Showing posts with label Cryoglobulinemia. Show all posts
Showing posts with label Cryoglobulinemia. Show all posts

Tuesday, September 25, 2018

Editorial: interferon‐free DAAs are a great boon for patients with hepatitis C and cryoglobulinaemia

Aliment Pharmacol Ther. 2018 Oct;48(7):770-771. doi: 10.1111/apt.14899.

INVITED EDITORIAL
Editorial: interferon‐free DAAs are a great boon for patients with hepatitis C and cryoglobulinaemia
M. Atsukawa, A. Tsubota
Pages: 770-771
First Published: 23 September 2018 

Chronic hepatitis C is often accompanied by various extrahepatic manifestations that affect the health‐related quality of life (HRQoL) and mortality of patients.1, 2 In particular, mixed cryoglobulinaemia (MC) and MC syndrome (MCS) are closely associated with hepatitis C virus (HCV) infection. Thus, the most rational treatment strategy for HCV‐related MC/MCS is HCV eradication. As expected, interferon (IFN)‐based treatment can alleviate MC/MCS in patients with a sustained virological response (SVR).3 However, the SVR rate is low and drug adherence is frequently reduced due to adverse events.4 MCS patients exhibit systemic complications that may attenuate the efficacy of IFN‐based treatment. Moreover, MC is a negative, independent predictor of virological response.5 Currently, IFN‐free direct‐acting antiviral (DAA) combination therapy that yields a high SVR rate with high tolerability is the standard of care for chronic hepatitis C. DAA treatment for MC patients reportedly achieved a SVR rate of 74%‐100% and reduced or resolved the symptoms in 61%‐100% of the patients with SVR.6

To our knowledge, Gragnani and colleagues were the first to conduct a prospective, case‐control study to evaluate the virological/clinical/immunological response and the HRQoL score following IFN‐free, DAA‐based treatment for cryoglobulinaemic vasculitis (CV) patients, MC patients without vasculitis, and control patients without CV/MC.7 This comparative study reconfirmed the excellent efficacy/safety profile of DAA‐based treatment even in CV/MC patients. The SVR rate (89.9%) was almost twice that (48.6%) with pegylated IFN/ribavirin treatment.5, 7 It was noteworthy that SVR persistently improved the clinical indices at a high rate in CV patients. Immunological response progressively improved in CV patients with SVR. Moreover, the HRQoL score, including physical and mental components, was lower at baseline in CV patients than in MC/control patients, while it significantly improved in CV patients with SVR. Therefore, the highly effective and safe DAA treatment is a great boon for CV patients, because it consequently reduces their physical and/or mental burden future healthcare costs.

However, the SVR rates in CV/MC patients (90.6% and 88.9%, respectively) were lower (although not significantly) than those in control patients (95.3%).7 In fact, most patients with treatment failure had cryoglobulinaemia and some exhibited severe manifestations before treatment. Such patients failed to experience clinical improvement during the post‐treatment period. These outcomes suggest the importance of early treatment for CV/MC patients before disease progression to severe stages.

DAAs are rapidly developing, and treatment options are increasing; therefore, personalised medication by regimen optimisation is possible for cryoglobulinaemic patients with various complications. For instance, sofosbuvir/ribavirin is administered to CV patients.6 However, 8%‐58% of cryoglobulinaemic patients have renal impairment.8 Sofosbuvir and ribavirin are mainly excreted in the urine; thus, both are contraindicated for, or should be carefully administered to, patients with moderate/severe renal dysfunction. Currently, the AASLD guidelines specify elbasvir/grazoprevir or glecaprevir/pibrentasvir as the first‐line treatment.9 Moreover, the EASL guidelines recommend ribavirin‐free treatment for cryoglobulinaemic patients with renal dysfunction.10 Precision medicine is required, particularly for cryoglobulinaemic patients with severe complications and refractory features.

ACKNOWLEDGEMENTS
Declaration of personal interests: M Atsukawa has served as a speaker for AbbVie, MSD and Gilead Sciences, and has received research funding from AbbVie and MSD. 

Source:
Zignego AL, et al. Aliment Pharmacol Ther. 2018

We would like to express our gratitude to Drs Atsukawa and Tsubota for their comments and the correct interpretation of the main messages that may be deduced from our study,1, 2 especially concerning the future challenges in the treatment of cryoglobulinaemic vasculitis (mixed cryoglobulinaemia syndrome, MCS), a HCV‐related disease that is often under‐estimated and not sufficiently known.3

The occurrence of MCS represents a condition that justifies careful prioritization of Interferon‐free anti‐HCV treatment. This appears to be the most effective as soon as it is carried out, whereas, when the therapy is too late and the patients have already developed severe damage (especially renal), MCS requires careful evaluation and accurate tailoring of non‐aetiological therapies (e.g, anti‐inflammatory and immunosuppressant) to be performed before, but also after, and sometimes concomitantly with anti‐viral therapy.

The complex pathogenetic cascade that underlies this lymphoproliferative disorder, and that originates from the clonal expansion of specific B‐cells (RF‐B cells), may lead to the subsequent overcoming of points of no return whose identification would be important for the assessment of a rational approach to the patients. Above all, in case of the persistence of MCS symptoms and/or signs, it would be important to distinguish the causes indicating the risk of evolution of the lymphomagenetic process (the overcoming of points of no return), from those without this risk, such as the simple occurrence of irreversible tissue damage.4

In this light, it seems conceivable that a key factor for the correct interpretation of the persistence of MCS stigmata even after viral eradication, is the evaluation of the persistence of B cell clonal expansion. Various factors have been suggested as playing a key role in inducing clonal expansion, first the important and sustained activation of the B‐cell compartment by both viral and host factors. Among the latter, special emphasis was placed on the binding of the viral E2 protein and the CD81 molecule on the surface of the B cells5 and the effect of the B‐cell‐activating factor (BAFF)/B‐lymphocyte stimulator (BLyS), especially in subjects harbouring particular genetic variants.6 Such an important and persistent B‐cell activation would cooperate to the lymphomagenetic process with B‐cell anti‐apoptotic factors including, first, the t (14; 18) translocation7 and could possibly be correlated with an exhaustion of the B cells observed during MCS.8 Consequently, it seems conceivable that the detection of persistent B cell expanded clones through sensitive methods, after HCV eradication, could help in understanding the condition that we are facing; this would be helpful in deciding the best approach to the patient (more frequent follow‐ups and/or specific therapies).

In conclusion, following the demonstration of the positive effect of viral eradication in MCS patients, the most important future challenge is the identification of markers useful in assessing the best approach to patients that maintain clinical and/or immunological MCS stigmata after SVR.

ACKNOWLEDGEMENT
The authors’ declarations of personal and financial interests are unchanged from those in the original article.2
Source:

Tuesday, October 24, 2017

October Series From HCV Advocate - HCV and Peripheral Neuropathy

New Online: HCV-related diseases

In October, HCV Advocate launched a series of patient-friendly articles about the Extrahepatic Manifestations of Hepatitis C, written by Alan Franciscus.

Browse through topics provided below, make sure not to miss new articles published later this month, sign up here to receive updates, follow HCV Advocate on Twitter or connect on Facebook. Find out what's new, here!

Begin with HCV Advocates Extrahepatic Manifestation Glossary and Fact Sheets.

October Blog Special
Extrahepatic Manifestations of Hepatitis C—Peripheral Neuropathy | Alan Franciscus
October 24, 2017
In the past, peripheral neuropathy was believed to be confined to people only infected with hepatitis C-related cryoglobulinemia, but now it is known that peripheral neuropathy may occur even in the absence of cryoglobulinemia.
Continue reading (LINK)



Friday, July 14, 2017

Extrahepatic manifestations of HCV & Treatment

If you are interested in reading full text articles about the treatment and management of HCV I highly suggest you follow Henry E. Chang on Twitter.

Latest Tweets By @HenryEChang on the extrahepatic manifestations of HCV.

July 14, 2017
Extrahepatic manifestations of HCV: The role of direct acting antivirals
María Laura Polo and *Natalia Laufer
Expert Review of Anti-infective Therapy DOI: 10.1080/14787210.2017.1354697

Introduction:
Hepatitis C virus (HCV) represents a major health concern, as nearly 3 million people become newly infected by this pathogen annually. The majority of infected individuals fail to clear the virus, and chronicity is established. Chronic HCV patients are at high risk for liver disease, ranging from mild fibrosis to cirrhosis and severe hepatocellular carcinoma. Over the last few years, the development of multiple direct acting antivirals (DAA) have revolutionized the HCV infection treatment, demonstrating cure rates higher than 90%, and showing less side effects than previous interferon-based regimens. Areas covered: Besides liver, HCV infection affects a variety of organs, therefore inducing diverse extrahepatic manifestations.

This review covers clinical, experimental, and epidemiological publications regarding systemic manifestations of HCV, as well as recent studies focused on the effect of DAA in such conditions.  Expert commentary: Though further research is needed; available data suggest that HCV eradication is often associated with the improvement of extrahepatic symptoms. Therefore, the emergence of DAA would offer the opportunity to treat both HCV infection and its systemic manifestations, requiring shorter treatment duration and driving minor adverse effects.
Link - Download Full Text Article.......
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Clinics in Liver Disease, Volume 21, Issue 3

Chronic Hepatitis C Virus Infection and Depression
Luigi Elio Adinolfi, Riccardo Nevola, Luca Rinaldi, Ciro Romano, Mauro Giordano

KEYWORDS
HCV Depression Quality of life

KEY POINTS

Depression is an extrahepatic manifestation of chronic hepatitis C virus (HCV) infection reported in one-third of patients.

The prevalence of depression in patients with HCV has been estimated to be 1.5 to 4.0 times higher than that observed in the general population.

Direct HCV neuro-invasion, induction of local and systemic inflammation, neurotransmission, and metabolic derangements are the hypothesized pathogenic mechanisms of depression.

Depression considerably impacts health-related quality of life of HCV-positive patients.

Clearance of HCV by antiviral treatments is associated with an improvement of both depression and quality of life.
Link - Download Full Text PDF
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Metabolic Manifestations of Hepatitis C Virus
Lawrence Serfaty

KEYWORDS
Hepatitis C Steatosis Hypobetalipoproteinemia Microsomal triglyceride transfer protein Insulin resistance. Tumor necrosis factor

KEY POINTS

Out of excessive alcohol consumption, steatosis should be classified into 2 types according to hepatitis C virus (HCV) genotypes: metabolic steatosis, which is associated with features of metabolic syndrome and insulin resistance in patients infected with nongenotype 3, and viral steatosis, which is correlated with viral load and hyperlipemia in patients infected with genotype 3.

HCV interacts with host lipid metabolism by several mechanisms, such as promotion of lipogenesis, reduction of fatty acid oxidation, and decreases of lipids export, leading to hepatic steatosis and hypolipidemia.

A strong link between HCV infection and diabetes mellitus has been found in subjectbased studies and, to a lesser degree, in population-based studies.

HCV-mediated insulin resistance may be promoted through multiple pathogenic mechanisms, such as direct inhibition of insulin signaling pathway by HCV core protein in the liver, overproduction of tumor necrosis factor-alpha, oxidative stress, modulation of incretins, or pancreatic ß-cells dysfunction.
Link - Download Full Text PDF
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Neurologic manifestations of hepatitis C virus infection
Sentia Iriana, MD, Michael P. Curry, MD, Nezam H. Afdhal, MD, DSc

KEYWORDS
Hepatitis C Fatigue Neurocognition MR spectroscopy Interferon Ledipasvir/sofosbuvir Cerebrovascular disease

KEY POINTS
The extrahepatic manifestations of hepatitis C virus (HCV) in the brain include neurocognitive dysfunction, which is manifested by subtle changes in memory, attention, and processing speed.

Neurocognitive defects are independent of the histologic stage of disease and may be induced by a direct effect of HCV on microglial cells or mediated by systemic cytokines crossing the blood-brain barrier.

Magnetic resonance spectroscopy demonstrates abnormal metabolism in basal ganglia and prefrontal and frontal cortex, which has been associated with fatigue and abnormal neurocognitive testing. Interferon and direct-acting antiviral therapy can improve cerebral metabolism and neurocognition if a sustained virologic response is obtained.

Cerebrovascular events and mortality are increased in patients with HCV and may be through an increased risk of carotid artery disease and plaque formation.
Link - Full Text PDF Article
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Rheumatologic manifestations of hepatitis C virus
Patrice Cacoub, Cloé Comarmond, Anne Claire Desbois, David Saadoun

KEYWORDS
Hepatitis C (HCV) Rheumatic disorders Arthritis Vasculitis Arthralgia Sicca syndrome

KEY POINTS
Main rheumatologic manifestations reported with hepatitis C virus (HCV) chronic infection include arthralgia, myalgia, cryoglobulinemia vasculitis, and sicca syndrome.

Immunologic factors predisposing to developsuch manifestations include stimulation of B cells, expansion of B-cell–producing immunoglobulin M with rheumatoid factor activity and of clonal marginal zone, like B cells, and a decrease of regulatory T cells.

The treatment of HCV infection with interferon alpha has been contraindicated for a long time in many rheumatologic autoimmune/inflammatory disorders.

New oral interferon-free combinations now offer an opportunity for patients with HCV extrahepatic manifestations, including rheumatologic autoimmune/inflammatory disorders, to be cured with a high efficacy rate and a low risk of side effects.
Link - Full Text PDF Download
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Other EHM of HCV infection (pulmonary, idiopathic thrombocytopenic purpura, nondiabetes endocrine disorders
Daniel Segna, Jean-François DuFour

KEYWORDS
Hepatitis C Extrahepatic manifestations Pulmonary Endocrine Idiopathic thrombocytopenic purpura

KEY POINTS

Hepatitis C Virus (HCV) infection may increase the risk for obstructive, interstitial, and vascular lung disease, lung cancer, and mortality in HCV-infected lung transplant recipients.

HCV infection may increase the risk of idiopathic thrombocytopenic purpura, nonresponse to corticosteroids during the treatment, and higher rates of splenectomy.

HCV infection may increase the risk of autoimmune thyroiditis, infertility, growth hormone and adrenal deficiency, osteoporosis, and low-trauma fractures.

Targeted prospective cohorts may confirm these results mostly obtained from small casecontrol studies with different study populations and low level of evidence.
Link - Full Text PDF Download
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Hepatitis C Virus–Associated Non-Hodgkin Lymphomas
Gabriele Pozzato, Cesare Mazzaro, Valter Gattei

KEYWORDS
Hepatitis C virus Marginal zone lymphoma Non-Hodgkin lymphoma Direct antiviral agents

KEY POINTS
Eradication of hepatitis C virus (HCV) in indolent non-Hodgkin lymphomas (NHLs), especially in marginal zone lymphomas(MZLs), determines the regression of the hematological disorder in a significant fraction of cases.

Because direct antiviral agents (DAAs) show an excellent profile in terms of efficacy, safety, and rapid onset of action, these drugs can be used in any clinical situation and the presence of any comorbidities.

To avoid the progression of the NHL, despite HCV eradication, antiviral therapy should be provided as soon as the viral infection is discovered; before that, the chronic antigenic stimulation determines the irreversible proliferation of neoplastic B cells.
Link - Full Text PDF Download
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Dermatologic manifestations of chronic hepatitis C
Mehmet Sayiner, Pegah Golabi, Freba Farhat, Zobair M. Younossi

KEYWORDS
Hepatitis C Extrahepatic manifestation Dermatologic manifestation Cryoglobulinemia Porphyria Lichen planus

KEY POINTS
HCV infection is associated with several dermatologic diseases, such as symptomatic mixed cryoglobulinemia, lichen planus, porphyria cutanea tarda, and necrolytic acral erythema.

Most of the dermatologic manifestations may be caused by immune complexes. In the interferon and ribavirin era, treatment was associated with dermatologic side effects.

The new generation of interferon-free and ribavirin-free anti-HCV regimens is devoid of dermatologic side effects.
Link - Full Text PDF Download
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Hepatitis C Infection - A systematic disease
Zobair M. Younossi
KEYWORDS
Hepatitis C virus Hepatic complications Extrahepatic complications

KEY POINTS
It is critical to recognize that hepatitis C virus (HCV) infection is a multifaceted systemic disease with both hepatic and extrahepatic complications.

The comprehensive burden of HCV should not only include its clinical burden, but also its burden on the economic and patient-reported outcomes.

It is only through this comprehensive approach to HCV infection that we can fully appreciate its true burden, and understand the full benefit of curing HCV for the patient and the society.
Link - Download PDF

Thank you Henry E. Chang

Friday, December 2, 2016

Sofosbuvir, daclatasvir combo best treatment for HCV cryoglobulinemia vasculitis

Conference Coverage
Sofosbuvir, daclatasvir combo best treatment for HCV cryoglobulinemia vasculitis
By: Deepak Chitnis
Frontline Medical News

– A combined regimen of sofosbuvir and daclatasvir is the best option to treat patients with hepatitis C virus infections experiencing cryoglobulinemia vasculitis, according to the findings of a new study presented at the annual meeting of the American College of Rheumatology.

“The HCV cryoglobulinemia vasculitis is a very important vasculitis because it represents 5% of chronically infected HCV patients in the world,” explained David Saadoun, MD, of Sorbonne Universities, Paris. “It’s sometimes a life-threatening vasculitis because patients may develop inflammation [so] there’s a need for very active and well-tolerated treatment.”​

Continue reading...

Tuesday, August 16, 2016

DAA Therapy Beneficial in HCV-Associated Mixed Cryoglobulinemia

DAA Therapy Beneficial in HCV-Associated Mixed Cryoglobulinemia

Abstract
Full Text

(HealthDay News) — Interferon-free direct-acting antiviral (DAA) therapy is beneficial for hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis, according to a study published online Aug. 2 in Hepatology.

Laura Gragnani, Ph.D., from the University of Florence in Italy, and colleagues conducted a prospective evaluation of the efficacy and safety of sofosbuvir-based DAA therapy, individually tailored according to the latest guidelines. The evaluation was conducted in a cohort of 44 patients with HCV-associated MC.

The researchers found that MC had evolved into an indolent lymphoma with monoclonal B cell lymphocytosis in two patients. All patients had negative HCV viremia at weeks 12 and 24 post-treatment; all had clinical response of vasculitis at this point. There were significant decreases in the mean Birmingham Vasculitis Activity Score from baseline through 24 weeks; significant decreases were also seen in the mean cryocrit value. Partial clinical response of vasculitis and about a 50 percent decrease of cryocrit were seen in the two patients with MC and lymphoma, although none experienced a significant decrease in monoclonal B cell lymphocytosis. Fifty-nine percent of patients had adverse events, although they were generally mild.

"Interferon-free, guideline-tailored therapy with DAA is highly effective and safe for HCV-associated MC patients," the authors write. "The overall 100 percent rate of clinical response of vasculitis, on an intention-to-treat basis, opens the perspective for curing the large majority of these so far difficult-to-treat patients."

http://www.empr.com/news/daa-therapy-beneficial-in-hcv-associated-mixed-cryoglobulinemia/article/516130/

Tuesday, July 1, 2014

Dual Antiviral Treatment:Treating HCV-Associated Cryoglobulinemic Vasculitis

Dual Antiviral Treatment May Have Edge in Treating HCV-Associated Cryoglobulinemic Vasculitis

NEW YORK (Reuters Health) - Dual antiviral therapy seems more effective than standard immunosuppression or rituximab only at treating cryoglobulinemic vasculitis associated with hepatitis C virus (HCV) infection, researchers from Russia report.

Cryoglobulinemic vasculitis may affect 5% of patients with HCV infection. Previous research has shown both rituximab and antiviral treatment to be effective in these patients, Dr. Sergey Moiseev and colleagues from First Moscow State Medical University note in Annals of the Rheumatic Diseases, online June 12.

The team looked at outcomes of 65 of their patients with HCV-associated mixed cryoglobulinemic vasculitis who were treated with conventional immunosuppressive drugs (n=30), monotherapy with interferon alpha (n=9), rituximab (n=8), or peginterferon alpha-ribavirin with or without rituximab (n=18).

Relapse-free survival was numerically longer with antiviral treatment than with rituximab or conventional treatment, the researchers found.

More than 70% (5/7) of patients treated with interferon alpha monotherapy experienced deterioration of vasculitis, compared with only one of 18 patients treated with dual antiviral therapy with or without rituximab.

Just over half of patients with genotype 1 (8/15) and all three patients with genotype 2 or 3 infection experienced sustained virological response with combination antiviral treatment. Seven of these 18 patients developed hematological complications.

The researchers acknowledge that lack of randomization and small sample size represent significant limitations of their study.

"Dual antiviral treatment is better tolerated and in our opinion can be offered to patients with higher probability of sustained virological response to peginterferon-alpha/ribavirin, for example, with favorable interleukin-28B polymorphism," the authors conclude.

"Recently, a large scale trial showed high efficacy and excellent safety of the single tablet regimen of ledipasvir-sofosbuvir for primary patients with HCV genotype 1 infection," they add. "The study of these and other interferon-free regimens are also warranted in patients with HCV-associated mixed cryoglobulinemic vasculitis."

Dr. Moiseev did not respond to a request for comments.

SOURCE
Ann Rheum Dis 2014.

Monday, April 21, 2014

HCV Next - A Conversation with Douglas T. Dieterich, MD

The following articles appeared in the March/April 2014 print edition of  HCV Next at Healio.

Editorial
Introducing our Chief Medical Editors

In this issue, you will read an in-depth cover story with expert opinion on the controversial costs of care surrounding implementation of the new approved direct-acting antiviral therapies. The feature article explores the debate between risk-based and universal HCV screening recommendations for baby boomers. HCV Next Editorial Board member Catherine T. Frenette, MD, and colleagues present an interesting Case Challenge about a patient with unique adverse events after receiving interferon therapy; Douglas T. Dieterich, MD, answers 5 questions about his life in and out of the office; and three HCV Next Editorial Board members provide their take on the most interesting news from CROI 2014.


5 Questions
A Conversation with Douglas T. Dieterich, MD
In this issue, HCV Next asks five questions of Douglas T. Dieterich, MD, professor of medicine in the division of liver diseases and director of continuing medical education at Icahn School of Medicine at Mount Sinai in New York. He maintains a triple appointment in the divisions of liver disease, gastroenterology and infectious diseases.

Case Challenges
An Interesting Case of Inclusion Body Myositis after 48-Week Treatment Course

Andrea Scherschel, MSN, FNP; William B. Minteer, BS; Catherine T. Frenette, MD
A 64-year-old male presents to the gastroenterology/hepatology clinic with chief complaints that included increased shortness of breath since stopping his interferon therapy, progressive lower-extremity weakness and dysphagia.

Cover Stories
DAA is $1,000 a pill; SVR is priceless 
The Price of a Cure
 
The new generation of direct-acting antiviral agents for the treatment of hepatitis C virus promise a potential cure for an estimated 3 million infected Americans, but also promise to come with a high price.


The therapies are making headlines in both the health care community and the mainstream media, largely for three reasons: the drugs’ unprecedented efficacy, attractive adverse event profiles and cost. Although recently approved drugs such as sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen Therapeutics) have been hailed as groundbreaking therapies with high sustained virologic response rates, the costs are under scrutiny.


A Collaboration for Improved Care

Ira M. Jacobson, MD; Michael S. Saag, MD
Hepatitis C is a multi-faceted disease, with coinfections and rare comorbidities seen in patients that have necessitated a more collaborative approach to care. As each progressive stage of disease often requires the expertise of a different specialist, increased communication and the sharing of knowledge between gastroenterologists, hepatologists, and infectious disease specialists is the optimal approach to comprehensive HCV care. 


Feature
Calling All Baby Boomers: HCV Screening Slowly Takes Hold

“A one-time blood test for hepatitis C should be on every baby boomer’s medical checklist,” CDC director Thomas R. Frieden, MD, MPH, stated in a recent press release. “The new recommendations can protect the health of an entire generation of Americans and save thousands of lives.”

HCV Rx
Simeprevir: A New NS3/4A Protease Inhibitor

Leah Molloy, PharmD
Several novel direct-acting antivirals are currently under development in the rapidly evolving field of hepatitis C virus treatment. The newest protease inhibitor, simeprevir, was approved for the treatment of HCV genotype 1 infection in November and appears to offer a significantly improved tolerability profile over 
the existing protease inhibitors boceprevir and telaprevir.


Patient Profile
Current Concepts on the Patient with HCV and Cryoglobulinemia

Sandeep T. Samuel, MD; Andrew H. Talal, MD, MPH; Anthony D. Martinez, MD
Among HCV-infected patients, 75% develop chronicity, which can lead to cirrhosis and hepatocellular carcinoma. The binding and replication of HCV in extra-hepatic sites, particularly lymphoid tissues and subsequent immune system modulation, is fundamental to the extra-hepatic manifestations of HCV infection such as mixed cryoglobulinemia, porphyria cutanea tarda, sicca syndrome, lichen planus and idiopathic thrombocytopenic purpura. 


The Take Home
The Take Home: CROI 2014
Meeting highlights and analysis from the Conference on Retroviruses and Opportunistic Infections.

Trend Watch
Sleep Disturbances Common for Patients with HCV

Chronic fatigue associated with hepatitis C virus is associated with poor sleep quality and increased nocturnal activity, leading researchers to suggest that there may be an alteration of sleep architecture behind fatigue in HCV-associated encephalopathy.


2.7 Million US Residents Have Chronic HCV Infection

Investigators for a new study estimated that approximately 2.7 million US residents have chronic hepatitis C virus, which is about 500,000 fewer than in a similar analysis between 1999 and 2002.


Researchers Identify HCV Surface Protein, Raise Hope for Vaccine

Scientists at Rutgers University and Emory University have identified the structure of a hepatitis C virus surface protein, a finding that could potentially further the development of a vaccine.


Liver Disease Persists in HIV/HCV Coinfection Despite Antiretroviral Therapy

Patients coinfected with HIV and hepatitis C virus have higher rates of liver compensation compared with patients with hepatitis C virus monoinfection, despite the use of antiretroviral therapy, according to recent study results.
 

Vantage Point 
Antiviral Therapy for HCV in Liver Transplant Candidates
Steven A. Gonzalez, MD, MS
The emergence of direct-acting antiviral therapy has transformed the management of chronic hepatitis C virus infection. The availability of telaprevir and boceprevir in 2012, followed recently by simeprevir (Olysio, Janssen Therapeutics) and sofosbuvir (Sovaldi, Gilead), has provided clinicians with more highly effective and well-tolerated treatment options. An important subgroup of patients who have historically experienced the greatest challenges in HCV therapy are those with cirrhosis awaiting liver transplantation. Although these individuals may have the most to gain by achieving viral eradication, they have also been faced with lower efficacy, poor tolerance and safety concerns while undergoing therapy.

Saturday, November 3, 2012

Hepatitis C virus infection and autoimmune diseases

Hepatitis C virus infection and autoimmune diseases

Authors: Paroli M, Iannucci G, Accapezzato D
Published Date October 2012 Volume 2012:5 Pages 903 - 907

DOI: http://dx.doi.org/10.2147/IJGM.S37580
Marino Paroli,1 Gino Iannucci,2 Daniele Accapezzato2
1Department of Biotechnology and Medical-Surgical Sciences, 2Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy

Abstract:
Hepatitis C virus (HCV) infection is associated with a number of extrahepatic disorders. The most studied conditions associated with HCV are type II mixed cryoglobulinemia and B cell lymphoma. However, many reports suggest that HCV might also be associated with a number of autoimmune disorders, both organ-specific and not organ-specific. Although concomitant treatment of HCV infection is a confounding factor when ascertaining the actual role of HCV in inducing autoimmune disease, a considerable amount of experimental data indicates that HCV is able to subvert the immune system and consequently induce autoimmunity. In the present review, we report a series of observations which associate chronic HCV infection with the onset of autoimmune disorders.

Keywords: hepatitis C virus, immune regulation, autoimmune diseases

Introduction
In 1987, hepatitis C virus (HCV) was discovered to be the causative agent of a type of hepatitis previously known as non-A, non-B hepatitis.

1 However, it has been observed with time that presence of the virus might be also responsible for extrahepatic manifestations.2 Therefore, the concept of systemic HCV infection has emerged.3,4 The most studied HCV-related conditions are lymphoproliferative disorders, including type II mixed cryoglobulinemia,5–7 which can evolve into frank lymphoma,8,9 and lymphomas unrelated to mixed cryoglobulinemia.10–12 Among the hematologic disorders, monoclonal gammopathies associated with HCV infection have also been described.13

This review focuses on non-lymphoproliferative disorders as a manifestation of chronic HCV infection, namely autoimmune diseases. HCV can in fact subvert the immune system in several ways, from expanding selective B cell subsets to induce breaking tolerance and by reaction of T cells against apoptosis-derived self-antigens, with consequent promotion of T helper-17 cells.14–18

The possible mechanisms by which autoimmunity can be triggered by HCV infection are shown in Figure 1. However, the causal relationship between HCV infection and the onset of clinically relevant autoimmunity is still a matter of debate. This review may help the clinician to understand whether the onset of autoimmune manifestation in the course of HCV might actually be related to the presence of the virus.

Figure 1
Possible mechanisms of autoimmunity induced by hepatitis C virus (HCV).


Notes:
HCVinfects hepatocytes and interacts with B lymphocytes. HCVand hepatocyte-derived apoptotic proteins are taken up by tissue-resident dendritic cells, which mature and migrate into the draining lymph nodes. Here they activate naïve HCV-specific and self-peptide-specific T cells. These cells in turn differentiate into effector proinflammatory T helper-1, T helper-17, or cytotoxic T lymphocytes. Effector T cells can recognize either HCV-derived peptides on the hepatocyte surface or peptides self-expressed by noninfected cells, with the possible triggering of autoimmunity. Specific B cells are activated by T helper cells via CD40L/CD40 interaction and are induced to produce both anti-HCV and natural nonorgan-specific autoantibodies. These autoantibodies can react against components of self. Finally, HCV-specific T and B cells can recognize self-antigens by a mechanism of molecular mimicry between virus and host.

Abbreviation: MHC, major histocompatibility complex.

Thyroid disorders
In the course of HCV infection, both hypothyroidism and hyperthyroidism may emerge. Hashimoto’s thyroiditis is the most common thyroid disorder observed in patients with HCV infection. Treatment with interferon-alpha (IFNA) can be an additional risk factor for the development of thyroid complications. In fact, IFNA can induce autoimmunity by several molecular mechanisms, including polymorphisms in the IFNA-signaling pathways, a feed-forward loop of IFNA production, and a mutually positive regulatory feedback loop between IFNA and estrogen receptor-α. Increased levels of IFNA have numerous immunomodulatory functions, including activating both innate and adaptive immune responses.

19 In a recent study, 293 patients with chronic HCV who underwent IFNA therapy for 24 or 48 weeks, were investigated for thyroid function.20 The investigators found that hypothyroidism was the most frequent thyroid disease, especially during the first cycle of IFNA. Genotype 1 virus was associated with a twofold risk of developing the illness. However, approximately 34% of thyroid disease was transient.

In a retrospective study of 288 patients who received IFNA-ribavirin for HCV over a 2-year period, thyroid function was assessed during a 24- or 48-week course of therapy.

21 The authors concluded that although thyroid disease was common in this cohort, just 2.3% patients required ongoing therapy. Interestingly, pre-IFNA-ribavirin serum thyroid-stimulating hormone and thyroid peroxidase antibody titers were found to predict development of thyroid disease in this group of patients. This finding highlights the fact that IFNA-associated thyroiditis during treatment of HCV infection is critically influenced by individual factors. In another report, a case of fluctuating and wavering thyrotropin autoantibodies of both a stimulating and blocking nature was described.22 The autoantibody profile was clearly modified during IFNA therapy and settled into a new equilibrium on completion of treatment. This case highlights the possible existence of a dual thyroid autoantibody population associated with HCV, and its possible modulation by IFNA therapy. There has also been a report of a 69-year-old Japanese man who developed Graves’ ophthalmopathy while receiving IFNA-ribavirin.23

However, several other studies have shown that the prevalence of thyroid disease is increased regardless in patients infected with HCV compared with normal subjects, after exclusion of patients being treated with IFNA.24–26

In this regard, genetic and environmental factors seem to play an important role,27–29 and subclinical hypothyroidism is observed in a significant proportion of patients with chronic HCV infection.30,31 To explain the relationship between HCV infection and thyroid disease, it has been hypothesized recently that HCV envelope proteins can induce thyroidal inflammation directly, thereby triggering thyroiditis via a so-called "bystander activation" mechanism.

In a recent study,32 significant levels of CD81 mRNA as well as CD81 protein (one of the putative HCV cell receptors 33) were found on thyroid cells. Incubation of thyroid cells with HCV envelope glycoprotein E2 resulted in binding of E2 to thyroid cells, with activation of interleukin-8, an important proinflammatory cytokine. Intriguingly, thyroid cells incubated with E2 continued to proliferate normally and did not undergo apoptosis, as was reported in hepatocytes.

The authors of this study concluded that HCV envelope glycoprotein E2 can bind to CD81 receptors expressed on thyroid cells and induce a cascade of signals, with possible onset of thyroiditis in genetically susceptible individuals. In conclusion, it is advisable for the clinician to monitor thyroid function regularly in the course of chronic HCV, and in particular during treatment with IFNA-based regimens.

Rheumatoid arthritis

Polyarthritis can be observed in the course of HCV infection, and in some cases is associated with mixed cryoglobulinemia.34,35 A recent study investigated 45 HCV-infected patients and 30 patients with rheumatoid arthritis fulfilling American College of Rheumatology classification criteria for rheumatoid arthritis but negative for HCV.36 The study focused on the significance of anti-mutated citrullinated vimentin (MCV) antibodies, which were recently suggested for inclusion in the diagnostic workup for rheumatoid arthritis. Anti-MCV antibodies, anti-cyclic citrullinated peptide (CCP) antibodies, rheumatoid factor, and cryoglobulins were measured. The most frequent pattern was symmetric polyarthralgia, and the joints most frequently involved were the wrists, metacarpophalangeal joints, shoulders, and knees. In HCV arthropathy, anti-MCV was positive in 30% of cases, anti-CCP in 0%, and rheumatoid factor in 73.3%, whereas in rheumatoid arthritis, anti-MCV was positive in 93.3%, anti-CCP in 96.7%, and rheumatoid factor in 86.7% of cases. Therefore, the authors concluded that anti-CCP still plays a major role in differentiating between rheumatoid arthritis and HCV arthropathy.

Another recent study assessed the diagnostic utility of anti-CCP antibodies in comparison with rheumatoid factor in distinguishing between rheumatoid arthritis and HCV-related polyarthropathy.
37 Serum anti-CCP antibodies and rheumatoid factor were measured in 30 patients with rheumatoid arthritis and 22 patients with HCV-related polyarthropathy. Anti-CCP antibodies were positive in 83.3% of patients with rheumatoid arthritis and in 4.5% in patients with HCV and polyarthropathy. Rheumatoid factor was positive in 90% of patients with rheumatoid arthritis and in 81.1% of HCV patients with polyarthropathy. Anti-CCP antibodies showed higher specificity than rheumatoid factor for rheumatoid arthritis (95.4% versus 18.2%). However, the sensitivity of anti-CCP was comparable with that of rheumatoid factor (83.3% versus 90%).

The conclusion of this study is again that anti-CCP antibodies are the most reliable laboratory markers for differentiating between rheumatoid arthritis and HCV-related polyarthropathy. Therefore, there is consolidated evidence indicating that "true" rheumatoid arthritis is uncommon in HCV patients, and that the arthritis observed is, in most cases, a nonerosive intermittent oligoarticular arthritis.

Sjögren’s syndrome

Sjögren’s syndrome is an autoimmune disease characterized by involvement of exocrine glands showing significant T cell infiltration. The inflammatory process involves mainly the salivary and lacrimal glands, leading to both xerostomia and xerophthalmia. Sjögren’s syndrome is also characterized by nonerosive arthritis, which may be accompanied by systemic symptoms, including asthenia. Laboratory investigation shows positivity for SSA and/or SSB autoantibodies, often associated with the presence of rheumatoid factor. Sjögren’s syndrome can present as a primary disease or secondary to rheumatoid arthritis or systemic lupus erythematosus.

38 Definitive evidence that HCV infection may trigger Sjögren’s syndrome is still lacking. A correlation between Sjögren’s syndrome and mixed cryoglobulinemia has been repeatedly reported.39,40 However, different studies have been carried out subsequently to ascertain the possible relationship between HCV infection and Sjögren’s syndrome.41,42 In an interesting study, the clinical and immunologic characteristics of 35 patients with chronic HCV infection and a well documented diagnosis of Sjögren’s syndrome were reported.43 Compared with 60 patients with primary Sjögren’s syndrome who tested negative for HCV antibodies, patients with Sjögren’s syndrome and HCV showed a higher mean age, a lower prevalence of parotidomegaly, and a higher prevalence of liver involvement. Moreover, the patients with HCV-related Sjögren’s syndrome showed a higher prevalence of anti-gastric parietal cell antibodies, anti-mitochondrial antibodies, cryoglobulinemia, hypocomplementemia, and a lower prevalence of SSA autoantibodies.44 Therefore, the immunologic characteristics of HCV infection and Sjögren’s syndrome appear to be different, although common mechanisms linking HCV-associated Sjögren’s syndrome and lymphoproliferative disorders have been hypothesized.45 Further studies are needed to clarify the role of HCV infection in Sjögren’s syndrome.

Anecdotal observations

Many other autoimmune conditions have been related to HCV infection. Glomerulonephritis has been associated with HCV, especially in children, 46,47 and immune-mediated skin diseases, especially oral lichen planus, have been linked with HCV.48–50 Neurologic autoimmune diseases, including myelitis51 and encephalomyelitis,52 as well as several neuromuscular diseases, have also been reported in the course of HCV infection.53 A case of relapsing polychondritis associated with HCV infection has been recently observed.54 Finally, autoimmune mechanisms have been implicated in thrombocytopenia associated with chronic HCV.55–57

Conclusion

HCV infection not only affects the liver, but is also associated with extrahepatic disorders, including autoimmune disorders. There is experimental evidence showing that HCV can subvert the immune system, possibly leading to the onset of autoimmunity. However, IFNA, used in the treatment of HCV infection, is a powerful inducer of autoimmunity, and it is sometimes difficult to discriminate between the effect of HCV and IFNA in inducing an autoimmune reaction. On the other hand, IFNA has been found to improve some HCV-related autoimmune diseases, suggesting that these might be mediated by inhibition of HCV replication or viral clearance. Therefore, IFNA can be considered on the one hand as a trigger for autoimmunity in patients with HCV but, on the other hand, as a therapeutic tool in some cases of autoimmune disease. In light of all these considerations, further study is needed to clarify the actual role of HCV infection in the induction of clinically significant autoimmunity, and to identify additional autoimmune disorders in which concomitant presence of HCV might possibly be involved in the pathogenesis.

Disclosure
The authors report no conflicts of interest in this work.

References


 

Wednesday, January 18, 2012

Rituximab Helpful Against HCV Cryoglobulinemic Vasculitis

By David Douglas

NEW YORK (Reuters Health) Jan 13 - Research funded by the National Institutes of Health shows that rituximab is an effective treatment for refractory mixed cryoglobulinemic vasculitis in patients with hepatitis C.

"Unlike conventional forms of immunosuppressive therapy often used to treat this disease, rituximab was well tolerated and did not worsen the underlying viral hepatitis," said lead investigator Dr. Michael C. Sneller in email to Reuters Health.

Mixed cryoglobulinemic vasculitis is a relatively uncommon complication of hepatitis C virus (HCV) infection, as Dr. Sneller and his colleagues noted online December 6th in Arthritis & Rheumatism.
It's characterized by clonal expansion of B cells that produce IgM rheumatoid factor. The major manifestations are cutaneous vasculitis, arthralgia/arthritis, peripheral neuropathy, and membranoproliferative glomerulonephritis.

Pegylated interferon alpha and ribavirin can result in sustained remission, according to the researchers, but more than 50% of patients with HCV genotype 1, the most common in Europe and the Americas, do not respond.

Rituximab, however, can potentially deplete the expanded population of B cells - although there's been some concerns that it may increase HCV replication.
In an open label study, Dr. Sneller - based at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland - and colleagues randomly assigned 24 patients to four weekly infusions of rituximab, or to continue with best available therapy. Everyone in the trial had either failed attempts to control the lymphoproliferative disease with interferon alpha and ribavirin, or they were intolerant of those drugs.

Patients in the rituximab group could continue on their immunosuppressive medications, but they could not increase the dose or receive new immunosuppressants or plasma exchange.
In the control group, patients were maintained on their current regimen and were allowed to increase or initiate new immunosuppressive treatments as needed.
At six months, 10 of the 12 rituximab patients (83.3%) were in remission, compared to only one control subject (8%).

Of the two rituximab patients not in remission at that point, one had to withdraw after two infusions because of febrile reactions. The other was in remission at four months but subsequently relapsed.
There were no adverse effects in terms of viremia or transaminase levels.

The researchers conclude that rituximab can induce sustained remissions, and "was well tolerated and did not appear to increase HCV replication or worsen the underlying hepatitis."
Dr. Sneller added in his email: "Rituximab may be a safer, more effective alternative to standard immunosuppressive therapy for patients with HCV-associated cryoglobulinemic vasculitis in whom antiviral therapy was not effective."

SOURCE: http://bit.ly/zeAest
Arthritis Rheum 2012.

Thursday, September 1, 2011

Sept 1 Hepatitis News Ticker

GI & Hepatology News-September

GI & Hepatology News is the official newspaper of the AGA Institute and provides the gastroenterologist with timely and relevant news and commentary about clinical developments and about the impact of health-care policy. The newspaper is led by an internationally renowned board of editors.GI & Hepatology News is published monthly and mailed to all U.S. members and available to all members online.
View Current Issue (VOL. 5 • NO. 9 • SEPTEMBER 2011):
Download; PDF Interactive Version

Bilateral Foot Necrosis Caused by Hepatitis C Virus–Induced Mixed Type II Cryoglobulinemia
Alejandro Velasco, Sameer Islam, Kenneth Nugent
Article Outline
References
Copyright

A 52-year-old woman was admitted for increasing severe pain in her feet during the previous month. Her symptoms began 2 years earlier when she noticed skin discoloration and occasional blisters in her feet that became worse before admission. Her medical history included dyslipidemia and hepatitis C virus (HCV) infection incompletely treated 4 years earlier. On physical examination, she had livedo reticularis (Figure A) with purple skin discoloration and blisters on the dorsum of the feet. In addition, severe distal necrosis of the toes with diminished pedal pulses was seen (Figure B). Significant laboratory results included positive serum mixed cryoglobulin type II titer, elevated rheumatoid factor (127 IU/mL), low C3 and C4 levels, and an HCV RNA viral load of 153,000 IU/mL.

Skin biopsy of lower extremities confirmed leukocytoclastic vasculitis (Figure C). An arterial ultrasound of lower extremities showed mild-to-moderate plaques bilaterally with no significant stenosis. Angiographic studies showed aneurysms in the abdominal aorta and right common femoral artery. Clinical and laboratory findings were attributed to mixed cryoglobulinemia. The patient underwent bilateral amputation of lower extremities and treatment with pulse steroids.



Cryoglobulinemia can be detected in 36%–55% of patients infected with HCV, but only 3% develop vasculitic manifestations.1, 2 The most common clinical manifestations are cutaneous vasculitis, arthritis, peripheral neuropathy, and glomerulonephritis.2 Cutaneous vasculitis in mixed type II cryoglobulinemia is characterized by an orthostatic purpura in lower extremities caused by venous stasis and a nonspecific leukocytoclastic vasculitis with infiltration of skin, vessel walls, and microvascular thrombosis3; typically the presentation is not livedo or skin necrosis.4 The bilateral nature of the necrosis with insignificant arterial stenosis in this patient suggests diffuse systemic medium and small vessel disease. Endothelial dysfunction, atherosclerotic plaques, and vascular infiltration by immunocomplexes could cause this rapid presentation of bilateral foot necrosis.

The virologic response to antiviral therapy in HCV patients is not affected by the concurrent presentation of mixed cryoglobulinemia, and small studies show an improvement of cutaneous symptoms.3, 5, 6 Symptomatic response can be as high as 80% in patients receiving antiviral therapy, even when not associated with serologic response.7 However, the clinical remission is mostly limited to mild-to-moderate disease activity, and it is doubtful if it will improve symptoms in cases like ours with severe manifestations.
Back to Article Outline

Incidence of amoebic liver abscess had decreased in the USA
A study in September's issue of Liver International investigates the incidence, temporal trends and mortality with amoebic liver abscess in the USA.
Amoebic liver abscess may be associated with significant morbidity and mortality, but nationwide American data is unavailable.
Dr Stephen Congly and colleagues from Canada described amoebic liver abscess epidemiology and outcomes in USA from a population-based perspective.
Patients hospitalized with amoebic liver abscess between 1993 and 2007 were identified using the Nationwide Inpatient Sample. Patient characteristics, interventions and outcomes including mortality were determined.

The annual incidence was 1.4 per million population
Liver International


The annual incidence of amoebic liver abscess and temporal trends were determined using the negative binomial regression models.
Between 1993 and 2007, 848 hospitalizations for amoebic liver abscess, corresponding to ∼4100 hospitalizations nationwide, were identified.
The team found that the annual incidence was 1.4 per million population with a 2% average annual decline during this study.
The research team observed that most patients were hospitalized in western and southern states, and 48% were Hispanic.
The team found that males had the highest incidence rates.
The researchers noted that percutaneous and surgical drainage was required in 48% and 7% of patients, respectively.
Although length of stay, and hospital charges were substantial, in-hospital mortality was rare.
Females, patients 60 years or older, and those with 3 or more comorbidities, particularly malnutrition, had an increased risk of death.
Dr Congly's team concludes, "Amoebic liver abscess is rare and the incidence has decreased in USA."
"Young, Hispanic males in southwestern states are most frequently affected."
"Mortality caused by amoebic liver abscess is lower than what was reported previously."
Liver Int 2011: 31(8): 1191–119801 September 2011

Non-Invasive Markers for Hepatic Fibrosis *Full Text Available
Ancha Baranova, Priyanka Lal, Aybike Birerdinc, Zobair M YounossiBMC Gastroenterology 2011, 11:91 (17 August 2011)

'Hepatitis C has been accepted as not being a dirty word'
Sept 1
Educating inmates about hepatitis C is rewarding for Kim Mudd, Marie Hair, Jayne Dodd and Sharon Pyatt
Hepatitis C is curable. Yet, it is responsible for some 86,000 deaths in Europe and 9 million people are infected, according to the World Health Organization. Tackling this are four nurses at HMP Forest Bank in Greater Manchester who are testing, treating and educating prisoners.
Jayne Dodd, hepatitis specialist nurse for prisons in Greater Manchester, is responsible for assessing suitability for treatment as well as comprehensive care and monitoring of patients being treated. Marie Hair is the lead nurse and works with Kim Mudd, healthcare assistant, to screen and treat patients until they are discharged. Sharon Pyatt, primary care manager, accesses, facilitates and funds training for the nurses.
Recognised by WHO this year for a Best Practice Award, the team also received a Sodexo Services Star Award for continuous improvement in hepatitis C service. Since 2009, it has increased awareness and testing in the prison and throughout Greater Manchester
Continue Reading...

HIV

Tackling the spread of HIV in the UK
Terrence Higgins Trust is launching ‘Tackling the Spread of HIV in the UK’, a plan to bring down HIV transmission and reduce the growing financial burden on the NHS at a time it can least afford it.

AIDS vaccine research
listen download (4.0MB)
Dr David Cook, who is the Executive Vice President of IAVI, the International AIDS Vaccine Initiative, visited Sydney last week. He talks about the latest research into AIDS vaccines. Read Transcript

Cancer

Cancer-stricken grandfather given just 12 months to live sees tumours killed in TWO DAYS after breakthrough treatment
By Jessica Satherley
Last updated at 12:51 PM on 1st September 2011
A cancer-stricken grandfather given just 12 months to live has undergone a breakthrough treatment which killed his tumours - in just two days.
Brian Brooks, 72, received the devastating prognosis after a random bowel screening test showed his colon and liver was riddled with cancer.

With nothing to lose, the father-of-two from Ely, Cambridgeshire, put himself forward for a trial therapy for liver cancer called Foxfire, spearheaded by Cancer Research UK's Bobby Moore Fund.

Great news: Brian Brooks (pictured with his wife Nicky) had his tumours killed in just two days by the new treatment

The radical treatment, called radioembolisation, places radioactive material inside blood vessels which deliver a dose of radiation directly into the liver.
Remarkably, his tumours were killed off after only two days of treatment - which meant doctors were then able to treat the cancer in his colon.
Experts now believe the breakthrough treatment could help treat thousands of cancer sufferers across Britain.

The Bobby Moore Fund was established by Stephanie Moore in 1993 in memory of her late husband Bobby. He was captain of the England team which won the World Cup and captained West Ham. He died from bowel cancer aged just 51.
Mr Brooks, of Ely, Cambridgeshire, is one of only 40 Britons to be treated in the Foxfire trial and one of the first to be given the all-clear.
He is now in remission - and describes his treatment as a ‘miracle’.

He said: ‘I was given a death sentence, it's a very difficult thing to get your head around.
'My family were devastated and one of the worst things for me was thinking I may not see my three year-old granddaughter grow up.
'But they never gave up hope and were tremendously supportive, that helped me through the treatment.
'To be told you have 12 months to live and then to have completely healed 12 months down the line, we believe is a miracle.
'Obviously there is always the risk that the cancer can come back but I am now in remission and that is something that the doctors did not believe was possible.'

His wife, Nicky, 67, said: 'It was completely random - Brian's name was picked and he underwent the trial alongside his chemotherapy.
'We've just had the results back and my doctors can't believe its success - they say they are astonished.
'If we hadn't been informed about this trial, Brian would not be here today.'
Brian, a retired boarding kennel owner from Ely, Cambridgeshire, went for a random bowel screening test at Addenbrooke's Hospital on September 6, 2010.
The scans showed a tumour in his colon and others in his liver - which doctors told him they were unable to operate on.
Brian and Nicky were forced to break the news to their son Iain, 45, daughter Joanne, 40, and grandson William, 3.
But they were given hope when Brian was accepted onto the Foxfire trial, to try radioembolisation therapy, which is only available on the NHS to patients treated the second time around.

Brian was given the treatment at Addenbrooke's Hospital in Cambridge and went for the first stage, when doctors plotted the blood flow over his liver, on November 17.
The following day he was given the second part of the treatment which involved a blast of nuclear spores into the blood cells which were feeding the tumour.

The grandfather-of-one was treated at Addenbrooke's Hospital in Cambridge
Four months later Brian was told the tumours in his liver had completely disappeared and he could now undergo chemotherapy to shrink the tumour in his colon.
He began 11 sessions of traditional chemotherapy to shrink the tumour in his colon, which doctors removed seven weeks ago.
Brian added: 'I remember seeing the results of my scan and reading 'Complete resolution of all liver tumours' - it was incredible.
'My family and I are so grateful to the Bobby Moore Fund, Cancer UK and of cause the wonderful doctors at Addenbrookes.'

Radioembolisation is a combination of radiation therapy and a procedure called embolisation to treat cancer of the liver.

Unlike traditional radiotherapy, which is directed at the tumour from outside the body, this delivers a high dose of radiation from inside the diseased area of the body.
Tiny resin beads called microspheres are placed inside the blood vessels that feed a tumour to block the supply of blood to the cancer cells.

Once these radioactive microspheres become lodged at the tumour site they deliver a high dose of radiation with minimal damage to healthy cells.
The trial co-ordinated by Oxford University was launched in February 2010 and 40 patients have so far enrolled.

Worldwide 800 patients have been treated, half receiving chemotherapy and radioembolisation and the other 400 given chemotherapy alone.

Kate Law, Cancer Research UK's director of clinical trials said: 'Without clinical trials like Foxfire, we wouldn't be able to improve techniques for cancer that are hard to treat.
'It's a promising trial and we look forward to following its progress and seeing the results.'
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UPDATE 1-Delcath says colorectal cancer treatment not effective
Thu Sep 1, 2011 7:22am EDT
* Says will continue to study the efficacy
* Says will start a new mid-stage in 2012 second half (Follows alerts)
Sept 1 (Reuters) - Delcath Systems Inc said its experimental cancer treatment failed to show any efficacy in patients with colorectal cancer in a mid-stage trial.
The company said its chemosaturation system, which was using melphalan for the treatment, did not prove to be efficacious as the patients had been heavily pre-treated with numerous other chemotherapies.

The fresh results come more than a week after the same treatment showed strong efficacy in treating primary liver cancer patients.

Delcath said it would also initiate a new mid-stage single-arm study in the second half of 2012.
"We will continue to study the efficacy of our chemosaturation system in this patient population that currently has few treatment options," Chief Executive Eamonn Hobbs said.
Sixteen patients with very late stage colorectal cancer, which had spread to the liver, were recruited into this arm of the trial, the company said.
The study included four patient cohorts -- hepatobiliary cancer, metastatic cancer of neuroendocrine, ocular or cutaneous melanoma, and colorectal cancer.
Delcath said the safety profile of the chemosaturation system was consistent with a previous late-stage melanoma trial.
Shares of the New York-based company closed at $4.14 on Wednesday on Nasdaq.
(Reporting by Kavyanjali Kaushik in Bangalore; Editing by Saumyadeb Chakrabarty)

Researchers report new understanding of role of telomeres in tumor growth
Study published in The American Journal of Pathology
Philadelphia, PA, September 1, 2011 –
The first report of the presence of alternative lengthening of telomeres (ALT) in cancers arising from the bladder, cervix, endometrium, esophagus, gallbladder, liver, and lung was published today in The American Journal of Pathology. The presence of ALT in carcinomas can be used as a diagnostic marker and has implications for the development of anti-cancer drug therapies.

Telomeres are nucleoprotein complexes located at the ends of chromosomes. During normal cell division, these telomeres become shorter with each division, potentially resulting in cell death. In some cancers, however, this shortening is counteracted by the ALT mechanism, thus allowing the unlimited growth of the cancer cells.

"The present study offers a springboard to guide future investigations in larger cohorts that specifically focus on the tumor types exhibiting ALT to more precisely determine the prevalence and potential prognostic value of this phenotype," commented lead investigator Christopher Heaphy, PhD, a postdoctoral research fellow at The Johns Hopkins School of Medicine.
"These results may have therapeutic consequences, given that cancers using the ALT pathway are predicted to be resistant to anti-telomerase therapies, some of which have entered phase I/II clinical trials. Further understanding of the molecular mechanisms of ALT will be paramount in designing novel anti-cancer therapeutics targeting cancers utilizing the ALT pathway," observed corresponding author Alan K. Meeker, PhD, Assistant Professor of Pathology at Johns Hopkins.

Meeker and co-investigators have assessed the prevalence of the ALT mechanism in a wide range of human cancer subtypes. Analyzing 6,110 tumor samples from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples, researchers found that the overall prevalence of the ALT phenotype was 3.73%. It was not observed in benign neoplasms or normal tissues.

Additionally, this is the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes.
The authors also note that they were able to identify many tumor types that apparently may not use the ALT pathway for telomere maintenance. In particular, they assessed hundreds of cases of adenocarcinomas arising from the prostate, colon, pancreas, or small intestine and did not observe a single ALT-positive tumor.

Previous studies have shown associations between ALT status and prognosis in some tumor types. The authors suggest that further studies are warranted to assess the potential prognostic significance and unique biology of ALT-positive tumors.
###
The article is "Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes" by Christopher M. Heaphy, Andrea P. Subhawong, Seung-Mo Hong, Michael G. Goggins, Elizabeth A. Montgomery, Edward Gabrielson, George J. Netto, Jonathan I. Epstein, Tamara L. Lotan, William H. Westra, Ie-Ming Shih, Christine A. Iacobuzio-Donahue, Anirban Maitra, Qing K. Li, Charles G. Eberhart, Janis M. Taube, Dinesh Rakheja, Robert J. Kurman, T.C. Wu, Richard B. Roden, Pedram Argani, Angelo M. De Marzo, Luigi Terracciano, Michael Torbenson, and Alan K. Meeker. (doi: 10.1016/j.ajpath.2011.06.018). It will appear in The American Journal of Pathology, Volume 179, Issue 4 (October 2011) published by Elsevier.

Cancer-killing viruses zero in on tumor cells
Doctors have known for nearly a century that when cancer patients catch a virus the infection can help to beat back their tumors. But developing therapies hinged upon this idea has not been easy. Researchers first have to engineer the viruses to discriminately attack only the cancer cells. Then the virus has to actually reach those tumor cells and kill them. Despite these barriers, research has plunged forward, with several viruses in late-stage clinical development (see ‘Recent deal highlights hopes for cancer-killing viruses’).

Clinicians typically inject these so-called ‘oncolytic viruses’ into the tumors themselves using a syringe. But this delivery approach lacks precision. Thus, researchers have long sought cancer-killing viruses that can hone in on their own on cancerous cells while leaving healthy tissue intact. (Scientists are similarly trying to develop bacteria that serve the same purpose, as we reported in March.) Now, for the first time, researchers have engineered a virus that, when injected into people’s bloodstreams, preferentially attacks only cancer cells.
“This data set really puts oncolytic virotherapy on the map as a very, very promising experimental approach to the systemic treatment of metastatic cancer,” Stephen Russell, director of the molecular medicine program at the Mayo Clinic in Rochester, Minnesota who was not involved with the research, wrote in an email

Family history of cancer
listen download (4.0MB)
Researchers in the US investigated the importance for doctors of obtaining knowledge of a family's cancer history to assess risks and initiate appropriate early interventions, that is screening recommendations, etc. Read Transcript

A step toward a saliva test for cancer
American Chemical Society 242nd National Meeting & Exposition;
A new saliva test can measure the amount of potential carcinogens stuck to a person's DNA -- interfering with the action of genes involved in health and disease -- and could lead to a commercial test to help determine risks for cancer and other diseases, scientists reported here today during the 242nd National Meeting & Exposition of the American Chemical Society (ACS).

Diabetes

Expert Discussion: The Continuing Challenge of Effectively Managing Type 2 Diabetes, Part I
Defining Prediabetes and Diabetes
Editor's Note: This is the first in a two-part series on the detection and treatment of type 2 diabetes mellitus focused on the educational needs of physicians. It is based on a live expert discussion, audio segments of which are available online at http://www.mdmag.com/. Part two of the series will appear in our September issue.

Infectious Disease & Viruses

The New Generation of Microbe Hunters
Gina Kolata(The New York Times, August 29, 2011)
"New methods of quickly sequencing entire microbial genomes are revolutionizing the field [microbiology]...Today researchers can sequence the DNA that constitutes a micro-organism’s genome in a few days or even, with the latest equipment, a day. (Analyzing it takes a bit longer, though.) They can simultaneously get sequences of all the microbes on a tooth or in saliva or in a sample of sewage. And the cost has dropped to about $1,000 per genome, from more than $1 million…One group [of molecular epidemiologists] is starting to develop what it calls disease weather maps. The idea is to get swabs or samples from sewage treatment plants or places like subways or hospitals and quickly sequence the genomes of all the micro-organisms. That will tell them exactly what bacteria and viruses are present and how prevalent they are...[and] take precautions against ones that are starting to emerge…Others are sequencing bacterial genomes to find where diseases originated."
Continue Reading..

Pharmaceuticals

Vertex Scores Big With Hepatitis Drug
The company's medication is outselling its rival
Aug 31, 2011, 12:20 pm EDT By Barry Cohen, Health Care Writer
Physicians and patients evidently like the advantages Incivek has over Victrelis, including data showing the Vertex drug had nearly an 80% cure rate and offers the possibility of even shorter treatment. In addition, Incivek is considered easier to use
Continue Reading...

Indians sitting ducks as drug trials turn fatal
In last 4 yrs, 1,725 persons have died in clinical trials; weak law compounds risks
Aditi Tandon/TNSTribune News Service
New Delhi, August 7
For the first time since 2010 when six tribal girls from Gujarat and Andhra Pradesh involved in the clinical trials of anti-cervical cancer HPV vaccine died, the government has admitted that 1,725 persons have lost their lives to drug trials in the last four years.
The number of deaths has risen from 132 in 2007 and 288 in 2008 to 637 in 2009 and 668 last year, indicating the complete ineffectiveness of regulatory controls over the $400 million sector. Last year, the government gave compensation in just 22 cases out of the 668 that resulted in deaths due to “serious adverse events” during drug trials, Health Minister Ghulam Nabi Azad told Parliament this week.

Stem Cells

Stem cell properties of hepatoma cells *Full Text Available
BMC Gastroenterology 2011, 11:71
Tumor spheres produced from hepatoma cell lines cultured in stem cell conditioned medium exhibit liver cancer stem cell (CSC) properties, and the CSL-independent Notch signalling pathway may play a role in the differentiation and propagation of liver CSCs.

Parents in India Bank on Stem-cells, Not the 'Tooth Fairy'
Stephanie Nolen
"In India, a fascination with stem-cell medicine combined with a growing demographic of affluent parents...have consumerized the stem-cell banking industry like nowhere else…India has no laws, and only unenforceable guidelines on what stem-cell research is permitted...The Indian stem-cell industry…is worth an estimated $500-million a year. As a consequence, there is a comparatively high level of awareness of stem-cell medicine in the general population…At the same time, as technological processes for the preservation of cells are 'indigenized,' they are becoming considerably cheaper to operate in India than they are in the West. That, combined with the sheer size of the Indian market, makes a practice such as banking baby teeth or menstrual cells suddenly feasible as a mainstream pursuit."
Continue Reading..

Pioneering UK stem cell trial passes safety test
By Paul Sandle
LONDON Thu Sep 1, 2011 4:25am EDT
LONDON (Reuters) - A pioneering clinical trial to inject stem cells into the brains of patients disabled by stroke has been cleared to progress to the next stage after the treatment raised no safety concerns in the first three candidates.
ReNeuron Group PLC, the British biotech behind the trial, said the independent Data Safety Monitoring Board had reviewed safety data from its ReN001 stem cell therapy and recommended the trial advance to the higher dose.
"Data from the laboratory safety tests, neurological examinations and neurofunctional tests conducted thus far indicate that the ReN001 treatment is safe and well-tolerated at the initial dose," the company said in a statement on Thursday.

The procedure involves injecting ReNeuron's neural stem cells into patients' brains in the hope they will repair areas damaged by stroke, thereby improving both mental and physical function.
It uses stem cells derived from human fetuses rather than embryos, which were used in a stem cell trial to treat patients with spinal cord injuries by Geron Corp of the United States.
ReNeuron's chief executive Michael Hunt said the clearance was an important milestone, and the preliminary data also backed up the group's other therapeutic programs using the CTX neural stem cell line that formed the basis of the ReN001 stroke treatment.

The principal investigator for the trial, Keith Muir from the University of Glasgow's Institute of Neuroscience and Psychology, said he looked forward to evaluating further patients at a higher dose.
"ReN001 has the potential to address a very significant unmet medical need in disabled stroke patients and I am pleased that our team is involved in this pioneering clinical trial," he said.
Shares in ReNeuron rose 3.3 percent in early trade.

Analysts at Matrix said ReNeuron was making excellent progress within the trial, which it believed could set the company apart from other stem-cell companies in the field, given the other advantages it has in terms of manufacturing, scalability and the off-the-shelf nature of the technology.

"The data generated thus far are all the more remarkable, in our view, given the fact that the patients receiving the cells have not been subject to immunosuppression" they said in a note.
"We look forward to the data from the next cohort within this study."
(Reporting by Paul Sandle; Editing by Helen Massy-Beresford)

US Health Care

Who Are the Most Powerful People in American Medicine?



Medical Clinics in Retail Settings Are Booming
Mary Brophy Marcus
"Insured patients are increasingly turning to the convenience of drugstore clinics…and other medical resources outside the traditional doctor's office setting when they can't schedule day-of appointments with their primary-care provider. Some without health insurance say they find them a faster, less pricey alternative to urgent care or emergency room visits…The satellite medical suites address acute, but not typically life-threatening conditions such as strep throat, flu symptoms and bladder infections. Many offer vaccinations, and sports and camp physicals as well…There are about 1,250 retail-based convenient care clinics in the USA. Two-thirds are in drug stores and one-third are in retail settings…and supermarket chains, says Tine Hansen-Turton, executive director of the Convenient Care Association in Philadelphia. The growth has been significant, she says: in 2006, there were only 175 such locations. Health insurers are getting in on the game, too... Continue Reading..

Disease exposure via medical devices a growing concern, CDC says
Milwaukee Journal-Sentinal
Diabetic patients who may have been exposed to blood-borne diseases at a Madison-based clinic are now getting tested for hepatitis and HIV.

In Case You Missed It

One Word Can Save Your Life: No!
Aug 14, 2011 10:00 AM EDT - Newsweek Cover Story
New research shows how some common tests and procedures aren’t just expensive, but can do more harm than good.

"Many doctors don't seem to be getting the message about useless and harmful health care. Medicare pays them more than $100 million a year for screening colonoscopies; some 40 percent are for people in whom they will almost certainly harm more than help. Arthroscopic knee surgery for osteoarthritis is performed about 650,000 times a year; studies show that it, too, is no more effective than placebo treatment, yet taxpayers and private insurers pay for it. And although several large studies, including the Occluded Artery Trial in 2006, have shown that inserting a stent to prop open a blocked artery more than 24 hours after a heart attack does not improve survival rates or reduce the risk of another coronary compared with drugs alone, the practice continues at a rate of 100,000 such procedures a year, estimate researchers led by Dr. Judith Hochman, a cardiologist at New York University. "We're killing more people than we're saving with these procedures," says UT's Goodwin. "It's as simple as that."... Continue Reading..

VA awards new contract for debunked PTSD drug
By Bob Brewin 08/25/2011
The Veterans Affairs Department continues to issue contracts to purchase an anti-psychotic drug to treat post-traumatic stress disorder despite research showing the drug, risperidone, is no more effective than a placebo.
Nextgov reported Aug. 22 that VA spent $717 million over the past decade to purchase risperidone, the generic name for Risperdal, a second-generation anti-psychotic drug originally developed by the Janssen Pharmaceuticals division of Johnson & Johnson to treat severe mental conditions such as schizophrenia and bipolar disorder.
VA doctors prescribe the drug to treat PTSD, but a study by department researchers published Aug. 2 in the Journal of the American Medical Association concluded, "treatment with risperidone compared with placebo did not reduce PTSD symptoms."
Despite these findings, on Aug. 11, VA awarded a contract to Mylan Pharmaceuticals Inc. for more than 200,000 bottles of risperidone containing more than 20 million pills in multiple dosages. The announcement of the contract to the Morgantown, W.V., generic drug manufacturer did not provide a dollar value for the contract.... Continue Reading....

Complementary and Alternative Medicine

Ask UNF: Are dietary supplements safe and necessary?
Posted: September 1, 2011
A dietary supplement is a product taken by mouth that may include vitamins, minerals, herbs or other botanicals, amino acids and substances such as enzymes, organ tissues, glandulars and metabolites. Judy Rodriguez, chair of the Department of Nutrition and Dietetics at the University of North Florida, discusses supplements, their safety and whether they're necessary in our diet.

What are some things I should consider before taking dietary supplements?
It's important to remember that dietary supplements are only meant to be supplements and because they're under the general umbrella of foods, not drugs, they don't have to be tested for safety prior to being put on the market as drugs do. Although the manufacturer is responsible for making sure dietary supplement products are safe before putting them on the market, the Federal Drug Administration doesn't approve dietary supplements for safety. Once a product is on the market, however, the FDA can recall it, if it's shown to be unsafe.

Should everyone take a supplement?
It isn't necessary for everyone to take a supplement, but it's necessary to make healthy food choices. A multivitamin or specific supplement may be useful for people who are on a calorie-restricted diet, vegetarians, trying to get pregnant or are pregnant or breastfeeding, post-menopausal, at risk for osteoporosis, have had digestive tract surgery or a specific medical condition (such as lactose intolerance, chronic diarrhea or a food allergy). Consult a physician and registered dietitian to find out which supplement is most appropriate for you.

Are all natural supplements safe?
No. Consumer Reports has identified some hazardous supplements, including androstenedione (or andro, used by athletes for body-building); aristolochic acid (used in Chinese medicine for eczema and backaches); bitter orange and germander (used for weight loss); chaparral (used as a cancer cure); and comfrey (a green tea for stomach ulcers). Other dangerous supplements are kava kava and skullcap (used for anxiety); lobelia (popular for asthma and bronchitis); organ/glandular extracts (used to treat hepatitis C and other ailments); pennyroyal oil (used as an insect repellent and sometimes ingested for other ailments); and yohimbe (referred to as a men's aphrodisiac).

The hazardous side effects depend on the supplement and dose but may include abdominal tenderness, difficulty breathing, convulsions, rapid heart rates, heartbeat irregularities, heart attacks, blood pressure changes, nerve damage, irreversible abnormal liver function or damage, kidney failure and even death.

What things should I consider if I want to take a supplement?
You should consider whether it may be more effective to improve your
overall dietary behaviors, if you are in one of the categories listed above; the costs of additional supplements, if you are taking other medications that may contraindicate the consumption of the supplement; and the time and effort required to take the supplement. Consult a physician and registered dietitian.

Where can I get information about supplements?
To find a local registered dietitian, go to eatrightjax.org/ and the National Center for Complementary and Alternative Medicine at nccam.nih.gov/ for information about different supplements.

Ask UNF is a monthly column that features the expertise of University of North Florida faculty and staff. If you have a question about this topic, contact Rodriguez at jrodrigu@unf.edu.
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Fish oil
Fish oil is LIKELY SAFE for most people, including pregnant and breast-feeding women, when taken in low doses (3 grams or less per day).Fish oil can cause side effects including belching, bad breath, heartburn, nausea, loose stools, rash, and nosebleeds. Taking fish oil supplements with meals or freezing them can often decrease these side effects.Taking high doses of fish oil is

POSSIBLY UNSAFE.

Taking more than 3 grams per day might keep blood from clotting and can increase the chance of bleeding.
High doses of fish oil might also reduce the immune system’s activity, reducing the body’s ability to fight infection. This is a special concern for people taking medications to reduce their immune system’s activity (HIV/AIDS patients, for example) and the elderly.
Taking fish oil supplements in larger amounts can increase levels of the “bad” LDL cholesterol in some people. You will need blood tests periodically to ensure LDL cholesterols do not become too high.
Some fish meats (especially shark, king mackerel, and farm-raised salmon) can be contaminated with mercury and other industrial and environmental chemicals, but fish oil supplements typically do not contain these contaminants.

Special precautions & warnings:Liver disease: Fish oil might increase the risk of bleeding.

Diabetes: There is some concern that taking high doses of fish oil might make the control of blood sugar more difficult.

Vitamin E
Fish oil can reduce vitamin E levels. Researchers aren't sure whether fish oil keeps vitamin E from being absorbed from food or whether it causes the body to use up vitamin E faster than it should... Continue Reading..

How acceptable is fish oil?
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Researchers at Flinders University in Adelaide have investigated the acceptability of fish oil, particularly by older adults.

Transcript
This transcript was typed from a recording of the program. The ABC cannot guarantee its complete accuracy because of the possibility of mishearing and occasional difficulty in identifying speakers.


Norman Swan: Now there's no question that fish are good for your diet and that fish oil has therapeutic benefits in its own right but usually at massive doses compared to what's in your grilled flathead or ocean trout regardless of the size of the portion.
Alison Yaxley is in the Nutrition and Dietetics Department at Flinders University in Adelaide and she's been testing how acceptable fish oil is as oil rather than wrapped up in capsules.

Alison Yaxley: Conditions which cause the body to have a higher level of inflammation are really common in older adults and these conditions are likely to benefit from the use of fish oil. To reduce inflammation it's necessary to have a high dose of fish oil. In order to get such a dose you would need to be taking something like 10 capsules a day. So in older adults because they commonly don't take their medication well anyway we needed to be sure that they would actually take a dosage that was that high.

Norman Swan: And the capsules are expensive and the oil is cheap.
Alison Yaxley: Yes, fish oil liquid is much, much cheaper as you say.

Norman Swan: So your question was would they take it if you offered it to them?
Alison Yaxley: Our question was would they take it, what were the frequency and the extent of the side effects, so what were they and how often did they happen and what was the short term acceptability?

Norman Swan: And what was the comparator?
Alison Yaxley: We had a range of different concentrations of fish oil, we had one group of 50 which took four different concentrations of fish oil, and we had one group of 50 which took only one which contained no fish oil, in order to tell if they could actually tell the difference between some fish oil and no fish oil.

Norman Swan: And that was olive oil was it, the dummy oil?
Alison Yaxley: Yes, we used extra light olive oil, there were a couple of reasons for this. One was it has very, very little taste and also because it contains very few of the chemicals which produce Omega 3 fatty acids.

Norman Swan: And what sort of dosage are we talking about here that's believed to be necessary in terms of the oil to get say arthritis helped or maybe your heart quelled?
Alison Yaxley: The evidence shows that as little as 1 gram a day can actually make an improvement to coronary heart disease but in order to improve inflammation patients are commonly asked to take 15 mls of fish oil to reduce their rheumatoid arthritis for example.

Norman Swan: And what does that translate to in grams?
Alison Yaxley: That's approximately 10 grams of Omega 3 fatty acids which is around where our 10 capsules would be

Norman Swan: And what did you find?
Alison Yaxley: In the multiple samples these participants were asked to consume approximately 200 mls of liquid so that was fish oil and orange juice and water over a very short period of time. And consequently there were almost 25% of them reported side effects when we asked them 24 hours after the sample. But none of those participants said that that would stop them taking it.

Norman Swan: And what sort of side effects did they complain of apart from the taste?
Alison Yaxley: They were mostly minor. There would be a fishy aftertaste that some of them had, a couple of people said that they experienced looser bowels than would be normal but again none of them said that that would stop them from taking fish oil in the longer term.

Norman Swan: And that was different from the placebo group from the olive oil group?
Alison Yaxley: From the group that tasted one single sample so it wasn't that they all had the olive oil, it was that there was a possibility that they could have had olive oil, they could have had a 10% or 40% or 100% dilution of fish oil and olive oil. Of that group there were very few, only one person said they had any unpleasant taste and 4 people reported side effects. Two of which said that that would stop them taking fish oil in the longer term. The interesting thing about that was that one of those participants who reported a side effect actually had a controlled sample so they reported that they had fishy aftertaste and fishy burps but they didn't actually take any fish oil in their sample.

Norman Swan: And was there a difference in symptoms in concentrations when you gave them the 100% fish oil compared to say the 25%?
Alison Yaxley: No, perception is very important and there's evidence that they are affected by non smell and non taste stimuli as a result of what other people say about fish oil. Somebody's neighbour might be taking it and say it's disgusting and then that would put that person off taking it.

Norman Swan: And lead them to have certain expectations about what to experience when they take it. Did they all have just have one dose or did you ask them to take it for a few weeks?
Alison Yaxley: No, no, it was a cross sectional one dose one time point study. Part of it was to see if we could actually get them to take it at all. Quite a number of people said they wouldn't even try to take it. They had a very negative perception of what fish oil would be like even though they'd never tasted it. People over 60 -

Norman Swan: The remember cod liver oil at school.
Alison Yaxley: Exactly, so that was their lasting memory of a fishy oil. It's relatively recently that marketing of fish oil has been such that they have acknowledged the fact that it has a fishy taste and they are masking it with fruit flavours and a much more positive image.

Norman Swan: So you found that there are side effects, not major, they're not all confined to fish oil, people can take a placebo and get the side effects, but it didn't seem to put them off once they'd actually understood a bit about fish oil. Where to next?
Alison Yaxley: Well we wanted to do this study because our research group wanted to do a much larger study in patients with inflammatory conditions but we obviously needed to be sure that they would take the fish oil. So after doing this study we were able to get funding from the National Health and Medical Research Council to conduct a much larger study with patients with fish oil. We believe that the sheer volume of the fish oil that we asked these patients, the 50 in the multiple sample group, we asked them to take a very large amount and we believe that the incidence of side effects at roughly 25% was mainly due to the actual volume that we asked them to take. So we would foresee that side effects in practice would be much more in line with the single sample group which was very, very minimal.

Norman Swan: Alison Yaxley is a dietitian at Flinders University in Adelaide.
Reference:
Yaxley A et al. Testing the acceptability of liquid fish oil in older adults. Asia Pc J Clin Nutr 2011;20(2):175-179


Healthy You

2011/2012 Flu shot guidelines
Dr. Lisa Dana
posted: 08/31/2011, 10:47 pm
The CDC(Centers for Disease Control) is recommending the flu vaccine for all persons aged 6 months of age and older. The flu is a viral illness caused by influenzae.
Symptoms of the flu include fever, cough, runny nose, chills, sore throat, headache, muscle aches, congestion and fatigue. Symptoms can range from mild to severe. Secondary infections and complications from the flu include pneumonia, bronchitis and other serious systemic illnesses.
Young children, the elderly, pregnant women and persons with certain chronic illnesses are more likely to get seriously ill from the flu. Everyone over the age of 6 months should receive the flu vaccine but the CDC believes it is very important for the following groups to be vaccinated:
Pregnant women
Children younger than 5, but especially children younger than 2 years old
People 50 years of age and older
People of any age with certain chronic medical conditions
People who live in nursing homes and other long-term care facilities
People who live with or care for those at high risk for complications from flu, including:Health care workers
Household contacts of persons at high risk for complications from the flu
Household contacts and out of home caregivers of children less than 6 months of age (these children are too young to be vaccinated)

Children under the age of 9 who did not receive a flu vaccine during the 2010/2011 season will need to receive two flu vaccines. If your child needs two vaccines this year, then the two vaccines should be seperated by 4 weeks.
The flu vaccine is offered in two different forms this year. You can receive the injectable killed vaccine or the live attenuated nasal flu mist vaccine. In our office, we offer the nasal flu mist as well as the flu vaccine injection.

The live attenuated nasal flu mist is available to persons between the ages of 2 – 49 years of age. Certain medical conditions restrict the use of the nasal flu mist. Patients with asthma, certain chronic medical conditions and patients who are immunocompromised or who are in close contact with immunocompromised people may not receive the nasal flu mist. Pregnant women and persons on long term aspirin therapy may also not receive this vaccine. Ask your doctor if the flu mist is right for you and your family.

The killed injectable flu vaccine can be given to persons over the age of 6 months.

Contraindications to the injectable flu vaccine include:
1. A history of Guillian-Barre ( a severe paralytic illness)2. Egg allergy 3. moderate or severe illness at the time of vaccine
You should receive the flu vaccine as soon as it is available. You can get the flu at any time, but most cases occur between October and May. The vaccine that you receive now will help protect you throughout the flu season.
The advice provided in this blog is for informational purposes only and is not a substitute for medical diagnosis, advice or treatment for specific medical conditions
Sources: SF Department of Public Health, CDC

FYI

Egg Farms Rack Up ViolationsFDA finds unsanitary conditions, keeps key data secret
Clark Kauffman(The Des Moines Register, August 28, 2011)
"One year after 1,900 people were sickened and a half-billion Iowa eggs were recalled, government inspectors continue to find unsanitary conditions and inadequate protections against salmonella on Iowa’s egg farms…Despite new federal regulations intended to give consumers greater protection against food-borne illnesses, government oversight of egg production remains a clumsy patchwork of state and federal laws. Among the gaps in the system: Inspections at egg farms are announced days in advance…and they are still based partly on the honor system, with government officials doing little on-site testing for salmonella. Federal inspectors review the companies’ self-reported, in-house test results, even though the laboratories that perform those tests are not required to be licensed or accredited. Penalties for health and safety violations that could lead to salmonella poisoning are nonexistent at both the state and federal levels…Iowa’s egg producers are required to test for salmonella, but they are not required to report any positive test results to either the state or the FDA…In recent months, however, the agency has said that long-awaited federal regulations are significantly reducing the risk of salmonella infections. The agency is inspecting many egg production facilities for the first time and now has the power to recall food products rather than rely on the producers to do so voluntarily…Iowa has been the No. 1 egg-producing state in the nation for the past 10 years…Analysts have attributed Iowa’s growth in egg production to low feed costs and an industry-friendly environment…Iowa exercises almost no oversight of egg production, leaving that job to the federal government…Today, the U.S. Department of Agriculture [USDA] oversees the health of chickens, while the FDA is responsible for whole eggs. Oversight shifts back to the USDA when it comes to transportation of whole eggs…but the FDA oversees the storage of eggs at the retail level. The USDA grades eggs in production facilities, but health inspections in those same facilities falls to the FDA, which, until last year, had no rules or standards to enforce…Consumers, meanwhile, took comfort in buying eggs with the distinctive shield logo of the U.S. Department of Agriculture, unaware that it signified only that the eggs had been graded for size, not inspected for safety or quality."
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