Improving clinical outcomes of chronic hepatitis B virus infection

Abstract

Chronic hepatitis B virus (HBV) infection is a global health problem, leading to cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. Universal hepatitis B vaccination is the most cost–effective way to eradicate HBV infection with the remarkable reduction of chronic carriage, neonatal fulminant hepatitis and childhood HCC. The introduction of highly effective antiviral agents, including lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir disoproxil fumarate and pegylated interferons further improve short-, medium- and long-term outcomes of chronic HBV infection, such as ALT normalization, HBV DNA suppression, HBeAg seroconversion, HBsAg seroclearance, fibrosis regression, reduction of cirrhosis, HCC, liver-related deaths and the need for liver transplantation. Above all, sustained and profound viral suppression is the key to improve the clinical outcomes of chronic hepatitis B.

Keywords:

• adefovir dipivoxil
• cirrhosis
• entecavir
• hepatocellular carcinoma
• interferon
• lamivudine
• liver transplantation
• telbivudine
• tenofovir disoproxil fumarate
• vaccination

Financial & competing interests disclosure

The work was supported by grants from the Ministry of Science and Technology, and Ministry of Health and Welfare, Executive Yuan, Taiwan; and National Taiwan University Hospital, Taiwan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The universal hepatitis B virus (HBV) vaccination markedly decreases chronic hepatitis B surface antigen (HBsAg) carriage, neonatal fulminant hepatitis and childhood hepatocellular carcinoma (HCC).

• The short-term therapeutic goals including alanine aminotransferase normalization, HBV viral suppression, HBeAg loss/seroconversion and histologic improvement continue to improve after extending antiviral therapy with maintained viral suppression.

• Serum quantitative HBsAg titer reflects the active transcription of covalently closed circular DNA in hepatocyte and its clearance is close to the cure of chronic hepatitis B.

• Regression of liver fibrosis after prolonged antiviral therapy with maintained viral suppression is possible.

• Successful pegylated interferons or nucleos(t)ide analog therapy can halt disease progression and delay or prevent the development of cirrhosis and its complications.

• Compared with untreated controls, long-term NA therapy can reduce the development of HCC, especially in compensated cirrhotic patients, but not in decompensated ones.

• Despite the reduction of HCC risk after NA therapy, periodic HCC surveillance is still recommended in high-risk patients.

• Safety profiles of prolonged NA therapy is a growing concern, and renal function, bone mineral density should be monitored regularly.

Notes