Hepatology, medicine and policy最新文献

Background: Hepatic encephalopathy (HE) is one of the most important severe complications of liver cirrhosis. Thought to be caused by elevated blood levels of gut-derived neurotoxins (particularly ammonia) entering the brain, HE manifests as a wide range of neurological or psychiatric abnormalities, which increase the risk of mortality, result in substantial morbidity and negatively affect the quality of life (QoL) of both patients and their caregivers. HE is also associated with a substantial economic burden. Rifaximin-α 550 mg is a locally acting oral antibiotic that reduces the effects of ammonia-producing intestinal flora, and which is used to help reduce the recurrence of overt HE. The efficacy of rifaximin-α 550 mg was established in a randomised controlled trial and long-term extension study. However, 'real-world' evidence is also required to assess how this efficacy may translate into effectiveness in clinical practice, including the potential impact of treatment on healthcare resource utilisation.

Methods: The Prospective Real-world Outcomes Study of HE Patients' Experience on Rifaximin-α 550 mg (PROSPER) is a multinational, multicentre, observational study that will be conducted under real-world clinical practice conditions. Comprising a retrospective phase (up to 12 months) and a prospective phase (up to 24 months), and employing a robust statistical methodology, PROSPER has been specifically designed to minimise the bias associated with observational studies. The primary endpoint will be the effect of rifaximin-α 550 mg treatment on HE- and liver-related hospitalisation rate and duration of hospitalisation. Secondary endpoints will include comprehensive assessments of the impact of treatment on the QoL and workplace productivity of patients and caregivers, a global assessment of treatment effectiveness and safety/tolerability. Approximately 550 patients will be enrolled.

Conclusions: PROSPER will provide valuable real-world information on the effectiveness of rifaximin-α 550 mg in reducing the recurrence of HE, and its impact on the QoL and work productivity of patients and their caregivers. By providing data on both the direct costs (e.g., hospitalisation rate, duration of hospitalisation) and indirect costs (such as work productivity) of HE, PROSPER should help confirm whether rifaximin-α 550 mg treatment represents a good use of economic resources.

Trial registration: ClinicalTrials.gov identifier NCT02488993.

Background: WHO hepatitis B guidelines recommend testing all new HIV patients, treating them accordingly or providing immunization. At the Infectious Diseases Institute (IDI) following an audit done in 2012, only 46% patients had been screened for hepatitis B with variable management plans therefore new internal guidelines were implemented. This study describes the uptake of hepatitis B screening and management of patients with hepatitis B and HIV con-infection after the implementation.

Methods: Data included for all HIV positive patients in care at IDI by October 2015. Data are expressed as median with interquartile range (IQR) and percentages were compared using the chi square test. Statistical analysis was performed using STATA version 13. The IDI laboratory upper limit of normal for alanine aminotransferase (ALT) and aspartate aminotransferase (ASTs) was 40 IU/ml.

Results: Number of hepatitis B screening tests increased from 800 by 2012 to 1400 in 2015. By 2015 8042/8604(93.5%) patients had been screened for hepatitis B. Overall hepatitis B positive were 359 (4.6%). 166 (81.4%) hepatitis B positives were switched to a tenofovir (TDF) containing regimen.

Conclusion: Our study confirms the importance of screening for hepatitis B and of using ART regimens containing tenofovir in hepatitis B co-infected patients. Whilst our program has made improvements in care still 18.6% of patients with hepatitis B were not on tenofovir regimens, 98.1% had no hepatitis B viral loads done. Clinicians should recognize the potential for hepatitis B in HIV positive patients and the importance of early diagnosis and treatment to ensure optimal management of cases and follow up.

Background: Viral hepatitis deaths from acute infection, cirrhosis, and liver cancer have risen from the tenth to the seventh leading cause of death worldwide between 1990 and 2013. Even in the oral direct acting antiviral (DAA) agent era there are still large numbers of patients with unmet needs. Medications approved for treatment of chronic hepatitis B virus (HBV) infection do not eradicate HBV often requiring treatment for life associated with risks of adverse reactions, drug resistance, nonadherence, and increased cost. Although DAAs increased virologic cure rates well over 90% in all hepatitis C virus (HCV) genotypes, HCV infection still cannot be cured in a small but significant minority of patients. While most of the medical issues of HCV treatment have been solved, the current costs of DAAs are prohibitive.

Results: The post-infection viral superinfection treatment (SIT) platform technology has been clinically proven to be safe and effective to resolve acute and persistent viral infections in 42 HBV and HCV patients (20 HBV, 22 HCV), and in 4 decompensated patients (2 HBV, 2 HCV). SIT employs a non-pathogenic avian double stranded RNA (dsRNA) virus, a potent activator of antiviral gene responses. Unexpectedly, SIT is active against unrelated DNA (HBV) and RNA (HCV) viruses. SIT does not require lifelong therapy, which is a major advantage considering present HBV treatments. The new viral drug candidate (R903/78) is homogeneously produced by reverse genetics in Vero cells. R903/78 has exceptional pH and temperature stability and also excellent long-term stability; therefore, it can be orally administered, stored and shipped without freezing. Since R903/78 is easy to stockpile, the post-infection SIT could also alleviate the logistic hurdles of surge capacity in vaccine production during viral pandemics.

Conclusion: To help large number of HBV and HCV patients with unmet needs, broad-spectrum antiviral drugs effective against whole classes of viruses are urgently needed. The innovative SIT technological platform will be a great additional armament to conquer viral hepatitis, which is still a major cause of death and disability worldwide.

Background: The current model of care for the treatment of chronic hepatitis B (CHB) in Australia is through specialist Hepatology or Infectious Diseases clinics, and limited accredited primary care practices. Capacity is limited, and less than 5% of Australians living with CHB currently access therapy. Increasing treatment uptake is an urgent area of clinical need. Nucleos(t)ide analogue therapy is safe and effective treatment for CHB that is suitable for community prescribing. We have evaluated the success of a community-based model for the management of CHB in primary care clinics using a novel web-based clinical tool.

Methods: Using guidelines set out by the Gastroenterological Society of Australia, we developed an interactive online clinical management tool for the shared care of patients with CHB in primary care clinics, with remote oversight from tertiary hospital-based hepatologists and a project officer. We call this model of care the "B in IT" program. Suitable patients were referred from the specialist liver clinic back to primary care for ongoing management. Compliance with recommended appointments, pathology tests and ultrasounds of patients enrolled in "B in IT" was assessed and compared to that of the same patients prior to community discharge, as well as a matched control group of CHB outpatients continuing to attend a specialist clinic.

Results: Thirty patients with CHB were enrolled in the "B in IT" program. Compliance with attending scheduled appointments within 1 month of the suggested date was 87% across all 115 visits scheduled. Compliance with completing recommended pathology within 1 month of the suggested date was 94% and compliance with completing recommended liver ultrasounds for cancer screening within 1 month of the suggested date was 89%. The compliance rates for visit attendance and ultrasound completion were significantly higher than the control patient group (p < 0.0001) and the "B in IT" patients prior to community discharge (p = 0.002 and p = 0.039, respectively).

Conclusions: The "B in IT" program's novel web-based clinical tool supports primary care physicians to treat and monitor patients with CHB. This program promotes community-based care and increases system capacity for the clinical care of people living with CHB.

Introduction: The 16 countries of the Eastern Europe and Central Asia (EECA) region are home to 6.6 million people in need of treatment for chronic hepatitis C virus (HCV) infection. Because of transformational change in HCV treatment, global efforts to address HCV are accelerating. Given its large regional burden, the EECA needs to ensure its inclusion in and benefit from any new developments.

Methods: Our 2015-16 survey aimed to collect and report on epidemiology, treatment access (including drug registration and prices, national HCV guidelines and treatment program coverage) and pertinent civil society organization (CSO) activities in 11 countries in the EECA.

Results: Major gaps in epidemiological data exist; reported anti-HCV prevalence ranged from 1.5 to 7.5% for the general population, 22.7 to 70-95% for people who inject drugs (PWID) and 18 to 80% for people living with HIV (PLHIV). Ten countries (91% of the sample) have registered one or more of the second-generation, direct-acting antiviral medications (DAA) for potential interferon-free treatment. However, intellectual property issues and prices limit access to these drugs. In 2014, HCV programs in the surveyed countries covered only 0.15% of the total number of people in need of treatment. CSO-driven, international donor-funded programs are starting to fulfill needs of PWID and PLHIV.

Conclusions: As feasible curative HCV treatment is now available, and given the significant regional disease burden, EECA countries need to ensure HCV surveillance and DAA availability at affordable prices in order to expand treatment and prevent the onward transmission of the infection. EECA CSOs have demonstrated their capacity to play a crucial role in advancing HCV issues, and they should continue leveraging these issues for the benefit of individual patients and public health in general.

Background: India is home to one in 14 of all chronic hepatitis B virus (HBV) cases, meaning that it is important to develop HBV interventions that are applicable in the Indian context. Vaccination is the foremost tool for interrupting the HBV infection cycle. HBV vaccination was not included in India's government-sponsored expanded immunisation program until 2011, and many children born earlier remain unvaccinated. This study sought to observe the impact of the HOPE Initiative's school-based intervention to increase vaccination coverage by increasing HBV awareness among students in Lucknow, Uttar Pradesh.

Methods: At 430 schools in the administrative areas within and surrounding Lucknow, students viewed an educational documentary film on HBV and completed two questionnaires, one immediately before the screening and the other six weeks later. Both questionnaires asked the same 14 questions, which were organized into five domains: knowledge of the magnitude of the problem of HBV; knowledge of modes of HBV transmission; knowledge of consequences of HBV infection; awareness of HBV; and attitudes regarding HBV. The baseline questionnaire also asked students whether they had been vaccinated against HBV. At two-year follow-up, researchers measured vaccination levels at a subset of 30 intervention schools and six non-intervention schools to further assess the impact of the intervention.

Results: Baseline questionnaires were completed by 11,250 students, and post-intervention questionnaires, by 9698 students. Scores for knowledge about the magnitude of the HBV problem improved from 41% at baseline to 74% at follow-up, and scores for knowledge about modes of transmission, from 38% to 75% (p < 0.05 for both). The baseline HBV vaccination level among students receiving the intervention was 21%. Two years after the intervention, 45% of students (N = 4284) reported being vaccinated at intervention schools compared to 22% (N = 1264) at non-intervention schools.

Conclusions: The observed increases in HBV awareness, knowledge and vaccination levels in this study indicate that school-based interventions can be used to achieve higher vaccination coverage among Indian children. The documentary film was found to be an affordable tool for reaching large audiences. More studies are needed to validate the impact of this intervention and to explore its applicability to other social causes.

The International AIDS Society convened the 3rd International HIV/Viral Hepatitis Co-Infection Meeting on 17 July 2016 as part of the pre-conference program preceding the 21st International AIDS Conference held in Durban, South Africa. The meeting brought together a diversity of scientific, technical and community interests to discuss opportunities and challenges for increased prevention, diagnosis and treatment of viral hepatitis in people living with HIV, particularly in low- and middle-income settings. The objectives of the meeting were:i.To review the latest therapeutic developments in viral hepatitis;ii.To identify challenges such as high cost of medications for hepatitis C virus (HCV) and risk of developing viral resistance, and successes, such as the provision of HCV treatment in community-based settings, movements to reduce drug costs and increasing access, in relation to scaling up diagnosis, screening, antiviral treatment and prevention of viral hepatitis;iii.To advance the agenda for elimination of viral hepatitis as a public health problem. Discussions centred around the six key interventions outlined by the World Health Organization Global Health Sector Strategy on Viral Hepatitis 2016-2021: hepatitis B virus (HBV) vaccination (including birth dose); safe injection practices plus safe blood; harm reduction among people who inject drugs; safer sex practices; hepatitis B treatment; and hepatitis C cure. This article summarizes the main issues and findings discussed during the pre-conference meeting. One of the recommendations from the meeting delegates is universal implementation of birth dose vaccination for HBV without further delay to prevent mother-to-child transmission of infection. There is also the need to implement screening and treatment of hepatitis among pregnant women. A call was made for concerted efforts to be put together by all stakeholders towards addressing some of the structural barriers, including criminalization of drug use, discrimination and stigma that people living with viral hepatitis face. Finally, the need for greater advocacy was highlighted to enable access to therapy of viral hepatitis at lower cost than currently prevails. Implementation of these resolutions will help in achieving the target of eliminating viral hepatitis as a public health threat.

Background: Comprehensive information on the incidence and duration of hepatitis C virus (HCV) infection for people who inject drugs (PWID) in Ireland is not available. We created an incidence curve of injecting drug use in Ireland and subsequently estimated incidence of hepatitis C virus (HCV) infection.

Methods: Anonymised data from the National Drug Treatment Reporting System (NDTRS) were used to identify all people who inject drugs (PWIDs) and who entered drug treatment for the first time between 1991 and 2014. A curve, estimating the incidence of injecting, was created to plot PWIDs by year of commencing injecting. The curve was adjusted for missing data on PWIDs in treatment and for PWIDs who were never treated. An adjustment was made to account for injectors who had never shared injecting equipment. The incidence of HCV infection and chronic infection in PWIDs was estimated by applying published rates.

Results: Between 1991 and 2014, 14,320 injectors were registered on NDTRS. The majority were young (median age 25 years), male (74%), lived in Dublin (73%) and injected an opiate (e.g. heroin) (94%). The estimated total number of injectors up to the end of 2014 was 16,382. An estimated 12,423 (95% CI 10,799-13,161) were infected with HCV, and 9,317 (95% CI 8,022-9,996) became chronically infected. The estimated annual number of new HCV infections among PWIDs increased steeply from the late 1970s and peaked in 1998. By 2014, almost 30% of injectors were estimated to have been infected for over 20 years.

Conclusions: This is the first comprehensive national estimate of the incidence of HCV in PWIDs in Ireland and will inform planning and developing appropriate health care services.

Hepatitis B is preventable and hepatitis C is treatable even if still at a high cost; most people who are infected with hepatitis B or C virus have not been screened yet and are unaware of their infections; and most countries, especially developing countries, do not have a national plan to prevent and control viral hepatitis. The advent of effective new treatments for hepatitis C has been an agent of change, allowing consideration of the feasibility of eliminating that disease and accelerating the control of viral hepatitis generally. These facts inspired the Viral Hepatitis Prevention Board (VHPB) to organize a meeting in London (8-9 June 2015) on innovative sources for funding of viral hepatitis prevention and treatment in low- and middle-income countries. The main focus of the meeting was to provide an overview of current health systems controlling viral hepatitis in low- and middle-income countries (LMICs); to identify ways to increase political commitment and financial sustainability of viral hepatitis prevention and control programmes in such countries; to identify potential funders and explore new funding mechanisms; to discuss lessons learnt about funding other disease programmes; to investigate how to convince and motivate decision-makers to fund viral hepatitis programmes in LMICs; to provide options for improving access to affordable screening and treatment of viral hepatitis in LMICs; and to list the commitments required for funding by donors, including governments, bilateral and multilateral organizations, non-traditional donors, development banks, foundations, and commercial financial institutions. To improve viral hepatitis prevention and treatment in LMICs participating hepatitis and financing experts identified the most urgent needs. Data on burden of disease must be improved. Comprehensive hepatitis policies and strategies should be drafted and implemented, and existing strategies and policies improved to increase access to treatment and prevention. Strong political will and leadership should be generated, potential partners identified and partnerships created. Potential funders and funding mechanisms have to be researched. The outcome of this meeting was integrated in a VHPB project to investigate creative financing solutions to expand access to and provision of screening and other preventive services, treatment and care of hepatitis B and C in LMICs. The report is available on www.vhpb.org.