October 11, 2012

PGI, AIIMS to hold conference on liver cancer

Express news service : Chandigarh, Fri Oct 12 2012, 01:16 hrs

Continuing with the Golden Jubilee celebrations of PGIMER, Chandigarh, the Department of Hepatology, PGIMER and the Chandigarh and Department of Gastroenterology, AIIMS, New Delhi will jointly organize the Single Theme Conference on Hepatocellular Carcinoma (liver cancer) under the aegis of Indian National Association for the Study of Liver (INASL) on October 13 and Current Perspective in Liver Diseases (CPLD)-2012 on October 14 covering various aspects of liver diseases.

The Department of Hepatology has been organizing these conferences by alternating the venue with AIIMS, New Delhi each year since 2001 and this will be the 11 th PGI-AIIMS joint conference which will be attended by more than 250 Doctors working in the field of hepatology, gastroenterology, radiology and internal medicine.

Liver cancer is a common problem in this part of the country and is usually related to the infection with Hepatitis B Virus and Hepatitis C Virus, alcohol consumption and fatty liver disease related to overweight and diabetes mellitus.

The first day of the conference will be devoted to the discussion revolving around the epidemiology, diagnosis, pathogenesis and medical and surgical treatment of liver cancer with experts from all over the country dwelling upon the various aspects.

The second day of the conference will cover various aspects of liver diseases including Hepatitis C Infection, Hepatitis B Infection, Non Alcoholic Fatty Liver Disease and various complications of cirrhosis liver including hepatic encephalopathy, ascites and renal failure.

Malignancies of the gall bladder and the bile duct are also common in this part of the country and their management will also be discussed during the conference.

The conference will also include a session about the awareness and problems related to the organ donation in this country and the inauguration of a website related to organ donation.

This website will be unique and one of its kind and will give all the required information to the general public about various aspects of organ donation, including the various organs which can be donated after death, how to pledge for organ donation by filling in a donor card and other aspects of the process that people may want to know in order to donate an organ.

The conference will be inaugurated by Prof N K Ganguly, Distinguished Biotechnology Fellow & Advisor Translational Health Sciences & Technology Institute and Ex-Director General, Indian Council of Medical Research (ICMR), New Delhi and will be graced by distinguished faculty.

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Prior Alcohol Consumption Does Not Impair HCV Treatment

Last Updated: October 11, 2012.

THURSDAY, Oct. 11 (HealthDay News) -- For patients with hepatitis C virus (HCV) treated with pegylated interferon-alpha and ribavirin (P/R), drinking patterns and the amount of alcohol consumed before treatment do not impact treatment success, according to a study published in the October issue of Hepatology.

Marcia Russell, Ph.D., from the Pacific Institute for Research and Evaluation in Berkeley, Calif., and colleagues examined the effect of alcohol on treatment outcome in 421 treatment-naive HCV-positive patients, who were members of an integrated health care plan and were treated with P/R. For 259 of the patients, a detailed drinking history was obtained.

The researchers found that, before HCV diagnosis, regular drinking was reported by 93.1 percent of patients. Between HCV diagnosis and treatment, 30.9 percent reported regular drinking, and this dropped to 1.9 percent during treatment and 11.6 percent after the end of treatment. Before starting treatment, 67.9 percent reported heavy drinking patterns, with 63.5 percent drinking more than 100 kg of ethanol, while 29.3 percent reported abstaining less than the requisite six months before initiation of treatment. In spite of these patterns, 80.2 percent of patients with HCV genotype 2 or 3 and 45.1 percent with genotype 1, 4, or 6 had a sustained virological response (SVR). Neither pretreatment drinking patterns nor total alcohol intake was related to SVR rates. Lower SVR rates were seen in moderate, but not heavy, drinkers who abstained for less than six months before treatment.

"These findings suggest that past heavy drinking and recent drinking represent low treatment risk in these patients," the authors write.

One author disclosed financial ties to Merck.

Abstract
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European Journal of Gastroenterology & Hepatology: August 2012

daCosta DiBonaventura, Marcoa; Yuan, Yongb; Wagner, Jan-Samuela; L'Italien, Gilbert J.b,d; Lescrauwaet, Benedictee; Langley, Paulc

aHealth Economics and Outcomes Research, Health Sciences Practice, Kantar Health, New York, New YorkbGlobal Health Economics and Outcomes Research, Princeton, New JerseycCollege of Pharmacy, University of Minnesota, Minneapolis, MinnesotadYale University School of Medicine, New Haven, Connecticut, USAeXintera Consulting, Brussels, Belgium

"This information is increasingly relevant in the context of pricing and reimbursement reforms of new medicines as well as the recent call to action for increased surveillance of HCV throughout the EU.......patients with HCV reported significantly lower health status scores.....Prevalence figures range between 1.1 and 1.3% across the entire European region......Patients with HCV reported significantly lower levels of emotional role limitations (means=66.4 vs. 70.6, P=0.040), physical functioning (means=63.8 vs. 71.9, P=0.001), general health (means=48.3 vs. 54.4, P=0.004), bodily pain (means=64.3 vs. 70.8, P=0.002), and PCS scores (means=42.9 vs. 45.3, P=0.002).....there was a significant effect of HCV status on the number of physician visits in the past 6 months (means=9.9 vs. 6.7, P<0.001)."

"Using a standardized methodology across France, Germany, Italy, Spain, and the UK, the presence of diagnosed HCV in the EU population has been shown, utilizing a propensity scoring model, to have a significant impact on several domains of health-related quality of life, presenteeism, and the number of visits to traditional healthcare providers. These analyses accounted for an exhaustive array of demographic, health history, and comorbidity information that is known to burden the HCV population and to be associated with health outcomes. In sum, these results add to the literature by documenting the population-level effect of HCV on a variety of patient-reported outcomes. This information is increasingly relevant in the context of pricing and reimbursement reforms of new medicines as well as the recent call to action for increased surveillance of HCV throughout the EU."

"A total of 336 patients across France (n=78), Germany (n=65), Italy (n=97), the UK (n=52), and Spain (n=44) reported being diagnosed with HCV. Applying sampling weights, these correspond to prevalence estimates of 0.59% in France, 0.44% in Germany, 1.42% in Italy, 0.82% in Spain, and 0.35% in the UK. Patients with HCV were predominantly men (54.2%) and had a mean age of 55.1 years (SD=15.4)."

Abstract

Objective: Hepatitis C virus (HCV) affects 170 million patients worldwide and is the leading cause of liver cirrhosis and hepatocellular carcinoma. The aim of the current study is to examine the burden of HCV in the European Union (EU) from a patient perspective.

Methods: Using data from the 2010 EU National Health and Wellness Survey, patients who reported a diagnosis of HCV (n=332) were compared with a propensity-score-matched non-HCV control group (n=332) on measures of quality of life (using the SF-12v2), work productivity, and healthcare resource utilization in the past 6 months. All analyses applied sampling weights to project to the respective country populations.

Results: Projected prevalence estimates of HCV were 0.59% in France, 0.44% in Germany, 1.42% in Italy, 0.82% in Spain, and 0.35% in the UK. HCV patients reported significantly lower levels of emotional role limitations (means=66.4 vs. 70.6, P=0.040), physical functioning (means=63.8 vs. 71.9, P=0.001), general health (means=48.3 vs. 54.4, P=0.004), bodily pain (means=64.3 vs. 70.8, P=0.002), and physical component summary scores (means=42.9 vs. 45.3, P=0.002) than the matched controls. Patients with HCV also reported significantly higher levels of presenteeism (means=27.1 vs. 21.0%, P=0.044) and a greater number of physician visits in the past 6 months (means=9.9 vs. 6.7, P<0.001).

Conclusion: Using a population-based survey methodology and a propensity-score matching analysis, these results add to the literature by documenting the significant effect that HCV has on a variety of both humanistic and economic outcomes in the EU.

Introduction

The hepatitis C virus (HCV) is a chronic blood-borne disease, which is a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide 1. Across Europe, an estimated 250 000 individuals die annually from HCV-related causes 2. Although the significant risk for developing cirrhosis and HCC in the later stages of infection is well recognized, the early phases of chronic HCV infection are often asymptomatic 3. Indeed, a number of patients in Europe are unaware that they are infected with the virus. Less than 60% of urban French residents with HCV-positive sera were aware of their status 4. The rates of awareness for most other European countries vary between 60 and 90%, although Germany and Poland have been estimated at closer to 10% 2.

Prevalence figures range between 1.1 and 1.3% across the entire European region, although the rates of HCV infection vary substantially between and within countries 5. According to the European Centre for Disease Prevention and Control, anti-HCV prevalence ranges from 0.4% (Germany, Sweden, the Netherlands) to 5.2% (Italy) 6. Because of the advances in blood screening techniques in the 1990s, there has been an overall reduction in the incidence of HCV. Most HCV transmission now occurs through intravenous drug use, although tattoo and piercing needles also pose a risk of transmission 7. However, some areas in Europe, such as central and southern Italy, are still considered to be hyperendemic 6,8. On the basis of data from the WHO, country-specific prevalence rates for the five large European nations have been estimated to be between 0.13 and 1.10% for France, 0.10 and 0.22% for Germany, 0.5 and 3.0% for Italy, 0.7 and 2.0% for Spain, and 0.02 and 0.70% for the UK 5,9. A recent systematic review by Cornberg et al. 10 reported the following estimates: 0.84% for France (with a 57% diagnosis rate), 0.40% for Germany (with a 38% diagnosis rate), 5.2% for Italy (with a 12% diagnosis rate), 2.64% for Spain (with a 17% diagnosis rate), and 0.60% for the UK (with a 36% diagnosis rate).

Because of the potential for HCV-related complications such as cirrhosis and HCC, HCV is considered to be a major public health issue in Europe 11-13. Indeed, the recent Summit Conference of Hepatitis B and C, under the auspices of the Belgian EU presidency, has issued a call to action for enhanced surveillance of these chronic illnesses 14. Besides additional information on incidence and prevalence rates, which have inconsistent methodologies across countries, making comparisons difficult, data are needed on its effect on health outcomes in the region. Although broad population-level measures of disease burden (e.g. 1.2 million disability-adjusted life years lost in 2002 because of HCV) have been reported by the WHO 5, these estimates largely represent the impact of late-stage infection and its associated sequelae (e.g. cirrhosis, HCC). The European Centre for Disease Prevention and Control report focused exclusively on the burden of HCV-related cirrhosis and HCC rather than on the infection itself 6. More sensitive assessments of the impact of HCV on the patient and healthcare system are currently lacking.

A few studies have assessed the effect of HCV on health status with respect to country-specific norms. Hauser et al. 15 and Cillo et al. 16, in Germany and Italy, respectively, each found that patients with HCV reported significantly lower health status scores as measured by the Short Form 36 (SF-36). A second study in Germany reached similar conclusions using the Short Form 12 17. Previous studies in Spain and the UK have also compared patients with HCV with healthy controls using the SF-36, finding marked differences 18,19. However, none of these studies were population-based and many potential confounding variables were not included in the analyses, limiting the inferences that can be drawn on the impact of HCV. Other aspects of the burden of HCV, particularly work-related and activity-related impairments, have not been assessed.

The aim of this study is to assess prevalence information about HCV, as well as its impact on health outcomes across five European countries (France, Germany, Italy, Spain, and the UK) using a standardized methodology. Detriments in health-related quality of life 20-22, and increased healthcare resource utilization 22,23, and work productivity loss 22,23 have been observed previously in the USA; however, few studies have examined these outcomes using representative European samples. Some studies have examined the impact of HCV on health-related quality of life 15-19 and healthcare resource use 24, but no single study has examined both patient-centered and economic (both indirect and direct) outcomes across multiple European countries using a consistent methodology. As reported in previous reviews, the lack of a standardized methodology in HCV research is a major obstacle to assimilating epidemiological information across the European region 5,14.

This analysis also attempts to overcome the methodological limitations of previous studies through the application of a propensity score-matching procedure. The use of propensity score matching allows for the elimination of selection biases through the inclusion of demographic, health history, and comorbid disease characteristics that may be associated with HCV disease status and patient outcomes. Using such a methodology, patients will be compared with matched controls to isolate the contribution of HCV. To quantify the disease burden of HCV on the selected European population, the current study compares the health-related quality of life, work productivity loss, and healthcare resource utilization between those with and without HCV across France, German, Italy, Spain, and the UK.

Patients and methods

National Health and Wellness Survey

Data were obtained from the 2010 European Union (EU) National Health and Wellness Survey (NHWS), which included respondents from France, Germany, Italy, Spain, and the UK (N=57 805). The NHWS is an annual, cross-sectional, self-administered Internet survey of a sample of adults (18 years and older) who are identified through a web-based consumer panel. Members of the panel are recruited through opt-in e-mails, co-registration with panel partners, e-newsletter campaigns, and online banner placements. All panelists explicitly agreed to become panel members, registered through unique e-mail addresses, and completed in-depth demographic registration profiles. Offline recruiting was used to supplement this sample source in areas of limited Internet penetration, particularly in Spain and Italy among the older subpopulations. All participants provided informed consent and the study protocol was approved a priori by the Essex Institutional Review Board (Lebanon, New Jersey, USA).

Using data from the International Database of the United States Census 25, a stratified random sampling method was implemented to ensure that the final demographic characteristics (specifically, age, and sex) of the NHWS sample matched those of the respective countries (Table A1). The International Database of the United States Census was used as it provides a uniform methodology for determining the size of the age by sex subpopulations of all European countries on an annual basis. The NHWS is a general health survey and respondents were not specifically made aware of the presence of HCV-related questions before taking part in the survey. All respondents of the NHWS were preliminarily included in the analyses (N=57 805).

Hepatitis C virus status

Respondents of the NHWS were asked whether a physician had diagnosed them with HCV. Only those who reported that they had been diagnosed (n=336) were considered part of the HCV group. All others were considered part of the control group (n=57 469).

Outcome variables

Health-related quality of life

The Medical Outcomes Study 12-Item Short Form Survey Instrument version 2 (SF-12v2) is a validated instrument used to assess health-related quality of life 26. The SF-12v2 instrument measures eight health domains: physical functioning, physical role limitations, bodily pain, general health, vitality, social functioning, emotional role limitations, and mental health. Along with these eight domains, two summary scores [physical (PCS) and mental component summary scores] and a health utility index (SF-6D) are also computed. PCS and mental component summary scores each have a population mean of 50, along with an SD of 10 (higher scores indicated greater quality of life). The health utility index has interval scoring properties and yields a summary score on a theoretical 0-1 scale.

Work productivity

The Work Productivity and Activity Impairment questionnaire was used to measure the impact of health on work productivity loss and impairment in daily activities 27. The Work Productivity and Activity Impairment questionnaire is a six-item validated instrument that consists of four metrics: absenteeism (the percentage of work time missed because of one's health in the past 7 days), presenteeism (the percentage of impairment experienced while at work in the past 7 days because of one's health), overall work productivity loss (an overall impairment estimate that is a combination of absenteeism and presenteeism), and activity impairment (the percentage of impairment in daily activities because of one's health in the past 7 days). Only respondents who reported being employed full-time, employed part-time, or self-employed provided data for absenteeism, presenteeism, and overall work impairment. All respondents provided data for activity impairment. The validity and accuracy of the instrument have been established in a number of disease states 28 and has been used previously among patients with HCV 29,30.

Absenteeism was calculated by dividing the number of work hours a patient missed in the past week because of his or her health by the total number of hours a patient could have worked (the number of hours he/she did work plus the number of hours missed because of his/her health) and converting this proportion into a percentage. Presenteeism was measured by a patient's rating of his or her level of impairment experienced while at work in the past 7 days (from 0 to 10, with higher numbers indicating greater impairment), which was then multiplied by 10 to create a percentage, with a range from 0 to 100%. Overall work impairment was measured by adding absenteeism and presenteeism to determine the total percentage of lost work time. Activity impairment was measured by a patient's rating of the level of impairment experienced in daily activities in the past 7 days (from 0 to 10, with higher numbers indicating greater impairment), which was then multiplied by 10 to create a percentage, with a range from 0 to 100%.

Healthcare resource utilization

Healthcare resource use was assessed by the number of visits in the last 6 months to healthcare providers, the emergency room, and the hospital for the patient's own medical condition. Healthcare providers included the following list: general practitioner/family practitioner, internist, allergist, cardiologist, dentist, dermatologist, diabetologist, endocrinologist, gastroenterologist, gynecologist, neurologist, nephrologist, nurse practitioner, oncologist, ophthalmologist, orthopedist, otolaryngologist, plastic surgeon, podiatrist, psychiatrist, psychologist/therapist, pulmonologist, rheumatologist, and urologist.

Predictor variables

Several variables were accounted for in the propensity score-matching process, including demographic, health history, and comorbidity information. Demographic variables included country of residence, age, sex, marital status (married/living with partner vs. all else), educational attainment (University degree vs. all else), and employment status (currently employed vs. not employed). Because of disparate healthcare systems across the five countries, insurance coverage was categorized as public health insurance, private health insurance, or unknown insurance. For similar reasons, annual household income was categorized as low income (<Û20 000), moderate income (Û20 000 to ²Û50 000), high income (>Û50 000), or decline to answer on the basis of the distributions of these variables. Health history variables included tobacco smoking (current smoker vs. nonsmoker), alcohol consumption (consume alcohol vs. abstain from alcohol), BMI, and physical exercise (exercise once or more per month for 20 min vs. no exercise in the past month). Comorbidity variables included the Charlson comorbidity index (CCI) 31, a single score that captures the overall comorbidity burden of each patient, and, separately, the presence of hepatitis B virus (HBV) and HIV/AIDS. Although HCV is a traditional component of the CCI ('liver disease'), it was excluded from our calculation of the CCI in the current study to ensure that the CCI was independent of HCV status.

Statistical analysis

As shown in previous research, patients with HCV have significantly different characteristics compared with those without HCV, including higher age and greater comorbidity burden as assessed with the CCI 22,30. To more appropriately address the potential issue of selection bias, a propensity score matching methodology was implemented. Specifically, country of residence, sex, age, marital status, education, household income, employment status, insurance coverage, tobacco smoking, alcohol consumption, BMI, physical exercise, HBV, and HIV/AIDS and comorbidity status using the CCI were entered into a single logistic regression model to predict HCV status (self-reported physician diagnosis of HCV vs. all others). Propensity score values from the logistic regression model were saved and used as part of the matching process. Each HCV patient was matched with a control whose propensity score was nearest using a greedy-matching algorithm. The greedy-matching algorithm allows for each case to be matched with the most suitable control available at that point in the matching process 32. This is done by performing up to seven passes to find one matched control for each case. First, the algorithm searches for a control with a propensity score within 0.0000001 of a case's propensity score value. If none is found, the algorithm searches for a control within 0.000001 and continues searching for a suitable control with decreasingly restrictive criteria (0.00001, 0.0001, 0.001, and 0.01) until a control is found 32.

Differences between the HCV group and the control groups (both before and after the matching process) were analyzed using χ2-tests for categorical variables and t-tests for continuous variables. Because the HCV group reported significantly higher rates of HBV even after the matching process, sensitivity analyses were carried out to ensure that HBV was not the reason for the difference in health outcomes. Multiple regressions were conducted controlling for HBV status on all outcomes. All analyses were carried out using SAS v9.1 (SAS, Cary, North Carolina, USA). Sampling weights from the NHWS were applied to all analyses to mitigate any sampling bias. Statistical significance was set a priori to a two-tailed P less than 0.05.

Results

A total of 336 patients across France (n=78), Germany (n=65), Italy (n=97), the UK (n=52), and Spain (n=44) reported being diagnosed with HCV. Applying sampling weights, these correspond to prevalence estimates of 0.59% in France, 0.44% in Germany, 1.42% in Italy, 0.82% in Spain, and 0.35% in the UK. Patients with HCV were predominantly men (54.2%) and had a mean age of 55.1 years (SD=15.4). Several demographic and patient characteristics were observed between HCV patients and those not diagnosed with HCV (Table 1).

Specifically, patients with HCV were significantly more likely to have public health insurance (84.5 vs. 75.2%) and currently smoke (46.7 vs. 27.5%) (all P's<0.05). Conversely, patients with HCV were significantly less likely to be women (45.4 vs. 51.4%), be employed (44.2 vs. 53.5%), to have private insurance (11.8 vs. 17.6%), and consume alcohol (67.8 vs. 76.8%) (all P's<0.05). Although 32.2% of patients with HCV reported not drinking alcohol, 39.3% still continued to drink at least once a week (10.9% reported drinking daily, 5.1% reported drinking 4-6 times per week, 12.3% reported drinking 2-3 times per week, and 10.8% reported drinking once a week).

The rates of HBV (14.7 vs. 0.9%, P<0.05) and HIV/AIDS infection (4.3 vs. 0.2%, P<0.05) were higher among patients with HCV as was an overall greater comorbidity burden as assessed using the CCI (mean=1.1 vs. 0.3, P<0.05). Only 2.2% of patients with HCV reported a diagnosis of cirrhosis. Table 2 lists the 15 most common comorbidities reported by patients with HCV.

During the matching process, four patients with HCV could not be matched with suitable controls because of their unique pattern of covariates. As a result, these four patients were excluded from the analyses. After the matching process, patients with HCV were equivalent to matched controls on all demographic and health history variables (Table 3). Although the overall comorbidity burden was also equivalent between groups, patients with HCV did report higher rates of HBV than the matched controls (14.3 vs. 7.1%, P=0.013).

Several health-related quality-of-life differences were observed between patients with HCV and the matched controls, as assessed using the domain scores of the SF-12v2 instrument (Fig. 1). Patients with HCV reported significantly lower levels of emotional role limitations (means=66.4 vs. 70.6, P=0.040), physical functioning (means=63.8 vs. 71.9, P=0.001), general health (means=48.3 vs. 54.4, P=0.004), bodily pain (means=64.3 vs. 70.8, P=0.002), and PCS scores (means=42.9 vs. 45.3, P=0.002). Although no other significant differences were observed, patients with HCV reported lower scores in all other domains of the SF-12v2 as well. Because the HBV rates were higher among those with HCV, a sensitivity analysis was carried out to determine whether controlling for differences in HBV accounted for the observed effects. In all cases, adjusting for HBV did not reduce the health-related quality-of-life detriments (emotional role limitations: adjusted means=66.0 vs. 70.6, P=.023; physical functioning: adjusted means=65.6 vs. 72.6, P=0.004; general health: adjusted means=48.4 vs. 54.6, P=0.004; bodily pain: adjusted means=64.1 vs. 70.0, P=0.007) and PCS scores (adjusted means=43.3 vs. 45.6, P=0.004).

Patients with HCV also reported significantly higher levels of presenteeism than the matched controls (means=27.1 vs. 21.0%, P=0.044). Absenteeism (means=7.1 vs. 6.7%, P=0.87), overall work impairment (means=31.1 vs. 25.6%, P=0.11), and activity impairment (means=34.1 vs. 31.8%, P=0.32) were all higher among patients with HCV, but not significantly so. As with health-related quality of life, a sensitivity analysis was carried out to control for HBV. The effect of HCV status on presenteeism became slightly more pronounced after this adjustment (adjusted means=26.3 vs. 19.8%, P=0.031).

Healthcare resource utilization was also compared between patients with HCV and the matched controls. No differences were observed in the number of emergency room visits in the past 6 months (means=0.38 vs. 0.32, P=0.50) or the number of hospitalizations in the past 6 months (means=0.25 vs. 0.28, P=0.80). However, there was a significant effect of HCV status on the number of physician visits in the past 6 months (means=9.9 vs. 6.7, P<0.001). This effect remained even after controlling for the presence of HBV (adjusted means=10.2 vs. 6.9, P<0.001).

Discussion

The aim of the present study was to assess the impact of the presence of HCV on health-related quality of life, work productivity loss, and healthcare resource utilization in France, Germany, Italy, Spain, and the UK. Although a few studies have examined the burden of HCV in Europe 5,14,19, no study has carried out such a comprehensive assessment of the health outcome burden of HCV across multiple European countries with a standardized methodology. Indeed, the lack of a standardized assessment of HCV and its effects has been identified as a major limitation in previous review papers 5.

Several European pricing and reimbursement decision-makers consider the public health impact of diseases as an integral part of a new medicine's therapeutic value assessment. More specifically, the French National Authority for Health, the German Institute for Quality and Efficiency in Health Care, and the recent UK Department of Health discussion paper on the UK value-based pricing all highlight the value of assessing disease severity, disease burden, and patient-relevant outcomes 33. Our research contributes to evidence generation of the burden associated with HCV in Europe.

The prevalence estimates reported using NHWS are consistent from those reported by the WHO, the Hepatitis C European Network for Co-operative Research, and Cornberg and colleagues, particularly when factoring in the diagnosis rate, which would be the most relevant comparison with the NHWS data 5,9,10. Both Italy and Spain reported the highest rates of HCV compared with those in France, Germany, and the UK. It is important to emphasize that given the self-reported methodology, the prevalence figures from NHWS represent only those who are aware of their HCV status. As shown in previous studies, many patients in Europe are unaware that they are infected 2,4. As such, the actual population levels may be underestimated. Nevertheless, the standardized representative methodology of NHWS provides valuable information on the relative prevalence figures across the five European countries. It also allows for a different perspective than previous studies, which have often recruited patients only from medical centers. Such a methodology may over-represent patients who are active in their healthcare.

A significant and pervasive burden of HCV was identified across the three health outcome domains, although the effects on health-related quality of life were the strongest. Patients with HCV, even when compared with the controls matched on a wide array of demographics, health history, and comorbidity information, reported significantly lower levels of several domain scores, including overall physical health (as assessed by PCS). Although the effects were not as strong as those observed in previous German studies, this is likely because of the more comprehensive set of covariates included in the present study. It is important to note that, because of its broad population focus, few of the HCV patients in NHWS were in the later stages of infection (the prevalence of cirrhosis was quite low). Nevertheless, a significant burden was observed even before these patients suffer from the severe sequelae associated with HCV. Complicating the management of these patients, several comorbidities were particularly prevalent including insomnia/sleep difficulties, pain, and anxiety. It is also interesting to note the continued frequency with which patients with HCV continued to consume alcohol; over a third drank more than once a week.

HCV status was also associated with higher levels of presenteeism. Although patients with HCV were no more likely to miss work than the matched controls, they were significantly less productive while at work because of their health. Patients also reported significantly more visits (almost 50% more) to their healthcare providers than the matched controls. Both of these effects have clear economic implications from a societal perspective. Patients with HCV use more healthcare resources because of their infection and, among those in the labor force, are less able to function in their employment. To our knowledge, this is the first study of its kind to examine the effect of HCV on workplace productivity in Europe, which contributes toward a better understanding of the societal-level impact of the virus.

Limitations

All HCV diagnoses, work productivity, and healthcare resource-use measures were patient-reported and may have introduced measurement error. As discussed above, many patients may be unaware that they are currently infected with HCV. It is possible that members of the control group were, in fact, infected with HCV without their knowledge. Patient report is a limitation from an epidemiological perspective, but it does allow for the analysis of variables such as health status and work productivity, which are best assessed from the patient directly. Although the propensity score-matching procedure included a wide array of demographic, health history, and comorbidity information, it is possible that additional variables may not have been included, which could explain the observed differences in health outcomes. For example, illicit drug use was not assessed in the NHWS. Of course, the most important confounders (HBV, HIV/AIDS, age, etc.) were included in the analyses. The NHWS uses a stratified random sample to ensure that the final sample is representative to the individual countries in terms of age and sex. However, because of the Internet survey methodology, it is possible that other differences between our sample and the population exist. Our methodology is unlikely to capture a truly representative mix of the HCV population, as disenfranchised groups (particularly injection drug users and those in poverty) and those in end stages of infection are unlikely to be adequately represented. Those differences may have an effect on the results, but, given the close match between the epidemiology of HCV in the NHWS and that of other sources (using completely different methodologies), the effect, if it exists, is likely not marked. The scope of this study was limited to France, Germany, Italy, Spain, and the UK; these results should not necessarily be extrapolated to other countries in Europe. For example, the evolving immigration patterns from the Middle East and Asia make each country unique with respect to epidemiology and disease burden.

Conclusion

Using a standardized methodology across France, Germany, Italy, Spain, and the UK, the presence of diagnosed HCV in the EU population has been shown, utilizing a propensity scoring model, to have a significant impact on several domains of health-related quality of life, presenteeism, and the number of visits to traditional healthcare providers. These analyses accounted for an exhaustive array of demographic, health history, and comorbidity information that is known to burden the HCV population and to be associated with health outcomes. In sum, these results add to the literature by documenting the population-level effect of HCV on a variety of patient-reported outcomes. This information is increasingly relevant in the context of pricing and reimbursement reforms of new medicines as well as the recent call to action for increased surveillance of HCV throughout the EU.

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Stem cell transfusions may someday replace the need for transplants in patients who suffer from liver failure caused by hepatitis B, according to a new study coming out of Beijing. . The results are published in the October issue of STEM CELLS Translational Medicine. Worldwide more than 500,000 people die each year from this condition.

Durham, NC (PRWEB) October 11, 2012

Stem cell transfusions may someday replace the need for transplants in patients who suffer from liver failure caused by hepatitis B, according to a new study coming out of Beijing. . The results are published in the October issue of STEM CELLS Translational Medicine. Worldwide more than 500,000 people die each year from this condition.

“In China, hepatitis B virus (HBV) infection accounts for the highest proportion of liver failure cases. While liver transplantation is considered the standard treatment, it has several drawbacks including a limited number of donors, long waiting lists, high cost and multiple complications. Our study shows that mesenchymal stem cell (MSCs) transfusions might be a good, safe alternative,” said Fu-Sheng Wang, Ph.D., M.D., the study’s lead author and director of the Research Center for Biological Therapy (RCBT) in Beijing.

Wang along with RCBT colleague, Drs. Ming Shi and Zheng Zhang of the Research Center for Biological Therapy, The Institute of Translational Hepatology led the group of physician-scientists from the centers and Beijing 302 Hospital who conducted the study.

MSC transfusions had already been shown to improve liver function in patients with end-stage liver diseases. This time, the researchers wanted to gauge the safety and initial efficacy of treating acute-on-chronic liver failure (ACLF) with MSCs. The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver define ACLF as an “acute deterioration of pre-existing chronic liver disease usually related to a precipitating event and associated with increased mortality at three months due to multisystem organ failure.” The short-term mortality rate for this condition is more than 50 percent.

MSCs have self-renewing abilities and the potential to differentiate into various types of cells. More importantly, they can interact with immune cells and cause the immune system to adjust to the desired level.

Of the 43 patients in this pilot study — each of whom had liver failure resulting from chronic HBV infection — 24 were treated with MSCs taken from donated umbilical cords and 19 were treated with saline as the control group. All received conventional therapy as well. The liver function, adverse events and survival rates were then evaluated during the 48-week or 72-week follow-up period.

Along with increased survival rates, the patients’ liver function improved and platelet count increased. No significant side effects were observed throughout the treatment and follow-up period.

“While the results are preliminary and this pilot study includes a small number of patients, MSC transfusions appear to be safe and may serve as a novel therapeutic approach for HBV-associated ACLF patients,” Dr. Shi said.

“The study also highlights several key issues that will need to be considered in the design of future clinical studies, such as the optimal type of stem cells that will be infused, the minimum effective number of the cells and the best route of administration,” Dr. Wang added.

“These results are certainly promising and the strategy merits additional study, especially considering the shortage of donor organs” said Anthony Atala, MD, Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

###

The full article, “Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients,” can be accessed at: http://www.stemcellstm.com/.

About STEM CELLS Translational Medicine: STEM CELLS TRANSLATIONAL MEDICINE (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® (http://www.StemCells.com), celebrating its 30th anniversary in 2012, is the world's first journal devoted to this fast paced field of research. The Oncologist® (http://www.TheOncologist.com), also a monthly peer-reviewed publication, entering its 17th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.

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Antivir Ther. 2012 Sep 13. doi: 10.3851/IMP2359. [Epub ahead of print]

Agarwal A, Zhang B, Olek E, Robison H, Robarge L, Deshpande M.

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Achillion Pharmaceuticals, Inc., New Haven, CT, USA. aagarwal@achillion.com .

Abstract
BACKGROUND: ACH-1625 is a linear peptidomimetic inhibitor that non-covalently binds to hepatitis C virus (HCV) NS3 protease with high potency and specificity. Short term monotherapy of HCV genotype-1 (GT-1) infection with ACH-1625 was found to be safe and resulted in ≥3.3 log(10) IU/mL mean viral load reduction. This viral load decay data was analyzed to compare HCV dynamics with prior reports and estimate the antiviral efficiency of ACH-1625.

METHODS: Drug efficiency (ε) was estimated by analyzing the viral decay following initiation of up to 5 days of monotherapy with ACH-1625 in 36 chronically-infected HCV GT-1 patients. During this monotherapy study, ACH-1625 was administered either twice a day for 4.5 days or once daily for 5 days at 5 different dose levels in 36 patients.

RESULTS: A sharp viral decay during first 48 hours following the initiation of ACH-1625 treatment afforded high drug efficiency estimates (≥ 0.9934). In addition, an increase in the estimated drug efficiency was observed with increasing ACH-1625 dose. The observed anti-HCV response was fairly uniform in this proof-of-concept study across the population of 36 patients.

CONCLUSIONS: Estimates of the treatment independent viral kinetics parameters were consistent with prior reports and the estimated drug efficiency of ACH-1625 monotherapy was very high (≥0.9934) in fasted and fed states.

PMID: 22976492 [PubMed - as supplied by publisher]

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J Med Virol. 2012 Nov;84(11):1744-50. doi: 10.1002/jmv.23399.

Manos MM, Shvachko VA, Murphy RC, Arduino JM, Shire NJ.

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Kaiser Permanente Division of Research, Oakland, California. michele.manos@kp.org.

Abstract

Hepatitis C virus (HCV) genotypes influence response to therapy, and recently approved direct-acting antivirals are genotype-specific. Genotype distribution information can help to guide antiviral development and elucidate infection patterns. HCV genotype distributions were studied in a diverse cross-section of patients in the Northern California Kaiser Permanente health plan. Associations between genotype and race/ethnicity, age, and sex were assessed with multivariate logistic regression models. The 10,256 patients studied were median age 56 years, 62% male, 55% White non-Hispanic. Overall, 70% were genotype 1, 16% genotype 2, 12% genotype 3, 1% genotype 4, <1% genotype 5, and 1% genotype 6. Blacks (OR 4.5 [3.8-5.5]) and Asians (OR 1.2 [1.0-1.4]) were more likely to have genotype 1 than 2/3 versus non-Hispanic Whites. Women less likely had genotype 1 versus 2/3 than did men (OR 0.86 [0.78-0.94]). Versus non-Hispanic Whites, Asians (OR 0.38 [0.31-0.46]) and Blacks (OR 0.73 [0.63-0.84]) were less likely genotype1a than 1b; Hispanics (OR 1.3 [1.1-1.5]) and Native Americans (OR 1.9 [1.2-2.8]) more likely had genotype 1a than 1b. Patients age ≥65 years less likely had genotype 1a than 1b versus those age 45-64 (OR 0.34 [0.29-0.41]). The predominance of genotype 1 among all groups studied reinforces the need for new therapies targeting this genotype. Racial/ethnic variations in HCV genotype and subtype distribution must be considered in formulating new agents and novel strategies to successfully treat the diversity of hepatitis C patients. J. Med. Virol. 84:1744-1750, 2012. © 2012 Wiley Periodicals, Inc.

Copyright © 2012 Wiley Periodicals, Inc.

PMID: 22997077 [PubMed - in process]

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Curr Med Res Opin. 2012 Sep 27. [Epub ahead of print]

Cure S, Diels J, Gavart S, Bianic F, Jones E.

Abstract

BACKGROUND & AIMS: To indirectly compare the efficacy of telaprevir (TVR) and boceprevir (BOC) combined with peginterferon/ribavirin α-2a/2b (PR) in achieving sustained viral response (SVR) in treatment-naïve and treatment-experienced patients with genotype 1 chronic hepatitis C virus (HCV) infection.

METHODS: A systematic literature review was conducted to identify randomized controlled trials reporting the efficacy of PR-based treatment in genotype 1 chronic HCV patients. A Bayesian network meta-analysis was performed on the endpoint of SVR, assuming fixed study effects. For treatment-experienced patients, only previous relapsers and partial responders were included, as no results in prior null-responders were available for boceprevir.

RESULTS: 11 publications were included. In treatment-naïve patients, the odds ratios (OR) (posterior median [95% credible interval]) for telaprevir (12 weeks + Response Guided Treatment (RGT) 24/48 weeks PR) and boceprevir (24 weeks + RGT 28/48 weeks PR) versus PR were respectively 3.80 [2.78-5.22] and 2.99 [2.23-4.01]. The OR between telaprevir versus boceprevir was 1.42 [0.89-2.25], with a probability for telaprevir being more effective (P[OR>1]) of 0.93. In treatment-experienced patients, the OR of telaprevir (12 weeks + 48 weeks PR) and boceprevir (32 weeks + RGT 36/48 weeks PR) versus PR were respectively 13.11 [7.30-24.43] and 5.36 [2.90-10.30]. The OR between telaprevir versus boceprevir was 2.45 [1.02-5.80], with telaprevir having a probability of 0.98 for being more effective. The main limitation of this study is the low number of trials included in the analysis, especially for the treatment-experienced patient population, which only allowed to explore random-effect models. We tried to identify potential biases due to study heterogeneity.

CONCLUSIONS: In the absence of direct comparative head-to-head studies between telaprevir and boceprevir for the treatment of chronic HCV genotype 1 patients, an indirect comparison based on Bayesian network meta-analysis suggests better efficacy for telaprevir than boceprevir in both treatment-naïve and treatment-experienced patients.

PMID: 23016967 [PubMed - as supplied by publisher]

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J Stud Alcohol Drugs. 2012 Oct;73(6):991-7.

Mitchell MC, Memisoglu A, Silverman BL.

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Division of Gastroenterology, Johns Hopkins Bayview Medical Center, Baltimore, Marylan.

Abstract

ABSTRACT. Objective: Naltrexone (Revia, Vivitrol) is recognized as having the potential for hepatotoxicity. We evaluated the safety of intramuscular extended-release naltrexone (XR-NTX) in a cohort of patients with a high prevalence of chronic hepatitis C virus (HC V) and HIV infection undergoing treatment for opioid dependence. Method: A total of 250 (88% male) opioid-dependent patients were randomized to receive monthly injections of XR-NTX 380 mg or placebo. Of the 250 subjects, 222 (88.8%) had a history of HCV; 42% were positive for HIV. Liver chemistry tests for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, gamma-glutamyl aminotransferase (GGT), alkaline phosphatase, serum albumin, and total protein were obtained at the screening visit, at baseline, and monthly for up to 6 months. Results: In a longitudinal analysis, the frequency of elevations in AST, ALT, and GGT greater than three times the upper limit of normal (ULN) was not statistically different in patients treated with XR-NTX compared with placebo (p = .71). Most of the elevations greater than three times the ULN occurred in patients with chronic HCV infection. In patients who had a treatment-emergent elevation in AST or ALT greater than three times the ULN, the aminotransferases improved and returned toward baseline in those patients with available follow-up data. No specific symptoms were associated with any of the elevations in ALT, AST, or GGT. The frequency of elevations in AST and ALT during treatment in patients with HIV infection was not significantly different compared with that in patients without HIV infection. Conclusions: XR-NTX can be used safely in eligible patients with opioid dependence, including those with underlying mild to moderate chronic HCV and/or HIV infections. (J. Stud. Alcohol Drugs, 73, 991-997, 2012).

PMID: 23036218 [PubMed - in process]

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South Med J. 2012 Oct;105(10):500-3. doi: 10.1097/SMJ.0b013e3182675d86.

Bakaj G, Valasiuk T, Prabhukhot R, Siraj D.

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From the Departments of Internal Medicine and Infectious Diseases, East Carolina University/Pitt County Memorial Hospital, Greenville, North Carolina.

Abstract
OBJECTIVES: The rate of treatment of hepatitis C virus (HCV) infection in human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infected patients remains historically low. We undertook a retrospective study to review our treatment rate and factors that have negatively influenced this rate. In those treated, we reviewed outcomes and compared results with prior studies.
METHODS: A total of 233 patients infected with HIV and HCV were followed for 7 years in the infectious diseases (ID) clinic of East Carolina University. Proper follow-up evaluation was determined based on the presence of HCV polymerase chain reaction viral load and genotype testing. The number of patients treated, response to treatment, and reason for no treatment were determined by chart review.

RESULTS: Of 233 patients with positive HCV serology, 48 were excluded due to undetectable HCV viral load. Of the remaining 185 patients, 142 (77%) were evaluated by testing for HCV viral load and genotype, but only 112 of those who were followed up in the clinic regularly were considered eligible for therapy. Fourteen of 112 (12.5%) of patients underwent treatment and only 1 in 14 (7%) attained sustained virological response (SVR). Of the patients tested, 96% had HCV genotype 1, and 81% were African American.

CONCLUSIONS: The majority of our HIV-HCV co-infected patients received a proper HCV evaluation, but only 12.5% were offered therapy. Of those treated, only one patient achieved SVR. The higher proportion of genotype 1 and African American patient population are considered the main reasons for the low SVR. Low SVR rate, high rate of adverse effects, and the unique demography of our patient population have been the main reasons for the lower treatment rate.

PMID: 23038477 [PubMed - in process]

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BMJ Open. 2012 Oct 7;2(5). pii: e001755. doi: 10.1136/bmjopen-2012-001755. Print 2012.

Swart A, Burns L, Mao L, Grulich AE, Amin J, O'Connell DL, Meagher NS, Randall DA, Degenhardt L, Vajdic CM.

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Prince of Wales Clinical School, Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.

Abstract

OBJECTIVE: To quantify cancer risk in opioid dependence and the association with infection by the oncogenic blood-borne viruses (BBVs) hepatitis C (HCV), hepatitis B (HBV) and HIV.

DESIGN: Cohort study.

SETTING: New South Wales, Australia.

PARTICIPANTS: All 45 412 adults aged 16 years or over registered for opioid substitution therapy (OST) between 1985 and 2007. Notifications of cancer, death and infection with HCV, HBV and HIV were ascertained by record linkage with registries.

MAIN OUTCOME MEASURES: The ratios of observed to expected number of cancers, standardised incidence ratios (SIRs), and the average annual per cent change (AAPC) in overall age and sex-standardised cancer incidence.

RESULTS: Overall cancer risk was modestly increased compared to the general population (SIR 1.15, 95% CI 1.07 to 1.23). Excess risk was observed for 11 cancers, particularly lung (4.02, 95% CI 3.32 to 4.82), non-Hodgkin's lymphoma (1.51, 95% CI 1.20 to 1.88) and liver (8.04, 95% CI 6.18 to 10.3). Reduced risk was observed for six cancers, including prostate (0.16, 95% CI 0.06 to 0.32) and breast (0.48, 95% CI 0.35 to 0.62). Individuals notified with HCV or HBV had a markedly increased risk of liver cancer; lung cancer risk was also increased in those with HCV. HIV was associated with an elevated risk of liver, anus and kidney cancer, non-Hodgkin lymphoma and Kaposi sarcoma. Cancer risk was not increased in individuals without a BBV notification, apart from pancreatic cancer (3.92, 95% CI 1.07 to 10.0). Cancer incidence increased significantly over time (AAPC 9.4%, 4.2% to 15%, p=0.001).

CONCLUSIONS: BBVs play a major role in the cancer risk profile of opioid-dependent individuals registered for OST. To address the dramatic increasing trend in cancer incidence, the OST setting could be utilised for cancer prevention strategies.

PMID: 23045358 [PubMed - in process] Free full text

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Antivir Ther. 2012 Sep 28. doi: 10.3851/IMP2415. [Epub ahead of print]

Lawitz EJ, Hill JM, Marbury T, Demicco MP, Delaney W, Yang J, Moorehead L, Mathias A, Mo H, McHutchison JG, Rodriguez-Torres M, Gordon SC.

Source

Alamo Medical Research, San Antonio, TX, USA. lawitz@alamomedicalresearch.com.

Abstract
BACKGROUND: GS-9451 is a novel inhibitor of the hepatitis C virus (HCV) NS3/4A protease and demonstrates potent in vitro suppression of HCV genotype 1 replicons.
METHODS: The safety, pharmacokinetics, and antiviral efficacy of GS-9451 were evaluated in a Phase 1 study in treatment-naïve, HCV genotype 1 infected patients. Patients were randomized to 3 days of once-daily dosing with placebo (n=8) or GS-9451 60 mg (n=8 genotype 1a), 200 mg (n=8 genotype 1a; n=8 genotype 1b), or 400 mg (n=9 genotype 1a). Plasma samples were collected through Day 14 for pharmacokinetic evaluation, serum HCV RNA quantitation, and NS3 sequencing.

RESULTS: No patients interrupted or discontinued dosing due to an adverse event. The median (range) maximal HCV RNA reductions from baseline were -0.88 (-1.24, -0.64), -3.19 (-3.31, -2.94), and -3.64 (-4.08, -3.54) log(10) IU/mL in genotype 1a patients receiving 60, 200, and 400 mg/d GS-9451, respectively, and -3.48 (-3.54, -3.03) log(10) IU/mL in genotype 1b patients receiving GS-9451 200 mg/d. Median half-life ranged from 14-17 hours. Day 3 mean C(tau) was 5.5- and 17-fold above protein-binding adjusted mean EC(50) in 200- and 400-mg cohorts, respectively. No resistance mutations were detected with GS-9451 60 mg/d. In the 200 mg/d or 400 mg/d groups, predominant mutations were NS3 R155 (R155K) in genotype 1a patients and D168 (D168E, D168V and D168G) in genotype 1b patients.

CONCLUSIONS: GS-9451 was well tolerated. During 3 days of monotherapy, GS-9451 200 mg/d or 400 mg/d demonstrated potent antiviral activity in both HCV genotype 1a and 1b infected patients. GS-9451 is currently being evaluated in combination regimens with and without peginterferon alfa.

PMID: 23047118 [PubMed - as supplied by publisher]

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Eur J Clin Invest. 2012 Jun;42(6):599-606. doi: 10.1111/j.1365-2362.2011.02623.x. Epub 2011 Nov 25.

Payer BA, Reiberger T, Aberle J, Ferenci P, Holzmann H, Rieger A, Peck-Radosavljevic M; Vienna HIV-HCV study group.

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Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Abstract
BACKGROUND: A polymorphism near the IL28B gene has been shown to be associated with virologic response to antiviral treatment in HCV-infected patients. The predictive value of interferon-gamma inducible protein 10 (IP10) on treatment outcome has been described in HCV patients. Data on combining these predictors in HIV-HCV-coinfected patients are not available.

METHODS: Virologic parameters, IL28B single nucleotide polymorphisms (SNP) and pretreatment serum IP10 were determined in HIV-HCV-coinfected patients having completed antiviral therapy with pegylated interferon/ribavirin.

RESULTS: A total of 72 HIV-HCV-coinfected patients were included in the study; 68% had HCV genotype (GT)-1/4 and 32% had HCV GT-2/3 infections. Rapid virologic response (63% vs. 28%; P = 0·023) and sustained virologic response (SVR: 81% vs. 51%; P = 0·008) rates were significantly higher in C/C vs. non-C/C patients. Patients with low pretreatment IP10 levels (< 400 pg/mL) achieved significantly higher SVR rates than patients with high (> 400 pg/mL) IP10 levels (78% vs. 13%; P < 0·0001). C/C SNP and low IP10 levels were associated with higher SVR rates in both patients with GT-1/4 and GT-2/3. The C/C patients with low IP10 achieved SVR rates of 97% compared with SVR rates of 9% in non-C/C patients with high IP10.

CONCLUSION: The IL28B SNP influences rapid viral response, relapse rates and SVR. The combination of IL28B and IP10 represents a predictive model of SVR in HIV-HCV coinfection.

© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

PMID: 22117591 [PubMed - indexed for MEDLINE]

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AIDS. 2012 Oct 1. [Epub ahead of print]

Mandorfer M, Reiberger T, Payer BA, Ferlitsch A, Breitenecker F, Aichelburg MC, Obermayer-Pietsch B, Rieger A, Trauner M, Peck-Radosavljevic M; Vienna HIV & Liver Study Group.

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aDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna bDivision of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna cDivision of Endocrinology and Metabolism, Department of Internal Medicine, Medical University Graz.

Abstract

BACKGROUND:: Low 25-hydroxyvitamin D (25(OH)D) levels are commonly found in HIV/HCV coinfected patients and are associated with liver fibrosis. No association between 25(OH)D levels and response to pegylated interferon α-2a/2b plus ribavirin (PEGIFN+RBV) has yet been reported for HIV/HCV coinfected patients. DESIGN:: Epidemiological characteristics, HIV and HCV infection parameters, liver biopsies, as well as data on virologic response was available in 65 patients who received chronic hepatitis C (CHC) therapy with PEGIFN+RBV within a prospective trial. 25(OH)D levels were retrospectively assessed using stored screening serum samples obtained within 35 days prior to CHC treatment. METHODS:: According to their 25(OH)D levels, patients were assigned to the normal (>30 ng/ml;D-NORM), the insufficiency (10-30 ng/ml; D-INSUFF), or the deficiency (<10 ng/ml; D-DEF) group. HCV-GT 1/4, high HCV-RNA load (>6 × 10IU/ml), advanced liver fibrosis (METAVIR F3/F4), and IL28B rs12979860 non-C/C SNP were considered as established risk factors for treatment failure in HIV/HCV coinfected patients. RESULTS:: 37 (57%) and 15 (23%) patients presented with D-INSUFF and D-DEF, respectively, while only 13 (20%) patients had normal 25(OH)D levels. Substantial differences in cEVR (D-NORM 92% vs. D-INSUFF 68% vs. D-DEF 47%; P = 0.008) and SVR (D-NORM 85% vs. D-INSUFF 60% vs. D-DEF 40%; P = 0.029) rates were observed between 25(OH)D subgroups. Especially in difficult-to-treat patients with multiple (3-4) established risk factors, low 25(OH)D levels were clearly associated with lower rates of SVR (patients without 25(OH)D deficiency 52% vs. D-DEF 0%; P = 0.012). CONCLUSIONS:: Low 25(OH)D levels may impair virologic response to PEGIFN+RBV therapy, especially in difficult-to-treat patients. Vitamin D supplementation should be considered and evaluated prospectively in HIV/HCV coinfected patients receiving CHC treatment.

PMID: 23032421 [PubMed - as supplied by publisher]

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Study reveals prehistoric journey of hepatitis B

15-studyreveals

The hepatitis B virus. Credit: Wellcome Images

October 11, 2012

(Medical Xpress)—A new study has revealed how the spread of hepatitis B coincides with dates of human migration throughout history, starting around 40 000 years ago. The study could provide a framework for studying the ongoing burden and evolution of the hepatitis B virus.

Hepatitis B is a global public health problem: there are approximately 2 billion infected people worldwide and more than 350 million carriers. There are currently several theories about where the infection in humans might have originated from, but until now there was little evidence to support them.

The new study provides evidence to show that HBV has been following the migration patterns of human populations for the past 40 000 years. The team of researchers, from the Universities of Athens, Oxford, Sydney and Cambridge, suggest that the hepatitis B virus (HBV) was infecting us on our journey out of Africa.

The team reviewed and analysed the spread of HBV infection with respect to ancient human populations and examined the relationship between the history of evolution of HBV and the genetic diversity of humans. They found that the distributions of HBV genotypes are consistent with prehistoric modern human migrations. The most pronounced increase also correlates with the increase in human population over the past 5000 years.

Dr Dimitrios Paraskevis, who led the study at the University of Athens, said: "This is the first consistent evidence to show when the hepatitis B virus first 'jumped' into humans." Dr Gkikas Magiorkinis, lead author for the University of Oxford, said: "Our approach could be used to shed light on the history of other infectious diseases and how they have evolved in line with their hosts over time."

The study also looked at non-human strains of the virus found in gibbons, orang-utans and chimpanzees and found evidence that the virus jumped from humans no less than 6000 years ago. The orang-utan HBV strain, in particular, is closely related to the human strain, whereas in chimpanzees it seems the transmission was from an ancient human group that is now extinct.

"Understanding where the virus came from is crucial because it gives us a framework to study how the virus has evolved to become more harmful in human populations over time," Dr Paraskevis added.

Understanding the emergence and transmission of infectious diseases is one of the Wellcome Trust's core strategic research challenges.

The study is published in the journal Hepatology.

More information: Paraskevis D, et al. Dating the origin and dispersal of hepatitis B virus infection in humans and primates. Hepatology, 2012.

Journal reference: Hepatology

Provided by Wellcome Trust

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