Hepatitis B e Antigen and the Risk of Hepatocellular Carcinoma

Yang, Hwai I.; Lu, Sheng; Liaw, Yun Fan; You, San Lin; Sun, Chien An; Wang, Li Yu; Hsiao, Chuhsing Kate; Chen, Pei‐Jer; Chen, Ding‐Shinn; Chen, Chien Jen

doi:10.1056/nejmoa013215

Cited by 1,124 publications

(811 citation statements)

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“…In terms of etiology, the dominance of CHB is on the decline while heralding a trend of increasing nonviral‐related HCC. Hepatitis B remains endemic in many parts of Asia and strongly correlates to the risk of HCC development 17, 18. Fortunately, with the development and successful implementation of nationwide hepatitis B immunization programs, a significant decline in seroprevalence of HBsAg and CHB has been observed in many countries, including Singapore.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

Goh

Chang

et al. 2017

Hepatology Communications

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Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers globally. With advances in therapy for chronic viral hepatitis, changing social circumstances, and increasing practice of HCC surveillance, the epidemiology of HCC is expected to change over time. We explored the temporal trends in HCC in Singapore, a multiethnic Asian country, over the last 3 decades. Patients with HCC were prospectively enrolled and stratified into two cohorts (C1, 1988‐2002; C2, 2003‐2016). Patient and tumor characteristics, management, and survival were compared between the two cohorts, and a survival census was performed on October 31, 2015. There were 1,401 patients, and the mean age at diagnosis of HCC for C1 and C2 was 60.1 and 63.5 years, respectively. Male patient preponderance decreased significantly, with the male to female ratio falling from 5.2:1 to 3.9:1 between C1 and C2. Hepatitis B, although still the predominant risk factor for HCC, showed a significant decline from C1 to C2 (76.5% to 68.2%), while the nonviral etiology increased significantly over the same period (14.4% versus 25.0%, respectively). Significantly more patients in C2 than C1 were diagnosed through surveillance (39.2% versus 11.3%, respectively) and had better physical performance (Eastern Cooperative Oncology Group 0, 62.1% versus 20.4%, respectively). While Child‐Pugh status was comparable, significantly more patients in C2 than C1 had early stage disease (Barcelona Clinic Liver Cancer 0‐A, 39.5% versus 7.4%, respectively), which translated into significantly higher median survival (18.6 months versus 3.8 months, respectively). Conclusion: Over the past 3 decades, hepatitis B‐related HCC has been decreasing while HCC due to nonviral etiology has been increasing significantly. Surveillance to diagnose early stage HCC is important in improving the outcome of HCC. (Hepatology Communications 2017;1:564–571)

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Section: Discussionmentioning

confidence: 99%

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

Goh

Chang

et al. 2017

Hepatology Communications

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“…The relationship between HBeAg seropositivity and the risk of developing HCC was evaluated in a long-term prospective study involving 11,893 Taiwanese men (age range = 30-65 years) without evidence of HCC [4]. During 92,359 person-years of follow-up, the incidence of HCC was higher for men who were positive for both HBsAg and HBeAg (1,169 cases per 100,000 person-years) than for men positive for HBsAg only (324 per 100,000 person-years).…”

Section: Hbeag Positivity and Disease Progressionmentioning

confidence: 99%

“…In regions of high HBV endemicity, such as the Asian-Pacific region where most individuals acquire the infection at birth or early in life, it is estimated that up to 40% of individuals with chronic hepatitis B (CHB) will progress to cirrhosis, end-stage liver disease, or hepatocellular carcinoma (HCC) during their lifetime [2,3]. Seropositivity for hepatitis B e antigen (HBeAg), a surrogate marker of active viral replication, has been shown to be a significant risk factor for the development of cirrhosis and HCC [4][5][6][7]. Spontaneous loss of HBeAg and development of antibodies to HBeAg (anti-HBe), referred to as HBeAg seroconversion, are associated with low HBV-DNA levels and clinical remission of liver disease in the majority of patients [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that profound and sustained suppression of HBV replication is a critical factor in achieving the goals of anti-HBV therapy, including improvement of liver histology and reduction in liver disease progression [4][5][6][7][19][20][21][22][23][24]. However, HBeAg seroconversion is still considered to be an important end point in the management of HBeAg-positive patients with CHB.…”

Section: Introductionmentioning

confidence: 99%

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HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

2009

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During the natural history of chronic hepatitis B virus (HBV) infection, the loss of serum hepatitis B e antigen (HBeAg) and the development of anti-HBe antibodies (HBeAg seroconversion) mark a transition from the immune-active phase of disease to the inactive carrier state. This review examines the evidence from natural history and cohort studies on the relationship between HBeAg seroconversion and disease progression. The role of HBeAg seroconversion as an important milestone in the management of HBeAg-positive patients with chronic hepatitis B (CHB), as well as the advantages and disadvantages of administering a finite course of therapy for HBeAg-positive CHB, is also discussed. The evidence from natural history and cohort studies indicates that spontaneous or treatment-induced HBeAg seroconversion is associated with lower rates of disease progression to cirrhosis and hepatocellular carcinoma, a potential of hepatitis B surface antigen seroconversion, and improved survival rates. Updated guidelines developed by major liver associations recommend stopping oral therapy for HBeAgpositive patients who achieve sustained HBeAg seroconversion with polymerase chain reaction-undetectable HBV-DNA on two separate occasions for 6 or more months apart, taking into consideration the individual's clinical and virologic response to therapy, as well as the severity of liver disease. Thus, early induction of HBeAg seroconversion with interferon-based therapy or oral nucleos(t)ide analogues has important clinical and socioeconomic implications for the management of CHB.

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“…14,15 As with HCV infection, the host immune response to HBV infection determines viral persistence, 16,17 which has been associated with polymorphisms in the human leukocyte antigen complex and other immune response genes. [18][19][20][21][22][23][24] Although there are likely important differences in the mechanisms of HBV persistence, there is also evidence that NK T (NKT) cells play an important role.…”

Section: Introductionmentioning

confidence: 99%

MICA and recovery from hepatitis C virus and hepatitis B virus infections

et al. 2004

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The polymorphic MHC class I chain-related A (MICA) gene encodes a ligand that has different binding affinities for the NKG2D activating receptor of CD8 þ T cells and natural killer (NK) cells. We hypothesized that MICA heterogeneity would affect recovery from hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To test the hypothesis, we initially typed known MICA polymorphisms for 228 persons who cleared HCV infection and 442 persons with persistent hepatitis C matched on other factors affecting viral persistence. Although MICA*015 was detected more than two-fold more often in persons with viral clearance (odds ratio 0.36, 95% confidence interval ¼ 0.19, 0.80), it occurred in fewer than 5% of the study population. In a similar analysis of 442 persons with chronic hepatitis B and 768 matched controls who recovered, MICA*015 was detected in 2.0% of persons with chronic hepatitis B and only 0.9% of controls. No significant associations were detected with other MICA polymorphisms. While further investigation may reveal a structural basis of the MICA*015 associations, these data provide little support for the hypothesis that differential distribution of MICA alleles substantially affects recovery from HCV and HBV infections.

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Hepatitis B e Antigen and the Risk of Hepatocellular Carcinoma

Abstract: Positivity for HBeAg is associated with an increased risk of hepatocellular carcinoma.

Cited by 1,124 publications

References 25 publications

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

MICA and recovery from hepatitis C virus and hepatitis B virus infections

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