The clinical outcomes of both hepatitis B and C virus infection are immensely variable, ranging from subclinical, self-limiting infection to end-stage liver disease with hepatocellular carcinoma. ...Knowledge of the host factors that determine these outcomes is important for the understanding and management of these diseases and may in the future guide rational drug development. Epidemiologic studies have elucidated the role of age (at the time of infection) and sex on disease outcome and the complex role of HIV coinfection has become clearer with time. More recently, investigation of genetic susceptibility to the most adverse outcomes of infection has identified the importance of polymorphisms in the MHC class I and II loci, mannose-binding protein, and the TNF alpha promoter. However, relative to malaria, the study of genetic susceptibility in viral hepatitis is still in its infancy.
Background. Through migration, diversity of chronic hepatitis B virus (HBV) infection has changed, affecting disease burden and control. We describe clinical and viral characteristics of chronic HBV ...in the United Kingdom. Methods. A total of 698 individuals with chronic HBV infection were recruited from referral liver centers. Demographic, clinical, and laboratory data were collected. Results. Sixty-one percent of patients were male, 80% were not born in the United Kingdom, and the largest ethnicity was East/Southeast Asian (36%). Twenty-two percent were hepatitis B e antigen (HBeAg) seropositive; 20.4% (59/289) had cirrhosis and 10 (1.7%) had hepatocellular carcinoma. Genotype D was most common (31%) followed by A, C, B, and E (20%, 20%, 19%, and 9%, respectively). Genotype was significantly associated with country of birth, length of time in the United Kingdom, HBeAg status, and precore and basal core promoter mutations. One-third were on treatment, with men independently more likely to be treated. Only 18% of those on treatment were on recommended first-line therapies, and 30% were on lamivudine monotherapy. Among treated individuals, 27% had antiviral drug resistance. Testing rates for human immunodeficiency virus, hepatitis C virus, and delta coinfections were low. Conclusions. We demonstrated diversity of chronic HBV infections in UK patients, suggesting that optimal management requires awareness of the variable patterns of chronic HBV in countries of origin. We also found less-than-optimal clinical management practices, possible gender-based treatment bias, and the need to improve testing for coinfections.
To determine whether combined therapy with interferon-alpha and ribavirin was more effective and cost-effective than no treatment for patients with mild chronic hepatitis C.
A multicentre, ...randomised, controlled, non-blinded trial assessed the efficacy of combination therapy. A Markov model used these efficacy data combined with data on transition probabilities, costs and health-related quality of life (HRQoL) to assess the lifetime cost-effectiveness of the intervention.
A multicentre NHS setting.
Treatment-naive, adult patients with histologically mild chronic hepatitis C (Ishak necroinflammatory scores <4 and fibrosis scores <3 on liver biopsy).
Patients were randomised to receive interferon-alpha and ribavirin for 48 weeks or no treatment (control).
The primary outcome measure was the proportion of patients having a sustained virological response (SVR), measured at 6 months after cessation of therapy. Secondary outcome measures were: the ability of early phase kinetics to predict the eventual outcome of treating mild disease; HRQoL measured using the Short Form 36 and EuroQol (5 Dimensions) questionnaires, and the cost per quality-adjusted life-year (QALY) of interferon-alpha and ribavirin for mild disease compared with no treatment.
In the treatment group, 32 out of 98 patients (33%) achieved an SVR. Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% versus 49%, p = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved an SVR. HRQoL fell during treatment and rose with treatment cessation. For patients having an SVR there were modest improvements in HRQoL at 6 months post-treatment. The mean cost per QALY gained was 4535 pounds sterling for 40-year-old patients with genotype non-1 and 25,188 pounds sterling for patients with genotype 1. For patients with genotype 1 aged 65, providing interferon-alpha and ribavirin for mild disease led to fewer QALYs gained, and a mean cost per QALY of 53,017 pounds sterling. The model using efficacy estimates from the literature, showed that the cost per QALY gained from providing pegylated interferon alpha-2b and ribavirin at a mild stage rather than a moderate stage was 7821 pounds sterling for patients with genotype non-1 and 28,409 pounds sterling for patients with genotype 1.
Based on the evidence collected in this study, interferon-alpha and ribavirin treatment for mild chronic hepatitis C patients is in general cost-effective at the 30,000 pounds sterling per QALY threshold previously used by policy-makers in the NHS. For patients with chronic hepatitis C aged 65 or over with genotype 1, antiviral treatment at a mild stage does not appear cost-effective. Further research is required on the cost-effectiveness of pegylated interferon and ribavirin, in particular the intervention's long-term impact on HRQoL and health service costs requires further evaluation. Further research is also needed to develop predictive tests, based on pharmacogenomics, that can identify those cases most likely to respond to antiviral therapy. Liver biopsy before treatment no longer appears justified apart from for older patients (aged 65 or over) with genotype 1. However, further research should monitor the impact this strategy would have on costs and outcomes.
In vitro proton magnetic resonance spectroscopy (MRS) allows changes in cell membrane lipid structure associated with dysplasia and malignant transformation to be investigated. Magic angle spinning ...(MAS) MRS allows small esophageal tissue specimens to be studied directly without the need to extract the tissue, but it is not known how intact the tissue architecture remains after MAS. We report the first prospective MAS MRS study of Barrett's esophagus using endoscopic biopsies with direct histological correlation.
Biopsies were obtained during surveillance esophagoscopy from Barrett's epithelium and adjacent normal squamous epithelium in 16 patients (34 samples). High-resolution MAS MRS was performed at 500 MHz. Following MRS, the histology was evaluated. A further, separate group of 14 biopsies were examined histologically to assess architectural damage caused by tissue preservation alone.
For squamous and Barrett's epithelium, respectively, metabolite ratios of choline-containing compounds to creatine plus phosphocreatine (Cho/Cr) were 1.99 and 5.65 (P < 10) and methyl lipid to creatine plus phosphocreatine ratios (lipid-CH3/Cr) were 4.07 and 7.4 (P < 10). There was no significant difference in histological preservation between the squamous and Barrett's mucosa without MRS (z = 0.67, P = 0.61), but significant differences were found post-MAS MRS (z = 4.06, P < 0.0001).
Squamous and Barrett's epithelium can be distinguished metabolically, based on Cho/Cr and lipid-CH3/Cr ratios. Although MAS does affect the histological architecture in Barrett's epithelium, compared with squamous epithelium, direct histological assessment was possible in the majority of samples.
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