We evaluated the use of blood serum N-glycan fingerprinting as a tool for the diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis induced by hepatitis B virus (HBV). A group of 450 HBV-infected patients with liver fibrosis or cirrhosis with or without HCC were studied. HCC was diagnosed by ␣-fetoprotein (AFP) analysis, ultrasonography, and/or computed tomography and was studied histologically. N-glycan profiles of serum proteins were determined with DNA sequencer-based carbohydrate analytical profiling technology. In this study, we found that a branch alpha(1,3)-fucosylated triantennary glycan was more abundant in patients with HCC than in patients with cirrhosis, patients with fibrosis, and healthy blood donors, whereas a bisecting core alpha(1,6)-fucosylated biantennary glycan was elevated in patients with cirrhosis. The concentration of these 2 glycans and the log ratio of peak 9 to peak 7 (renamed the GlycoHCCTest) were associated with the tumor stage. Moreover, for screening patients with HCC from patients with cirrhosis, the overall sensitivity and specificity of the GlycoHCCTest were very similar to those of AFP. Conclusion: This study indicates that a branch alpha(1,3)-fucosylated glycan is associated with the development of HCC. The serum N-glycan profile is a promising noninvasive method for detecting HCC in patients with cirrhosis and could be a valuable supplement to AFP in the diagnosis of HCC in HBV-infected patients with liver cirrhosis. Its use for the screening, follow-up, and management of patients with cirrhosis and HCC should be evaluated further.

The study was designed to investigate whether serum hepatitis B virus (HBV) RNA is a strong surrogate marker for intrahepatic HBV covalently closed circular DNA (cccDNA) compared with serum HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) in HBeAg-positive chronic hepatitis B (CHB) patients. Serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA were quantitatively detected at baseline (n ϭ 82) and 96 weeks (n ϭ 62) after treatment with nucleos(t)ide analogue (NUC) in HBeAg-positive CHB patients. The correlations among serum HBV RNA, HBV DNA, HBsAg, HBeAg, and intrahepatic cccDNA levels were then statistically analyzed. The results showed that pretreatment intrahepatic cccDNA levels correlated better with serum HBV DNA levels (r ϭ 0.36, P Ͻ 0.01) than with serum HBV RNA levels (r ϭ 0.25, P ϭ 0.02), whereas no correlations were found between pretreatment intrahepatic cccDNA levels and HBsAg (r ϭ 0.15, P ϭ 0.17) or HBeAg (r ϭ 0.07, P ϭ 0.56) levels. At 96 weeks after NUC treatment, intrahepatic cccDNA levels correlated well with HBsAg levels (r ϭ 0.39, P Ͻ 0.01) but not with serum HBV RNA, HBV DNA, and HBeAg levels (all P Ͼ 0.05). Besides, the decline in the intrahepatic cccDNA level from baseline to week 96 correlated better with the reduction in the serum HBsAg levels than with the decreases in the levels of the other markers (for the HBsAg decline, r ϭ 0.38, P Ͻ 0.01; for the HBV DNA decline, r ϭ 0.35, P ϭ 0.01; for the HBV RNA decline, r ϭ 0.28, P Ͻ 0.05; for the HBeAg decline, r ϭ 0.18, P ϭ 0.19). In conclusion, the baseline serum HBV RNA level or its decline after 96 weeks of NUC therapy correlated with the corresponding intrahepatic cccDNA level, while it was less than that seen with serum HBV DNA at baseline and HBsAg (or its decline) at 96 weeks after treatment, respectively. KEYWORDS chronic hepatitis B, covalently closed circular DNA, HBV DNA, HBV RNA, hepatitis B surface antigen, nucleos(t)ide analogue H epatitis B virus (HBV) infection is a global health problem; an estimated 240 million persons are chronically infected, and about 650,000 people die annually due to chronic hepatitis B (CHB) worldwide (1). Though the currently available antiviral drugs can effectively reduce HBV DNA levels in serum of CHB patients, HBV may not be eliminated due to the persistence of HBV covalently closed circular DNA (cccDNA) in the infected hepatocytes, which represents the key HBV replicative intermediate (2). The fundamental role of intrahepatic cccDNA is as a template for transcription of all viral RNAs, including pregenomic RNA (pgRNA), which further produces the offspring virion

SUMMARY BackgroundTransient elastography is a non-invasive method for staging liver fibrosis. The meta-analysis using the hierarchical models to evaluate the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B was rarely reported.