S D Ryder

The British Society for Gastroenterology, Londinium, England, United Kingdom

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Publications (118)1207.99 Total impact

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    ABSTRACT: Alcoholic hepatitis (AH) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods, which is characterised by jaundice and liver failure. Severe disease is associated with high short-term mortality. Prednisolone and pentoxifylline (PTX) are recommended in guidelines for treatment of severe AH, but trials supporting their use have given heterogeneous results and controversy persists about their benefit. Objectives The aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX. Design The trial was a randomised, double-blind, 2 × 2 factorial, multicentre design. Setting Sixty-five gastroenterology and hepatology inpatient units across the UK. Participants Patients with a clinical diagnosis of AH who had a Maddrey’s discriminant function value of ≥ 32 were randomised into four arms: A, placebo/placebo; B, placebo/prednisolone; C, PTX/placebo; and D, PTX/prednisolone. Of the 5234 patients screened for the trial, 1103 were randomised and after withdrawals, 1053 were available for primary end-point analysis. Interventions Those allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days. Outcomes The primary outcome measure was mortality at 28 days. Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year. Rates of recidivism among survivors and the impact of recidivism on mortality were assessed. Results At 28 days, in arm A, 45 of 269 (16.7%) patients died; in arm B, 38 of 266 (14.3%) died; in arm C, 50 of 258 (19.4%) died; and in arm D, 35 of 260 (13.5%) died. For PTX, the odds ratio for 28-day mortality was 1.07 [95% confidence interval (CI) 0.77 to 1.40; p = 0.686)] and for prednisolone the odds ratio was 0.72 (95% CI 0.52 to 1.01; p = 0.056). In the logistic regression analysis, accounting for indices of disease severity and prognosis, the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 (95% CI 0.41 to 0.91; p = 0.015). At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups. Serious infections occurred in 13% of patients treated with prednisolone compared with 7% of controls ( p = 0.002). At the 90-day follow-up, 45% of patients reported being completely abstinent, 9% reported drinking within safety limits and 33% had an unknown level of alcohol consumption. At 1 year, 37% of patients reported being completely abstinent, 10% reported drinking within safety limits and 39% had an unknown level of alcohol consumption. Only 22% of patients had attended alcohol rehabilitation treatment at 90 days and 1 year. Conclusions We conclude that prednisolone reduces the risk of mortality at 28 days, but this benefit is not sustained beyond 28 days. PTX had no impact on survival. Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection. Trial registration This trial is registered as EudraCT 2009-013897-42 and Current Controlled Trials ISRCTN88782125. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 19, No. 102. See the NIHR Journals Library website for further project information. The NIHR Clinical Research Network provided research nurse support and the Imperial College Biomedical Research Centre also provided funding.
    Full-text · Article · Dec 2015 · Health technology assessment (Winchester, England)

  • No preview · Article · Nov 2015 · The Lancet
  • Mark R Thursz · Ewan H Forrest · Stephen Ryder

    No preview · Article · Jul 2015 · New England Journal of Medicine
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    ABSTRACT: Introduction Directly-acting antiviral (DAA) therapy achieves sustained virological response (SVR) in over 90% of those with chronic hepatitis C (CHC), but even in those with SVR, the risk for liver related morbidity and mortality persists albeit at a lower level. It is hypothesised that the residual risk of liver related outcome in those with SVR is related to the progression or non-regression of structural and haemodynamic changes of advanced liver disease at the time of HCV therapy. Here, we investigate the effect of DAAs on the hepatic architecture and splanchnic haemodynamics in patients with decompensated cirrhosis, using quantitative MRI techniques. Method We prospectively recruited patients receiving DAAs for CHC related decompensated cirrhosis from the East Midlands hub of the Early Access Programme commissioned by NHS England. MRI was performed before and at the end of a 12-week treatment with Daclatasvir, Sofosbuvir and Ribavarin. A respiratory-triggered inversion recovery scheme was used to measure the longitudinal (T1) relaxation time of the liver employing a fat suppressed Echo Planar Imaging-acquisition. Phase-contrast (PC)-MRI was used to assess the velocity, area and bulk flow in the splanchnic circulation without any intravenous contrast agents. Results 9 patients have undergone baseline and post-treatment MR scans and end-of-treatment response (EOTR) was achieved in all 9 patients, but one patient has had virologic relapse. There was a significant reduction in the T1 relaxation time in patients with SVR (baseline T1: 765 ± 112 ms; post-treatment 737 ± 118 ms; p = 0.043) (Figure 1). There were no significant changes in the hepatic artery, portal vein, superior mesenteric artery and splenic artery flow. The changes in the Model for End-Stage Liver Disease (MELD) and United Kingdom Model for End-Stage Liver Disease (UKELD) score are shown in Table 1. Conclusion Treatment of decompensated CHC related cirrhosis with DAA is associated with early improvement in the MR markers of liver architecture. These early changes are likely to reflect the reduction in the inflammation associated with EOTR and is evident before any improvement in conventional liver function tests. This novel quantitative MR methodology will allow us to non-invasively monitor HCV related liver disease. Disclosure of interest None Declared.
    No preview · Article · Jun 2015 · Gut
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    ABSTRACT: Introduction Epidemiological studies have attributed the rising cirrhosis incidence and mortality in the UK predominantly to excess alcohol consumption. However, obesity acts synergistically with alcohol to increase the risk of cirrhosis. In addition, asymptomatic liver disease goes undetected; as a result nearly 50% of cirrhotics are diagnosed when presenting with hepatic decompensation. We utilised Transient Elastography (TE) to screen at-risk individuals in the general population, aiming to establish the prevalence of undetected liver cirrhosis and the risk factors underlying these cases. Method The study was undertaken in 4 general practices in Nottingham between February 2012 and September 2014. The total adult patient population was 20,868. Patients with pre-defined risk factors for chronic liver disease (hazardous alcohol use as identified by general practitioner (GP), type 2 diabetes and/or persistent ALT rise with negative serology) were identified from the GP electronic records and invited for TE even if liver enzymes were normal. TE was performed by trained nurses at the general practice sites. Liver stiffness of ≥8 kilopascals prompted review by a Consultant Hepatologist and liver cirrhosis was confirmed by established histological, radiological and biochemical methods. Results Of 2,022 patients eligible, 919 attended TE; 899 (97.8%) had valid liver stiffness measurements. Elevated liver stiffness was detected in 230 patients (25.6%) and cirrhosis in 26 (2.9%). Liver enzymes were normal in 16/26 (61.5%) of cirrhosis cases. Prior to the study, 23 patients with cirrhosis (aetiologies: alcohol (14), viral hepatitis (5), Non-alcoholic steatohepatitis (1), other (3)) had been identified; a diagnosed cirrhosis prevalence which was not significantly different compared to general population estimates of 76.3 cases per 100,000. Following the study, the prevalence of cirrhosis diagnosis was 49/20,868 (234.8 cases per 100,000 (95% CI 201.3–268.3)) was 3 fold higher than the previous general population estimate. Risk factors for new cirrhosis diagnoses were obesity and/or type 2 diabetes in 16 patients (61.5%), alcohol alone in 3 (11.5%) and both alcohol and obesity and/or diabetes in 7 (26.9%). Conclusion Investigating defined risk factors for liver disease using TE in a community setting detects a significant amount of previously unidentified cirrhosis. Cirrhosis prevalence in the general population is at least 3 times recent UK estimates. Obesity and type 2 diabetes are the predominant risk factors underlying previously undetected cirrhosis cases. Disclosure of interest None Declared.
    No preview · Article · Jun 2015 · Gut
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    ABSTRACT: Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists. We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline. A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002). Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).
    Preview · Article · Apr 2015 · New England Journal of Medicine
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    Stephen D Ryder
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    ABSTRACT: Until recently in the UK the treatment of HCV depended on combination regimes of interferon (IFN) and the antiviral drug ribavirin. These regimes required regular injections and were of variable duration (generally for a minimum of 12 weeks), and the use of IFN often caused unacceptable side effects (thrombocytopenia, leukopenia and depression). Of the common HCV genotypes in the UK, genotype 1 responded relatively poorly to these regimes (50-60% viral clearance), while most (80% plus) of genotype 3 patients responded with sustained viral clearance. Patients with severe liver disease (decompensated cirrhosis) tolerated these regimens very poorly and often their liver function deteriorated. The recent introduction of a series of direct anti-viral agents (DAAs) offers the potential to revolutionise treatment, particularly in genotype 1 patients and those with advanced liver disease, as drug regimens avoiding IFN have been developed, and can be curative in, for example, 95% of genotype 1 patients. The DAAs are currently being evaluated and introduced into UK clinical practice. Choice of drug regime, and strategies for identifying patient groups suitable for treatment, are discussed, as are the prospects for eventual complete control of the HCV epidemic. © 2015 Royal College of Physicians.
    Preview · Article · Apr 2015 · Clinical medicine (London, England)

  • No preview · Article · Apr 2015 · Journal of Hepatology
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    ABSTRACT: Koretz and colleagues argue that hepatitis C virus (HCV) screening should be delayed.1 We disagree. HCV transmission was common in the 1960s-80s, and because mortality occurs 30-40 years after infection deaths will rise exponentially over the next decade.2 Delaying effective intervention will have a massive impact. The authors argue that because a community study showed an increase in liver and non-liver mortality most infected people will not die from HCV. Infection can cause or exacerbate renal disease, diabetes, and dyslipidaemia and treatment reduces all cause mortality,3 indicating that both liver and non-liver related deaths are caused by HCV and reversed by treatment. Disease outcome is improved by lifestyle changes, but this requires diagnosis. Identification also allows action to reduce transmission, and because chronic infection is associated with treatment reversible neurocognitive dysfunction, the detection of infection has additional benefits.4The benefits of viral elimination can be shown by comparing mortality in treated patients who respond to treatment with those who don’t. The authors argue that these benefits are due to “differences in people who respond”—people who respond don’t develop liver disease. If this were true, patients with cirrhosis wouldn’t respond, but many are successfully treated, with disease regressing.5 The authors compare different studies with different underlying cancer rates and imply that cancer incidence is the same in successfully and unsuccessfully treated patients. This is misleading—comparisons within the same cohorts show reduced liver cancer rates in treated patients. It is not valid to take the highest cancer rate from a treated population and compare it with a selected untreated population with a strikingly low rate of cancer and conclude that treatment has no effect.Current standard of care for HCV no longer involves interferon but uses oral drugs that eliminate virus in more than 90% of cases.6 Telaprevir (with many side effects) has been replaced by drugs that are virtually free from side effects—most side effects in the pivotal trials of oral drugs were not drug related.Independent European and US experts have reviewed the data on HCV treatment and screening and conclude that increased testing and screening is the right response. The development of new highly effective drugs gives us an opportunity to eliminate the harm caused by this virus. To delay a process with clear benefit in order to satisfy demands for more data would expose thousands of undiagnosed treatable patients to the risks of cancer and cirrhosis. This must not be regarded as acceptable.NotesCite this as: BMJ 2015;350:h998
    Full-text · Article · Feb 2015 · BMJ Clinical Research
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    ABSTRACT: Liver disease in the UK stands out as the one glaring exception to the vast improvements made during the past 30 years in health and life expectancy for chronic disorders such as stroke, heart disease, and many cancers. Mortality rates have increased 400% since 1970, and in people younger than 65 years have risen by almost fi ve-times. Liver disease constitutes the third commonest cause of premature death in the UK and the rate of increase of liver disease is substantially higher in the UK than other countries in western Europe. More than 1 million admissions to hospital per year are the result of alcohol-related disorders, and both the number of admissions and the increase in mortality closely parallel the rise in alcohol consumption in the UK during the past three decades. The new epidemic of obesity is equally preventable. Of the 25% of the population now categorised as obese, most will have non-alcoholic fatty liver disease many (up to 1 in 20 of the UK population) will have ongoing infl ammation and scarring that fi nally leads to cirrhosis. Of those patients with cirrhosis, 5-10% will get liver cancer. This increasing burden of liver disease is added to by chronic viral hepatitis; annual deaths from hepatitis C have almost quadrupled since 1996 and about 75% of people infected are estimated to be still unrecognised. The same applies to chronic hepatitis B infection, in which progression to cirrhosis and liver cancer also happens. The number of silently infected individuals in the UK is increasing every year as a result of immigration from countries with a high prevalence of hepatitis B and hepatitis C infections. Costs to the UK's National Health Service are equally staggering, with estimates of £3.5 billion per year for alcohol-related health problems and £5.5 billion per year for the consequences of obesity. Obesity costs are almost certainly an underestimate now that the disorder is recognised as an important factor in several common cancers, including breast cancer and colon cancer.1 Obesity is a factor in metabolic disorders-the basis of diabetes, hypertension, cardiac diseases, and strokes. Furthermore, the poorest and most susceptible in society have the highest incidence of liver disorders, making liver disease a major issue for health inequalities. Of particular concern is the 2013 National Confi dential Enquiry into Patient Outcome and Death (NCEPOD) report,2 which showed that the care of patients acutely sick with liver disease dying in hospital was judged to be good in less than half of patients; other unacceptable fi ndings were the inadequate facilities and lack of expertise of those caring for patients. Also, it is increasingly evident that defi ciencies exist in primary care, which has crucial opportunities for early diagnosis and prevention of progressive disease. The aim of this Commission is to provide the strongest evidence base through involvement of experts from a wide cross-section of disciplines, making fi rm recommendations to reduce the unacceptable premature mortality and dsease burden from avoidable causes and to improve the standard of care for patients with liver disease in hospital. From the substantial number of recommendations given in our Commission, we selected those that will have the greatest eff ect and that need urgent implementation. Although the recommendations are based mostly on data from England, they have wider application to the UK as a whole, and are in accord with the present strategy for health-care policy by the Scottish Health Boards, the Health Department of Wales, and the Department of Health and Social Services in Northern Ireland. Our ten key recommendations are based on the strong evidence base and are in line with reports in 2014 of several other enquiries, including from the 2014 All Party Parliamentary Group on Hepatology3 and the All Party Parliamentary Group on alochol misuse. Results showing the value of a minimum unit price policy in targeting heavy drinkers were published in The Lancet in May, 2014, and the European Observatory on Health Polcy, together with the Department of Health and NHS England, has drawn attention to four areas of premature mortality, including liver disease, in which the UK lags behind other European countries. Such stark contrasts with our European neighbours are unacceptable and in this Commission we give clear, evidence-based policy proposals for the UK Government to use in closing the gap in liver disease.
    Full-text · Article · Nov 2014 · The Lancet
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    ABSTRACT: Background & aims: Tenofovir alafenamide, a phosphonate prodrug of tenofovir with greater plasma stability than tenofovir disoproxil fumarate, provides efficient delivery of active drug to hepatocytes at reduced systemic tenofovir exposures. Methods: Non-cirrhotic, treatment-naïve subjects with chronic hepatitis B were randomized (1:1:1:1:1) to receive tenofovir alafenamide 8, 25, 40, or 120 mg, or tenofovir disoproxil fumarate 300 mg for 28 days and assessed for safety, antiviral response, and pharmacokinetics, followed-up by off-treatment for 4 weeks. Results: 51 subjects were randomized and all completed study treatment. Groups were generally well matched (67% male, 57% Asian, 53% HBeAg-negative, mean HBV DNA approximately 6.0 log10 IU/ml) with HBV genotypes reflective of the population. No subject experienced an adverse event that was serious or severe (grade 3/4). Across the tenofovir alafenamide groups, similar mean changes in serum HBV DNA were found at Week 4 (-2.81, -2.55, -2.19, and -2.76 log10 IU/ml for the 8, 25, 40, and 120 mg groups, respectively) which were also comparable to the control (-2.68 log10 IU/ml for tenofovir disoproxil fumarate 300 mg). Kinetics of viral decline were also similar among groups. Tenofovir alafenamide pharmacokinetics were linear and proportional to the dose; doses⩽25 mg were associated with ⩾92% reductions in mean tenofovir area under the curve relative to tenofovir disoproxil fumarate 300 mg. Conclusions: Tenofovir alafenamide was safe and well tolerated; declines in HBV DNA were similar to tenofovir disoproxil fumarate at all doses evaluated. Tenofovir alafenamide 25 mg has been selected for further hepatitis B clinical development.
    No preview · Article · Oct 2014 · Journal of Hepatology
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    ABSTRACT: Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37–48% HCV chronic prevalence among PWID), East London (37–48%), Manchester (48–56%), Nottingham (37–44%), Plymouth (30–37%), Dundee (20–27%) and North Wales (27–33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33–57%] and 61% genotypes 2/3 [95%CI 47–76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.
    Full-text · Article · Oct 2014 · Journal of Viral Hepatitis
  • Stephen Ryder · John Dillon

    No preview · Article · May 2014 · The Health service journal
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    ABSTRACT: The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
    Full-text · Article · May 2014 · Journal of Viral Hepatitis
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    ABSTRACT: Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
    Full-text · Article · May 2014 · Journal of Viral Hepatitis
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    ABSTRACT: The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
    Full-text · Article · May 2014 · Journal of Viral Hepatitis
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    ABSTRACT: Background Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting.AimsTo assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines.Methods All Phase 2 and 3 studies, as well as abstract presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment-naïve and experienced individuals, as well as cirrhotic and co-infected individuals were included.ResultsSofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication.Conclusions Therapies for chronic HCV have evolved dramatically in recent years. Interferon-free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.
    Full-text · Article · Apr 2014 · Alimentary Pharmacology & Therapeutics

  • No preview · Article · Apr 2014 · Journal of Hepatology

  • No preview · Article · Apr 2014
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    ABSTRACT: Patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have poor response rates after 24 weeks treatment with pegylated interferon and ribavirin. Treatment for 48 weeks is therefore recommended, although the benefits of this are untested. We examined extended therapy in patients with genotype 3 HCV and advanced fibrosis METHODS: Multicentre, open labelled randomised trial comparing therapy with 24 weeks pegylated interferon and ribavirin to 48 weeks of the same therapy. 136 patients completed the study. 67 received 24 weeks therapy and the SVR rate (48%) did not differ from that seen in the 69 patients who received 48 weeks therapy (42%). The response rates in patients with biopsy proven cirrhosis (13 patients treated for 24 weeks, 18 patients treated for 48 weeks) or cirrhosis proven on imaging (28 patients treated for 24 weeks and 25 patients treated for 48 weeks) were 46% in those treated for 24 weeks and 40% in those treated for 48 weeks. The differences were not significantly different. Treatment failure was due to relapse in the majority of patients. Patients with genotype 3 HCV and advanced fibrosis do not benefit from extended therapy with pegylated interferon and ribavirin.
    No preview · Article · Nov 2013 · Journal of Hepatology

Publication Stats

3k Citations
1,207.99 Total Impact Points

Institutions

  • 2015
    • The British Society for Gastroenterology
      Londinium, England, United Kingdom
  • 2007-2015
    • Nottingham University Hospitals NHS Trust
      • Division of Histopathology
      Nottigham, England, United Kingdom
  • 1998-2015
    • University of Nottingham
      • • Nottingham Digestive Diseases Centre Biomedical Research Unit
      • • Centre for Sports Medicine
      • • School of Medicine
      Nottigham, England, United Kingdom
    • University College London
      • Institute for Liver and Digestive Health
      Londinium, England, United Kingdom
  • 2012
    • University of Southampton
      Southampton, England, United Kingdom
  • 2011
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
  • 2009
    • University of Dundee
      • Undergraduate Tayside Centre for General Practice
      Dundee, Scotland, United Kingdom
  • 2004
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2001
    • The Queen's Medical Center
      Honolulu, Hawaii, United States
  • 1995-1996
    • King's College London
      • Department of Immunobiology
      Londinium, England, United Kingdom
  • 1990-1995
    • University of Liverpool
      • School of Medicine
      Liverpool, England, United Kingdom
  • 1994
    • Middlesex Hospital
      मिडलटाउन, Connecticut, United States
    • The Peninsula College of Medicine and Dentistry
      Plymouth, England, United Kingdom
  • 1993
    • Royal Liverpool and Broadgreen University Hospitals NHS Trust
      • Department of Medicine
      Liverpool, England, United Kingdom