Is it better to treat chronic hepatitis B as early as possible?—Con

Ideally, treatment of chronic hepatitis B in its early stage prior to irreversible liver damage should be most effective in preventing adverse clinical outcome. However, currently available treatments have low efficacy in achieving sustained response among patients in the early phase of chronic hepatitis B infection when the immune response to hepatitis B virus is weak. This review will provide evidence why a ‘wait and monitor’ approach is appropriate for chronic hepatitis B patients who are in the immune tolerant phase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73513/1/j.1440-1746.2004.03660.x.pd

Sustained response after a 2-year course of lamivudine treatment of hepatitis B e antigen-negative chronic hepatitis B

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72882/1/j.1365-2893.2004.00556.x.pd

Novel mutation in YMDD motif and direct neighbourhood in a child with chronic HBV-infection and clinical lamivudine and adefovir resistance - a scholarly case

<p>Abstract</p> <p>Context</p> <p>Chronic HBV infection is a major cause of hepatocellular carcinoma (HCC) which meanwhile has become the 5^thmost reason for a fatal outcome of cancer. Worldwide, approximately 350 million people are chronically HBV infected and as such of risk to develop HCC, of those an estimated high rate of children. Treatment of chronic infection is sufficient to reduce the rate of HCC but the rate of sustained virological response remains to low, not at least due to emergence of resistant virus strains. Less is known on HBV infection in children despite the extremely high rate of chronicity.</p> <p>Objective, Design, Setting, and Patient</p> <p>The case of a nine years old male with a 6 year history of chronic HBV infection, of those 5 years with antiviral treatment is described.</p> <p>Interventions and Main Outcome Measure(s)</p> <p>Before our lab was consulted, the patient was unsuccessfully treated with interferon, an obscure drug named Hepon, which should activate antiviral immune response, and Lamivudine, the latter most likely becoming ineffective due to the mergence of resistant subpopulations (rtL180 M, rtV207 M, two strains with stop codons at position rt188 and rt198, rtM204V (YVDD), rtM204K (YKDD)). Replacement of Lamivudine by adefovir displayed no advantage despite the lack of resistance mutations, thus no decrease in viremia was observed under adefovir treatment.</p> <p>Results and Conclusions</p> <p>Novel mutations in the YMDD motif and its direct neighbourhood were observed, both being compatible with Lamivudine resistance. No mutations were found that are associated with ADF resistance. Both, the clinical course of treatment and the genotypic resistance profile emphasize the need for systematic analyses of the HBV resistance mechanisms and structured therapy concept also for children chronically infected with HBV.</p

Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference.

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic hepatitis B virus (HBV) treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilizing cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase 3 trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss, 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity in predicting sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive and HBeAg-negative chronic hepatitis, treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with increase in bilirubin or INR should prompt temporary or permanent cessation of investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase 3 trials for hepatitis D virus (HDV) co-infection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalization of ALT is considered an intermediate goal. CONCLUSION: For HBV 'functional cure', sustained HBsAg loss with undetectable HBV DNA after completion of treatment is the primary goal and sustained undetectable HBV DNA without HBsAg loss after stopping treatment an intermediate goal

Investigation of stacking faults in MOVPE-grown zincblende GaN by XRD and TEM

X-ray diffraction and bright-field transmission electron microscopy are used to investigate the distribution and density of {111}-type stacking faults (SFs) present in a heteroepitaxial zincblende GaN epilayer with high phase purity, grown on a 3C-SiC/Si (001) substrate by metalorganic vapour-phase epitaxy. It is found that the 4° miscut towards the [110] direction of the substrate, that prevents the formation of undesirable antiphase domains, has a profound effect on the relative densities of SFs occurring on the different {111} planes. The two orientations of SFs in the [-110] zone, where the SF inclination angle with the GaN/SiC interface is altered by the 4° miscut, show a significant difference in density, with the steeper (111) SFs being more numerous than the shallower (-1-11) SFs by a factor of ~ 5 at 380 nm from the GaN/SiC interface. In contrast, the two orientations of SFs in the [110] zone, which is unaffected by the miscut, have densities comparable with the (-1-11) SFs in the [-110] zone. A simple model, simulating the propagation and annihilation of SFs in zincblende GaN epilayers, reproduces the presence of local SF bunches observed in TEM data. The model also verifies that a difference in the starting density at the GaN/SiC interface of the two orientations of intersecting {111} SFs in the same zone reduces the efficiency of SF annihilation. Hence, (111) SFs have a higher density compared with SFs on the other three {111} planes, due to their preferential formation at the GaN/SiC interface caused by the miscut.the Ministry of Education, Youth and Sports of the Czech Republi

Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B

BACKGROUND: Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS: In this phase 3, double-blind trial, we randomly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necroinflammatory score, without worsening of fibrosis). RESULTS: Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated (70 percent), as compared with 174 of 287 such patients in the lamivudine group (61 percent, P=0.01). More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus (HBV) DNA levels according to a polymerase-chain- reaction assay (90 percent vs. 72 percent, P<0.001) and normalization of alanine aminotransferase levels (78 percent vs. 71 percent, P = 0.045). The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine (5.0 vs. 4.5 log [on a base-10 scale] copies per milliliter, P<0.001). There was no evidence of resistance to entecavir. Safety and adverse-event profiles were similar in the two groups. CONCLUSIONS: Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue, the rates of histologic improvement, virologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine. The safety profile of the two agents was similar, and there was no evidence of viral resistance to entecavir. Copyright © 2006 Massachusetts Medical Society.published_or_final_versio

Survival and hepatitis status among Asian Americans with hepatocellular carcinoma treated without liver transplantation

<p>Abstract</p> <p>Background</p> <p>Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) are established causes of HCC. HCC patients are often diagnosed late and receive palliative therapies, however, the survival of Asian American patients with HCC treated without transplantation has not been well studied. We reviewed our institution's experience to determine predictors and rates of survival in Asian American HCC patients treated without transplantation.</p> <p>Methods</p> <p>We identified Asian American patients with HCC referred to M. D. Anderson Cancer Center. Patients were tested for HBV and HCV. Survival curves were generated by Kaplan-Meier method. Multivariate Cox proportional hazards regression was used to test the relationship between prognostic factors and survival.</p> <p>Results</p> <p>Of 82 Asian American HCC patients, most had advanced disease (65%) and received treatment (68%); however, only 11% had surgical resection. 94% had positive anti-HBc and 61% had positive HBsAg. 20% had positive anti-HCV. There were no significant changes in the rates of HBV and HCV over time. Male gender, high alpha-fetoprotein levels, and stage IV disease were associated with shorter survival Overall median survival was 9.2 months (95% CI 6.5–11.9), and the survival of HCV and HBV patients was not statistically different.</p> <p>Conclusion</p> <p>The survival rate of Asian American patients with advanced HCC, for whom transplantation was not available, was low. Timely hepatitis screening and interventions by primary care physicians may be the most logical solution to reduce the burden of hepatitis-associated HCC among Asian Americans.</p

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120