Better tests for liver toxicity would mean more medicines -- and safer medicines -- for patients

Public release date: 8-Sep-2013

Contact: Michael Bernstein
m_bernstein@acs.org
317-262-5907 (Indianapolis Press Center, Sept. 6-11)
202-872-6042

Michael Woods
m_woods@acs.org
317-262-5907 (Indianapolis Press Center, Sept. 6-11)
202-872-6293

American Chemical Society

INDIANAPOLIS, Sept. 8, 2013 — How many breakthrough new drugs never reach patients because tests in clinical trials suggested a high risk of liver damage when the drug actually was quite safe?

That question underpins major international research efforts to modernize tests for drug-induced liver injury, mentioned here today at the 246th National Meeting & Exposition of the American Chemical Society (ACS), the world's largest scientific society. The meeting, which features almost 7,000 reports on new discoveries in science and other topics, continues through Thursday in the Indiana Convention Center and downtown hotels.

Paul B. Watkins, M.D., who made the presentation, explained that drug-induced liver damage is a rare drug side effect, but so serious — the No. 1 cause of sudden liver failure — that it has a disproportionate impact on a drug's fate. Liver toxicity is also the No. 1 safety concern causing pharmaceutical companies to halt development of new medicines — sometimes after spending hundreds of millions of dollars on clinical trials to establish the drug's safety and effectiveness. Likewise, it is the leading reason why drugs already on the market must be restricted or banned.

"Blood tests used today in clinical trials for assessing liver safety are the same ones we've used for at least 40 years," said Watkins, referring to tests that measure substances released into the blood when liver cells die. "The tests do indicate damage to liver cells, and everyone assumed over the years that a positive result raised a red flag about a drug's safety. We now know, however, you can have abnormalities in these tests — even pretty remarkable ones — with drugs that pose no serious threat of damaging the liver."

Watkins described research, done with colleagues at the Hamner-University of North Carolina Institute for Drug Safety Sciences, in which healthy volunteers took prescription and non-prescription medicines that have been in use for decades and have an established safety record. The volunteers then got the standard blood tests for liver damage. Those tests measure levels of two enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are released into the blood when liver cells die. The results showed alarmingly high AST/ALT levels, which the scientists first thought were false-positive results, meaning that liver cells weren't really dying. Follow-up tests, however, verified that liver cells were dying.

Those experiments led to a realization that drugs can cause liver cells to die, produce elevated AST/ALT levels in patients, but not cause the kind of permanent liver damage that can mean a liver transplant or death. In most cases, the liver recovers and adjusts, and patients actually can continue taking the medication without risking permanent damage, Watkins explained.

In other patients, Watkins suspects, the immune system goes into overdrive in response to the initial damage and mistakenly begins to attack and kill liver cells. If that's the case, a test that accurately predicts the risk of permanent liver damage would detect the proteins and genes associated with activation of the immune system.

Watkins' group and other research teams in the Drug-Induced Liver Injury Network (DILIN), which he leads, are now on the hunt to find markers that could be better indicators of liver safety. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) established DILIN to collect and analyze cases of severe liver injury caused by prescription drugs, over-the-counter drugs and alternative medicines, such as herbal products and supplements.

DILIN is among major international efforts to develop better tests for predicting serious side effects of medicines. The European Union, for instance, is seeking better tests for liver, kidney and heart damage with its SAFE-T consortium. And the Predictive Safety Testing Consortium (PSTC) helps drug companies come together to validate safety testing methods. The U.S. Food and Drug Administration and its European and Japanese counterparts — the European Medicines Agency and the Japanese Pharmaceutical and Medical Devices Agency — advise the PSTC.

Better tests would help save some drugs from being abandoned during development and might mean new life for medicines dropped on the basis of AST/ALT tests during the last 40 years, Watkins said. Dozens or more such drugs could find a new life in medicine, he said.

Improved liver toxicity tests may be a long way off. Watkins explained that development of such tests is just the first step. Then the tests must be validated on thousands of blood samples from patients with different diseases taking different drugs. Watkins is currently working to set up a liver safety consortium to get drug companies to work together and collect these samples to evaluate new tests.

###

A press conference on this topic will be held Sunday, Sept. 8, at 11 a.m., in the ACS Press Center, Room 211, in the Indiana Convention Center. Reporters can attend in person or access live audio and video of the event and ask questions at http://www.ustream.tv/channel/acslive.

Watkins acknowledged funding from the National Institute of Diabetes and Digestive and Kidney Diseases, which is part of the National Institutes of Health.

The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With more than 163,000 members, ACS is the world's largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

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Abstract

Biomarkers for the diagnosis and management of drug-induced liver injury

Genome-wide association studies (GWAS) have linked specific HLA alleles to the risk for developing DILI due to several drugs. These insights have not yet led to personalized medicine approaches to risk management of DILI because the associations lack specificity. That is, although prospective genetic testing would identify most patients susceptible to DILI, it would deny treatment to many more patients who could be safely be treated with the drug. For this and other reasons, there is intense interest in developing non-genetic biomarkers that could be useful in DILI risk management. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been used for over 40 years to monitor the liver safety of drugs and are sensitive measures of liver injury. However, there are drugs that, when administered at recommended doses, are quite safe for the liver yet cause marked elevations in serum ALT and AST. We have been exploring whether current mechanistic biomarkers can distinguish benign enzyme elevations from those that may lead to clinically important liver injury. We have analyzed serial serum samples obtained from cohorts of healthy adult volunteers treated with different therapeutic drug regimens that can cause marked elevations in serum ALT and AST but have low or no risk for serious hepatotoxicity (acetaminophen, various heparins, and cholestyramine). We and our collaborators have employed a variety of techniques, including transcriptomics, metabolomics and proteomics to identify biomarkers that may provide insight into the mechanisms underlying these benign and self-limited laboratory abnormalities. These studies indicate that recurrent therapeutic doses of acetaminophen, heparins and cholestyramine cause hepatocyte death, but the mechanisms involved in cell death differ between these treatments. The reason why these treatments are safe for the liver remains unclear but several theories will be discussed.

Source

A Significant Share of Surveyed Treatment-Naive and Prior Failure HCV Patients Plan to Initiate an HCV Treatment Regimen in the Next Year

However, Patient Awareness of Products in Development is Low, According to a New Report from BioTrends Research Group

EXTON, Pa., Sept. 9, 2013 /PRNewswire/ -- BioTrends Research Group, one of the world's leading research and advisory firms for specialized biopharmaceutical issues, finds in their PatientTrends®: Hepatitis C Virus (US) 2013 report that approximately 40 percent of surveyed treatment-naive hepatitis C virus (HCV) patients and half of the prior treatment failure patients plan to receive an HCV antiviral regimen within the next year. However, the majority of these respondents did not know which regimen they will be initiating and only 9 and 14 percent, respectively, indicated they are planning to receive a treatment other than a currently-available regimen. Further, almost 40 percent of surveyed HCV patients also reported that their physician has previously recommended delaying treatment until new regimens become available and findings suggest that many patients are willing wait for safer and more effective regimens, especially if their liver disease is not advanced. The study also finds that awareness of therapies in development among HCV patients is low. Despite over two-thirds of the respondents indicating discussing products in development with their physician, more than three-quarters of the patients lacked unaided awareness of any emerging HCV products.

(Logo: http://photos.prnewswire.com/prnh/20130103/MM36805LOGO )

"While most treatment-naive and prior treatment failure HCV patients who do not plan to be treated in the next year cite the future availability of better therapies as a reason, many of these patients specifically indicated waiting for interferon-free regimens to become available," said Infectious Diseases Therapy Leader Mladen Tomich, Ph.D. "However, patients overall prioritized effects on liver damage progression and reversal, and achieving sustained virologic response as the most important attributes in an HCV regimen, while exclusion of interferon or ribavirin was perceived as least important. Our research reveals that most HCV patients are prepared to endure a certain level of temporary disability as long as the treatment is efficacious."

Of note, surveyed treatment-naive HCV patients overall believe they have more influence on the management and treatment of their infection than their treating physicians. Also, the level of perceived personal influence over treatment decisions is significantly higher among surveyed treatment-naive patients than among treatment-experienced patients.

PatientTrends®: Hepatitis C Virus (US) 2013 is an annual report that includes data from 245 chronically-infected HCV patients and provides insight into patient demographics, patient-physician relationship, treatment history and plans to initiate treatment. The report also investigates the importance of drug attributes to patients, satisfaction with currently-available HCV therapies and awareness of emerging therapies, including AbbVie's ABT-267, ABT-333 and ABT-450, Boehringer Ingelheim's deleobuvir and faldaprevir, Bristol-Myers Squibb's asunaprevir and daclatasvir, Janssen/Medivir's simeprevir and Gilead's sofosbuvir and ledipasvir.

About BioTrends Research Group
BioTrends Research Group provides syndicated and custom primary market research to pharmaceutical manufacturers competing in clinically evolving, specialty pharmaceutical markets. For information on BioTrends publications and research capabilities, please visit www.bio-trends.com. BioTrends is a Decision Resources Group company.

About Decision Resources Group
Decision Resources Group is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources Group at www.DecisionResourcesGroup.com.

All company, brand, or product names contained in this document may be trademarks of their respective holders.

For more information, contact:

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Christopher Comfort
781-993-2597
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Source

Long-term benefit of hepatitis C therapy in a safety net hospital system: a cross-sectional study with median 5-year follow-up

BMJ Open 2013;3:e003231 doi:10.1136/bmjopen-2013-003231

Infectious diseases

Amit G Singal1,2, Tushar D Dharia1, Peter F Malet1, Saleh Alqahtani1, Song Zhang2, Jennifer A Cuthbert1

+ Author Affiliations

Correspondence to: Dr Jennifer A Cuthbert; jennifer.cuthbert@utsouthwestern.edu

Received 15 May 2013 , Revised 16 July 2013,  Accepted 19 July 2013, Published 2 September 2013

Abstract

Objectives To demonstrate the survival benefit from sustained virological response (SVR) in a safety net hospital population with limited resources for hepatitis C virus (HCV) therapy.

Design and setting We conducted a retrospective study at an urban safety net hospital in the USA.

Participants and intervention 242 patients receiving standard HCV therapy between 2001 and 2006.

Primary and secondary outcome measures Response rates, including SVR, were recorded for each patient. Univariate and multivariate analyses were performed to identify predictors of SVR and 5-year survival.

Results A total of 242 eligible patients were treated. Treatment was completed in 197 (81%) patients, with 43 patients discontinuing therapy early—32 due to adverse events and 11 due to non-compliance. Complications on treatment were frequent, including three deaths. SVR was achieved in 83 patients (34%). On multivariate analysis, independent predictors of a decreased likelihood of achieving SVR included African–American race (OR 0.20, 95% CI 0.07 to 0.54), genotype 1 HCV infection (OR 0.25, 95% CI 0.13 to 0.50) and the presence of cirrhosis (OR 0.26, 95% CI 0.12 to 0.58). Survival was 98% in those achieving SVR (median follow-up 72 months) and 71% in non-responders and those discontinuing therapy (n=91, median known follow-up 65 and 36 months, respectively). On multivariate analysis, the only independent predictor of improved survival was SVR (HR 0.12, 95% CI 0.03 to 0.52). Both cirrhosis and hypoalbuminaemia were independent predictors of increased mortality.

Conclusions Treatment before histological cirrhosis develops, in combination with careful selection, may improve long-term outcomes without compromising other healthcare endeavours in safety net hospitals and areas with financial limitations.

Article summary

Article focus

• Chronic hepatitis C is common in urban populations with limited financial resources.
• Individual patient characteristics can limit success.

Key messages

• Selection process identifies candidates with greater likelihood of better compliance.
• Survival benefit from successful treatment can be achieved with less expensive, older therapies.

Strengths and limitations of this study

• Clear demonstration of long-term survival benefit in a high-risk population.
• Single institution retrospective study.

Introduction

For many years, standard of care for patients with chronic hepatitis C virus (HCV) included treatment with pegylated interferon and ribavirin1 based on evidence from randomised controlled trials (RCTs).2–4 Conditions in RCTs are often very different than those of clinical practice. Given this potential discrepancy between an intervention's efficacy (the effect under carefully controlled conditions) and effectiveness (the effect when implemented in real-world settings), there is increasing emphasis on comparative effectiveness research to improve delivery of care.5 ,6 Accordingly, the National Institute of Health recently included the evaluation of real-world outcomes of healthcare interventions in liver disease as a priority area for future research.

Prior studies evaluating HCV therapy have primarily included well-insured, Caucasian patients followed in academic centres. However, HCV therapy is less well described among the underinsured, urban, minority patients. Some have concluded that current HCV therapy may be ineffective for these patients, warranting new strategies.7 However, we hypothesised that improved HCV outcomes are possible among this difficult-to-treat population with the aid of careful patient selection.

Screening for infection in the birth cohort with the highest prevalence of chronic HCV infection, that is, those born between 1945 and 1965, was controversial. While the Centers for Disease Control and Prevention have made a strong recommendation for this approach,8 the USA Public Service Task Force (USPSTF) was initially less enthusiastic (Grade C).9 However, USPSTF now supports screening in those at high risk (Grade B), previously considered optional, and also birth cohort screening.10 The primary aim of our study was to report the long-term benefit of HCV therapy in an American urban population with a high proportion of difficult-to-treat patients who were followed in a safety net hospital.

Methods

Study population

We conducted a chart review of all patients initiated on HCV treatment between November 2001 and October 2006. Eligible patients were seen in the faculty attending supervised Liver Clinic at Parkland Health and Hospital System (PHHS). Clinic patients were evaluated initially by a member of the clinic nursing staff followed by Gastroenterology trainees and/or Internal Medicine residents, under the supervision of Hepatology faculty members (n=6). After patients had fulfilled a list of basic requirements (figure 1), the final decision to initiate treatment for any individual patient was made by the supervising attending physician based on his/her assessment of the patient's candidacy

Figure 1 Screening algorithm.

Once the treatment decision was made, demographics for all patients were entered into an electronic file maintained by the clinic nursing staff. The electronic file was used for this retrospective medical record review. The clinic nursing staff also saw all patients to provide instructions on medications as well as on interim follow-up visits and offered telephone advice. Patients were regularly seen in the Liver Clinic while on treatment and followed until sustained virological response (SVR) or discontinuation, at which time they returned to primary care or remained in the Liver Clinic, depending on the complications of liver disease experienced. Long-term follow-up was accomplished using the Social Security Death Index (prior to the regulatory 10-year embargo on information and removal of records from the State of Texas) and the combined electronic medical records of PHHS and the University Hospitals of UT Southwestern.

Treatment regimen

On the basis of consensus guidelines, patients were treated with weekly pegylated interferon α-2b 1.5 µg/kg and daily ribavirin 800–1200 mg. A combination of growth factors and dose reductions were used for patients with haemoglobin <10 g/dL, granulocyte count <500/µL or platelet counts <50 000/µL according to a standard protocol. The intended duration of therapy for genotypes 1, 4 and 6 was 48 weeks, and the intended duration of therapy for genotypes 2 and 3 was 24 weeks. All patients were scheduled to be seen at regular intervals during treatment, as deemed necessary based on treatment tolerance, and were followed for an additional 24 weeks after completion of therapy to determine the presence or absence of SVR.

Data collection

The patient demographics, clinical history, laboratory data and imaging results were obtained through review of computerised and paper medical records. Demographics, date of HCV therapy initiation, medication starting doses, medication dose reductions, use of growth factors, date of treatment discontinuation and response rates while on therapy were documented. Response rates included early virological response, end-of-treatment response and/or SVR rates. We also recorded complication rates, including any hospitalisations and/or deaths. Laboratory data recorded included HCV genotype, baseline HCV viral load, white cell count, haemoglobin, platelet count, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, international normalised ratio and α fetoprotein. Imaging and liver biopsy data were reviewed to determine the presence or absence of cirrhosis. The presence of cirrhosis was based on histology or imaging showing a cirrhotic appearing liver with associated signs of portal hypertension including splenomegaly, varices or thrombocytopenia. Date of death for patients was ascertained using the PHHS electronic medical record and Social Security Death Files.

Statistical analysis

For continuous variables, we summarised the data by mean and SD, and compared groups using a two-sample Student's t test. For categorical variables, we computed percentages and compared groups using Fisher's exact test. We used a multivariate logistic regression model, with stepwise variable selection, to determine predictors for SVR. Statistical significance was defined as a p value <0.05 on univariate and multivariate analyses. All analyses were performed using SAS V.9.2 (SAS Institute, Cary, North Carolina, USA).

Results

Eligibility for therapy

The study participants comprised all patients in the Liver Clinic meeting selection criteria and undergoing antiviral treatment for chronic HCV infection between November 2001 and October 2006. Every patient with chronic HCV being followed in the Liver Clinic or newly referred by a primary care provider was considered for treatment once pegylated interferon was approved by the Pharmacy and Therapeutics Committee in 2001. Between 2001 and 2006, 1966 patients accounted for 2370 new referrals; of these 126 received at least one dose of pegylated interferon and ribavirin. The remaining patients never became eligible or were deemed unsuitable. In an electronic look-back over new patient referrals from a 2-year period (2004 and 2005, n=989), 366 referrals (37%) were for patients ineligible for clinic appointments at that time (see algorithm, figure 1). Clinic appointments were offered to 597 individuals (623 referrals), of whom 389 attended the clinic at least once (ie, 35% did not keep the clinic appointment). A total of 57 individuals were started on treatment (15% of those keeping at least one appointment).

Common reasons for initial exclusion after electronic medical record review, that followed referral from a primary care provider, included severe thrombocytopenia (defined as platelet count <50 000/µL), uncontrolled diabetes (defined as HbA1C>9%), uncontrolled depression and positive urine toxicology screen (figure 1). Reasons for not initiating patients on therapy after physician evaluation in the clinic included comorbid conditions (autoimmune disease, heart disease, lung disease and psychiatric disease), continued alcohol consumption, early-stage histology and/or socioeconomic barriers that would prevent regular follow-up during treatment.

Patient characteristics

Demographic and clinical characteristics of the study population are shown in table 1 and the online supplemental table. The study participants included 166 (68%) patients with genotype 1 infection, 64 (27%) with genotype 2 or 3 and 12 (5%) patients with other genotypes. The median age of the patients was 48 years (range 20–68 years), 72% were in the birth cohort 1945–1965 and 51% (n=123) were men. The patients were racially and ethnically diverse with 31% African-American, 14% Hispanic and 47% non-Hispanic white. Common comorbid conditions included depression or other psychiatric disease (74 patients, 31%), hypertension (68 patients, 28%) and diabetes mellitus (40 patients, 17%). Comorbid conditions potentially associated with decreased response rates included morbid obesity (body mass index (BMI)>40; 22 patients, 9%) and HIV (7 patients, 3%). Cirrhosis was present histologically in 31%, 36 patients biopsied before treatment initiation and another 40 patients by clinical criteria.

Newly referred patients (n=126 patients, with 164 separate referrals) were largely similar to patients entering the clinic through other processes (see online supplemental table). The latter group included patients seen in the clinic while meeting selection criteria, being followed awaiting formulary approval and those referred after an inpatient hospitalisation. The significant differences were the higher prevalence of diabetes (p=0.003) and the higher viral load (p=0.02) in the newly referred patients. The referral patient population had trends towards more African-Americans, higher BMI and fewer deaths in follow-up.

Treatment response

Therapy was completed in 197 (81%) patients, with 43 patients discontinuing treatment prematurely (figure 2). Therapy was discontinued for adverse events in 32 patients including three deaths and another 11 patients were non-compliant with the follow-up appointments. There was a trend towards higher treatment discontinuation rates for genotype 1 than genotype 2/3 patients but this did not reach statistical significance (p=0.16). Of the seven patients with HIV (6 Caucasian and genotype 1, 1 Hispanic and genotype 3), four discontinued therapy after side effects, none achieved SVR.

Figure 2 Results of patient evaluation and treatment. RNA negative=hepatitis C virus RNA negative at last measurement, on treatment (n=19) or less than 6 months off-treatment (n=6).

Overall, SVR was achieved in 83 (34%) patients, including 39 (24%) of those with genotype 1 and 39 (61%) with genotype 2/3 infection (p<0.001). There was no significant difference in rates of SVR between patients newly referred to the clinic (46/126, 37%) and patients in the clinic awaiting formulary approval or referred after an inpatient hospitalisation (36/116, 32%). Of note, 10 of 22 patients with morbid obesity (BMI range 41–50) were treated successfully; seven had genotype 1 infection, two of whom were African-American women.

SVR was obtained in only 11% of African-American patients, compared with 44% of non-Hispanic whites (p<0.001) and 38% of Hispanic patients (p=0.001). This difference in SVR rates was primarily seen among those with genotype 1 infection. SVR was achieved in only 7% of African-Americans with genotype 1 infection, compared with 40% of non-Hispanic whites (p<0.001) and 24% Hispanics (p=0.03). SVR rates did not significantly differ by race/ethnicity among patients with genotype 2/3 infection. African-Americans with genotype 2/3 infection had SVR in 60% of cases, compared with 55% of non-Hispanic whites (p=0.82) and 78% Hispanics (p=0.48).

Cirrhosis was associated with significantly lower rates of SVR, only 10 (13%) cirrhotic patients achieved SVR. Among genotype 1 patients, SVR was achieved in 34 (31%) of 108 patients without cirrhosis compared with only 5 (9%) of 57 patient with cirrhosis. Similarly, SVR rates were significantly higher among non-cirrhotic genotype 2/3 patients than those with cirrhosis (70% vs 35%, p=0.01).

In small numbers of patients (n=14), having three or more comorbid conditions reduced the likelihood of achieving SVR (3/14, 21%). Patients with diabetes were less likely to respond favourably (7/40, 18% SVR) as were those with hypertension (15/68, 22% SVR). Psychiatric disease (depression or schizophrenia) did not affect SVR rates (26/66, 39%).

Negative predictors of SVR on univariate analysis included HCV genotype 1 infection (p<0.001), African-American race (p<0.001), presence of cirrhosis (p=0.001), thrombocytopenia (p=0.005) and diabetes (p=0.02). Neither Hispanic ethnicity nor anaemia (Hb <12 g/dL) was a significant predictor of response. On multivariate analysis (table 2), independent predictors of failure to achieve SVR included African–American race (OR 0.20, 95% CI 0.07 to 0.54), genotype 1 HCV infection (OR 0.25, 95% CI 0.13 to 0.50) and the presence of cirrhosis (OR 0.26, 95% CI 0.12 to 0.58). These three factors were highly predictive of failure to achieve SVR, with a c-statistic of 0.77 (data not shown).

From long-term follow-up after the start of treatment, we found that a total of 43 (18%) patients died, including 34 (20%) with genotype 1 infection and 9 (14%) with genotype 2/3. Survival was significantly more likely among patients who achieved SVR than non-responders (98% vs 71%, p<0.001) and those who discontinued therapy (98% vs 71%, p<0.001). Of the patients with cirrhosis achieving SVR, 90% (9/10) were presumed or known to be alive at least 5 years later. In contrast, 28 of the 43 patients known to have died had cirrhosis at the time of treatment (65%). Both diabetes and hypertension were associated with an increased risk of dying. Complete follow-up and survival analysis are shown in figure 3 and table 3. On multivariate analysis, cirrhosis and hypoalbuminaemia independently increased mortality, whereas SVR decreased mortality.

Figure 3 Kaplan-Meier survival plot.

Adverse effects

As summarised above, 43 (18%) patients discontinued treatment prior to completion including 32 patients for adverse events. Of the patients discontinued for adverse events, 26 required hospitalisation. The most common reasons for hospitalisation included infection (n=13), severe cytopenias (n=4), volume depletion (n=3) and chest pain (n=2). There were two patients whose therapy was discontinued after they developed hepatocellular carcinoma. Three (1%) patients died during therapy. One patient, whose course was complicated by depression and another, whose course was complicated by infection (pneumonia and tooth abscess), died out of the hospital from unknown causes. The third patient had gastrointestinal bleeding in the setting of non-steroidal anti-inflammatory drug use and died after developing streptococcal bacteraemia and acute renal failure.

Discussion

While we found that SVR was achieved in only one-third of treated patients, the lower rates among African-American patients and those with underlying cirrhosis explain most of the difference. In addition, patients in safety net hospitals have multiple barriers to therapy initiation, with only a small minority being treatment eligible by the selection criteria used. In our cohort, less than 10% of patients referred for HCV were initiated on treatment. Finally, HCV therapy has potentially severe adverse effects and careful patient selection is crucial. Our study, therefore, highlights several concepts applicable to current-day HCV practice despite the approval of telaprevir and boceprevir for patients with genotype 1 infection.11 ,12 In addition, our findings support early screening and detection of chronic HCV so that therapy can be started before progression to cirrhosis.

HCV infection is particularly common among patients followed in safety net hospitals where resources are limited, making this an important population to study.13 ,14 Patients followed in safety net hospitals tend to be quite different from most clinical trial patients. Safety net hospitals have higher proportions of racial/ethnic minority patients, as well as higher rates of comorbid illnesses and socioeconomic barriers to care.15 Compared with a representative RCT of HCV treatment,2 our population was older, more obese, had a higher proportion of African-Americans and more advanced liver disease at presentation. In a prior study from a safety net hospital in New York City, only 14% of genotype 1 patients achieved SVR, with significantly lower rates among minority patients.7 Our ability to achieve higher SVR rates than that reported by Feuerstadt and colleagues may be related to differences in treatment eligibility. Although both protocols selected for suitable medical candidates, our protocol also selected more compliant patients. Whereas nearly 26% of patients in the study by Feuerstadt and colleagues were non-compliant with clinic visits, this led to therapy discontinuation in only 5% of patients in our study (p<0.001). The importance of adherence cannot be underestimated, with both early and SVRs being dependent on this single factor.16 Compliance will continue to be important in future therapy until regimens are simple and consist of long half-life oral medications with minimal side effects.

Our study has several limitations. It was performed in a single large safety net hospital and may not be generalisable to other practice settings. Not all patients underwent liver biopsy prior to HCV treatment so the presence or absence of cirrhosis was also determined by imaging, which may not be as accurate. However, we believe that the limitations of this study are outweighed by its notable strengths including the size of our cohort, the unique patient population and the length of follow-up.

In conclusion, our study highlights several important lessons to remember even when using new protease inhibitor therapy. Multiple challenges, including socioeconomic barriers precluding compliance and comorbid illnesses, make only a small minority of patients followed in safety net hospitals eligible for HCV therapy. SVR occurs in only one-third of patients, with even lower rates among minority patients and those with underlying cirrhosis. Both early detection and careful patient selection remains crucial, given that severe adverse effects are seen in nearly 15% of patients. Data from long-term benefit studies, such as ours, as well as real-world effectiveness should be taken into account more than efficacy data from clinical trials, when weighing the risks and benefits of screening for chronic HCV and starting HCV therapy among patients followed in safety net hospitals in clinical practice.17

Footnotes

AGS and TDD equal first authors.

Contributors AGS participated in analysis and interpretation of the data; drafting of the manuscript; critical revision of the manuscript for important intellectual content. TDD and JAC participated in study design; acquisition of the data; review of clinical records; analysis and interpretation of the data; drafting of the manuscript; critical revision of the manuscript for important intellectual content. PFM participated in study design; critical revision of the manuscript for important intellectual content. SA participated in critical revision of the manuscript for important intellectual content. SZ participated in analysis and interpretation of the data; critical revision of the manuscript for important intellectual content.

Funding This project was supported in part by grants KL2 RR024983-04 and the ACG Junior Faculty Development Award.

Competing interests None.

Ethics approval University of Texas Southwestern Medical Center Institutional Review Board.

Provenance and peer review Not commissioned; externally peer reviewed.

Data sharing statement Extra data can be accessed via the Dryad data repository at http://datadryad.org/ with the doi:10.5061/dryad.qc57j.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

References

Source

Fatty Liver Disease: More Prevalent in Children

Cleveland Clinic

The Cleveland Clinic's Pediatric Preventive Cardiology and Metabolic Clinic treats and studies nonalcoholic steatohepatitis (NASH).

IN THE LAB Updated September 9, 2013, 7:27 p.m. ET

A type of liver disease once thought to afflict primarily adult alcoholics appears to be rampant in children.

Some 1 in 10 children in the U.S., or more than 7 million, are thought to have the disease, according to recent studies.

The condition, in which the normally rust-colored organ becomes bloated and discolored by yellowish fat cells, has become so common in non-drinkers that it has been dubbed nonalcoholic fatty liver disease.

The disease's prevalence is alarming doctors who worry about its progression to nonalcoholic steatohepatitis, or NASH, when the fatty liver becomes inflamed and cells are damaged. That leads to the end stage of cirrhosis, when the liver forms scar tissue and ultimately stops working.

The condition's rise is tied to the obesity epidemic—about 40% of obese children have it—but isn't caused solely by being overweight. The disease appears to be growing among normal-weight children too, experts say.

And even though obesity rates are starting to level off, the prevalence of fatty liver disease continues to rise, they say.

It also has no symptoms, which means a person could have it for decades without knowing.

"The disease is very silent," said Naim Alkhouri, director of the Pediatric Preventive Cardiology and Metabolic Clinic at the Cleveland Clinic.

Because fatty liver disease has been recognized only fairly recently in children, it's unclear how the disease progresses into adulthood. Roughly 10% of people with fatty liver disease will develop NASH; another 15% to 20% of those will get cirrhosis. While the early stages of fatty liver disease and NASH are reversible, cirrhosis is not.

"This is just really worrisome to have this number of children who have a disease this severe," said Miriam Vos, a pediatrics professor at Emory University School of Medicine who studies and treats kids with fatty liver disease.

In a study published this year, Dr. Vos and her colleagues looked at data from a national health study for elevated liver enzymes, a sign of fatty liver disease. The percentage of children in the sample suspected of having the disease grew to 10.7% between 2007 and 2010, from about 4% between 1988 and 1994.

In the last decade, more scientists have started studying fatty liver disease and NASH, trying to figure out who gets them and why. Last week, the U.S. Food and Drug Administration held a two-day meeting to discuss with industry and other stakeholders the best way to study new treatments and speed up clinical trials.

NASH, the inflamed fatty liver condition, is currently the third-most-common reason for liver transplants, behind alcoholism and hepatitis C. Experts expect it will eclipse the other two by 2030. The liver helps digest food, absorb nutrients and expel toxins from the body.

It's likely there are multiple factors that worsen fatty liver disease. Early research shows that the disease is partly genetic but likely needs to be triggered by environmental conditions, like obesity or insulin resistance. Much of the current research has focused on genes and specific nutrients in the diet that might cause the disease. One culprit is fructose, a type of sugar found in corn syrup and fruit juice, which are widely consumed in western diets, according to Dr. Vos's research.

Some imaging studies of children born from obese women show that even the infants have more fat on their liver.

Also, certain ethnic groups, including Mexican-Americans, appear to be particularly susceptible, whereas African-Americans appear more protected against fatty liver disease, even though rates of obesity are high in the U.S. population. Scientists have discovered several genes linked to the disease. At least one, PNPLA3, appears more often in the Mexican-American population, according to Dr. Vos.

Usually fatty liver disease is detected when other health problems arise. Obesity, insulin resistance or diabetes may prompt a doctor to order blood work to determine how the liver is functioning.

Sherry Waskowski's son Gregory was 12 when he was diagnosed with fatty liver disease two years ago. He had gone to see a doctor for his long-standing acid reflux, but because he was overweight, the physician checked his cholesterol levels, blood sugar, and—unbeknown to Ms. Waskowski—his liver enzymes, his mother says. His liver enzymes came back elevated and the ultrasound that followed glowed bright, indicating an accumulation of fat.

"It was very frightening and I felt so totally responsible," Ms. Waskowski says.

The medical team educated the Waskowskis, who live in Cleveland, about the condition and what Gregory needed to do to reduce his weight, which is the primary recommendation for treatment. He now exercises five hours a week, mostly by walking on the treadmill, and eats more fruits and vegetables. The Cleveland Clinic's Dr. Alkhouri, one of his doctors, wrote a note to his school advising against excess snacking there for Gregory.

Gregory's weight is now in the normal range and his last ultrasound, in March, showed his liver had much less fat, according to Ms. Waskowski.

There's a debate in the field about whether kids should be routinely screened for the condition and, if so, the best way to do it, Dr. Alkhouri says.

While elevated liver enzymes can be a sign of the disease, hepatitis C and other metabolic liver diseases must be ruled out first. Ultrasound helps detect the presence of fat on the liver, but is expensive. The best way of diagnosing a fatty liver is to take a sample of the liver with a biopsy, but this procedure can be painful and has side effects.

Researchers are trying to identify biomarkers detectable through breath or blood samples instead. At a major conference in the field called Digestive Disease Week, Dr. Alkhouri and his colleagues presented the results of a pilot study. It showed that different concentrations of chemicals were found in the breath of obese kids with fatty liver disease compared with those without. If the test is validated upon further study, it may be useful clinically in several years, he says.

Treatments for fatty liver disease are limited. They include weight loss through diet and exercise. Another way to battle the condition is vitamin E, an antioxidant found in supplements and foods including eggs and some leafy vegetables like spinach, that helps to reduce inflammation in adults and children with NASH, according to Joel Lavine, chief of Gastroenterology, Hepatology and Nutrition at Columbia University.

Several trials are under way for treatments for pediatric NASH. The National Institute of Diabetes and Digestive and Kidney Diseases is sponsoring one study and co-sponsoring another.

Bariatric surgery is also being studied as a possible treatment, though it's controversial because no randomized studies exist looking at NASH. Preliminary data from the Cincinnati Children's Hospital Medical Center—not yet published—suggest the procedure is very effective in adolescents with NASH, according to Stavra Xanthakos, medical director of the Surgical Weight Loss Program for Teens there, who collected data.

"If you could mimic the effect of surgery without going through the surgery, that's where a lot of interest is," said Dr. Xanthakos.

Write to Shirley S. Wang at Shirley.Wang@wsj.com

Organ Damage

Some facts about nonalcoholic fatty liver disease:

About 10% of children in the U.S. are thought to have the condition.

Several factors likely contribute, including genetics, obesity, diet and insulin resistance.

It has no detectable symptoms.

Weight loss is the standard treatment for earlier stages of liver disease.

—Source: Miriam Vos, Emory University

Source

Appna Seminar: Hepatitis C incidence in Punjab ‘alarming’

By Our Correspondent

Published: September 8, 2013

Incidence of hepatitis C in some districts is as high as 13.1 per cent, experts warn.

LAHORE: The hepatitis C incidence in the Punjab has reached alarming proportions, ranging from 6.6 per cent to 13.1 per cent in various districts, said a hepatitis expert at a seminar here on Friday.

By comparison, the hepatitis C incidence in India ranges from 1.1 per cent to 2 per cent, said Dr Maqbool Arshad, the chair of the Association of Physicians of Pakistani Descent of North America (Appna) Hepatitis C programme, at the seminar, which was organised by the King Edward Alumni Association, an Appna component.

Dr Arsahd said that there were three million hepatitis C sufferers in Pakistan, who would go on to suffer liver failure and oesophageal varices, which bleed and lead to slow death. “There will be up to three million deaths [in Pakistan due to hepatitis C] in the next one or two decades,” he said.

Most people can’t afford liver transplants, he said. There is also an alarmingly high incidence of liver cancer, one of the most common cancers in Pakistan, he added.

Hepatitis C is commonly spread through reuse of needles among drug addicts and blood transfusion, he said, adding that up to 25 per cent of blood transfusions occur without screening the donor’s blood. The use of low quality disinfectants for sterilisation of dental and surgical instruments and poor hygiene practices at barber shops and beauty parlours are also sources of infection.

Dr Muhammad Abid from the United Kingdom also addressed the seminar.

The experts at the seminar recommended various measures to curb the hepatitis C infection rate, including use of auto-destructive syringes; registration of hepatitis C screening kits and removal of defective kits from the market; enforcement of proper medical waste disposal to eliminate the recycling of disposable equipment; and cutting out unnecessary injections. The experts estimated that 90% of injections given in Pakistan were unnecessary.

Published in The Express Tribune, September 8^th, 2013.

Source

Medicare/Medicaid May Cover Hepatitis C Screening As Preventive Service; Obamacare Next?

Many people who are infected with Hepatitis C don't know it. (AP File Photo)

September 6, 2013 - 7:08 AM

By Susan Jones

(CNSNews.com) - The Centers for Medicare and Medicaid Services (CMS) plans to make screening for Hepatitis C in adults part of the preventive services it covers. And free screening under Obamacare may come eventually.

The formal review, initiated by CMS on Thursday, is expected to be completed next June, and public comments will be accepted until October 5.

Hepatitis C is a liver disease spread by blood-to-blood contact. According to the federal Centers for Disease Control and Prevention, there is no vaccine for Hepatitis C. "The best way to prevent Hepatitis C is by avoiding behaviors that can spread the disease, especially injection drug use."

The virus also can be spread by blood transfusions, organ transplants, and sexual contact.

CMS notes that as of Jan. 1, 2009, under the Medicare Improvements for Patients and Providers Act of 2008, it is allowed to add coverage of "additional preventive services" if that service is recommended with a grade A (strongly recommended) or grade B (recommended) rating by the United States Preventive Services Task Force  and meets certain other requirements.

CMS said it decided to initiate an analysis on paying for preventive Hep-C screening in adults, which received a grade B (recommended) rating from the U.S. Preventive Services task force. (The U.S. Preventive Services Task Force, created in 1984, is an independent, volunteer panel of national experts in prevention and evidence-based medicine.)

In July, the U.S. Department of Health and Human Services marked "World Hepatitis Day," noting that viral hepatitis is the leading cause of liver cancer in the United States, claiming some 15,000 American lives each year.

In a statement issued on July 26, HHS said the Affordable Care Act "by requiring health plans to offer certain free preventive services...provides tremendous opportunities to expand access to viral hepatitis testing, care, and treatment services."

Source

Indonesia’s Hidden Hepatitis C Time Bomb

By Claudia Stoicescu & Edo Agustian on 12:20 am September 10, 2013.
Category Featured, Health, News
Tags: antivirals, hepatitis C

A nurse loads a syringe with a vaccine against hepatitis B. No vaccine exists yet for hepatitis C, with which 28 million Indonesians are infected. (AFP Photo/Robyn Beck)

Aris was diagnosed with hepatitis C in 2001. For the previous four years, he had injected heroin daily. Sometimes he shared needles, syringes and other injecting equipment with friends, unaware that this practice can easily transmit blood-borne viruses like hepatitis B and C, and HIV, the virus that can lead to acquired immune deficiency syndrome (AIDS).

“I didn’t know anything about safe injecting and harm reduction,” he said. “I was offered to be tested for HIV by a health worker, and thought, ‘It wouldn’t hurt to find out about hepatitis C, too.’ I tested positive for both.”

Indonesia has one of the highest rates of viral hepatitis in Southeast Asia. Aris is one of 28 million people in the country living with the hepatitis C virus. Of these 28 million, half could potentially progress to chronic liver disease, and over a third to liver fibrosis and liver failure or cancer. Hepatitis and other liver-related disease is a leading cause of death among Indonesians.

According to the Health Ministry, more than 7 million people across 21 provinces — or more than 2 percent of the country’s population — had hepatitis C as of 2007. People who inject drugs and live with HIV carry an especially heavy disease burden. Anecdotally, it’s estimated that over two-thirds of Indonesian drug injectors have hepatitis C, with about 60 percent to 90 percent of these also living with HIV. Co-infection with HIV more than triples the risk for liver disease, liver failure, and liver-related death from hepatitis C.

Two years after his double diagnosis, Aris started taking antiretroviral treatment (ARV) to manage his HIV infection.

“By that point I was so weak that I had to resort to bed rest every few days,” he recalls. “I didn’t find out until years later that my HIV infection was worsening my liver disease. At the time, I lived in Salatiga, a small town in Central Java, where access to information about hepatitis and co-infection was very limited.”

Curable

Hepatitis C is preventable, treatable and curable. Effective, evidence-based strategies for preventing hepatitis C transmission among drug injectors include a combination of long-term, consistent provision of harm-reduction services like needle syringe exchange programs and opioid substitution treatment, and antiviral treatment for those who already have the virus.

First-line recommended treatment consists of pegylated interferon alfa and ribavirin, both of which are included in the World Health Organization’s so-called complementary Model Essential Medicines List, an internationally recognizable set of safe, cost-effective medicines to guide countries in treating critical health needs.

“In Indonesia, these proven strategies are not implemented at the level or quality needed to have a significant impact on the explosive HIV epidemic,” says Suhendro Sugiharto, program manager at the Indonesian Drug Users’ Network (PKNI).

Research conducted by PKNI earlier this year among 240 members of the drug-using community across eight cities in Indonesia revealed that in contrast to government reports that existing harm reduction services reached nearly two-thirds of people who inject drugs, close to half of service beneficiaries reported never receiving any information on hepatitis C testing and treatment.

Twelve years after his diagnosis, Aris still hasn’t accessed antiviral treatment. In order to determine what treatment course and duration are most appropriate, he is required to undergo a series of diagnostic tests that, combined, cost up to Rp 6.5 million ($580) — almost three times the average monthly salary in Indonesia. Depending on which genotype he is infected with — there are six genotypes of the hepatitis C virus, each of which may respond differently to treatment — he could face costs up to Rp 144 million for treatment alone.

“I got the basic liver function tests because those are the cheapest. But the rest are too expensive for me,” Aris admits. “Although part of my stomach is permanently swelled up and increasingly painful by the day, I only take traditional herbal medicine. Even if I could cover the diagnostic tests and the huge cost of treatment, I am worried about the side effects and the interactions it might have with my ARV treatment.”

Limited reach

Hepatitis C treatment in several Southeast Asian countries, including in Indonesia, is licensed to pharmaceutical companies Roche and Merck.

On July 28, a group of 16 international and regional advocates, including PKNI, sent a joint, open letter to Roche and Merck to demand lower prices for peginterferon alfa in Asia. In his reply, Roche chief executive Severin Schwan acknowledged the role of treatment access in hepatitis care but stayed clear of mentioning price reductions as an option for facilitating such access. The groups are due to meet with the pharmaceutical company in the near future.

Officially, the Indonesian government publicly funds treatment for hepatitis C under a number of insurance schemes, including Askes, which covers health costs including treatment for hepatitis C for government employees, Jamsostek, which acts as social insurance for employers that choose to register with the scheme, and Jamkesmas, Indonesia’s health waivers for low-income individuals.

But the reach of existing insurance and support schemes is extremely limited. A majority of people either don’t know these subsidies exist or don’t qualify for them.

Speaking on Sunday at Aksi Hepatitis, an event held at Monas commemorating World Hepatitis Day, Indonesia’s Minister of Health Nafsiah Mboi announced that hepatitis C treatment will be covered by National Health Insurance beginning in 2014, in accordance with the 2004 National Social Security Law.

“This is an important step forward,” says the PKNI’s Suhendro. “But we need to make sure that such schemes facilitate treatment access for the most vulnerable among us, and that they do so with minimal bureaucracy attached. Hepatitis C among our community is a ticking time bomb,” he adds.

Continue to die

Indonesia does not conduct routine surveillance for hepatitis C, and that makes it challenging to assess the true scale of the crisis. It was not until 2011 that the Health Ministry established a national program focused on viral hepatitis, under the Sub-Directorate for Gastrointestinal Infections and Diarrheal Diseases.

“We are currently preparing an action plan for hepatitis control to be implemented between 2015 and 2019, as well as national guidelines for management of hepatitis C,” said Naning Nugrahini, who heads the sub-directorate. “We also plan to strengthen data collection and surveillance among most affected populations.”

A policy briefing launched on Sunday by the PKNI to coincide with Aksi Hepatitis demands that the government scales up its commitment to hepatitis by joining affected communities in negotiating price reductions with pharmaceuticals.

“I want treatment,” Aris says. “My dream is to see hepatitis C medication produced locally and affordably. Until pharmaceutical companies drop their patents, people will continue to die.”

Claudia Stoicescu is a doctoral researcher investigating sexual and drug injecting risk behaviors among women who inject drugs in Indonesia. She is based in Jakarta. Edo Agustian Edo is the national coordinator of PKNI (www.pkni.org).

Source

Social Networking Technologies as an Emerging Tool for HIV Prevention: A Cluster Randomized Trial

Original Research | 3 September 2013

Sean D. Young, PhD, MS; William G. Cumberland, PhD; Sung-Jae Lee, PhD; Devan Jaganath, MPH; Greg Szekeres, BA; and Thomas Coates, PhD

[+-] Article and Author Information

Ann Intern Med. 2013;159(5):318-324. doi:10.7326/0003-4819-159-5-201309030-00005

Background: Social networking technologies are an emerging tool for HIV prevention.

Objective: To determine whether social networking communities can increase HIV testing among African American and Latino men who have sex with men (MSM).

Design: Randomized, controlled trial with concealed allocation. (ClinicalTrials.gov: NCT01701206)

Setting: Online.

Patients: 112 MSM based in Los Angeles, more than 85% of whom were African American or Latino.

Intervention: Sixteen peer leaders were randomly assigned to deliver information about HIV or general health to participants via Facebook groups over 12 weeks. After participants accepted a request to join the group, participation was voluntary. Group participation and engagement were monitored. Participants could request a free, home-based HIV testing kit and completed questionnaires at baseline and 12-week follow-up.

Measurements: Participant acceptance of and engagement in the intervention and social network participation, rates of home-based HIV testing, and sexual risk behaviors.

Results: Almost 95% of intervention participants and 73% of control participants voluntarily communicated using the social platform. Twenty-five of 57 intervention participants (44%) requested home-based HIV testing kits compared with 11 of 55 control participants (20%) (difference, 24 percentage points [95% CI, 8 to 41 percentage points]). Nine of the 25 intervention participants (36%) who requested the test took it and mailed it back compared with 2 of the 11 control participants (18%) who requested the test. Retention at study follow-up was more than 93%.

Limitation: Only 2 Facebook communities were included for each group.

Conclusion: Social networking communities are acceptable and effective tools to increase home-based HIV testing among at-risk populations.

Primary Funding Source: National Institute of Mental Health.

Source

Methadone Linked to Prolonged QTc Interval

September 5, 2013

Keith Henry, MD reviewing Vallecillo G et al. Clin Infect Dis 2013 Aug 14. Keith Henry, MD

A prolonged QTc interval in HIV-infected patients on methadone was associated with higher methadone doses, hepatitis C liver disease, and ART-naive status. Keith Henry, MD

Illicit opioid use is associated with increased risk for HIV infection. Methadone is an effective drug for the long-term management of opioid-dependent HIV-infected patients, although safety concerns have been identified (i.e., cardiac arrhythmias such as prolonged QTc interval and torsades de pointes).

In a cross-sectional study, HIV-infected patients on methadone maintenance therapy followed at a single outpatient clinic in Spain underwent 12-lead electrocardiography 24 hours after supervised methadone administration. Individuals with known cardiac disease, drug-positive urine tests, electrolyte abnormalities, or changes in antiretroviral therapy (ART) regimen or methadone dose in the preceding 2 months were excluded.

Of the 91 study participants (64% men; 100% white; median age, 44.5), 68 (75%) were on ART; the regimen for 56 of them included a boosted protease inhibitor. The median nadir and current CD4 counts were 232 and 438 cells/mm3, respectively. The median methadone dose was 70 mg/day, and the mean QTc interval was 438 milliseconds. A prolonged QTc interval (>450 ms) was documented in 33 participants (36%), including 3 with intervals >500 milliseconds. On multiple linear regression analysis, higher methadone dose, chronic hepatitis C–induced cirrhosis, and ART-naive state were associated with a prolonged QTc interval.

Comment

In a cross-sectional study without a control population, it is difficult to fully assess the clinical risk posed by the reported QTc abnormalities.

A prolonged QTc interval was associated with being antiretroviral-naive, but was not observed with use of protease inhibitors (which have been linked in other studies to QTc prolongation). Complicating the situation was the common use of other QTc-prolonging drugs (58% of the participants were taking antipsychotics, antidepressants, antiepileptics, or antibiotics). The study findings remind clinicians of the possible effects of drugs on cardiac conduction and the need to be diligent in monitoring for potential problems (often including input from an HIV-savvy pharmacist, as well as baseline and follow-up electrocardiograms).

Citation(s):

Vallecillo G et al. Risk of QTc prolongation in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. Clin Infect Dis 2013 Aug 14; [e-pub ahead of print]. (http://dx.doi.org/10.1093/cid/cit467)

Source

New Survey of People Living with HIV Shows Desire for Greater Doctor-Patient Dialogue about Treatment and Disease Impact

PRESS RELEASE 

September 9, 2013, 9:05 a.m. ET

Survey Results Reinforce Need for Improving Communication between Patients and Doctors, a Goal of I Design HIV Education Campaign 

WHITEHOUSE STATION, N.J., Sept. 9, 2013 /PRNewswire/ -- Today, results from an online nationwide survey of more than 300 people living with HIV on antiretroviral therapy show that participants are very involved in engaging with their healthcare providers in the management of their HIV; nearly all (97 percent) said that they are proactive about managing their HIV condition, including drug treatment. However, the survey findings also show that about three in four participants would like to spend more time discussing topics with their doctor about HIV drug treatment (74 percent) and the impact of HIV on their lives (71 percent) during doctor office visits.

Results of the survey, which examined the breadth and depth of communications between people living with HIV and their doctors, including level of preparation by patients for visits, content of discussions during visits and commonly used information resources, were released during the 2013 United States Conference on AIDS (USCA), the largest annual HIV gathering in the nation. The survey was conducted complementary to Merck's national HIV education campaign, I Design (www.ProjectIDesign.com) to help empower people living with HIV to have open and meaningful discussions with their doctors. 

"The results of this survey are very encouraging, however they underscore the need for more in-depth discussions between people living with HIV and their doctors - not only regarding their treatment regimens, but also how the disease is affecting their lives overall," said Dr. Michael Gottlieb, Associate Clinical Professor of Medicine, David Geffen School of Medicine, UCLA. "Communication between healthcare providers and patients is the cornerstone of developing and maintaining a successful HIV treatment plan."

Key findings from the survey show that respondents are active about managing their HIV, with most indicating that they are proactive about making doctor appointments (85 percent), talking to their doctor about things that concern them (84 percent) and talking to their doctor about HIV drug treatment options (77 percent). In addition, more than half (56 percent) research HIV and HIV-related topics, and many (42 percent) talk to others living with HIV to proactively manage their HIV condition.

Respondents selected that they would like to spend more time discussing how their current HIV drug treatment regimen is working (40 percent), other HIV treatment options (30 percent), health conditions they have other than HIV (30 percent), side effects of their current HIV medications (28 percent) and taking their current HIV treatment as directed (13 percent). Respondents also indicated that they would like to spend more time discussing the physical impact of HIV on their bodies (51 percent) and the impact of HIV on their sex lives (26 percent), day-to-day lives (25 percent), mental or emotional well-being (29 percent) and relationships with their loved ones or family (15 percent).

"As someone who has lived with HIV for close to 20 years, I know there are numerous topics to discuss during each visit to the doctor, and can understand why many people may find it difficult to cover all of them," said Duane Cramer, renowned photographer and I Design campaign spokesperson. "Preparing for discussions with my healthcare provider by prioritizing what I want to discuss about my medicines, my other health conditions and relevant aspects of my life have been important factors to my HIV treatment plan over the years. This is what I encourage people to do as part of the I Design campaign."

Additional Survey Findings

Preparation for Doctor's Appointments 

   -- 79 percent of respondents reported they did something to prepare for 
      visits with their doctors over the past year; specifically: 
 
          -- 62 percent prepared a list of questions or topics to discuss, 32 
             percent conducted background research on topics other than HIV 
             drug treatment options, 25 percent conducted background research 
             on available HIV drug treatment options and 17 percent talked to 
             others living with HIV 
 
          -- One in five (21 percent) respondents reported they did not do 
             anything to prepare for visits with their doctors

Patient -- Doctor Communication 

   -- Overall, respondents understand the information their doctor shares with 
      them about the management of their HIV drug treatment: 
 
          -- 39 percent indicated that they understand all the information 
             shared by their doctor about the management of their HIV drug 
             treatment 
 
          -- 53 percent chose that they understand a great deal of this 
             information 
 
          -- 8 percent selected that they understand some of the information 
 
          -- No respondents selected that they understand "very little" 
             information 
 
   -- Of the topics listed in the survey related to drug treatment 
      conversations, only 3 percent of respondents selected that they did not 
      feel comfortable discussing any of them with their doctor; survey 
      participants indicated that they are comfortable discussing with their 
      doctor: 
 
          -- How their current HIV drug treatment regimen is working (88 
             percent) 
 
          -- Health conditions they have other than HIV (82 percent) 
 
          -- Side effects of their current HIV drug treatments (79 percent) 
 
          -- Taking their current HIV treatment as directed (77 percent) 
 
          -- Other HIV drug treatment options (72 percent)

Additional Sources of Information 

   -- 74 percent of respondents have referred to other resources in the past 12 
      months to help them better understand the management of their HIV 
      condition, including HIV drug treatment: 
 
          -- 55 percent utilized online resources such as news, websites, blogs 
             or forums; 27 percent used medication reminders/trackers or 
             checklists; 26 percent employed the services of an AIDS Service 
             Organization (ASO); 18 percent referred to support 
             groups/services; and 20 percent used a resource other than those 
             listed above 
 
          -- 26 percent didn't use any resources beyond what their doctor 
             shares with them or tells them 
 
   -- Respondents who have utilized the services of an ASO (n = 211; 67 percent 
      of total respondents) indicated that they accessed the following: HIV 
      education (50 percent), counseling (47 percent), financial assistance (43 
      percent), testing (37 percent), food bank assistance (34 percent), legal 
      services (27 percent), AIDS policy (19 percent), AIDS activism (18 
      percent), housing services (18 percent) and substance abuse treatment or 
      counseling (9 percent) 

About the Survey

The survey was conducted online by Kelton, an independent global insights firm, from July 2 -- 29, 2013 among 316 people living with HIV who are on antiretroviral therapy. Respondents were 18 years of age and older, and had a median age of 49. About half (46 percent) of survey participants indicated having been diagnosed with HIV for more than 15 years. Respondents represented varying demographic areas (Northeast, Midwest, South and West) within the United States. Results of any sample are subject to sampling variation. Support for the research was provided by Merck, Whitehouse Station, NJ.

About I Design

I Design is a national HIV education campaign led by Merck, notable fashion designer Mondo Guerra and award-winning photographer Duane Cramer aimed at helping to empower people living with HIV to have open and meaningful discussions with their doctors about their treatment plan based on their medical and lifestyle needs.

To learn more about the campaign, visit www.ProjectIDesign.com where you can download a conversation checklist, which offers tips on how to engage in an open and honest dialogue with your doctor; design a digital textile illustrating your approach to managing HIV; and view videos and photos. To help you track and manage your health, there are the "My Health Matters" and "My Positive Agenda" mobile and desktop apps. These easy-to-use tools help you track the symptoms of your HIV, set up reminders to take your medications on time, and keep a record of when you have taken them, which can serve to prompt you on important discussion points when you are with your doctor. For additional tips and to follow Merck, Mondo, and Duane's collaboration on I Design, join them on Twitter @Merck, @LoveMondoTrasho and @DuaneCramer.

Merck's Commitment to HIV

For close to 30 years, Merck (NYSE: MRK) has been at the forefront of the response to the HIV epidemic, and has helped to make a difference through our proud legacy of commitment to innovation, collaborating with the community and expanding global access to medicines. In the United States, we are helping to address healthcare disparities through educational programs and resources that align with the National HIV Strategy. Merck is dedicated to applying our scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HIV worldwide.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

SOURCE Merck

/CONTACT: Doris Li, 908-423-6451; Melanie McCoy, 212-798-9873

/Web site: http://www.merck.com

Source

Hepatitis C services in the UK: an interview with Louise Campbell, senior liver nurse at Imperial College Healthcare NHS Trust

Provided by News-Medical.Net

Published on September 9, 2013 at 6:31 AM ·

Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)

How do UK hepatitis C services compare to those in other countries?

Within the UK there are several centres whose nurse specialists work to a best practice model, delivering care and achieving outcomes which are extremely high in areas of patient retention, adherence to medication and completion of the treatment regimen. With this they achieve cure rates which are some of the highest in the World.

Unfortunately there are areas treating HCV in the UK which are not given the staff resources or support required to achieve this which can reduce the number of patients entering into and completing treatment.

Charles Gore, Chief Executive of The Hepatitis C Trust, has recently said, “The alarming rise in hepatitis C related deaths must be addressed”. Why do you think treatment rates for hepatitis C are declining?

In some situations treatment rates have declined as patients wait to access the ‘all oral’ treatment regimens which are currently in clinical trials. This should however be done in the knowledge of underlying liver condition and with the best information available in discussion with the patient's Hepatologist.

We are currently seeing an increasing rise in HCV diagnosis and the National Institute for Health and Care Excellence delivered guidance to increase testing and awareness for HCV and Hepatitis B which I would like to think that some of the increase is as a result of this although as yet. There does not appear to be a reflection in the referral rates to the treatment centres for these patients as yet and there is significant variability in where there is access to treatment services for many patients. If the estimated 300,000 – 700,000 people suspected to be infected with HCV in England (most of who are unaware) is accurate then there are insufficient treatment units in the UK to deal with the health burden.

GPs are responsible for over 25% of all HCV tests performed each year but many of these patients never get referred or attend treatment centres for a condition which can lead to permanent liver damage and death but is increasingly curable.

What impact do you think the NHS reforms will have on hepatitis treatment services in the UK?

We are currently experiencing one of the largest alterations to the Health Service funding system and whilst the new Clinical Commissioning Groups (CCGs) organise themselves then I feel we will see a drop in those patients detected as HCV positive being referred into the services.

This may be as a result the CCGs commissioning other areas of care. There are very few other disease areas which have the same cost implications to CCGs as severe liver related conditions of which HCV is one three main causes (obesity and alcohol being the other two) which as a result contribute significantly to increasing type II diabetes and heart disease yet have as great potential for improved patient care, increased survival and improved mortality and reduced cost as the treating and curing HCV.

HCV treatment is traditionally seen as long and difficult treatment (with chemotherapeutic-like side effects) as many patients require 48 weeks of treatment with specialised medications which require large amounts of support for the patients. This is nearly all delivered via specialist nurse services but for the majority of patients this can result in a CURE a return to a rewarding family life, job, career and can often prevent them from developing any long term liver condition.

If hepatitis treatments are reduced as a result of the NHS reforms many of those not cured will continue to have to live with a liver disease which can infect others, the condition of their liver may continue to deteriorate and they could develop significant complications.

I would like to see patients with HCV and other liver related conditions given due consideration and attention in the new NHS reformed structure as they account for the 5^th highest cause of mortality in the UK.

Please can you give an overview of the recent HALO report project?

I believe that the report has been relatively successful as several of the initiatives used demonstrate best practice, high patient experience and cost effective care.

I remain unclear as to where it has been circulated and as a result the sphere of influence it can have in the wider world of healthcare. The frameworks used can be beneficial for other disease areas and in areas with similar patient groups or where co-infection with HCV is common.

What were the findings of this report?

I have found the findings favourable and encouraging that whilst we are undergoing health reforms there are many areas where new initiatives are encouraged not only from medical colleagues but from nurse specialists within experienced multidisciplinary groups.

The key for me from the HALO Report was increased evidence that that a well operating, multidisciplinary team can affect patient care and experience in a really positive way and some of these initiatives provide a cost effective pathway for the NHS and local CCGs.

How do you think current diagnosis and treatment rates of hepatitis C in the UK can be improved?

I would suggest that we probably need a national coordinated approach to diagnose and assess those with HCV, this for many is a disease which carries significant stigma often born out of a lack of knowledge, unfortunately this stigma and that associated with alcohol and obesity results in the avoidance of discussing liver disease as a consequence leads to a population dying young which is not seen in any of the other major disease areas.

The average age of death with liver disease is 59 years in the UK yet much of this is preventable with early detection and effective treatments.

We can learn lessons from many other countries; the USA currently has a nationwide campaign targeting adults born between 1945 and 1965! Being born does not carry stigma and if an adult presents to a healthcare provider in this age range they are offered testing automatically.

One of the motivations for this is that a significant number of patients detected with advanced liver disease now experimented with some form of drug use even once, obtained a tattoo or blood transfusions before 1989 many of whom who do not feel they are at risk.

HCV is easier to cure before the liver is too badly affected and locating those who have had the disease longer could allow healthcare professionals an opportunity to do this preventing progression of disease and complications such as cirrhosis, cancer, and the need for transplant which improves survival rates.

There are many initiatives which can encouraged, the use of advocates within the higher prevalence populations to raise awareness for testing as highlighted by Dean Lindzey’s project prove beneficial and can reduce suspicion within communities.

In HBV the Jade Ribbon campaign is driven from within the Asia pacific populations and has groups within local communities and universities raising awareness and treatment.

The testing of pregnant women can assist to keep the risk of transmission to the baby at and after birth to a minimum. Immigration screening assists in identifying health requirements so these can be met and delivered to those who need these.

Positive and appropriate health information within the media can assist greatly in helping to reduce the stigma. Soap operas have recently been criticized for always showing drinking in all episodes it would be very welcome for them to carry positive health story lines on these areas. Having a main cast character dealing with a HCV diagnosis through the real pathway to cure could have a great positive health potential.

Why do you think people don't like to talk about it?

I believe that stigma prevents most people from discussing most areas of liver disease; some may feel guilty for a behaviour which they deem responsible.

As a society we like to enjoy ourselves which can include over indulgence in alcohol, food or recreational/illicit drug use (even once as a tester) in some this can become a significant problem and stigma can prevent them accessing health advice support and treatments. Unfortunately this results in significant disease before many symptoms are experienced and a low age of mortality.

What can be learnt from examples of best practice outlined in the HALO report?

The examples of best practice in the HALO report I hope can assist other healthcare areas to implement projects/support business cases to expand departments improving patient care and outcomes using real-life evidence which has proven cost effective in the management and support of people infected with HCV. I have certainly gained some ideas from this report.

I hope that this in turn enables commissioners, healthcare providers and the specialist teams to fund, diagnose and treat more people with HCV, gaining high cure rates which can improve the quality of life substantially for those patients with HCV.

For those in whom current treatments do not afford a cure that there is possibly something newer in development that may offer this.

The use of these examples may also empower patients to ask for access to resources and care.

How do you think the future of hepatitis C services in the UK will develop?

It is difficult to predict the future for HCV services as these are currently highly skilled areas of care given the chemotherapeutic nature of the medications used.

Differences in requirements are being seen within individual genotypes of the virus.

HCV however is and should be a patient specific plan designed for the individual and the team with the most appropriate medications and support available preferably at the time the patient feels is most appropriate.

In the future it is hoped that for all genotypes that the treatment will be one tablet or a combination of tablets only with minimal side effects. These may prove highly expensive which may result in limited access to these for patient populations.

My concern is should treatment become all oral, some people may mix medications, which is extremely risky, untested and may result in problems with HCV becoming multiple resistant to oral medications.

If the new medication development becomes a reality then I would like to think as a country with some of the best expert hepatitis teams and healthcare facilities and in the world that we would be willing to increase the hepatitis resources significantly and be encouraged to locate, treat and cure those with this virus as this would be within our ability to do so and assist significantly in increasing liver related mortality from 59 years of age.

HCV treatment is an exciting field of rapid development and we are successfully curing more of those infected, preventing future infections and reducing the cost burden to the NHS. There’s still however the inaccuracy out there that HCV is not curable. Hepatitis C is extremely curable for the majority of patients and this is increasing.

Therefore, I really would encourage all healthcare providers to identify those in your areas who are at risk and offer testing. For people to be asking could I be at risk? They should ask themselves the following questions: was I born between 1945 and 1965; have I had a blood transfusion prior to 1989; have I received vaccinations or body piercings outside of the UK, ever experimented with drugs (even once), had a tattoo? If you can ask yourself those questions and answer yes to any of them then there is a legitimate risk and a legitimate reason to ask your GP to be tested.

Where can readers find more information?

The report is available to view online at: http://www.hepctrust.org.uk/News_Resources/resources/reports

Readers can also find information at:-

• http://www.hepctrust.org.uk/
• http://www.britishlivertrust.org.uk/
• http://www.hcvaction.org.uk/
• http://www.imperial.nhs.uk/

About Louise Campbell

RN, RMN, Cert MHSC, MSc (Distinction) Advancing Practice
Senior Nurse Liver Unit, Imperial College Healthcare NHS Trust

Louise Campbell undertook RN training at Kings College Hospital and then worked in the Liver Unit for 12 years is duel training in mental health and has attained a master’s degree in advancing practice. Louise joined the Hepatology team at Imperial College Healthcare in 2006 and currently manages the Liver and Anti-viral Unit including the Hesketh Hepatology Clinical Research facility at St Mary’s hospital campus.

Prior to this she worked for 3 years in liver and renal transplantation and hepatitis C in the Royal Prince Alfred Hospital, Sydney Australia having been a hepatitis nurse specialist at the Chelsea & Westminster hospital, London since 2001.

Louise is a strong advocate for and speaks both nationally and internationally on nurse led services and high quality patient care for patients with hepatitis and liver disease. Louise was the chair of the first European Association for the study of liver (EASL); Nurses and associates forum in 2012, which is now a permanent addition to this renowned meeting.

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