April 20, 2013

Donor livers kept alive outside the body for 24 hours

17:00 15 March 2013 by Andy Coghlan

Donated livers can survive for at least a day outside the body thanks to a new device which keeps the organ ticking over as if it hadn't been removed. The machine is likely to more than double the availability of livers for transplant.

The device was unveiled today in London by its developer Peter Friend, professor of transplantation surgery at the University of Oxford.

In the US and Europe, 2000 livers get discarded each year because they deteriorate in transit, damaged by the ice packs and solutions that, for the past 40 years, have been the usual way to preserve them. At present, a quarter of the 30,000 people on US and European liver transplant waiting lists die each year before receiving an organ.

The new device can keep a donated liver at body temperature, supplying it with blood, sugar, oxygen and nutrients.

Whereas most frozen livers become unusable after about 14 hours of cold storage, the new device keeps them alive and in perfect condition for at least 24 hours. "In animals, we've gone up to 72 hours and see no reason why it shouldn't go even further than that," says Friend.

Buying time

He is hopeful that as well as buying precious time in which to use the organ, the device will enable surgeons to better judge a liver's condition before transplanting it, because in the device, it carries on functioning as normal.

"It gives the opportunity to test-drive the organ before transplanting it," says Constantin Coussios, co-developer of the device and founder of OrganOx, the company set up by the University of Oxford to commercialise it.

Video footage shows Friend plumbing a donated liver into the device. Within seconds of connection, the brown-grey organ turns bright red as blood floods into its capillaries. As in the body, blood and nutrients enter through the hepatic artery and the portal vein, and exit through the inferior vena cava. A fourth connection to the bile duct enables the liver's functioning to be monitored.

The box containing the liver and its plumbing is connected to a master console that monitors and controls the organ's life support.

A pump mimics the heart, an oxygenator mimics the lungs and tubes supply donated blood, explains Stuart Kay of Team Consulting in Cambridge, UK, which miniaturised and optimised the original system developed at Oxford. "The key is that the system 'listens' to the organ to find out how much blood to supply, and at what pressure," says Kay.

Sensors for fluid flow and pressure, plus levels of oxygen, carbon dioxide and sugar in the blood, are part of the disposable circuitry, he adds. Also, the device is fully automated so that non-specialist medical staff can use it and load it easily into planes or ambulances.

Clinical pilot

Two people have received livers kept alive using the device. They were both treated at King's College Hospital, London, in February, and are among 20 people taking part in a pilot clinical trial that, if successful, should allow the device to win approval for use in Europe by next year.

Further randomised trials are planned to compare the performance of the device with existing preservation methods using freezing. Friend says that animal experiments, mainly in pigs, have already demonstrated that the device outperforms freezing. It also enables surgeons to transplant fatty livers that would normally be rejected because they do not respond well to the freezing process, he says.

Friend says that with modifications, the same technology could be applied to preserve the pancreas, kidneys, small bowel and lungs.

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Hepatology April 2013

"study highlight the significant barriers that may impede the prompt, appropriate treatment of HCV infection......Key findings of our study include marked regional variation in perceived barriers, the importance of patient-level obstacles, concerning deficits in provider knowledge, and the shared pessimism regarding the current state of HCV care......In multivariable regression analysis, only global region, years of experience, and knowledge were significantly associated with perceived barriers to care.........only 35% of physicians believed that patients have adequate access to HCV providers......more than half of HCV-infected persons were unaware of their diagnosis.29 Among injection drug users, this number is as high as 72%-90%.....less than one quarter of respondents believing that the public is aware of HCV and its consequences.....A lack of trained specialists......Recent advances in antiviral therapy have produced dramatic improvements in the treatment of HCV infection. Unfortunately, only a minority of HCV-infected persons will receive treatment as a result of multiple barriers to care. Globally, physicians cite patient-level factors, including fear of side effects and concerns regarding treatment duration and cost, as the greatest barriers to treatment. Inadequate physician knowledge and limited specialist availability may further contribute. Efforts to improve patient and physician education, public awareness, and access to treatment providers are needed......Specific patient-related barriers included fear of side effects and concerns regarding treatment duration, cost, and effectiveness (Supporting Table 1). Payer-related barriers were most prominent in Latin American and Middle East/Africa and included lack of coverage leading to out-of-pocket expense and excessive paperwork requirements. Only one region (Central/Eastern Europe) cited government-related barriers (insufficient funding and lack of treatment promotion) as most significant"

Christopher E. McGowan,1 Ali Monis,2 Bruce R. Bacon,3 Josep Mallolas,4 Fernando L. Goncales,5 Ioannis Goulis,6 Fred Poordad,7 Nezam Afdhal,8 Stefan Zeuzem,9 Teerha Piratvisuth,10 Patrick Marcellin,11 and Michael W. Fried1 From the 1UNC Liver Center, University of North Carolina at Chapel Hill, Chapel Hill, NC; 2Ain Shams Medical School, Cairo, Egypt; 3Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO; 4Infectious Diseases Service, Hospital Clinic, Barcelona, Spain; 5FCMUniversity of Campinas, Sa÷o Paola, Brazil; 6Aristotle University of Thessaloniki, Thessaloniki, Greece; 7Cedars-Sinai Medical Center, Los Angeles, CA; 8Beth Israel

Deaconess Medical Center, Boston, MA; 9Department of Medicine, J.W. Goethe University Hospital, Frankfurt, Germany; 10NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Hat Yai, Thailand; and 11Service d'Hepatologie and Centre de Recherches, Hopital Beaujon, Clichy, France.

Abstract

Chronic infection with the hepatitis C virus (HCV) is a leading cause of global morbidity and mortality. Although recent advances in antiviral therapy have led to significant improvements in treatment response rates, only a minority of infected patients are treated. Multiple barriers may impede the delivery of HCV therapy. The aim of this study was to identify perceived barriers to care, knowledge, and opinions among a global sample of HCV treatment providers. An international, multidisciplinary survey of HCV treatment providers was conducted. Each physician responded to a series of 214 questions concerning his or her practice characteristics, opinions regarding the state of HCV care, knowledge regarding HCV treatment, and perception of treatment barriers. A total of 697 physicians from 29 countries completed the survey. Overall, physicians viewed patient-level barriers as most significant, including fear of side effects and concerns regarding treatment duration and cost. There were distinct regional variations, with Central and Eastern European physicians citing government barriers as most important. In Latin America, the Middle East, and Africa, payer-level barriers, including lack of treatment coverage, were prominent. Overall, the perception of barriers was strongly associated with physician knowledge, experience, and region of origin, with the fewest barriers reported by Nordic physicians and the most reported by Middle Eastern and African physicians. Globally, physicians demonstrated deficits in basic treatment principles, including the role of viral kinetics and the management of treatment nonresponders. Two thirds of surveyed physicians believed that patients do not have adequate access to providers in their community.

Conclusion: Barriers to HCV treatment vary globally, though patient-level factors are viewed as most significant by treating physicians. Efforts to improve awareness, education, and specialist availability are needed.

Hepatitis C virus (HCV) infection affects between 130 and 170 million persons worldwide, is a leading indication for liver transplantation, and contributes to 350,000 deaths each year.1 HCV is a potentially curable disease, with the majority of treated patients currently afforded the promise of a sustained virologic response (SVR).2-5 Unfortunately, less than half of HCV-infected persons are aware of their diagnosis, and among those with known infection, only 1%-30% will receive treatment.6-11

Multiple factors serve as impediments to the delivery of antiviral therapy. These barriers may arise at the patient, provider, payer, and/or government level.12 Patients cite fear of treatment-related side effects, lack of symptoms, financial constraints, and social stigmatization as primary reasons for declining therapy.13-16 Physicians may fail to refer patients for subspecialty evaluation or may place undue emphasis on purported contraindications.17 As a result, more than 70% of patients are deemed ineligible for treatment based on psychiatric disease, substance use, or medical comorbidities,6, 7 despite evidence that these factors are not absolute.18, 19 A lack of available and competent specialists may further interfere.20, 21 Finally, limitations in funding, medical coverage, and office staffing may prevent treatment.11, 22 Increasingly, hepatitis C is recognized as a global health crisis, demanding an international, coordinated emphasis on promotion, prevention, and treatment.23 To inform these initiatives, we surveyed an international sample of HCV treatment providers, with an aim of assessing knowledge, opinions toward HCV therapy, and perceived barriers to care.

Materials and Methods

An international, mixed-mode survey study of HCV treatment providers was conducted in December 2010 with an aim to identify physician and practice characteristics, opinions regarding HCV care, knowledge of treatment principles, and perceived barriers to care. A 214-item questionnaire was developed by the International Conquer C Coalition (I-C3; see Appendix), an organization of hepatitis C experts formed with the goal of optimizing global HCV care. The questionnaire was piloted by a 67-member focus group of I-C3 members. Physicians were considered eligible for the study if they treated a minimum of 10 HCV patients each month and if they resided in one of the eight predetermined global regions: United States; Canada; Latin America; Western Europe; Central/Eastern Europe; Nordic; Asia/Pacific; and Middle East/Africa. Target respondents included hepatologists, gastroenterologists, infectious disease (ID) physicians, internists, and general practitioners. The survey was distributed to a sample of 1,400 physicians identified by an international market research database24 and was administered by 25-minute phone interview or internet-based format by a professional survey company (Phoenix Marketing International, Rhinebeck, NY). Participants were asked a series of open-ended, multiple-response, and Likert-scale questions. Translation was provided for non-English-speaking participants. Each participant received a modest honorarium for completing the survey. All responses were anonymous.

Physician/Practice Characteristics and Opinions Regarding HCV Care. Each physician was asked about his or her medical specialty, practice location, patient volume, and patient characteristics. Opinions regarding the current state of HCV care were assessed according to level of agreement with the following statements: (1) national treatment guidelines are available in my country; (2) treatment guidelines and policies are consistent among professional societies, payers, and government; (3) government and/or payers recognize national or international treatment guidelines; (4) healthcare providers have knowledge of screening and treatment guidelines; (5) the general public is aware of HCV; (6) patients understand the consequences of HCV if it is not treated; (7) most patients are aware that HCV is curable; and (8) patients have adequate access to HCV providers in their community; responses were rated on a 10-point Likert scale, with 0 representing "strongly disagree," 5 "neither agree nor disagree," and 10 "strongly agree."

Knowledge.

Physician knowledge was assessed according to level of agreement with the following eight statements: (1) the addition of ribavirin (RBV) to pegylated interferon (Peg-IFN) improves the likelihood of SVR; (2) maintaining an optimal dose of RBV with interferon (IFN) is necessary to achieve an SVR; (3) different viral genotypes require different treatment durations; (4) treatment should be discontinued for patients who fail to achieve a 2-log decrease in HCV RNA by treatment week 12; (5) treatment should be discontinued for patients who have detectable HCV RNA at treatment week 4; (6) patients with stage 1 fibrosis have worse treatment outcomes than patients with stage 4 fibrosis; (7) level of HCV RNA has no correlation with severity of liver disease; and (8) maintenance therapy should be prescribed for treatment nonresponders. Each response was rated on a 10-point Likert scale, with 0 representing "strongly disagree," 5 representing "neither agree nor disagree," and 10 representing "strongly agree." Barriers to Care.

The main focus of this study was to assess perceived barriers to HCV care. Each respondent was presented with 31 potential barriers categorized by patient-, provider-, government-, and payer-related categories (Table 1). Responses were based on a 10-point Likert scale, with 0 representing "not a barrier to treatment," 5 representing "somewhat of a barrier to treatment," and 10 representing "large barrier to treatment."

Statistical Analysis.

Mean, range, standard deviation (SD), and shape of the distribution were examined for each continuous variable, with frequencies tabulated for each categorical variable. Physician and practice characteristics were compared across global regions using Pearson's chi-square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. Bivariable analysis was used to examine the relationship between physician and practice characteristics and perceived barriers to care using Pearson's correlation analysis for continuous independent variables and one-way ANOVA for each categorical independent variable. Multiple linear regression was used to identify characteristics independently associated with perceived barriers to care. All analyses were performed using Stata 11 (StataCorp LP, College Station, TX).

Abbreviations

ANOVA, analysis of variance; EVR, early virologic response; GI, gastroenterology; HCV, hepatitis C virus; IDs, infectious diseases; IFN, interferon; Peg-IFN, pegylated interferon; RBV, ribavirin; SD, standard deviation; SVR, sustained virologic response.

Results

A total of 697 physicians were surveyed across eight global regions, representing 29 individual countries (Supporting Fig. 1). Overall response rate was 50%. Physician and practice characteristics are summarized in Table 2. Overall, physicians were in practice for a mean of 16 years and treated an average of 46 HCV patients each month (range, 5-500). Physician specialty varied by region, with HCV care more commonly provided by hepatologists and gastroenterologists in the United States and Western Europe, by infectious disease specialists in Central/Eastern Europe, and by internists or general practitioners in remaining regions. Physicians most frequently worked in a private, urban facility, though a government-affiliated practice was most common in Central/Eastern Europe and Nordic regions. Dedicated treatment nurses and/or assistants were more frequently employed in European countries. Source of medical coverage varied significantly, with patients in Europe, Canada, and Asia/Pacific regions covered primarily by public insurance. A mix of public and private coverage was noted in the United States and Latin America. More than one third of patients in the Middle East and Africa were reportedly uninsured. Overall, approximately one quarter of patients were reported to refuse therapy, with the highest refusal rate in Asia/Pacific countries and the lowest in Nordic countries (37% versus 14%; P < 0.0001).

Opinions Regarding HCV Care.

Physician opinions regarding the current state of HCV care are shown in Table 3.
The majority of physicians indicated that national treatment guidelines existed in their country; however, less than half felt that guidelines were consistent across sources. Only 36%-38% of physicians in North America, Latin America, and Middle East/Africa believed that government and/or payers recognized treatment guidelines, compared to 71%-83% in European countries. Between 20% and 54% of respondents felt that healthcare providers have adequate knowledge of HCV guidelines, with higher levels of agreement across European countries. Globally, less than one quarter of physicians felt that the general public is aware of HCV and know that it is a curable disease. Only 35% of all surveyed physicians believed that patients have adequate access to HCV treatment providers, with the lowest percentage in the United States (17%) and the highest in Nordic countries (62%).

Knowledge.

Knowledge of HCV treatment principles varied significantly by region, with physicians in Western Europe correctly answering the most knowledge questions, and those in Middle East and African countries correctly answering the fewest (6.4 versus 3.2; P < 0.001; Fig. 1A). Overall, physicians understood that RBV is a necessary component of treatment, treatment duration varies by genotype, and treatment should be discontinued for patients who fail to achieve an early virologic response (EVR). However, a majority of physicians incorrectly believed that HCV RNA level correlates with liver disease severity, and that treatment nonresponders should receive maintenance therapy (Table 4). In Middle East/African countries, a majority of respondents also did not appreciate the importance of RBV, the role of HCV viral kinetics, and the significance of liver fibrosis stage. Globally, knowledge was highest among hepatologists and lowest among general practitioners (P < 0.001 for overall comparison; Fig. 1B). Source of treatment information varied by region, with national and government guidelines used most frequently in all regions except in the United States, where guidelines from the American Association for the Study of Liver Diseases were most commonly used (Supporting Fig. 2).

Barriers to Care.

There was significant regional variation in perceived barriers to care, with the greatest barriers reported in Middle East/Africa and the fewest in Nordic countries (P < 0.0001 for overall comparison; Fig. 2A). Globally, patient-related barriers were viewed as most significant, representing the highest rated barrier category in five of eight regions, including the United States (Fig. 2B). Specific patient-related barriers included fear of side effects and concerns regarding treatment duration, cost, and effectiveness (Supporting Table 1). Payer-related barriers were most prominent in Latin American and Middle East/Africa and included lack of coverage leading to out-of-pocket expense and excessive paperwork requirements. Only one region (Central/Eastern Europe) cited government-related barriers (insufficient funding and lack of treatment promotion) as most significant.

Along with geographic region, perceived barriers were significantly associated with physician specialty, physician experience, practice setting, and physician knowledge (Table 5). Subspecialists (hepatology, gastroenterology [GI], and IDs) reported fewer perceived barriers than internists and general practitioners. Likewise, physicians with more experience and higher knowledge scores reported fewer barriers. In multivariable regression analysis, only global region, years of experience, and knowledge were significantly associated with perceived barriers to care (Supporting Table 2).

Discussion

This international, multidisciplinary survey study provides insight into the current state of hepatitis C care, as viewed by treating physicians. Key findings of our study include marked regional variation in perceived barriers, the importance of patient-level obstacles, concerning deficits in provider knowledge, and the shared pessimism regarding the current state of HCV care.

Foremost, barriers to care were not perceived equally across global regions.

Physicians from Nordic and Western European countries had remarkably low perceptions of treatment barriers (mean Likert responses of 1.7 and 2.1, respectively, on a 10-point scale). In contrast, Middle Eastern and African physicians perceived all barrier categories as problematic (mean Likert response: 6.1 of 10). Despite regional differences in the magnitude of perceived barriers, there was agreement regarding the nature of these barriers. Across all global regions, patient-level factors were viewed as the greatest obstacles to treatment. This is consistent with previous surveys of physicians and patients in the United States and United Kingdom.13, 15, 16, 22 Specifically, fear of treatment-related side effects was the most frequently cited barrier in our study. This fear is not unfounded, because nearly all patients will experience at least one treatment-related side effect, and 10%-14% of patients will discontinue treatment as a result.2, 4 Though side effects are common, appropriate pretreatment counseling, along with a structured plan for monitoring and management, may help alleviate such fears.25

Further patient-level barriers included concerns regarding treatment duration and antiviral effectiveness. Fortunately, the recent introduction of direct-acting antivirals offers the potential for improved response rates and reduced treatment lengths. However, these benefits will need to be balanced against a greater incidence of treatment-related side effects.4, 5 Nevertheless, each of these patient-level barriers is addressable and, in many cases, modifiable.

To properly address patient fears, physicians must have a thorough understanding of antiviral therapy. This study identified concerning knowledge deficits, which were most apparent in Middle East/African countries. Physicians in this region often did not acknowledge important treatment principles, including the significance of RBV in HCV therapy, although the frequency of non-specialty physician respondents was also highest in this region. Interestingly, across all regions, more than half of physicians indicated that they would treat nonresponders with maintenance IFN therapy, despite its lack of efficacy.26

Similarly, most physicians incorrectly believed that HCV RNA level reflects liver disease severity. Though previous studies of healthcare providers have demonstrated significant knowledge gaps related to HCV,27 our study documented these deficits in experienced HCV treaters. This is concerning, because inadequate physician knowledge is a known barrier to care.20 Furthermore, independent of geographic region, medical specialty, or experience level, physicians who scored lower on the knowledge assessment tended to perceive greater barriers to care. The implication here is 2-fold: Physicians with less knowledge may treat fewer patients as a result of incorrectly perceived barriers, and these perceived barriers may be overcome through improved education.

Recognizing the current deficits in physician knowledge, the Institute of Medicine recently recommended the development of HCV educational initiatives, emphasizing a need for increased awareness and improved adherence to guidelines.28 In our study, only 40% of respondents believed that providers have adequate knowledge of treatment guidelines, highlighting this need. Physicians held similar views regarding public awareness, with less than one quarter of respondents believing that the public is aware of HCV and its consequences. This view is supported by findings from the National Health and Nutrition Examination Survey, in which more than half of HCV-infected persons were unaware of their diagnosis.29 Among injection drug users, this number is as high as 72%-90%.30, 31 Unfortunately, awareness does not guarantee treatment. In our study, only 35% of physicians believed that patients have adequate access to HCV providers. A lack of trained specialists, combined with their concentration at academic medical centers, may limit the widespread availability of treatment. Indeed, market surveys in the United States indicate that 80% of HCV patients are managed by 20% of gastroenterologists.21 Models of expanded HCV treatment, including the use of tele-health, have shown promise.32 These warrant broader exploration and implementation.

This is the first international study to examine barriers to care among HCV treatment providers. The findings are strengthened by a comprehensive questionnaire, developed and piloted by a panel of internationally recognized HCV experts. The survey achieved a 100% item response rate, eliminating the potential for nonresponse bias. However, as with any survey, the findings in our study may not be representative of the entire population. Likewise, it was not feasible to survey physicians within every country, leading to the potential for coverage error. By grouping our findings into global regions, we may not have adequately addressed the differences that exist between individual countries. Furthermore, the perceptions identified in this study may not be representative of less-experienced physicians. This may have led to an underestimation of treatment barriers. Finally, HCV treatment is frequently delivered by mid-level providers (i.e., nurse practitioners and physician assistants), particularly in the United States. This study did not address the perspective of these providers, which may differ from those of physicians.

Still, the findings of this study highlight the significant barriers that may impede the prompt, appropriate treatment of HCV infection. A focus on patient and provider education, increased awareness, and treatment promotion is necessary if progress is to be made in the global fight against HCV infection. Recent advances in antiviral therapy have produced dramatic improvements in the treatment of HCV infection. Unfortunately, only a minority of HCV-infected persons will receive treatment as a result of multiple barriers to care.

Globally, physicians cite patient-level factors, including fear of side effects and concerns regarding treatment duration and cost, as the greatest barriers to treatment. Inadequate physician knowledge and limited specialist availability may further contribute. Efforts to improve patient and physician education, public awareness, and access to treatment providers are needed.

Source

BMC Infect Dis. 2013 Apr 18;13(1):181. [Epub ahead of print]

Hahné SJ, Veldhuijzen IK, Wiessing L, Lim TA, Salminen M, Laar M.

Abstract
BACKGROUND: Treatment for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is improving but not benefiting individuals unaware to be infected. To inform screening policies we assessed (1) the hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV-Ab) prevalence for 34 European countries; and (2) the cost-effectiveness of screening for chronic HBV and HCV infection.

METHODS: We searched peer-reviewed literature for data on HBsAg and anti-HCV-Ab prevalence and cost-effectiveness of screening of the general population and five subgroups, and used data for people who inject drugs (PWID) and blood donors from two European organizations. Of 1759 and 468 papers found in the prevalence and cost-effectiveness searches respectively, we included 124 and 29 papers after assessing their quality. We used decision rules to calculate weighted prevalence estimates by country.

RESULTS: The HBsAg and anti-HCV-Ab prevalence in the general population ranged from 0.1%-5.6% and 0.4%-5.2% respectively, by country. For PWID, men who have sex with men and migrants, the prevalence of HBsAg and anti-HCV-Ab was higher than the prevalence in the general population in all but 3 countries. There is evidence that HCV screening of PWID and HBsAg screening of pregnant women and migrants is cost-effective.

CONCLUSION: The prevalence of chronic HBV and HCV infection varies widely between European countries. Anti-HCV-Ab screening of PWID and HBsAg screening of pregnant women and migrants are European public health priorities. Cost-effectiveness analyses may need to take effect of antiviral treatment on preventing HBV and HCV transmission into account.

Source

Hepatology. 2013 Mar 28. doi: 10.1002/hep.26431. [Epub ahead of print]

Martin NK, Vickerman P, Grebely J, Hellard M, Hutchinson SJ, Lima VD, Foster GR, Dillon JF, Goldberg DJ, Dore GJ, Hickman M.

School of Social and Community Medicine, University of Bristol, Bristol, UK; Social and Mathematical Epidemiology Group, Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK. natasha.martin@bristol.ac.uk.

Abstract
BACKGROUND:

Substantial reductions in HCV prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake low, but new highly effective and tolerable interferon-free direct-acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings.

METHODS:

A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three-quarters within 15 years.

RESULTS:

Current HCV treatment rates may minimally impact prevalence in Melbourne and Vancouver (<2% relative reductions), but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale-up to 15, 40, or 76 per 1000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2, 13, 15-fold increases, respectively). Scale-up to 22, 54, or 98 per 1000 PWID annually could reduce prevalence by three-quarters within 15 years. Less impact occurs with delayed scale-up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of USD$3.2 million in Edinburgh and ˜$50 million in Melbourne and Vancouver.

CONCLUSION:

Interferon-free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale-up, and should be addressed. (HEPATOLOGY 2013.).

Copyright © 2013 American Association for the Study of Liver Diseases.

Source

Asahina Y, Tsuchiya K, Nishimura T, Muraoka M, Suzuki Y, Tamaki N, Yasui Y, Hosokawa T, Ueda K, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Nakagawa M, Kakinuma S, Watanabe M, Izumi N.

Hepatology. 2013 Apr 8. doi: 10.1002/hep.26442. [Epub ahead of print]

Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180-8610, Japan; Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Department of Liver Disease Control, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. asahina.gast@tmd.ac.jp.

Abstract

The effects of interferon (IFN) treatment and the post-IFN treatment α-fetoprotein (AFP) levels on risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) are unknown. To determine the relationship between AFP and alanine transaminase (ALT) levels and HCC risk, the cohort consisted of 1818 patients histologically proven to have CHC treated with IFN were studied. Cumulative incidence and HCC risk were analyzed over a mean follow-up period of 6.1 years using the Kaplan-Meier method and Cox proportional hazard analysis. HCC developed in 179 study subjects. According to multivariate analysis, older age, male gender, advanced fibrosis, severe steatosis, lower serum albumin levels, sustained virological response (SVR), and higher post-IFN treatment ALT or AFP levels were identified as independent factors significantly associated with HCC development. Cutoff values for ALT and AFP for prediction of future HCC were determined as 40 IU/L and 6.0 ng/mL, respectively, and negative predictive values of these cutoffs were high at 0.960 in each value. Cumulative incidence of HCC was significantly lower in patients whose post-IFN treatment ALT and AFP levels were suppressed to less than the cutoff values even in non- SVR patients. This suppressive effect was also found in patients whose post-IFN treatment ALT and AFP levels were reduced to less than the cutoff values despite abnormal pre-treatment levels. Conclusion: Post-IFN treatment ALT and AFP levels are significantly associated with the hepatocarcinogenesis. Measurement of these values is useful for predicting future HCC risk after IFN treatment. Suppression of these values after IFN therapy reduces HCC risk even in patients without HCV eradication. (HEPATOLOGY 2013.).

Copyright © 2013 American Association for the Study of Liver Diseases.

PMID
23564522 [PubMed - as supplied by publisher]

Full text: John Wiley & Sons, Inc.

Source

If We Want an AIDS-Free Generation, Why Are We Cutting PEPFAR?

Chris Collins Vice President and Director of Public Policy, amfAR: The Foundation for AIDS Research

Posted: 04/18/2013 9:31 am

The persistent shortchanging of PEPFAR, the President's Emergency Plan for AIDS Relief, is one of the more significant and perplexing trends in America's global health policy. Funding for PEPFAR (America's bilateral global AIDS program) has been falling consistently from its peak in fiscal year 2010. In fiscal year 2012, $250 million was transferred out of the program to the Global Fund to Fight AIDS, Tuberculosis and Malaria. For fiscal year 2013, the White House proposed cutting PEPFAR by $550 million (11 percent) and in March of this year Congress went part way, taking $176 million from the program in the Continuing Resolution.

Funding for PEPFAR has fallen 12 percent since 2010 in the State Department HIV bilateral budget line. Last week, the White House proposed an additional $50 million cut for 2014. When the mandated sequestration cut is taken into account, the program is now at its lowest funding level since 2007.

This downward funding spiral might make sense if there was a consensus that tackling AIDS has become less important, or if PEPFAR was not producing results. But the opposite is true. In November 2011, Secretary of State Hillary Clinton announced that achieving an AIDS-free generation was a "policy priority" for the U.S. government. President Obama went on to set bold new targets for AIDS treatment and other services through PEPFAR. In November 2012, the Administration released a PEPFAR Blueprint lauding the program's accomplishments and affirming the need to "rapidly scale-up core ... interventions." Doing so, the Blueprint argued, would accelerate declines in HIV incidence globally.

In February of this year, President Obama inspired all those engaged in the response to AIDS when, in his State of the Union address, he reaffirmed his commitment to the goal of an AIDS-free generation. The same month, the Institute of Medicine (IOM) weighed in with their assessment of PEPFAR, four years in the making. It concluded that the program has been "globally transformative" and has "had major positive effects on the health and well-being of individual beneficiaries, on institutions and systems in partner countries, and the overall global response to AIDS."

Why the mismatch between results, rhetoric, and financing? Budget deficit pressures do not explain it: total U.S. global health spending is just a quarter of one percent of the federal budget. Politics doesn't explain it either, with PEPFAR maintaining a unique level of bipartisan Congressional support.

The more likely reason for steady reductions in PEPFAR funding is an Administration decision to gradually de-emphasize bilateral AIDS investments in favor of multilateral institutions and multiyear commitments to these institutions. Increased investments in the Global Fund and other multilateral health organizations are a badge of honor for President Obama. These institutions have demonstrated clear results in countries around the world, and U.S. funding leverages investments from others.

The question is not whether increased funding for the Global Fund is good, because clearly it is. The question is whether those increases justify year-on-year reductions in our bilateral AIDS program. It is not a matter of choosing between multilateral and bilateral approaches, but of marshaling sufficient resources to end AIDS.

One concern is that as Global Fund and PEPFAR funding trends head in opposite directions, net U.S. resources dedicated to tackling AIDS are in decline. Since on average approximately 57 percent of Global Fund resources are allocated to combating HIV/AIDS, the $600 million increase in support for the Global Fund since 2010 and the $543 million decrease in funding for PEPFAR during that time adds up to an overall decline in U.S. government funding to tackle the global AIDS epidemic.

Another problem is the lost opportunities to strengthen health systems when PEPFAR is cut. According to the distinguished IOM panel, the program is helping build health systems through improved laboratory capacity, supply chains, and staff training. The IOM observed that PEPFAR is "uniquely situated as a platform for research to spur innovation and to address knowledge gaps" in the global AIDS response.

And then there is the move toward to greater "country ownership" of healthcare financing and decision making. Clearly country ownership is an important goal and should be pursued at a rate that is appropriate for each individual country setting. But a reduced commitment to PEPFAR could lead to an accelerated and premature hand-off of AIDS programs with potentially disastrous consequences. Already there are concerns. A Center for Strategic and International Studies (CSIS) report released in March noted the "legitimate fears" that a rushed transition in South Africa could disrupt the delivery of AIDS treatment to people there.

In many countries where PEPFAR operates, those groups most severely affected by the epidemic, including gay men, people who inject drugs, and sex workers, are socially and legally marginalized. Last year UNAIDS reported that more than 90 percent of funding to address HIV among these populations in low- and middle-income countries came from external sources, not the countries themselves. Though PEPFAR still needs to pay greater attention to these most-at-risk groups, the program has been a leader in tending to their HIV-related needs. If PEPFAR is scaled back, real progress to address the epidemic among the most vulnerable could be in serious jeopardy.
Congress has been broadly supportive of domestic and global AIDS funding for many years. And the President deserves praise for his leadership on AIDS, which includes game changers like the Affordable Care Act, the National HIV/AIDS Strategy, and funding increases for domestic AIDS and the Global Fund. The President is to be commended for being outspoken against HIV-related stigma and for equality for gay people, including young Black gay men, who are perhaps the most vulnerable in America's epidemic.

With the end of AIDS within reach, it is time to think about legacy -- the President's and our own. The most damaging consequence of continual reductions in funding for PEPFAR is slower than necessary progress in pursuing the end of the AIDS pandemic. The PEPFAR Blueprint shows how expanded delivery of proven interventions will yield falling HIV incidence and mortality rates within a few years. The Global Fund has an essential role to play in this effort, and other donors and affected countries need to invest more.

But the honest truth is that the world won't end AIDS without PEPFAR. Some will say, judge PEPFAR on its outcomes, not its funding. But when PEPFAR's own Blueprint calls for rapid scale-up of effective services in order to show tangible gains, it's hard to understand why now is the time to cut back. The urgency of delivering lifesaving services remains acute, with the IOM observing that there is a "substantial remaining unmet need for all services ... that are part of an effective response to HIV."

Congress and the President should not set the AIDS budget based on short-term expediency. Instead they should recognize the longer game: defeating a major infectious disease, and securing this generation's legacy as beginning the end of AIDS. To achieve that goal, both the Global Fund and PEPFAR need appropriate funding.

The IOM panel assessing PEPFAR's work concluded that the program "has the opportunity and the potential to once again transform the way global assistance for health is envisioned and implemented." The question is, will we allow it to seize the opportunity and fulfill its potential?

Chris Collins is vice president and director of public policy at amfAR, The Foundation for AIDS Research. His email is chris.collins@amfar.org

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