Hepatitis B Virus Genotype and DNA Level and Hepatocellular Carcinoma: A Prospective Study in Men

Yu, Ming‐Whei; Yeh, Shiou–Hwei; Chen, Pei‐Jer; Liaw, Yun–Fan; Lin, Chih–Lin; Liu, Chun‐Jen; Shih, Wei-Liang; Kao, Jia‐Horng; Chen, Ding‐Shinn; Chen, Chien‐Jen

doi:10.1093/jnci/dji043

Cited by 501 publications

(471 citation statements)

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“…In Japan, the prevalence of HBV infection was estimated to be 0.8% in 2000, and the vast majority of individuals are infected with HBV genotype C [4][5][6]. Genotype C virus has been associated with high rates of progression to the complications of CHB, including cirrhosis and HCC [7][8][9][10][11]. In addition to genotype, the level of HBV DNA in the serum is strongly associated with liver disease progression [12,13].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

et al. 2010

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Purpose Lamivudine treatment of chronic hepatitis B (CHB) is associated with frequent resistance and loss of clinical benefit. We present outcomes of lamivudinerefractory Japanese patients treated with entecavir for 3 years. Methods Eighty-two patients refractory to lamivudine therapy received entecavir 0.5 or 1 mg daily for 52 weeks in phase II study ETV-052, directly entered rollover study ETV-060, and received entecavir 1 mg daily. Responses were evaluated among patients with available samples.Results After 96 weeks in ETV-060 (148 weeks total entecavir treatment time), 55% (36/65) of patients had hepatitis B virus (HBV) DNA of [400 copies/mL, 85% (52/61) had alanine aminotransferase (ALT) of C1 9 upper limit of normal (ULN), and 14.6% (7/48) achieved HBe seroconversion. A subset of 42 patients received entecavir 1 mg from phase II baseline through 148 weeks: 54% (19/35) had HBV DNA of [400 copies/mL, 84% (27/32) had ALT of C1 9 ULN, and 15% (4/27) achieved HBe seroconversion. Sixteen patients in the 1-mg subset had baseline and week 148 evaluable biopsy pairs: 81% (13/16) showed histologic improvement and 38% (6/16) showed 123Hepatol Int (2010) 4:414-422 DOI 10.1007/s12072-009-9162-x improvement in fibrosis. Genotypic resistance to entecavir emerged in 31 patients for a 3-year cumulative resistance probability of 35.9%. Entecavir was generally well tolerated during ETV-060, with no on-treatment ALT flares. Conclusions Long-term entecavir treatment of lamivudine-refractory CHB resulted in virologic suppression, ALT normalization, and improvements in liver histology. Resistance was consistent with that observed in worldwide studies.

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Section: Introductionmentioning

confidence: 99%

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

et al. 2010

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“…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%

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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“…Differences between genotypes B and C in Asia [Kao et al, 2000;Orito et al, 2001;Tsubota et al, 2001;Chan et al, 2004;Yu et al, 2005] have not been reproduced, probably due to selection bias for the patients with severe disease [Sumi et al, 2003] or subgenotypes of B different between Japan (Bj) and Hong Kong (Ba) [Yuen et al, 2004]. Liver disease, once advanced beyond a certain severity, will progress spontaneously irrespective of HBV genotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Eight HBV genotypes have been classified by a sequence divergence in the entire genome exceeding 8% [Okamoto et al, 1988], and they are named by capital Alphabet letters from A to H [Okamoto et al, 1988;Norder et al, 1992;Stuyver et al, 2000;ArauzRuiz et al, 2002]. Recently, HBV genotypes have attracted an increasing attention because they influence the clinical outcome and treatment response in patients with chronic liver disease Kao, 2002;Miyakawa and Mizokami, 2003;Schaefer, 2005;Yu et al, 2005]. Due to their uneven geographical distribution, however, only two HBV genotypes prevail in most countries; the United States is the only exception with seven (A-G) genotypes [Chu et al, 2003;Westland et al, 2003].…”

Section: Introductionmentioning

confidence: 99%

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C

Kobayashi

Akuta

Suzuki

et al. 2005

Journal of Medical Virology

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In a single hospital in Tokyo, the 87 patients infected persistently with hepatitis B virus (HBV) genotype A, the 413 with B, and the 3,389 with C were compared for virological outcome. Hepatitis B surface antigen (HBsAg) was cleared from the serum in 12% (3/26), 2% (2/112), and 3% (23/826) of patients with genotypes A, B, and C, respectively, at 5 years of follow-up (P ¼ 0.0395). Hepatitis B e antigen (HBeAg) was cleared from serum more frequently in patients with genotype B than those with A or C (78% [32/41] vs. 58% [11/19]

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Hepatitis B Virus Genotype and DNA Level and Hepatocellular Carcinoma: A Prospective Study in Men

Abstract: Measurements of HBV viral load and genotype may help to define which male HBV carriers aged 30 years or older are at high risk for HCC.

Cited by 501 publications

References 35 publications

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

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

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C

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