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One small step for man, one giant leap for mankind: words that will be forever echoed in the annals of history from 1969 when Neil Armstrong set foot on the moon. Earlier that decade, another major landmark occurred in the field of hepatology with the discovery of hepatitis B (HBV) in 1967. The cure for HBV has since remained elusive; however, the recent discovery of sodium taurocholate contransporting polypeptide (NTCP), a key cell-surface transmembrane glycoprotein involved in HBV entry into hepatocytes1–3 marks a major opportunity for the development of novel therapeutic strategies.
In this issue of Gut, Hu and colleagues4 report on the role of NTCP in the natural history of HBV infection and its link to the risk of HBV-related complications in a large cohort of Taiwanese patients. Chronic HBV remains a major global public health problem with an estimated 350 million people infected worldwide5 ,6 leading to approximately 780 000 deaths every year due to HBV complications.7 New strategies are needed to identify patients at risk of progression of liver disease and those at risk of developing hepatocellular carcinoma (HCC), thus allowing for more targeted therapeutic interventions, more cost-effective and more focused screening approaches in high-prevalence populations.
NTCP is encoded by the SLC10A1 gene and specifically expressed on the basolateral membrane of differentiated hepatocytes,8 likely serving as a key factor in the hepatotropism and species specificity of the virus.9 NTCP cotransports sodium and bile acids across the cellular membrane as part of the enterohepatic circulation.8 ,10 The N-terminus of the pre-S1 domain of the large envelope protein binds to NTCP, facilitating HBV entry into hepatocytes in cell culture model.1 Transfection of NTCP allows HBV entry into non-susceptible HCC cell lines but not to non-human, non-hepatic cells,11 suggesting …
Contributors NR drafted the manuscript. JJF revised the manuscript.
Competing interests JJF: consulting/research grants from Abbvie, Bristol Myers Squibb, Gilead, Janssen, Merck.
Provenance and peer review Commissioned; internally peer reviewed.
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