Hepatocellular Carcinoma and Hepatitis B Virus

Beasley, R. Palmer; Hwang, Lu-Yu; Lin, Chia Chin; Ch, Chien

doi:10.1016/s0140-6736(81)90585-7

Cited by 2,346 publications

(391 citation statements)

References 12 publications

Supporting

Mentioning

381

Contrasting

Unclassified

Order By: Relevance

“…Infection with this virus causes severe liver diseases, including acute, chronic, and fulminant hepatitis; cirrhosis; and hepatocellular carcinoma (HCC) 3. Although effective vaccines against HBV are available in many countries, chronic hepatitis B (CHB) infection remains a significant global health problem.…”

Section: Introductionmentioning

confidence: 99%

Resistance mutations of hepatitis B virus in entecavir‐refractory patients

Yamada

Sugiyama

Nitta

et al. 2017

Hepatology Communications

View full text Add to dashboard Cite

The emergence of resistance mutations in the reverse transcriptase gene of hepatitis B virus (HBV) is associated with treatment failure. Entecavir (ETV) is one of the most potent anti‐HBV reagents; it has a very low resistance rate and is used as the first‐line treatment for chronic hepatitis B. In this study, we isolated HBVs in 4 ETV‐refractory patients (2 with viral breakthrough, 1 with partial virological response, and 1 with flare‐up) and assessed ETV resistance using replication‐competent 1.38‐fold HBV genome‐length molecular clones. The full genome sequences of infected HBVs in ETV‐refractory patients were determined. The HBV molecular clones were generated with the patient‐derived sequences. After transfection of these molecular clones into HepG2 cells, viral replications and ETV susceptibilities were evaluated by measuring the amount of intracellular core‐particle‐associated HBV DNA using Southern blotting and real‐time polymerase chain reaction. Among these cases, ETV‐resistant variants were detected in 2 patients with viral breakthrough and responsible amino acid mutations in reverse transcriptase were successfully identified in these variants. No ETV‐resistant mutation was detected in the other cases. The identified ETV‐resistant mutations did not confer resistance to tenofovir disoproxil fumarate. Conclusion: The HBV replication model with patient‐derived sequences is useful for assessing replication efficiency, susceptibility to anti‐HBV reagents, and responsible resistance mutations and can aid in choosing the appropriate treatment strategy for treatment‐failure cases of chronic hepatitis B. (Hepatology Communications 2017;1:110‐121)

show abstract

Section: Introductionmentioning

confidence: 99%

Resistance mutations of hepatitis B virus in entecavir‐refractory patients

Yamada

Sugiyama

Nitta

et al. 2017

Hepatology Communications

View full text Add to dashboard Cite

show abstract

“…Originally identified as a sequel to alcoholic cirrhosis, hemochromatosis, some metabolic disorders, certain types of drug injury (such as from oral contraceptives), or exposure to environmental toxins (such as aflatoxin), the cause of the bulk of cases remained obscure for many years, although linked in most instances to cirrhosis of unknown origin. This uncertainty held sway until the discovery of the hepatitis B virus (HBV) in the mid 1960s (Blumberg et al, 1965), and its subsequent association with HCC (Beasley et al, 1981), and the recognition about 20 years later of the hepatitis C virus (HCV) (Choo et al, 1989) with the subsequent evidence that it, too, was linked to HCC (Bruix et al, 1989). It, thus, became clear that the vast majority of cases of HCC were in fact a consequence of infection by one of these two viruses.…”

Section: Introductionmentioning

confidence: 99%

“…It, thus, became clear that the vast majority of cases of HCC were in fact a consequence of infection by one of these two viruses. That HCC was among the most common of cancers worldwide could then be accounted for by the fact that HBV infection, the leading cause for HCC, is endemic in southeast Asia (Beasley et al, 1981), the most populous area in the world, as well as in sub-Saharan Africa. More recently, it has become apparent that obesity, with its accompanying problems of diabetes mellitus and nonalcoholic steatohepatitis (NASH), represents a growing addition to the causes of HCC (Marrero et al, 2002;Caldwell et al, 2004;El-Serag et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity

2006

View full text Add to dashboard Cite

“…Chronic infection by the human hepatitis B virus (HBV), has for long been shown to dramatically increase the risk of liver cancer (Beasley et al, 1981). According to the World Health Organization (Kane, 1998), persistent HBV infection a ects 350 000 000 humans worldwide and this ®gure will likely increase due to the lack of fully-and cost-e ective anti-viral treatments.…”

Section: Introductionmentioning

confidence: 99%

UVDDB p127-binding modulates activities and intracellular distribution of Hepatitis B virus X protein

2000

View full text Add to dashboard Cite

Mammalian hepatitis B viruses encode a unique regulatory protein termed X, which is essential for infection and likely plays a role in the carcinogenic process associated with hepadnaviral infection. Among the numerous properties ascribed to X protein, two have been widely documented: promiscuous transcriptional transactivation and proapoptosis. However, full understanding of the mechanisms underlying these activities requires the identi®cation of the genuine X partners among the multiple X-binding host proteins. Here we show that (i) mutations in X protein, which markedly alter a nity for the host protein UVDDBp127, inactivate both transactivation and proapoptosis; (ii) ectopic fusion of a functional UVDDB-binding domain to a de®cient binding X mutant restored its activity; (iii) in contrast to the loss-of-binding mutants, a mutant with a strong gain-of-binding exerted trans-dominant negative e ects on wt X activity and localized in the nucleus and (iv) increase in intracellular UVDDB concentration enhanced both wt X-mediated transactivation and apoptosis. Taken together, our data provide strong evidence for a common upstream step in X mode of action, consisting of its productive interaction with UVDDB, via a structurally and functionally autonomous module. In addition, they underscore a nuclear location step of the viral protein that depends on its ability to bind UVDDB. Oncogene (2000) 19, 4417 ± 4426.

show abstract

Hepatocellular Carcinoma and Hepatitis B Virus

Cited by 2,346 publications

References 12 publications

Resistance mutations of hepatitis B virus in entecavir‐refractory patients

Resistance mutations of hepatitis B virus in entecavir‐refractory patients

Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity

UVDDB p127-binding modulates activities and intracellular distribution of Hepatitis B virus X protein

Contact Info

Product

Resources

About