Published online Jun 8, 2015. doi: 10.4254/wjh.v7.i10.1421
Peer-review started: December 6, 2014
First decision: January 20, 2015
Revised: January 29, 2015
Accepted: February 10, 2015
Article in press: February 12, 2015
Published online: June 8, 2015
Liver transplantation remains the only curative option for eligible patients with complications of chronic hepatitis B (CHB) infection, including severe acute hepatitis flares, decompensated cirrhosis, and hepatocellular carcinoma. In general, all patients with CHB awaiting liver transplantation should be treated with oral nucleos(t)ide analogs (NAs) with high barriers to resistance to prevent potential flares of hepatitis and reduce disease progression. After liver transplantation, lifelong antiviral therapy is also required to prevent graft hepatitis, which may lead to subsequent graft loss. Although combination therapy using NA and hepatitis B immune globulin (HBIG) has been the regimen most widely adopted for over a decade, recent studies have demonstrated that newer NAs with low rates of resistance are effective in preventing graft hepatitis even without the use of HBIG, achieving excellent long term outcome. For patients without pre-existing resistant mutations, monotherapy with a single NA has been shown to be effective. For those with resistant strains, a combination of nucleoside analog and nucleotide analog should be used. To date, clinical trials using therapeutic vaccination have shown suboptimal response, as CHB patients likely have an immune deficit against HBV epitopes. Future strategies include targeting different sites of the hepatitis B replication cycle and restoring the host immunity response to facilitate complete viral eradication.
Core tip: In the era of highly potent nucleoside and nucleotide analogues for the treatment of hepatitis B, long term viral suppression can be achieved with minimal risk of drug resistance. The use of these agents without hepatitis B immune globulin has been shown to be highly effective in preventing hepatitis B-related graft hepatitis, with excellent long-term outcome. Complete eradication of hepatitis B from the host however is unlikely, and long-term therapy is therefore required. Future developments aiming at different target sites together with immune restoration of the host against hepatitis B may make this elusive goal possible.