Long-term clinical outcome of antiviral therapy for chronic hepatitis B

Treatment of chronic hepatitis B currently consists of long-term therapy with oral nucleos(t)ide analogues or one year peginterferon injections. Within this thesis, Roeland Zoutendijk explores the long term clinical outcome of the currently most potent nucleos(t)ide analogues entecavir and tenofovir on virological, serological and clinical endpoints within several (inter)national cohort studies. Main findings of this thesis are that adaptation of entecavir therapy does not seem necessary in the majority of patients with a partial virological response at week 48, as prolonged therapy after week 48 leads to undetectable HBV DNA in the majority of patients. In addition, achieving a virological response during entecavir therapy is associated with a lower probability of clinical disease progression (development of HCC, hepatic decompensation and death) in patients with cirrhosis, underlining the importance of achieving this endpoint especially in those with more advanced liver disease

Close monitoring of hepatitis B surface antigen levels helps classify flares during peginterferon therapy and predicts treatment response

Background. Alanine aminotransferase (ALT) flares occur frequently during peginterferon (PEG-IFN) therapy. We related occurrence of flares to presence of precore (PC) and/or basal core promoter (BCP) mutants and studied kinetics of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels during flares.Methods. Fifty of 214 (23%) patients treated with PEG-IFN ± lamivudine for 52 weeks experienced flares. Flares were host-induced (ALT elevation followed by HBV DNA decline, n = 19), virus-induced (HBV DNA increase with subsequent ALT elevation, n = 17) or indeterminate (n = 14

Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

A selected bibliography on parameter optimization methods suitable for hybrid computation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68333/2/10.1177_003754976700800610.pd

Cored dark-matter profiles in z≃1 star forming galaxies

Galaxie

The MUSE extremely deep field: evidence for SFR-induced cores in dark-matter dominated galaxies at z ≃ 1

Galaxie

Pivoting in Linear Complementarity: Two Polynomial-Time Cases

We study the behavior of simple principal pivoting methods for the P-matrix linear complementarity problem (P-LCP). We solve an open problem of Morris by showing that Murty’s least-index pivot rule (under any fixed index order) leads to a quadratic number of iterations on Morris’s highly cyclic P-LCP examples. We then show that on K-matrix LCP instances, all pivot rules require only a linear number of iterations. As the main tool, we employ unique-sink orientations of cubes, a useful combinatorial abstraction of the P-LCP