefits of NA therapy in such patients are more difficult to prove than short- or medium-term benefits. Thus, the recent literature was reviewed to evaluate the impact of NA therapy on the long-term outcomes of treatment-naive CHB patients. Methods: A literature search of the MEDLINE/PubMed database was undertaken to identify studies published since 2010 of the long-term use of NAs with high potency and low drug resistance profiles in treatment-naive CHB patients. A total of 22 studies were identified, many of which were retrospective analyses or case control studies, as well as three meta-analyses and one systematic review. Results: Analysis of the retrieved studies showed that long-term NA therapy in treatment-naive CHB patients did prevent or delay the occurrence of complications, including hepatic decompensation, HCC, and liver-related death, in comparison with no treatment. However, it did not completely eliminate the risk of these complications, particularly in those with cirrhosis. Although long-term NA therapy improved the clinical status of patients with decompensated cirrhosis, the risk of cirrhotic complications including HCC, liver transplantation, and liver-related mortality remained significant in comparison with those with compensated cirrhosis. Conclusions: Long-term administration is generally advised in all CHB patients treated with NAs because of the high rates of virological and clinical relapse after stopping therapy. The findings of this analysis lend support to the choice of highly potent agents with a low drug resistance profile to maximize viral suppression in CHB patients and halt or delay progression to end-stage liver disease.