Combination therapy for chronic hepatitis B: Current updates and perspectives
Journal
Gut and Liver
Journal Volume
11
Journal Issue
5
Pages
590-603
Date Issued
2017
Author(s)
Abstract
Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades to treat chronic hepatitis B; however, the therapeutic response remains unsatisfactory. Although NUC therapy exhibits potent on-Treatment viral suppression, frequent off-Therapy virological relapses suggest an indefinite treatment course. Interferon modulates the innate and adaptive antiviral immune responses and thus increases the chance of viral eradication. Interferon therapy has the advantage of a finite duration, absence of drug resistance, and durable posttreatment responses. Therefore, the combination of NUCs and interferon can theoretically facilitate a synergistic therapeutic effect. This paper summarizes the current strategies of various combination therapies into three categories: The simultaneous "dual" strategy, sequential combination "add-on" strategy, and "switch" strategy. Generally, dual therapy exhibits greater on-Treatment and off-Therapy viral suppression and lower drug resistance compared with NUC monotherapy. Compared with interferon monotherapy, dual therapy has greater on-Treatment viral suppression but shows no difference in off-Therapy sustained virological responses. Specific add-on or switch strategies provide promising on-Treatment efficacy in select patients. Pretreatment or on-Treatment quantitative hepatitis B surface antigen and e antigen are predictive for the treatment efficacy of combination therapy. The optimal schedule of combination regimens and individualized therapy remain to be comprehensively evaluated.
SDGs
Other Subjects
adefovir; alpha interferon; alpha2b interferon; antiretrovirus agent; entecavir; interferon; lamivudine; peginterferon; peginterferon alpha; peginterferon alpha2a; peginterferon alpha2b; telbivudine; tenofovir; adefovir; adenine; alpha interferon; antivirus agent; lamivudine; nucleic acid synthesis inhibitor; phosphonic acid derivative; telbivudine; tenofovir; thymidine; adaptive immunity; add on therapy; chronic hepatitis B; chronic hepatitis C; clinical effectiveness; cytokine production; drug substitution; drug withdrawal; hepatitis B; human; innate immunity; nonhuman; protein expression; Review; seroconversion; sustained virologic response; treatment duration; treatment outcome; treatment response; virus capsid; virus immunity; virus load; virus replication; analogs and derivatives; chronic hepatitis B; combination drug therapy; drug effect; Adenine; Antiviral Agents; Drug Therapy, Combination; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Nucleic Acid Synthesis Inhibitors; Organophosphonates; Tenofovir; Thymidine; Treatment Outcome; Viral Load
Publisher
Joe Bok Chung
Type
review