September 13, 2013

HIV warning over anabolic steroid injections

Provided by Nursing Times

13 September, 2013 | By The Press Association

One in 10 men who inject themselves with anabolic steroids or tanning drugs have been exposed to HIV, hepatitis B or hepatitis C, according to a study.

Public Health England (PHE) said the research was vital because while the number of those who use image and performance-enhancing drugs has rapidly grown over the past 20 years, their risk of exposure to such viruses has not been thoroughly investigated.

Co-author Jim McVeigh, from the Centre for Public Health at Liverpool John Moores University, said: “Injectors of anabolic steroids and associated drugs are now the biggest client group at many needle and syringe programmes in the UK.

“This research shows that anyone who injects drugs is at risk of HIV and other blood-borne viruses, regardless of their substance of choice.”

Lead author of the report Dr Vivian Hope, PHE’s expert in infections among people who inject drugs, said: “Our study suggests that levels of HIV and hepatitis infection among men using image and performance-enhancing drugs have increased since the 1990s.

“While we must be cautious in generalising these early findings, they are concerning and show that further research is required.”

Researchers from PHE and Liverpool John Moores University questioned 395 men who use such drugs for the study, published in BMJ Open.

They found one in 18 injectors had been exposed to hepatitis C, one in 11 had been exposed to hepatitis B and one in 65 has HIV.

Overall, one in 10 had been exposed to one or more of the blood-borne viruses.

The survey also looked at the lifestyle of those surveyed and found that only 20% said they had always used a condom when having sex in the previous year.

Dr Fortune Ncube, consultant epidemiologist and the PHE’s lead on injecting drug use, said: “These findings suggest serious health implications for users of image and performance-enhancing drugs, but also for their sexual partners and ultimately the wider community.

“These findings suggest we must maintain and strengthen public health interventions focused on reducing injection-related risk behaviours to prevent HIV and hepatitis infections in this group.

“This includes ensuring those providing voluntary confidential testing services and care related to HIV and hepatitis are alert to the risks associated with image and performance-enhancing drug use.”

The National Aids Trust (NAT) said those using performance or image-enhancing drugs needed to know the risks that came with injecting them.

Yusef Azad, drector of policy and campaigns at the NAT, said: “People who inject steroids and tanning drugs often don’t understand safe injecting practices and aren’t being targeted by harm reduction messages in the way traditional drug injectors such as heroin users are - and this poses a serious risk of HIV.

“In fact our research has found only 45% of the general public know HIV can be transmitted through sharing injecting equipment.

“If newer communities are starting to inject drugs, then there is an urgent task to ensure health promotion and harm reduction messages reach them.

“NAT has written to all local authorities in the UK bringing this issue to their attention and calling on them to find innovative ways to inform these groups of the risks of blood-borne viruses. We hope they rise to this challenge.”

Source

Gilead's (GILD) Sofosbuvir FDA Panel Review Date Set for October 25th

September 13, 2013 9:08 AM EDT

4160-01-P

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0001]

Antiviral Drugs Advisory Committee; Notice of Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug Administration (FDA). The meeting will be open to the public.

Name of Committee: Antiviral Drugs Advisory Committee.

General Function of the Committee: To provide advice and recommendations to the Agency on FDA's regulatory issues.

Date and Time: The meeting will be held on October 25, 2013, from 8 a.m. to 5 p.m.

Location: Sheraton Silver Spring Hotel, Cypress Ballroom, 8777 Georgia Ave., Silver Spring, MD. The hotel phone number is 301-589-0800.

Contact Person: Karen Abraham-Burrell, Food and Drug Administration, Center for Drug Evaluation and Research, 10903 New Hampshire Ave., Bldg. 31, rm. 2417, Silver Spring, MD 20993-0002, 301-796-9001, FAX: 301-847-8533, email: AVAC@fda.hhs.gov or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area).

A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the Agency's Web site at http://www.fda.gov/AdvisoryCommittees/default.htm and scroll down to the appropriate advisory committee meeting link, or call the advisory committee information line to learn about possible modifications before coming to the meeting.

Agenda: The committee will discuss new drug application (NDA) 204671, sofosbuvir (an NS5B polymerase inhibitor), manufactured by Gilead Sciences, Inc. (Nasdaq: GILD), with a proposed indication for the treatment of chronic hepatitis C infection, in combination with other agents in adult patients with genotypes 1 to 6 and/or adult patients awaiting liver transplantation. FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA's Web site after the meeting. Background material is available at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm. Scroll down to the appropriate advisory committee meeting link.

Procedure: Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. Written submissions may be made to the contact person on or before October 9, 2013. Oral presentations from the public will be scheduled between approximately 1 p.m. and 2 p.m. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before October 1, 2013. Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by October 2, 2013. Persons attending FDA's advisory committee meetings are advised that the Agency is not responsible for providing access to electrical outlets.

FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Karen Abraham-Burrell at least 7 days in advance of the meeting.

FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site at http://www.fda.gov/AdvisoryCommittees/AboutAdvisoryCommittees/ucm111462.htm for procedures on public conduct during advisory committee meetings

Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app. 2).

Dated: September 10, 2013.
Jill Hartzler Warner,
Acting Associate Commissioner for Special Medical Programs.
[FR Doc. 2013-22427 Filed 09/13/2013 at 8:45 am; Publication Date: 09/16/2013]

Source

Locations and Reasons for Initial Testing for Hepatitis C Infection

Morbidity & Mortality Weekly Report

Chronic Hepatitis Cohort Study, United States, 2006-2010

Joseph A. Boscarino, PhD, Stuart C. Gordon, MD, Loralee B. Rupp, MBA, Mark A. Schmidt, PhD, Vinutha Vijayadeva, MBBS, Anne Moorman, MPH, Fujie Xu, MD, Scott D. Holmberg, MD, Stephen C. Ko, MD

Morbidity & Mortality Weekly Report. 2013;62(32):645-648. 

Introduction

Chronic hepatitis C virus (HCV) infection causes substantial morbidity and mortality in the United States.[1] Testing and treatment of asymptomatic persons might avert progression to more advanced disease. In 1998, CDC published guidelines for HCV testing based on risk factors for infection; however, recent studies indicate that at least one half of all persons living with HCV infection in the United States are unaware of their infection status.[2–4] To increase testing rates, in 2012 CDC recommended one-time testing of all persons born during 1945–1965.[5] To better understand where and why persons with chronic HCV infection sought their initial testing, 2006–2010 data were analyzed from a survey conducted as part of the ongoing Chronic Hepatitis Cohort Study.[6] Of 4,689 patients with HCV infection who responded to the survey, 60.4% reported that their initial HCV test occurred in a physician's office. CDC's risk-based indications (e.g., injection drug use and hemodialysis) were cited by 1,045 (22.3%) of the patients as reasons for testing, whereas clinical indications (e.g., abnormal liver function tests or liver-related symptoms such as jaundice) were cited by 2,121 (45.2%), suggesting that many HCV infections were identified only after the patient had become symptomatic. Promoting U. S. Preventive Services Task Force[7] and CDC recommendations for testing[5] and identifying strategies that help physicians implement HCV testing in their offices might help facilitate timely identification of HCV infection and reduce morbidity and mortality.

The Chronic Hepatitis Cohort Study follows patients with confirmed chronic HCV or hepatitis B virus infection who receive care at four integrated health-care systems in the United States:[3,6] Geisinger Health System, Danville, Pennsylvania; Henry Ford Health System, Detroit, Michigan; Kaiser Permanente Hawaii, Honolulu, Hawaii; and Northwest Permanente, Portland, Oregon. Of 12,529 patients aged ≥18 years who met the inclusion criteria for confirmed chronic HCV infection,[6] 10,380 (82.8%) were sampled randomly for the current analysis. After excluding 1,451 patients who died and 828 who could not be contacted because of an invalid telephone number or address, incarceration, long-term care, or because of a physician's request that contact should not be made, the remaining 8,101 (64.7%) patients were surveyed by U.S. mail or telephone during 2011–2012. Up to eight telephone contact attempts were made; a small incentive was offered to encourage participation. The study protocol was reviewed and approved by an institutional review board approved by the federal Office for Human Research Protections at each participating site.

The survey was designed to collect data regarding the location and reasons for initial HCV testing. Participants were asked to choose from a list of reasons for HCV testing. Their responses were then grouped and analyzed in four categories: 1) CDC risk indications, according to the 1998 guidelines for testing (e.g., injection drug use and hemodialysis); 2) clinical indications (e.g., abnormal liver function tests or liver-related symptoms such as jaundice or abdominal pain); 3) institutional requirements (e.g., from blood banks, insurance or health maintenance organizations, prison, work/school, or the military); and 4) other miscellaneous reasons, including a doctor recommendation, "thought I was exposed," spouse's recommendation, foreign-born (from a country where hepatitis is endemic), and sexual contact with an HCV-infected person. Reasons for testing were not mutually exclusive; patients could choose more than one reason.

Of the 8,101 patients contacted, 4,689 (57.9%) completed the survey. Compared with nonrespondents, survey participants were slightly older (mean age: 57.4 years compared with 56.9 years, p=0.003), more likely to be white (72.8% compared with 61.4%, p<0.001), and more likely to be women (43.9% compared with 38.0%, p<0.001).

Of the 4,689 participants, 3,663 (78.1%) were born during 1945–1965; 87.4% had a high school diploma or its equivalent; 98.1% had insurance; 45.5% were employed; and 23.2% received disability payments (Table 1). Most respondents (60.4%) reported receiving the HCV test in a physician's office (Table 2). For those born during 1945–1965: 62.1% were tested in physicians' offices, 9.4% in blood banks or at blood drives, 7.4% in public health or specialty clinics, and 5.4% in inpatient settings (Table 2). For those born before 1945 or after 1965, a smaller proportion (54.3%) of tests occurred in physicians' offices, whereas testing in clinics (11.9%) and inpatient settings (7.5%) constituted larger proportions.

Table 1.  Characteristics of HCV-infected patients (N = 4,689) — Chronic Hepatitis Cohort Study, United States, 2006–2010

Characteristic No. (%)*
Birth year
   After 1965 587 (12.5)
   1945–1965 3,663 (78.1)
   Before 1945 439 (9.4)
Sex
   Men 2,628 (56.1)
   Women 2,061 (43.9)
Race
   White 3,328 (72.8)
   Black or African American 888 (19.4)
   Asian 143 (3.1)
   American Indian or Alaska Native 138 (3.0)
   Native Hawaiian or Other Pacific Islander 76 (1.7)
   Unknown 116
Hispanic ethnicity
   Yes 208 (4.6)
   No 4,317 (95.4)
   Unknown 164
Education
   Less than high school diploma 529 (12.6)
   High school/General Equivalency Diploma 1,192 (28.5)
   Some college/Technical school 1,507 (36.0)
   College graduate or higher 961 (22.9)
   Unknown 500
Health-care coverage
   Private 2,941 (66.0)
   Medicare plus 812 (18.2)
   Medicaid 459 (10.3)
   Medicare only 161 (3.6)
   None 86 (1.9)
Employment
   Part-time/Full-time 2,035 (45.5)
   Disability 1,090 (23.2)
   Retired 897 (20.1)
   Unemployed 448 (9.6)
   Unknown 219

Abbreviation: HCV = hepatitis C virus.

* Missing values were excluded from percentage distributions
.

Table 2.  Locations for testing of HCV-infected patients — Chronic Hepatitis Cohort Study, United States, 2006–2010

Location Year of birth
Total (N = 4,689) Before 1945 (n = 439) 1945–1965 (n = 3,663) After 1965 (n = 587)
No. (%) No. (%) No. (%) No. (%)
Physician office 2,832 (60.4) 276 (62.9) 2,275 (62.1) 281 (47.9)
Blood bank or blood drive 424 (9.0) 31 (7.0) 345 (9.4) 48 (8.2)
Clinic* 393 (8.4) 24 (5.5) 271 (7.4) 98 (16.7)
Hospital inpatient 275 (5.9) 26 (5.9) 198 (5.4) 51 (8.7)
Insurance exam site 141 (3.0) 8 (1.8) 122 (3.3) 11 (1.9)
Emergency department 141 (3.0) 10 (2.3) 100 (2.7) 31 (5.3)
Prison 71 (1.5) 2 (0.5) 46 (1.3) 23 (3.9)
Army 20 (0.4) 2 (0.5) 18 (0.5) 0 (0)
Other 99 (2.1) 8 (1.8) 74 (2.0) 17 (2.9)
Unknown 293 (6.3) 52 (11.8) 214 (5.8) 27 (4.6)

Abbreviation: HCV = hepatitis C virus.

* Clinics included prenatal/family planning, sexually transmitted disease, infectious disease, tuberculosis, drug treatment, community, school/work, and unspecified clinics.

Included obstetrics wards
.

The 4,689 participants reported 7,649 reasons for their initial HCV test. Of the total, 3,473 responses (45.4%) were "miscellaneous reasons" not included in CDC's risk indications for testing (Table 3).

Among the 4,689 survey participants, clinical indications were reported by 2,121 (45.2%) as a reason for testing and CDC risk indications by 1,045 (22.3%). Among the 1,045 participants citing CDC risk indications, 986 (94.4%) reported injection drug use. Institutional requirements were reported by 781 (16.7%), and doctor-recommended testing was reported by 1,725 (36.8%) participants (Table 3).

For the 3,663 participants born during 1945–1965, clinical indications were cited by 1,713 (46.8%) participants, with 781 (21.3%) reporting CDC risk indications as a reason for their initial HCV test. Among those born during 1945–1965, institutional requirements were reported as a reason by 638 (17.4%), and 1,319 (36.0%) reported doctor recommendations as a reason for testing (Table 3).

Table 3.  Reported reasons for testing* among HCV-infected patients (N = 4,689), by year of birth — Chronic Hepatitis Cohort Study, United States, 2006–2010

Category of reasons Year of birth
Total reasons (N = 7,649) Before 1945 (n = 645) 1945–1965 (n = 5,926) After 1965 (n = 1,078)
No. (%) No. (%) No. (%) No. (%)
CDC risk indications 1,045 (13.7) 39 (6.0) 781 (13.2) 225 (20.9)
   Injection drug use 986 (94.4) 31 (79.5) 736 (94.2) 219 (97.3)
   Hemodialysis 59 (5.6) 8 (20.5) 45 (5.8) 6 (2.7)
Clinical indications 2,121 (27.7) 219 (34.0) 1,713 (28.9) 189 (17.5)
   Abnormal liver function test 1,497 (70.6) 158 (72.1) 1,212 (70.8) 127 (67.2)
   Liver symptoms 624 (29.4) 61 (27.9) 501 (29.2) 62 (32.8)
Institutional requirement 781 (10.2) 57 (8.8) 638 (10.8) 86 (8.0)
   Blood donor 506 (64.8) 38 (66.7) 410 (64.3) 58 (67.4)
   Insurance/HMO 145 (18.6) 9 (15.8) 126 (19.7) 10 (11.6)
   Prison 80 (10.2) 6 (10.5) 57 (8.9) 17 (19.8)
   Work/School 39 (5.0) 2 (3.5) 36 (5.6) 1 (1.2)
   Military 11 (1.4) 2 (3.5) 9 (1.4) 0
Miscellaneous 3,473 (45.4) 294 (45.6) 2,618 (44.2) 561 (52.0)
   Doctor recommendation 1,725 (49.7) 205 (69.7) 1,319 (50.4) 201 (35.8)
   "Thought I was exposed" 639 (18.4) 28 (9.5) 458 (17.5) 153 (27.3)
   Sexual contact with HCV 338 (9.7) 16 (5.4) 243 (9.3) 79 (14.1)
   Many sex partners 228 (6.6) 8 (2.7) 177 (6.8) 43 (7.7)
   Household contact with HCV 200 (5.8) 10 (3.4) 154 (5.9) 36 (6.4)
   Spouse recommendation 76 (2.2) 8 (2.7) 58 (2.2) 10 (1.8)
   MSM 46 (1.3) 0 (0) 31 (1.2) 15 (2.7)
   Born in country with endemic HCV 32 (0.9) 6 (2.0) 22 (0.8) 4 (0.7)
   Other 189 (5.4) 13 (4.4) 156 (6.0) 20 (3.6)
Unknown 229 (3.0) 36 (5.6) 176 (3.0) 17 (1.6)

 

Abbreviations: HCV = hepatitis C virus; MSM = men who have sex with men; HMO = health maintenance organization.

*Categories were not mutually exclusive; more than one response was allowed per patient.

Liver-related symptoms included but were not limited to 1) jaundice/yellowing of the eyes and skin and 2) abdominal pain.

Editorial Note

The Chronic Hepatitis Cohort Study survey data analyzed in this report indicate that most initial HCV tests occurred in a physician's office, and nearly half of those infected with HCV only sought testing after experiencing clinical indications of liver disease. Testing for HCV infection in a location other than a physician's office occurred for about one third of respondents. Other locations included clinics, inpatient settings, and emergency departments. Other studies have shown a greater proportion (50.7%) of testing in locations other than a physician's office or laboratory.[8] The results in this report suggest that, in addition to increasing testing in physicians' offices, other locations might be important for increasing the number of HCV-infected persons who are tested and referred to care.

Less than one fourth of HCV-infected patients gave CDC risk indications as a reason for testing, but many reported various other reasons (e.g., doctor recommendation, "thought I was exposed," and having many sex partners) that were not included in the 1998 CDC recommendations.[2] Other reasons for testing (e.g., multiple sex partners) also have been reported.[8,9] Responses in the study, such as "thought I was exposed" or doctor recommendation, suggest improved patient education could enhance patient's understanding of the risks for HCV infection.

This analysis indicates that approximately four out of five patients in this study of 2006–2010 data were born during 1945–1965, and therefore were within the birth cohort targeted in the 2012 CDC HCV testing guidelines.[5] Only 21.3% of those born during 1945–1965 gave a reason for testing (injection drug use or hemodialysis) that was included in the earlier 1998 CDC risk indications.

CDC is identifying strategies to help health-care providers implement its new HCV testing guidelines, which target all persons born during 1945–1965. These strategies include simplification of HCV testing algorithms in primary care and public health settings, development of national educational strategies for testing those born during 1945–1965, and supporting evidence-based care models that enhance delivery of high-quality HCV assessment and management.[10]

The findings in this report are subject to at least three limitations. First, patients surveyed from the four health sites were not from a nationally representative sample, so these results are not generalizable to the U.S. population of persons with HCV infection. Almost all patients were covered by some form of health insurance, and risk-based behaviors (e.g., injection drug use) were less common in this group than has been observed in surveillance-based studies.[9] Second, only 57.9% of persons contacted completed the survey, which might have resulted in response bias. Finally, the long interval between initial testing and time of interview and the potential for inconsistency between self-reported reasons for testing and a health-care provider's rationale for testing might have resulted in recall bias.

This survey of patients with HCV infection enrolled in the Chronic Hepatitis Cohort Study indicates that nearly four out of five participants were born during 1945–1965, a cohort for whom CDC recommends HCV testing in its 2012 guidelines.[5] Because a substantial proportion of HCV infections were identified after testing for clinical indications and few patients reported the 1998 CDC risk indications as a reason for initial testing, these data further support the CDC recommendation for testing all persons in the birth cohort of 1945–1965 in addition to risk-based testing. Physicians' offices and other locations might be important venues for implementing these guidelines to increase HCV testing.

References

  1. Institute of Medicine. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Washington, DC: The National Academic Press; 2010.

  2. CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No. RR-19).

  3. Spradling PR, Rupp L, Moorman AC, et al. Hepatitis B and C virus infection among 1.2 million persons with access to care: factors associated with testing and infection prevalence. Clin Infect Dis 2012;55:1047–55.

  4. Denniston MM, Klevens RM, McQuillan GM, Jiles RB. Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001–2008. Hepatology 2012;55:1652–61.

  5. CDC. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR 2012;61(No. RR-4).

  6. Moorman AC, Gordon SC, Rupp LB, et al. Baseline characteristics and mortality among people in care for chronic viral hepatitis: the Chronic Hepatitis Cohort Study. Clin Infect Dis 2013;56:40–50.

  7. Moyer VA. Screening for hepatitis C virus infection in adults: US Preventive Services Task Force recommendation statement. Ann Intern Med 2013. Epub. Available at http://annals.org/article.aspx?articleid=1700383.

  8. Tohme RA, Xing J, Liao Y, Holmberg SD. Hepatitis C testing, infection, and linkage to care among racial and ethnic minorities in the United States, 2009–2010. Am J Public Health 2013;103:112–9.

  9. Mahajan R, Liu SJ, Klevens RM, Holmberg SD. Indications for testing among reported cases of HCV infection from enhanced hepatitis surveillance sites in the United States, 2004–2010. Am J Public Health 2013;103:1445–9.

  10. CDC. Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR 2013;62:362–5.

Sidebar

What is Already Known on This Topic?

Since 1998, CDC has recommended testing for viral hepatitis C virus (HCV) infection among persons most likely to be infected. These recommendations have led to significant progress in identifying patients with HCV infection. However, a substantial percentage of patients with HCV infections have not been tested and remain unaware of their infection.

What is Added by This Report?

An analysis of 2006–2010 data from the Chronic Hepatitis Cohort Study indicated that a substantial proportion of HCV-infected patients were tested only after clinical indications that their infection had progressed and became symptomatic. Of the 4,689 patients with HCV infection who responded to the survey, 45.2% reported clinical indications as a reason for testing, with 78.1% born during 1945–1965, the birth cohort recommended by CDC for one-time HCV testing.

What are the Implications for Public Health Practice?

Promoting CDC's risk factor and birth cohort–based recommendations for HCV testing, along with implementing HCV testing in physicians' offices and other venues can allow timely identification of HCV infections and reduce HCV-related morbidity and mortality.

Source

Journal of Gastroenterology and Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Clinical Hepatology

Vincent Wai-Sun Wong1,2, Grace Lai-Hung Wong1,2, Angel Mei-Ling Chim1,2, Tsz-Fai Cheng2, Shirley Wing-Yan Cheung2, Carol Man-Sze Lai2, Kylie Joan-Yi Szeto2, Sharon Tsang2, Stephen Ho-Chun Wu2, Kenneth Kar-Lung Yan3, Alex Yui Hui3, Desmond Chi-Him Yiu3, Brian Bing-Ying Wu3, David Cheung4, Cedric Sze-Lai Chung4, Camey Wai-Man Lai1,2, Henry Lik-Yuen Chan1,2,*

DOI: 10.1111/jgh.12355

This article is protected by copyright. All rights reserved.

Abbreviations:HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IDU, injection drug user; IQR, interquartile range; SD, standard deviation

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jgh.12355

Keywords: Liver cirrhosis; interferons; elasticity; opioid-related disorders; patient compliance

Abstract

Background and Aim

Chronic hepatitis C virus (HCV) infection is one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. It is highly prevalent among injection drug users (IDUs) but is often undiagnosed because they represent an underprivileged group that faces multiple barriers to medical care. Here we report the results of the New Life New Liver Project, which provides targeted HCV screening and education for ex-IDUs in the community.

Methods

Patients were recruited through the social worker networks and referrals by fellow ex-IDUs, and rapid diagnosis was based on point-of-care anti-HCV testing at rehabilitation centers.

Results

From 2009 to 2012, we served 234 subjects. 130 (56%) subjects were anti-HCV positive. The number needed to screen to detect 1 patient with positive anti-HCV was 1.8 (95% confidence interval, 1.6-2.0). However, only 69 (53%) HCV patients attended subsequent follow-up at regional hospitals, and 26 (20%) received antiviral therapy. Patients who attended follow-up were older, had higher education level and more active disease as evidenced by higher alanine aminotransferase, HCV RNA and liver stiffness measurement by transient elastography.

Conclusions

Targeted screening in ex-IDUs is effective in identifying patients with HCV infection in the community. Improvement in the referral system and introduction of interferon-free regimens are needed to increase treatment uptake.

Source

NHS hepatitis C infection warning for women

DA1NGR

Some people do not notice the symptoms of hepatitis C

Wednesday September 11 2013

Women who gave birth or had an obstetric or gynaecological operation at 16 UK hospitals between 1975 and 2003 may have come into contact with a healthcare worker infected with hepatitis C.

While the risk of infection is small, the numbers affected likely to be few and the health consequences may not be particularly noticeable, concerned women should seek help and advice.

It has recently come to light that the healthcare worker transmitted the virus to two patients while working at Caerphilly District Miners Hospital in Wales from 1984 until they stopped working with patients in 2002.

Fewer than 400 women in England have so far been identified as having definitely or possibly had operations conducted by the affected healthcare worker. They will be contacted directly and blood tests can arranged at their GP practice.

What is being done to help women potentially infected?

Local health officials are looking at more than 3,000 former hospital patients’ notes and records from the Caerphilly District Miners Hospital (where the worker was employed for nearly 20 years). Around 200 former hospital patients from two other hospitals in Wales where the healthcare worker practised for a short time are also being contacted.

Those patients identified as exposed or possibly exposed to hepatitis C are being sent individual letters and asked to call a special confidential helpline, inviting them to attend a hospital clinic or, if they have moved away from the area, their GP for a blood test. Treatments for hepatitis C will be offered if necessary.

As it has been almost 30 years since the individual worked in hospitals in England, records of women who may be at risk are in some cases incomplete, for example if the hospital has been renamed or patients have moved around the country.

Who might potentially be at risk from hepatitis C infection?

The person worked in obstetrics and gynaecology at several hospitals around the UK between 1975 and 2003. Potentially, women who gave birth or had obstetric/gynaecological operations at these hospitals may be at a small risk of infection. The hospitals in question are:

  • Grimsby General Hospital (September 3 1975 to March 6 1978) – now Diana, Princess of Wales Hospital
  • Burnley General Hospital (April 5 to 30 1978)
  • Wrexham Maelor Hospital (May 15 to June 27 1978)
  • Bedford Hospital (July 3 to August 6 1978 & November 4 to 19 1978)
  • City General Hospital, Carlisle (August 31 to September 17 1978 and April 12 to May 2 1982) – now Cumberland Infirmary
  • Herts and Essex Hospital (December 4 1978 to January 10 1979)
  • The Mid Ulster Hospital, Magherafelt (January 11 to November 4 1979)
  • All Saints Hospital, Kent (November 5 to 16 1979) – now Medway Maritime Hospital
  • Fife Hospitals (March 25 to July 3 1981)
  • Stepping Hill Hospital, Stockport (July 20 to November 2 1981)
  • Doncaster Gate Hospital, Rotherham (July 23 to August 18 1982) – now Rotherham Hospital
  • Royal Victoria Hospital, Boscombe (September 27 to October 10 1982) – now the Royal Bournemouth and Christchurch NHS Foundation Trust
  • Royal General Hospital, Treliske (February 8 to March 19 1983 & May 9 to June 21 1983) – now the Royal Cornwall Hospital
  • Peterborough District Hospital (November 28 to December 2 1983) – now Peterborough City Hospital
  • East Glamorgan Hospital (May 28 1984 to July 17 1984)
  • Caerphilly District Miners Hospital (May 1984 to July 2003)

What is the risk if you were treated at these hospitals?

Public Health England says that there is only a small chance that a patient might acquire hepatitis C infection through surgical contact with an infected healthcare worker. The risk is very low as this can only occur if the healthcare worker is infectious and leads or assists in an operation or procedure on the patient. However, even in such circumstances transmission is very rare.

What happens if you are infected with hepatitis C?

Around one in 250 adults in England have chronic hepatitis C infection and it does not automatically lead to health problems. Each year 10,000 people are newly infected.

Treatment can help clear hepatitis C in up to 80 per cent of cases, although hepatitis C can have serious complications.

Why was the healthcare worker allowed to work in the NHS while infected with hepatitis C?

Like most people who are infected with hepatitis C, the healthcare worker had no symptoms and was unaware of the infection until after they retired.

As soon as the risk of infection was recognised, and a transmission was confirmed, their occupational history was traced.

What are the symptoms of hepatitis C?

Only around one in four people will have symptoms during the first six months of a hepatitis C infection. The flu-like symptoms can include high temperature and feeling sick. Some may also experience jaundice (yellowing of the eyes and skin).

In around three-quarters of people, the virus persists for many years (chronic hepatitis). Some may not notice symptoms but others will be greatly affected. Signs of chronic hepatitis include feeling tired all the time (with no benefit from sleep), headaches, depression, problems with short-term memory (“brain fog") and itchy skin.

What is being done about the risk of hepatitis C in the NHS?

Since 2007, all new NHS healthcare workers have been tested for hepatitis C.

Healthcare workers also have a professional duty to get tested if they consider themselves at risk of contracting a blood-borne virus.

Links to the headlines

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Microscopic image offers clues to HIV riddle

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The HIV drug Maraviroc grabs hold of a crucial receptor, preventing it from entering cells. (Wu lab, Shanghai Institute of Materia Medica)

By Geoffrey Mohan

September 12, 2013, 3:44 p.m.

Researchers seeking weapons against HIV have solved a molecular riddle about how the pathogen docks with immune system cells to unleash its viral mayhem.

Their computer-generated images of the molecules, which are 185,000 times smaller than the width of a human hair, offer researchers promising avenues for developing a drug that might impede HIV's cellular invasion, according to a study published online Thursday in the journal Science Express.

“We don’t have the whole scenario of what happens when HIV enters a cell, but this is going to be a major jigsaw-puzzle piece,” said Dr. P.J. Klasse, a virologist at Weill Cornell Medical College in New York, who was not part of the research team. “These authors have really accomplished a lot in explaining how the virus chooses between different co-receptors.”

The researchers, based at the Shanghai Institute of Materia Medica and the Scripps Research Institute in La Jolla, Calif., sought to illustrate how proteins on the surface of the virus help it dock with the membrane of a victim's helper T-cells, a kind of white blood cell.

To do so, the immunodeficiency virus takes advantage of cell receptors, which are crucial to thousands of genetic signaling functions in living things from amoebas to animals. These unseen facilitators are largely responsible for how the body pulls off unique and complex tricks such as vision, smell and the firing of neurons. They also are central to inflammatory responses that can be the root of chronic disease.

HIV was known to take advantage of two such helpers in a class known as chemokine receptors. A member of the Shanghai-based team had helped solve the structure of one, CXCR4, while at Scripps, and researchers had developed a drug to impede the second co-receptor, CCR5, that is more commonly used by strains of HIV1. Together, the receptors trigger a process that allows the virus' membrane to fuse with the membrane of human T-helper lymphocytes and other vulnerable cells.

The Shanghai team used a crystallized form of the CCR5 receptor, bound to the blocking drug Maraviroc, to determine the receptor's structure. That enabled them to compare it with the structure of the other receptor to discern subtle differences.

“Our previous success … helped us to better understand the protein behavior of the more challenging CCR5 receptor,” lead researcher Beili Wu said in written remarks.

The images published Thursday reveal subtle differences in the “binding pockets” of the receptors. They also offer details about how Maraviroc (marketed as Selzentry) alters the shape of the receptor, indirectly blocking HIV’s invasion. The breakthrough could offer ways to improve the drug's effect or develop new pathways to defeating the virus.

“If you could unleash the trigger of the virus before it reaches the cell, you would for all practical purposes irreversibly inactivate, or to use more drastic language, kill the virus,” Klasse said.

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HIV Patients With Cancer Pose Tx Challenge

Published: Sep 12, 2013 | Updated: Sep 13, 2013

By Michael Smith, North American Correspondent, MedPage Today

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

  • This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Note that this single-center, retrospective study demonstrated better outcomes when HIV patients with cancer were treated with raltegravir compared with protease inhibitors.
  • Be aware that, in the absence of a randomized trial, it remains unclear what the preferred regimen in HIV patients with cancer may be.

DENVER -- HIV patients with cancer should avoid antiretroviral therapy based on protease inhibitors (PIs) if possible, a researcher said here.

In a retrospective analysis, patients on a PI-based regimen had more side effects and were less likely to maintain anti-HIV efficacy 6 months after diagnosis, according to Harrys Torres, MD, of the MD Anderson Cancer Center in Houston.

On the other hand, patients taking a regimen based on either an integrase inhibitor (INSTI) or and non-nucleoside reverse transcriptase inhibitor (NNRTI) had fewer adverse events and better efficacy, Torres reported here at the annual Interscience Conference on Anti-Microbial Agents and Chemotherapy.

The issue is important, Torres said, because non-AIDS defining malignancies have been an increasing issue among HIV patients and now account for about 33% of all HIV-related deaths. Despite that, he said, there is little evidence pointing to the best HIV regimen for such patients.

To help clarify the issue, he and colleagues looked at the safety and efficacy of various HIV regimens among men who were treated for both cancer and HIV at MD Anderson over a 12-year period.

HIV regimens, in general, consist of a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs) along with a PI, an NNRTI, or an INSTI. During the study, the only INSTI available was raltegravir (Isentress) but others are now on the market.

Of the 154 patients, 80% were male, 51% were white, and 58% had hematologic malignancies, including 42% with non-Hodgkin's lymphoma.

For this analysis, the researchers defined efficacy at 6 months as the absence of virologic failure or virologic rebound.

The NRTI backbone was combined with PIs for 37% of the patients, with NNRTIs for 32%, and with raltegravir for 19%, Torres reported. (The remaining 11% had other combinations, such as one drug from each class.)

Analysis showed that:

  • Side effects occurred in 35% of the patients getting a PI, in 14% of those getting NNRTIs, and 3% of those getting raltegravir, a trend that was significant (P=0.001).
  • The 6-month efficacy rates of raltegravir and NNRTI-based regimens were comparable at 96% and 97%, respectively.
  • The 6-month efficacy of PI-based regimens was 65%, significantly less than either of the other main regimens types ( P=0.005 and P=0.001).
  • Interruption of HIV therapy treatment was less common in patients receiving raltegravir than in those receiving PIs or NNRTIs -- 7%, 28%, and 26%, respectively.

The message of the study is that raltegravir is a safe choice for doctors who might not be completely familiar with all of the possible drug-drug interactions, commented Jean-Michel Molina, MD, of Saint-Louis Hospital in Paris, who was not involved with the research but who moderated a session at which it was presented.

In the complicated universe of drugs for cancer and drugs for HIV, most physicians are likely to be familiar with one area or the other, but not both, Molina told MedPage Today.

Picking the safest HIV drugs means choosing those least likely to increase the toxicity of chemotherapy, he said. In general, the HIV drugs will continue to be effective as long as they are taken, but if chemo toxicity is high -- causing nausea and vomiting, for instance -- it might interfere with patient adherence.

The reason PIs perform worse, Molina noted, is that they inhibit liver cytochromes, which can increase the toxicity of some cancer medications, so one option is to switch HIV regimens, perhaps to one based on raltegravir.

But if a patient is unwilling or unable to change, he said, another option might be to stop HIV therapy 24 hours before and after the administration of chemotherapy.

The study had support from Merck. Torres reported financial links with Merck, Vertex, Novartis, Astellas, and Pfizer.

Molina reported financial links with Janssen, ViiV Healthcare, Gilead Sciences, Bristol-Myers Squibb, and Merck, Sharp & Dohme.

Primary source: Interscience Conference on Anti-Microbial Agents and Chemotherapy
Source reference: Torres HA, et al "Efficacy and safety of antiretrovirals in hiv-infected patients with cancer" ICAAC 2013; Abstract H-1255.

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Effects of Hepatitis B Vaccination

September 12, 2013

Richard T. Ellison III, MD reviewing Chiang C-J et al. JAMA 2013 Sep 4. Richard T. Ellison III, MD

Data from Taiwan show marked reduction in deaths from chronic liver disease and hepatocellular carcinoma following the launch of a nationwide HBV vaccination program for newborns in 1984. Richard T. Ellison III, MD

Because of the clear association between chronic hepatitis B virus (HBV) infection and the development of both chronic liver disease (CLD) and hepatocellular carcinoma (HCC), Taiwan began a nationwide HBV immunization program. Previous studies have shown that this program — launched in July 1984 for newborn infants at high risk for infection and extended progressively thereafter to cover all infants, preschool children, and primary school children — has reduced the incidence of HCC, the prevalence of chronic HBV carriage, and mortality from infant fulminant hepatitis (IFH) in vaccinated birth cohorts. With the program at its 30-year anniversary, researchers used national mortality and cancer registry data to assess its effects on mortality from IFH, CLD, and HCC.

The sex-adjusted mortality rate for IFH declined for children born between 1981 and 2011; for birth years 2009–2011, it was 97% lower than for birth years 1977–1980 (a baseline period before program launch). Similar declines in CLD and HCC mortality were seen for individuals born between 1981 and 2004 (the last birth year analyzed). CLD mortality was 89% lower, and HCC mortality was 92% lower, for the 2001–2004 birth cohort than for the 1997–1980 group. Protection against death from CLD (35% reduction) and HCC (30% reduction) was also noted for the children born between 1981 and 1984, who were immunized at preschool ages rather than during early infancy.

Comment

These results confirm a striking benefit from the nationwide hepatitis B virus immunization program. The steady decline in deaths from chronic liver disease and hepatocellular carcinoma suggests a herd immunity effect, with progressively fewer parents having HBV infection that could be transmitted to their children.

Citation(s):

Chiang C-J et al. Thirty-year outcomes of the national hepatitis B immunization program in Taiwan. JAMA 2013 Sep 4; 310:974. (http://dx.doi.org/10.1001/jama.2013.276701)

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