Showing posts with label HCV symptoms. Show all posts
Showing posts with label HCV symptoms. Show all posts

Friday, January 23, 2015

Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C

Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C

April D. Thames, PhD, Steven A. Castellon, PhD, Elyse J. Singer, MD, Rajakumar Nagarajan, PhD, Manoj K. Sarma, PhD, Jason Smith, PharmD, Nicholas S. Thaler, PhD, Jonathan Hien Truong, MD, Daniel Schonfeld, BS, M. Albert Thomas, PhD and Charles H. Hinkin, PhD

Published online January 14, 2015 doi: 10.1212/NXI.0000000000000059Neurol Neuroimmunol Neuroinflamm February 2015 vol. 2 no. 1 e59

Objective: This study examined neurologic abnormalities (as measured by proton magnetic resonance spectroscopy imaging and diffusion tensor imaging), neurocognitive performance, and fatigue among a sample of adults with hepatitis C virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural brain abnormalities and neurocognitive compromise consistent with frontostriatal dysfunction as well as increased fatigue compared to controls.

Method: Participants were 76 individuals diagnosed with HCV and 20 controls who underwent a comprehensive neurocognitive evaluation and clinical assessments. A subset of the HCV+ participants (n = 29) and all controls underwent MRI.

Results: Individuals diagnosed with chronic HCV infection demonstrated greater fractional anisotropy in the striatum as well as greater mean diffusivity in the fronto-occiptal fasciculus and external capsule compared to HCV− controls. HCV+ participants also demonstrated lower levels of N-acetylaspartate in bilateral parietal white matter and elevations in myo-inosital (mI) in bilateral frontal white matter compared to HCV− controls (all p values < 0.05). HCV+ participants also demonstrated significantly poorer neuropsychological performance, particularly in processing speed and verbal fluency. HCV+ patients reported higher levels of fatigue than controls, and fatigue was significantly correlated with diffusivity in the superior fronto-occipital fasciculus, elevations in mI in frontal white matter, and overall cognitive performance.

Conclusions: Our results suggest that HCV-associated neurologic complications disrupt frontostriatal structures, which may result in increased fatigue and poorer cognitive performance, particularly in those cognitive domains regulated by frontostriatal regions.

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The current study examined the effects of chronic HCV infection on microstructural brain abnormalities, cerebral metabolites, fatigue, and neurocognitive performance. Major strengths of the current investigation include the use of DTI and MRSI in combination with measures of neurocognitive functioning and fatigue, and the use of a control group for comparison. As hypothesized based on prior literature, we observed microstructural abnormalities in such areas as the striatum, external capsule, and fronto-occipital fasciculus, which is consistent with previous DTI studies of HCV9,10 and findings among individuals with HIV infection.28,29

We observed greater FA in gray matter regions of the striatum in HCV+ patients compared to healthy volunteers. Higher FA in the striatum has been found among patients with Huntington disease32 and is thought to be due to degeneration of efferent pathways that increase the coherence of gray matter structures. In a study of patients with chronic subdural hematoma, increased FA was found in the striatum, which reduced following surgical intervention.33 Therefore, our findings are consistent with other investigations of neuropathology in regions that are affected in HCV.

Increased diffusivity in the fronto-occipital tract and external capsule was also found in the HCV+ group compared to controls. The fronto-occipital tract has been suggested as modulating frontal lobe–related inhibitory control and occipital lobe–related sensory inputs.34 Alterations of this tract may interfere with integrating sensory information and inhibiting control over impulses and emotion, which is problematic among drug abusers. The external capsule contains a variety of different nerve bundles and pathways connecting the cerebral cortex to subcortical nuclei as well as connecting different parts of the cortex to each other. Therefore, disruption to fibers of the external capsule may result in dysfunction of frontal-subcortical circuitry.

HCV+ participants demonstrated lower levels of NAA in bilateral parietal white matter and elevations of mI in bilateral frontal white matter compared to controls, which was associated with poorer performance in the cognitive domains of processing speed and verbal/language fluency. Further, there was a correspondence between our DTI and MRSI measures. Specifically, higher NAA in parietal white matter was significantly correlated with lower diffusivity in the fronto-occipital fasciculus, whereas greater frontal white matter mI was significantly correlated with higher diffusivity in the fronto-occipital fasciculus.

That stated, our MRSI results were generally consistent with previous MRSI studies of HCV+ cohorts,8,12,35 although we did not observe abnormal cerebral metabolite levels in basal ganglia as was expected.

However, in the current study we were careful to exclude participants with medical (e.g., cirrhosis) and psychiatric conditions that potentially could have confounded interpretation of the neuroimaging findings. Through this process we may have excluded HCV+ individuals with more severe neurologic impairments and neuropathologic changes in subcortical structures that are detectable by H-MRS. Although HCV+ patients demonstrated poorer global neurocognitive performance than controls, examination of performance data suggests normal range of performance (i.e., T > 40). Again, because of the use of stringent inclusion/exclusion criteria, this group may not be fully representative of the general HCV+ population. Despite the potential recruitment of higher-functioning HCV+ individuals, we still found the poorer performance in the cognitive domains of processing speed and verbal fluency (relative to controls) that has been reported across other studies,4,5,13,15,16 and this performance was independent of such factors as liver fibrosis and history of substance abuse.

HCV+ participants also reported greater fatigue than controls, which was associated with abnormalities in frontal white matter, whereas poorer cognitive performance was associated with abnormalities in both frontal white matter and subcortical structures. These results suggest that HCV-associated neurologic complications that are specific to changes in frontal-subcortical structures give rise to both reduced cognitive performance and fatigue. The specific cognitive deficits observed in verbal/language fluency and information processing speed are all regulated by frontal-striatal structures.36 In our sample, verbal fluency demonstrated the greatest degree of performance difference between HCV+ and control groups and the strongest correlation with elevated levels of mI in frontal white matter.

There are limitations to the current study. First, while structural neuroimaging methods are helpful in identifying microstructural pathology that may not be detected on standard MRI, they do not provide a clear understanding about the functions of these neural circuits. Hence, existing disruptions in a neural circuit may make a patient more vulnerable to developing symptoms such as fatigue. Second, although we attempted to control for a number of demographic variables between HCV patients and controls, we recognize that there are a myriad of psychosocial differences (e.g., stress, past drug use) that may account for the reduced cognitive performance and structural brain differences that were observed in the current study. For instance, we were unable to examine past drug abuse differences between our HCV+ and control groups because information on past drug abuse was not collected from the controls. We recognize that in order to precisely rule out the effects of past drug abuse we would have needed to recruit a sample of past drug abusers who were HCV−. However, considering that 61% of our HCV+ patients reported a lifetime history of cocaine or opiate use, we attempted to address this concern by examining the effects of past drug abuse within this subgroup. While we did not find significant differences in our neuroimaging or neurocognitive data as a function of past drug abuse (all p values > 0.10), we cannot rule out the residual confounding effects of distant substance use on neurologic function.

Despite these limitations, the current study represents a significant extension of the extant literature on HCV's effects on neurologic and neurobehavioral functioning by demonstrating how abnormalities in frontal/parietal and subcortical structures have independent and overlapping relationships with cognitive performance and fatigue.

It has long been known that HCV is hepatotoxic; increasingly there is reason to believe that it is neurotoxic as well. While the precise pathophysiologic mechanism remains unclear, findings from the current study as well as others have demonstrated that HCV infection is associated with neurophysiologic and neurobehavioral abnormality. While advances in the pharmacologic treatment of HCV hold incredible promise, there remain millions of HCV-infected adults in the United States and approximately 100 million worldwide. Continued study of the neurologic effects of HCV is needed. 

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Sunday, September 30, 2012

Poster - "Fatigue, Cognitive Function, and Sleep Quality in Patients with Chronic Hepatitis C

Bailey Presents at 2012 State of the Science Congress on Nursing Research

September 30, 2012
Friday, September 28, 2012

Chip Bailey presented a poster entitled "Fatigue, Cognitive Function, and Sleep Quality in Patients with Chronic Hepatitis C (CHC)" at the Council for the Advancement of Nursing Science 2012 State of the Science Congress on Nursing Research in Washington, D.C., September 13-15. He co-authored the abstract with Shelly Epps, Trina Walker, Justin Levens, Karin Weissenborn, Richard Keefe, and Hans L. Tillmann.

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Fatigue, Cognitive Function, and Sleep Quality in Patients with Chronic Hepatitis C (CHC)

Donald E. Bailey, Jr. 1
Shelly Epps 2
Trina Walker 3
Justin Levens 2
Karin Weissenborn 4
Richard Keefe 3
Hans L. Tillmann 3

1 Duke University School of Nursing, Durham, NC;
2 Duke Office of Clinical Research, Durham, NC;
3 Duke University School of Medicine, Durham, NC;
4 Department of Neurology, Medizinische Hochschule, Hannover, Germany

Fatigue is a frequent complaint in CHC patients. CHC patients also often experience problems with cognitive function: difficulties with attention, concentration, memory.

Study Aims
Describe cognitive processing difficulties in adults with CHC. Explore relationship of cognitive function in these patients with fatigue, sleep quality, and disease stage.

Sample (n=29)
Adult patients with CHC:
*18 with fatigue
*11with no fatigue
*Convenience sample
* Recruited at Duke University Medical Center, Gastroenterology Clinic
*Baseline data for sample demographic and clinical characteristics are shown in tables

Fatigue: Revised Piper Fatigue Scale (PFS).
*22-item scale (each item scaled 0-10); use summary score.
*Summary score scaled 0-10 (higher score indicates more fatigue).
*Administered only to patients reporting fatigue (n=18)

Sleep Quality:
*Sleep Timing & Sleep Quality Screening Questionnaire: 1 item
Disease Stage and Disease Grade :
*Clinical data abstracted from medical record

Measures of Cognitive Function
*Brief Assessment of Cognition (BAC) includes 6 tasks:
List Learning -- Verbal Memory
Digit Sequencing Task -- Working Memory
Token Motor Task – Motor Spped Verbal Fluency
Semantic/Letter Fluency Tower of London
Reasoning & Problem Solving / Executive Function Symbol Coding
Attention and Processing Speed

B. Continuous Phase Trials – Identical Pairs (CPT – IP)
Measures Sustained Attention and Vigilance

* Standardized z-scores calculated for BAC cognitive function test (based on comparisons with normative healthy control sample). Separate z-scores for each of the 6 BAC measures; BAC composite z-score

*Means, 95% CI for BAC task & composite scores calculated for:
CHC patients with fatigue (n=18) vs. without fatigue (n=11) Patients at each disease grade (0-3; measures inflammation) Patients at each disease stage (I-IV; measures fibrosis)

*Mann-Whitney rank sum test used to compare z-scores on BAC and CPT-IP score for CHC patients with vs. without fatigue.

*Pearson correlation used to evaluate relationships between BAC z-scores and PFS fatigue scores, sleep quality ratings.


HCV patients in this study showed significant impairment independent of fatigue for 3 of the 6 BAC tasks.

In the graphs below, z-score for healthy controls on each task = 0.0 (shown in graphs below as a red dotted line)

Mean z-scores for all HCV patients were significantly lower than healthy control scores (no overlap of 95% CI with control line) for the 3 tasks identified by red star

These findings suggest HCV-related impairment of cognitive function in the 3 domains of verbal memory, working memory, reasoning/problem solving.


*No significant differences between HCV patients with fatigue vs. without fatigue on BAC composite scores (cognitive function) or CPT–IP (attention/vigilance).

*BAC composite scores of HCV patients lower than those of healthy controls.

*Disease stage (fibrosis) had no effect on BAC composite scores.

*Higher disease grade (liver inflammation) may be weakly associated with poorer cognitive function in patients with HCV.

Pearson correlation analysis of relationships between scores on 6 individual BAC tasks and: Level of Fatigue, Quality of Sleep:
Piper Fatigue Scale summary score (level of fatigue): No correlation with scores on any BAC cognitive task.

Sleep Quality Item: Poor sleep quality (high scores) was significantly correlated with impairment on three BAC tasks: Digit Sequencing, Symbol Coding, and Tower of London.

Examples below shows Pearson correlation analyses for symbol coding:

Findings of this study support previous reports of cognitive processing difficulty in patients with CHC. Differences in cognitive processing between CHC patients with vs. without fatigue at baseline were not significant in this sample, but merit further study in a larger sample.

This study was supported by a research grant from the National Institute of Nursing Research (NIH/NINR: 1 R15 NR 008794-01A1, Bailey, PI) and by a small grant from the Duke University School of Nursing Office of Research Affairs (Bailey, PI).

Sunday, February 6, 2011

Chronic Fatigue Syndrome:ME/CFS

Digital Art / Photomanipulation

Hepatitis C has been associated with a wide spectrum of symptoms, with chronic fatigue being the most commonly reported. The symptom can be so devastating that sleep does not seem to solve the problem; with patients waking up feeling as if they have never gone to sleep. However, medical research connecting HCV with Chronic fatigue syndrome-CFS has yet to be proven. In this entry we revisit the studies over the last few years on CFS, including the 2009 discovery of the retrovirus XMRV.


Chronic fatigue syndrome (CFS) is a disease characterized by fatigue and chronic inflammation that can last years and may affect ~1% of the world’s population.


ME/CFS is the acronym for Myalgic Encephalomyelitis or Myalgic Encephalopathy / Chronic Fatigue Syndrome, a condition that has never been properly named. The disease has had many names, including: post-viral fatigue syndrome, low natural killer cell disease, chronic Epstein-Barr virus syndrome, chronic fatigue and immune dysfunction syndrome (CFIDS), and the insulting Yuppie flu. While all diagnosed ME/CFS patients are “functionally impaired by definition,” according to the Centers for Disease Control, the CDC studies indicate the illness can be as disabling as multiple sclerosis, lupus, rheumatoid arthritis, heart disease, chronic obstructive pulmonary disease, or end-stage (terminal) renal failure.


ME/CFS is also a relapsing, remitting illness that often follows a cyclical course. Typically the ME/CFS patient’s fatigue is made worse by either physical or mental activity, so that giving in to the temptation to overdo is repaid by “post-exertional malaise” (extreme, prolonged exhaustion and a worsening of symptoms following physical or mental exertion). The worse the illness, the less activity is possible. Indeed, the first means of testing objectively for ME/CFS may be a “Two-day Exercise Test” demonstrating diminished cardiopulmonary capacity in patients on the day following an initial exercise test.


Because of the difficulties surrounding the diagnosis of this condition, some physicians have suggested that the condition is imaginary or the result of depression or other mental disorder. Research, however, supports that ME/CFS is a real physiological condition that causes a substantial amount of suffering and is not a form of psychiatric illness or depression.



The XMRV debate

In December of 2010 you may recall the half page ad placed in the The Washington Post by patients bringing attention to HIV-like retroviruses, including XMRV. This new retrovirus has been linked to CFS and other diseases including aggressive prostate cancer. It was also detected in healthy blood donors suffering from chronic fatigue syndrome.

According to MCWPA

"A major scientific breakthrough occurred in October 2009 when the Whittemore Peterson Institute (WPI) at the University of Nevada, Reno, working with the National Cancer Institute and Cleveland Clinic, published the results of a landmark study. The seminal study, published in the leading scientific journal, Science, discovered the third human retrovirus, XMRV, in the blood of 67% of ME/CFS patients and in 3.7% of healthy controls. This suggests that up to 10 million US citizens could already be infected. This finding was later confirmed by the FDA, NIH and Harvard Medical School in a study published in the Proceedings of the National Academy of Sciences. Their results linked a family of human gamma retroviruses (to which XMRV belongs) to ME/CFS at a rate of 86.5% and 6.8% in the healthy population, bringing the total of Americans who may be infected up to 20 million people."


With this new 2009 research from the Whittemore Peterson Institute patients felt finally there was proof; CFS was not all in their head. The scientific community had an interest in chronic fatigue syndrome, so did the media, help was on the way.

Then research in October of 2010 changed all that; Medscape reported online in October 2010 the latest from researchers; "In More Studies Find No XMRV in Chronic Fatigue Syndrome, HIV, or Hepatitis C"


These are the three studies published at the same time in the Journal of Infectious Diseases.


This information is from; XMRV in Chronic Fatigue Syndrome: More Studies, More Controversy


1-J Infect Dis. 2010 Nov

Failure to Detect XMRV in Blood of Individuals at High Risk of Blood-Borne Viral Infections.

This study looked for the retrovirus somewhere you'd expect to find it -- the bodies of people with compromised immune systems. Examining the blood of 230 people with HIV and hepatitis C, they found nothing. This was a European study, and thus far, European studies have all come up empty handed, regardless of their collection and detection methods.


2-J Infect Dis. 2010 Nov 15;202(10):1478-81. Epub 2010 Oct 11.

XMRV Prevalence in Patients with Chronic Fatigue Syndrome or Chronic Immunomodulatory Conditions

Researchers in Boston looked for XMRV in 293 people seen at academic hospitals in the city. Patients came from 1 of 5 groups -- chronic fatigue syndrome, HIV, rheumatoid arthritis, transplants, and general patients. They found no evidence of XMRV in any of them, in spite of using the same detection methods as the FDA/NIH study released over the summer, which did detect XMRV (and other related retroviruses) in similar numbers to the Whittemore Peterson research. The lead researcher brought up the possibility of geographical differences in the presence of XMRV.


3-J Infect Dis. 2010 Nov 15;202(10):1470-7. Epub 2010 Oct 11.

Detection of XMRV in Normal and Tumor Tissue ... [in] Prostate Cancer is Dependent on Specific Polymerase Chain Reaction Conditions.

This study involved 144 prostate cancer patients from the southern United States, and researchers looked first at whether XMRV was present, and then whether it was linked to a abnormality in RNase L (an immune marker believed to be associated with some cases of both prostate cancer and chronic fatigue syndrome.) They found XMRV in 22% of patients, in normal tissue and in tumor tissue, suggesting that infection may precede cancer. They did not find a link with the RNase L polymorphism.



XMRV & Chronic Fatigue Syndrome: Where Do We Stand?
Wednesday January 5, 2011

It's been 15 months since the Whittemore Peterson Institute (WPI) published its study linking a retrovirus to chronic fatigue syndrome (ME/CFS) and a lot more research has been done, but if anything, the waters are only growing cloudier. The loudest voices right now are shouting "cross contamination."...continue reading...


Hepatitis C Patients Understand All To Well How The Game Is Played

Patients and researchers know that medical science will continue to evolve with improved sophisticated means of testing, in time research will again come full circle. What was once medical evidence will be reversed, what was once reversed will become medical evidence. The revolving door of medical science is a proven dilemma, for us and for them. Until that time CFS patients go back to the holding tank, waiting for validation of a disease that medical researchers and even friends do not really understand.

This familiar scenario has played out over and over with other diseases. HCV patients were ignored for years, even with elevated LFTs. With some female patients feeling discriminated against as physicians attributed their symptoms to depression, environmental stress, or lifestyle. This female blogger/patient felt neurotic as I left numerous appointments ashamed and embarrassed, was I just lazy ? The irony is patients wait for medical validation knowing before the research comes out; what they have is real. When will the medical community put in place a system which will bring to light the fact "a patients dialogue" is the most valuable entry into research.

Now CFS patients will start all over , as the wait for medical validation continues............


Symptoms / Diagnostic criteria

The most commonly used diagnostic criteria and definition of CFS for research and clinical purposes were published by the United States Centers for Disease Control and Prevention (CDC).

The CDC definition of CFS requires the following two criteria be fulfilled:
A new onset (not lifelong) of unexplained, persistent fatigue unrelated to exertion and not substantially relieved by rest, that causes a significant reduction in previous activity levels.
Four or more of the following symptoms that last six months or longer:

Impaired memory or concentration
Post-exertional malaise, where physical or mental exertions bring on "extreme, prolonged exhaustion and sickness"

Unrefreshing sleep
Muscle pain (myalgia)
Pain in multiple joints (arthralgia)
Headaches of a new kind or greater severity
Sore throat, frequent or recurring
Tender lymph nodes (cervical or axillary)
Other common symptoms include:
Irritable bowel, abdominal pain, nausea, diarrhea or bloating
Chills and night sweats
Brain fog
Chest pain
Shortness of breath
Chronic cough
Visual disturbances (blurring, sensitivity to light, eye pain or dry eyes)
Allergies or sensitivities to foods, alcohol, odors, chemicals, medications or noise
Difficulty maintaining upright position (orthostatic instability, irregular heartbeat, dizziness, balance problems or fainting)

Psychological problems (depression, irritability, mood swings, anxiety, panic attacks)

The CDC recommends that persons with symptoms resembling those of CFS consult a physician to rule out several treatable illnesses: "sleep disorders, depression, alcohol/substance abuse, diabetes, hypothyroidism, mononucleosis (mono), lupus, multiple sclerosis (MS), chronic hepatitis and various malignancies." Medications can also cause side effects that mimic symptoms of CFS.

Top Five Myths

Misinformation can kill. Let’s put these myths to bed.

Myth: ME/CFS is when you are tired a lot
Fact: For the severe cases, a patient’s experience is more like a “living death,” much more than just being tired. Nausea, headaches, dizziness, cognitive problems, light sensitivity, vertigo, and pain, in addition to feeling like their body is made of lead, can be so debilitating that many sufferers are largely housebound or bedbound. Symptoms can be mild, medium or severe. It is also not uncommon for sufferers to make some recovery only to relapse later and become bedridden again, sometimes for years.

Myth: ME/CFS is a psychological problem
Fact: Most ME/CFS patients have immune system abnormalities, infection reactivation, abnormal brain scan readings and many other biological signs of an organic disease. Some of the symptoms, such as a sore throat, swollen lymph nodes, and low grade fevers are not associated with psychiatric problems but are associated with infections or immune system responses.

Myth: ME/CFS is a disease of middle-aged women
Fact: ME/CFS can strike anyone at any time. Children as young as four and people as old as 70 can develop the disease. Men of all ages also develop this disease. While middle-aged women make up a large percentage of cases, teenagers of both genders are also commonly seen within our patient community.

Myth: ME/CFS is not infectious
Fact: ME/CFS has occurred in outbreaks reported to the CDC in the 1980s. It also occurred in an outbreak at the Royal Free Hospital in the 1950s. Other outbreaks of illnesses with similar or matching symptoms go back to the early 1900s in numerous countries. Many experts now think these illness outbreaks were really what is now called ME/CFS, even though they were given other names, such as atypical poliomyelitis, encephalitis, abortive poliomyelitis, Akureyri disease, Iceland disease and epidemic neuromyasthenia. As research is now linking a retrovirus to this disease, which appears higher in family members of CFS patients, evidence is mounting that the disease is infectious.

Myth: ME/CFS is not fatal
Fact: An inquest into Sophia Mirza’s death showed she died from acute renal failure as a result of dehydration, caused by chronic fatigue syndrome. She died at age 33. Casey Fero was diagnosed with ME/CFS at the age of nine and died at age 23 from myocarditis, which means he had heart damage. A 2006 study of 166 deceased ME/CFS patients shows an increased risk of premature death from the following:
General population average age of death from cancer – 72, ME/CFS patients – 47.8
General population average age of death from heart failure – 83.1, ME/CFS patients – 58.7
General population average age of death from suicide – 48, ME/CFS patients – 39.3

Chronic fatigue syndrome patients address the CDC ,

Wednesday, January 19, 2011

Vague symptoms help to keep hepatitis C "hidden" inside the body for years

Radio Show

Experts at Europe's largest liver transplant unit - at King's College Hospital in London - explain how vague symptoms help to keep hepatitis C "hidden" inside the body for years. Dr Mark Porter looks at the latest ways to manage this condition.
Producer: Helen Sharp.

Additional Information
Symptoms Of HCV