Carmine Pariante's MRC research award-Persistent fatigue induced by interferon-alpha

Dolphin

Senior Member
Messages
17,555
Likes
28,242
I thought I'd give this it's own thread:
Persistent fatigue induced by interferon-alpha: a new immunological model for chronic fatigue syndrome

Principal investigator: Dr Carmine Pariante

Institution: Kings College London

Summary:

Researchers will examine the effects of a protein called interferon-alpha (IFN-alpha) on the immune system. IFN-alpha is produced as a protective response to viral infection and is commonly used to treat infections such as hepatitis C. IFN-alpha also induces fatigue and flu-like symptoms in patients, similar to that experienced by patients with CFS/ME.

The team will follow patients undergoing IFN-alpha treatment for Hepatitis C over a number of months to define the biological changes that occur in relation to the development of fatigue. Their work could lead to a check-list of blood measures to predict who will develop CFS/ME, as well as identifying new targets for therapy.

from: http://forums.phoenixrising.me/show...arch-Projects-Worth-£1-6m&p=228393#post228393
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
I can't say I know much about her. But this paper with Simon Wessely was highlighted on another forum:

Fatigue, depression and chronic hepatitis C infection.

Psychol Med. 2002 Jan;32(1):1-10.

Wessely S, Pariante C.

Source
Department of Psychological Medicine, Guy's King's and St Thomas' School of Medicine and Institute of Psychiatry, London.

Abstract

BACKGROUND:
We aimed to determine if an association exists between uncomplicated hepatitis C virus (HCV) infection and depression or fatigue.

METHOD:
A review of the literature was undertaken.

RESULTS:
There is an association between HCV infection and either depression or fatigue in certain circumstances--those who are aware they are HCV positive, those with advanced liver disease and those seen in specialist referral centres. All these studies are subject to important biases. There are only a few studies in which knowledge of HCV status and assessment of fatigue or depression is independent. These studies do not suggest an association. There is no association between conventional markers of liver disease and depression or fatigue.

CONCLUSIONS:
Despite anecdotal evidence to the contrary, at the moment there is no evidence that HCV infection per se is associated with fatigue or depression, and there is a suggestion that it is not. The same risk factors that exist for fatigue in other physical illnesses, such as metabolic disorder, mood disorder, demographics and lack of exercise, certainly exist for HCV. Although there are elegant theoretical mechanisms, there is no compelling epidemiological evidence for an additional HCV specific fatigue or depression factor.
PMID: 11883721 [PubMed - indexed for MEDLINE]
If it does "go wrong", one plus is that any psychological speculation or lack of association with fatigue, etc they find will be to do with Hep C, so will undermine us less.
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
(Junk?) 2 more loose connections with Simon Wessely

Somebody posted these on another forum. How much they prove, I'm not sure.

Max Pemberton wrote a very annoying column in a UK paper soon after this. I get the impression the meeting might have been a bit biased.

http://www.iop.kcl.ac.uk/iopweb/blob/downloads/event/2011330_e_1312_Time_table_d\
raft-_website.doc

Institute of Psychiatry / Royal College of Psychiatrists 3rd Medical Students
Summer School - July 2011


Thursday
21st July
Lisa Conlan

Professor Simon Wessely

Professor of Psychological Medicine
The Gulf war and its Aftermath


10:00- 11:00



Coffee Break

`Concept of Mind' -
Interactive session

Dr Gareth Owen
Clinical Research Fellow

Dr Robert Harland
Consultant Psychiatrist


11.20-12.30
Psychsoc Session -

Lunch with Researchers
Lunch in canteen
12.30-13.30

Psychiatry in the Media

Dr Max Pemberton, Writer Psychiatrist
Dr Ben Goldacre, Writer, Broadcaster, Psychiatrist
Dr Carmine Pariante, Reader in Biological Psychiatry
Dr Avie Luthra, Film Director, Screen Writer and Forensic Psychiatrist

13.30- 15.30
18:00-21:00 Drinks & Light Supper at the Royal College
(Dress code smart)
RCPsych, 17 Belgrave Square,
London SW1X 8PG

http://www.justgiving.com/simonwessely

Simon Wessely's Fundraising Page

A bottle of good Wellsh wine is worth much more than this donation! Donation by Mansel Aylward on 22/09/09

You don't exactly have the habitus of a long-distance cyclist, but obviously appearances can be deceptive. I'm impressed. Well done! Donation by George Szmukler on 11/09/09

I'll love to see the pictures... Donation by Carmine Pariante on 10/09/09

Good luck with the cycle Simon. I'll be right behind you.......in spirit! Donation by Trudie on 03/07/09

Simon, you're a splendid person supporting an excellent cause. Donation by
Caroline Richmond
on 13/06/09
 

Enid

Senior Member
Messages
3,309
Likes
866
Location
UK
Don't tell me this lot are on it and grinding through their own ignorance at our expense. Clever lot the psychos just about latching on to real pathologies ? - to save their bacon. We do not have to watch their growing up now - science left far behind and the whole international community knows.
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
The CDC CFS program has funded research into the effects of alpha-interferon

The CDC CFS program has funded research into the effects of alpha-interferon - article added Dec 2011

http://www.cdc.gov/cfs/news/features/cytokines-and-cfs-symptoms.html

Cytokines and the Symptoms of CFS

An important area of research in chronic fatigue syndrome (CFS) is to look at the ways viruses can lead to fatigue and other symptoms that are found in CFS. For many years, scientists have suspected that viruses may be involved in the cause of CFS. In order to understand how viruses may lead to symptoms of CFS, scientists from CDC have been working with researchers from Emory University to study how cytokines, such as interferon-alpha, cause CFS symptoms like fatigue.

Cytokines are chemical messengers produced by white blood cells in our bodies, and they help the body fight infection. One cytokine, interferon (IFN)-alpha, protects the body against viruses, because it "interferes" with the ability of viruses to spread.

Studies by the Emory research group have shown that IFN-alpha gets into the brain and causes the release of other cytokines 1. One of these cytokines, interleukin (IL)-6, was found to be related to decreases in a breakdown product of serotonin. Serotonin is a chemical in the brain that helps regulate whether you feel happy or sad. Decrease in the breakdown product of serotonin suggests that IL-6 may decrease serotonin in the brain leading to depression 1.

IFN-alpha has also been found to cause problems in sleeping. People given IFN-alpha developed insomnia (difficulty falling or staying asleep), which was related to fatigue 2.

IFN-alpha also has been shown to cause changes in the secretion of the hormone, cortisol, that are similar to the changes in cortisol found in people with CFS and in breast cancer survivors with fatigue 3. Cortisol is an important hormone that regulates body metabolism and the immune system.

Using brain scans, including magnetic resonance imaging (MRI) and positron emission tomography (PET), Emory scientists have found that IFN-alpha affects two parts of the brain, the basal ganglia and the dorsal anterior cingulate cortex (dACC) 4,5. The basal ganglia play an important role in the regulation of motor activity and motivation as well as symptoms of fatigue. Indeed, IFN-alpha effects on the basal ganglia were linked with symptoms of fatigue 4. Ongoing studies at CDC are currently evaluating whether similar changes in the basal ganglia occur in patients with CFS.

The dACC is a brain region associated with arousal and alarm, and changes in this brain region have been found in connection to anxiety 5.

Research on the ways by which viruses and the body's response to viruses can lead to the symptoms of CFS will help us understand how CFS symptoms are caused and may lead to new treatments for CFS.

References
Raison, C.L., Borisov, A.S., Majer, M., Drake, D.F., Pagnoni, G., Woolwine, B.J., Vogt, G., Massung, B., Miller, A.H. Activation of CNS inflammatory pathways by interferon-alpha: relationship to monoamines and depression. Biol Psychiatry, 65(4):296-303, 2009.
Raison, C.L., Rye, D.B., Woolwine, B.J., Vogt, G.J., Bautista, B.M., Spivey, J.R., Miller, A.H. Chronic interferon-alpha administration disrupts sleep continuity and depth in patients with hepatitis C: association with fatigue, motor slowing and increased evening cortisol. Biol Psychiatry. In Press
Raison, C.L., Borisov, A.S., Woolwine, B.J., Massung, B., Vogt, G., Miller, A.H. Interferon-alpha effects on diurnal hypothalamic-pituitary-adrenal axis activity: relationship with proinflammatory cytokines and behavior. Molecular Psychiatry, 15, 535547, 2010.
Capuron, L., Pagnoni, G., Demetrashvili, M., Lawson, D.H., Fornwalt, F., Woolwine, B.J., Berns, G.S., Nemeroff, C.B., Miller, A.H. Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy. Neuropsychopharmacology, 32(11): 2384-92, 2007.
Capuron, L., Pagnoni, G., Demetrashvili, M., Woolwine, B.J., Nemeroff, C.B., Berns, G.S., Miller, A.H. Anterior cingulate activation and error processing during interferon-alpha treatment. Biological Psychiatry, 58:190-6, 2005.

Centers for Disease Control and Prevention
1600 Clifton Rd
Atlanta, GA 30333
800-CDC-INFO
(800-232-4636)
TTY: (888) 232-6348
New Hours of Operation
8am-8pm ET/Monday-Friday
Closed Holidays
cdcinfo@cdc.gov
Page last reviewed: December 6, 2011
Page last updated: December 6, 2011
Content source: Centers for Disease Control and Prevention
National Center for Emerging and Zoonotic Infectious Diseases (NCEZID)
Division of High-Consequence Pathogens and Pathology (DHCPP)
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
Links to pages on the CDC CFS website about interferon-alpha studies it has supported

Links to pages on the CDC CFS website about interferon-alpha studies it has supported:

Association of Exaggerated HPA Axis Response to the Initial Injection of Interferon-Alpha with Development of Depression During Interferon-alpha Therapy http://www.cdc.gov/cfs/publications/studies_of_causes/hpa_axis_response.html

Anterior Cingulated Activation and Error Processing During Interferon-alpha Treatment http://www.cdc.gov/cfs/publications/studies_of_causes/anterior_cingulated_activation.html

Depressive Symptoms and Viral Clearance in Patients Receiving Interferon-a and Ribavirin for Hepatitic C Brain, Behavior, and Immunity 2005;19:23-27.
http://www.cdc.gov/cfs/publications/studies_of_causes/depressive_viral.html

Interferon-alpha-induced Changes in Tryptophan Metabolism:
Relationship to Depression and Paroxetine Treatment Biological Psychiatry 2003;54:906-914.
http://www.cdc.gov/cfs/publications/studies_of_causes/tryptophan_metabolism.html

Neurobehavioral Effects of Interferon-A in Cancer Patients:
Phenomenology and Paroxetine Responsiveness of Symptom Dimensions Neuropsychopharmacology 26:643-652, 2002.
http://www.cdc.gov/cfs/publications/studies_of_causes/phenomenology_paroxetine.html
 
Messages
1,383
Likes
362
Location
UK
Thanks for posting all that info, Dolphin. I'm going to post stuff here as I read through the papers.

First, here's a rationale of why IFNa is used as a model:
Studies examining the pathophysiology of CFS have been complicated by patient heterogeneity with respect to chronicity and co-morbid illnesses. "Model" systems in which symptom-free subjects develop CFS-like illness following exposure to a known immune system stimulus obviate these problems and permit controlled studies of the pathophysiology of fatigue and associated symptoms as they relate to immune and endocrine activation. Interferon-alpha (IFN-alpha), a cytokine widely used in the treatment of hepatitis C and malignant melanoma, represents a model system of great promise, given that IFN-alpha activates the immune system and produces a high rate of symptoms commonly observed in CFS, including fatigue, cognitive complaints, pain, sleep disturbance and depression. Thus, the CDC/Emory University Collaborative Group has undertaken a series of integrated studies using INF-alpha-associated fatigue to model CFS.
Though I'm not sure the studies themselves are that compelling. Here's the one on
Association of Exaggerated HPA Axis Response to the Initial Injection of Interferon-Alpha with Development of Depression During Interferon-alpha Therapy:

Half of patients developed major depression and these patients had higher levels of ACTH and cortisol after IFNa administration, but with n=14 I'm not sure we can rely on this finding. Hopefully Pariante will have a decent sample size.
 
Messages
1,383
Likes
362
Location
UK
Key study: how the effects of IFN-alpha on fatigue and depression are different

Neurobehavioral Effects of Interferon-A in Cancer Patients: Phenomenology and Paroxetine Responsiveness of Symptom Dimensions, 2002

One of the problems of using Interferon-alpha (IFN-a) treatment as a model of CFS is that IFN-a often causes depression too, which causes fatigue - and that takes us back to the problems of confusing depression with CFS/fatigue. This study, on cancer patients undergoing IFN-a treatment, shows that fatigue appears within the first 2 weeks of IFN-therapy starting, while depression can take a couple of months to develop. And crucially, treating patients with paroxetine (an antidepressant) before starting the IFN-a therapy largely blocks depression but has only a very limited effect on fatigue. This suggests that fatigue after IFN-a develops largely independently of depression, so probably occurs via a different mechansim:
Given the noted differences in the appearance and treatment responsiveness of certain IFN-ainduced symptoms (mainly fatigue and depression), it is reasonable to speculate that different pathways may mediate different symptom complexes during IFN-a treatment. Thus, while mood and cognitive symptoms appear to be mediated by pathways responsive to paroxetine, anorexia and fatigue appear to be mediated by separate pathway(s)
The authors note the similarity with CFS:
the fatigue of patients diagnosed with chronic fatigue syndrome has been reported to be unresponsive to antidepressant treatment (Vercoulen et al. 1996)
and, interestingly, with cancer patients undergoing chemotherapy:
a recent study by Morrow et al. (2001) found that paroxetine significantly reduced depression but had no effect on fatigue in a double-blind randomized study of 738 cancer patients undergoing chemotherapy
Nb the study was quite small with initially 20 each in the antidepressant group and placebo group, and quite a high attrition rate (approx 35%) so it would have been nice to see the study replicated.

The challenge for the new MRC study will be "to define the biological changes that occur in relation to the development of fatigue" without confusing them with the biological changes linked to depression, given that up to half of Hepatitis C patients treated wtih IFN-a develop depression.
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
Neurobehavioral Effects of Interferon-A in Cancer Patients: Phenomenology and Paroxetine Responsiveness of Symptom Dimensions, 2002

One of the problems of using Interferon-alpha (IFN-a) treatment as a model of CFS is that IFN-a often causes depression too, which causes fatigue - and that takes us back to the problems of confusing depression with CFS. This study, on cancer patients undergoing IFN-a treatment, shows that fatigue appears within the first 2 weeks of IFN-therapy starting, while depression can take a couple of months to develop. And crucially, treating patients with paroxetine (an antidepressant) before starting the IFN-a therapy largely blocks depression but has only a very limited effect on fatigue. This suggests that fatigue after IFN-a develops largely independently of depression, so probably occurs via a different mechansim:

The authors note the similarity with CFS:
and, interestingly, with cancer patients undergoing chemotherapy:

Nb the study was quite small with initially 20 each in the antidepressant group and placebo group, and quite a high attrition rate (approx 35%) so it would have been nice to see the study replicated.

The challenge for the new MRC study will be "to define the biological changes that occur in relation to the development of fatigue" without confusing them with the biological changes linked to depression, given that up to half of Hepatitis C patients treated wtih IFN-a develop depression.
Thanks for that - interesting. We will have to see what happens with your last paragraph. If Simon Wessely and/or others from the "chronic fatigue" team in KCL (big CBT and CBT-model fans) are involved, I'm not sure we should be confident about it. They haven't been particularly interested in biological changes that they can not explain by the CBT model (deconditioning, etc.).
 
Messages
1,383
Likes
362
Location
UK
I think the goals of the new study are laudable but it will be hard to pull off, and the stable invovled doesn't exactly inpsire confidence. More on the studies above:

Anterior Cingulated Activation and Error Processing During Interferon-alpha Treatment, 2005
(nb the CDC page with this title, above, discusses a completely different experiment).

Hepatitis C (HCV) patients who were given IFNa were compared with HCV patients who were not - both groups were given visuospatial tasks to complete while undergoing functional MRI scans (fMRI).

RESULTS: Despite endorsing symptoms of impaired concentration and fatigue, IFN-alpha-treated patients (n = 10) exhibited task performance and activation of parietal and occipital brain regions similar to that seen in HCV-infected control subjects (n = 11). Interestingly, however, in contrast to control subjects, IFN-alpha-treated patients exhibited significant activation in the dorsal part of the anterior cingulate cortex (ACC), which highly correlated with the number of task-related errors. No such correlation was found in control subjects.
You can't help wondering if this is the same situation as for measuing CFS fatigue where the test is too short to detect fatigue (repeat testing would have been interesting). But it is a slightly bigger study than the one above, and I believe other studies have implicated the ACC in fatigue too. Full paper (pdf, and I haven't read it myself, my comments are mainly on the abstract).


Depressive Symptoms and Viral Clearance in Patients Receiving Interferon-a and Ribavirin for Hepatitic C (2005)

This study found that Hepatitis C patients who developed depression when treated with Interferon-alpha plus Ribavarin (an antiviral drug) were less likely to respond to the treatment than patients who did not develop depression. Overall, 56 patients (ex 102) were Hepatitis C negative after the treatment but the most depressed patients (30% of total) were more than 3x less likely to clear the virus than non-depressed patients. According to the authors:
This suggests that fatigue and depression during IFN-? therapy may be a manifestation of a physiologic response associated with an impaired immune response.
but the abstract doesn't mention fatigue and the authors descirbe their findings as 'preliminary'. I'm not sure this study tells us anything useful about how fatigue works.



Interferon-alpha-induced Changes in Tryptophan Metabolism: Relationship to Depression and Paroxetine Treatment, 2003


Uninspiring. This study found that IFN-alpha treatment led to greater reductions in tryptophan (a precursor of serotonin) in patients who developed depression than those that did not. Tells us nothing about fatigue pathways. And again it's rather small study: 13 in the paroxetine treated group and 13 in the placebo group; the authors then compared placebo patients who developed depression with placebo patients who did not, but n is getting very small at this stage
 
Messages
1,383
Likes
362
Location
UK
... I'm not sure the studies themselves are that compelling. Here's the one on
Association of Exaggerated HPA Axis Response to the Initial Injection of Interferon-Alpha with Development of Depression During Interferon-alpha Therapy:

Half of patients developed major depression and these patients had higher levels of ACTH and cortisol after IFNa administration, but with n=14 I'm not sure we can rely on this finding. Hopefully Pariante will have a decent sample size.
There's a slightly bigger 2010 study from some of the same authors that found a moderate correlation (approx 0.45) between cortisol patterns and fatigue after IFN-alpha administration. Changes in diurnal cortisol patterns are the sort of thing they get excited about at KCL, judging by their previous publications on CFS.
 
Messages
1,383
Likes
362
Location
UK
Thanks for that, Snow Leopard - interesting.

More studies:

Basal Ganglia Hypermetabolism and Symptoms of Fatigue During Interferon-a Therapy, Capuron 2007

Researchers compared the metabolic map of patients' brains before and during IFN-alpha therapy (using PET) and found there was an increase of metabolic activity in the basal ganglia that correlated with IFN-alpha induced fatigue. Interesting: could this be the brain location of fatigue?

Unfortunately I can't access the paywalled paper to see how big the study was, but such brain studies are usually quite small. The finding also contrasts with the study mentioned above that found activation in IFN-alpha-treated patients in a different brain area, the anterior cingulate cortex (ACC). However, the ACC finding came from a study using fMRI to look at performance during a visuospatial task, so is not directly comparable.


Chronic Interferon-Alpha Administration Disrupts Sleep Continuity and Depth in Patients with Hepatitis C: Association with Fatigue, Motor Slowing, and Increased Evening Cortisol, Raison 2010 (full paper)

IFN-alpha treatment can also disrupt sleep, and decreased sleep quality was associated with increased fatigue, though "Despite IFN-alpha-induced increases in fatigue, daytime sleepiness did not increase."

This finding potentially raises the question of whether IFN-alpha directly affects fatigue or is a side effect of sleep problems. However, it appears from the literature that while most IFN-alpha-treated patients suffer fatigue, only a minority have sleep problems (80% with fatigue vs 35% in the only data I've seen, though n was small), suggesting the fatigue effect is independent of sleep effects, at least in some patients.

It's also worth noting that in CFS, sleep disturbances are common yet by definition cannot alone explain the fatigue.
 
Messages
1,383
Likes
362
Location
UK
Comment on the planned study of Interferon-alpha induced Fatigue

When the MRC grants were announced last week there was a lot of scepticism about the Pariente study of fatigue in Interferon-alpha treated Hepatitis C patients. First, it isn't actually studying CFS and second, Carmine Pariente is a psychiatrist from the Institute of Pschiatry, Kings College London, making him a stablemate of Simon Wessely, which understandably causes some suspicion.

Points in favour of the study
However, looking at some of the literature, I can see the case for using IFN-alpha treatment as a model of how fatigue is generated. IFN-alpha treatment rapidly induces fatigue in most patients, and quite often causes sleep disturbances, pain and cognitive dysfunction too, which are also common in CFS. While IFN-alpha often causes depression too, this usually takes much longer to develop than the fatigue, can be blocked by pre-treating patients with anti-depressants (unlike the fatigue) i.e. depression appears to be caused by a mechanism independent of fatigue.

The brain imaging findings are intriguing too. The PET study found the basal ganglia of fatigued IFN-alpha-treated patients were more active than untreated patients, and another study found a correlation between fatigue and errors in another part of the brain during a demanding visuo-spatial task.

And of course, cytokines have long been suspects in CFS research, though no one has really pinned down the role. The most interesting finding to date has come from the Dubbo studies of Post Viral Fatigue, which found a strong correlation between acute illness cytokines and illness severity, and later development of fatigue. The authors suggested that the intial high levels of cytokines in the body led to long-term cytokine production in the brain, causing fatigue and other symptoms of CFS.

Unfortunately most of the work on biological changes associated with IFN-alpha treatment have been focused on the link with depression - in fact, it's widely used as a model of inflammation-linked depression. The link with fatigue has received relatively little attention.

Issues for the study
A confounding factor with this study is that depression and sleep problems, both of which can contribute to fatigue. Around 30% of IFN-alpha patients develop a Major Depressive Disorder, but more have lesser levels of depression. The study will need to control for this so will need to be quite big. As with CFS research, many of the findings in this field to date have been based on small samples with no attempts to replicate them. An MRC grant should provide the funds for a substantive study

Of course, whatever the findings about the nature of fatigue in IFN-alpha-treated Hepatitis C patients, they won't automatically apply to CFS patients. But should the study make significant findings about the nature of fatigue in IFN-alpha-treated patients, it will provide a clear target for investigating fatigue in CFS. And there aren't too many of those currently.

Whether or not Carmine Pariente will share Simon Wessely's preference for psychological explanations of fatigue remains to be seen. However, unlike Wessely, Pariente is Biological Pyschiatrist and by inclination biological psychiatrists tend to prefer biological explanations for things.
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
Thanks oceanblue for researching it.

Small point:

second, Carmine Pariente is a psychologist from the Institute of Pschiatry, Kings College London, making him a stablemate of Simon Wessely, which understandably causes some suspicion.
He's a psychiatrist i.e. a qualified medical doctor who has gone on to specialise in psychiatry.

--
Another (small) point in its favour is that some ME/CFS clinicians such as Dr. John Chia have used the therapy [interferon-alpha] so its useful to know as much as possible about the treatment's effects.
 

Enid

Senior Member
Messages
3,309
Likes
866
Location
UK
Is this psychiatry moving into the world of biology - well what do you know - there's some hope for all !

(All psychiatrists are qualified Docs first - not specialists in medical fields so much to learn and rant I've seen too many ill caught up in their mumbo jumbo)
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
Link to free full text of Wessely and Pariante Hep C study

Wessely S, Pariante C. Fatigue, depression and chronic hepatitis C infection. Psychological Medicine 2002: 32: 1-10.
is available for free at:
hxxp://simonwessely.com/Downloads/Publications/CFS/142.pdf
 
Messages
1,383
Likes
362
Location
UK
Wessely S, Pariante C. Fatigue, depression and chronic hepatitis C infection. Psychological Medicine 2002: 32: 1-10.
is available for free at:
http://simonwessely.com/Downloads/Publications/CFS/142.pdf
Thanks.
Conclusions. Despite anecdotal evidence to the contrary, at the moment there is no evidence that
HCV infection per se is associated with fatigue or depression, and there is a suggestion that it is not
.
The same risk factors that exist for fatigue in other physical illnesses, such as metabolic disorder,
mood disorder, demographics and lack of exercise, certainly exist for HCV. Although there are
elegant theoretical mechanisms, there is no compelling epidemiological evidence for an additional
HCV specic fatigue or depression factor.
This ties in with the Interferon-alpha studies which show very low levels of fatigue for HCV patients at baseline, before interferon treatment. Which is just as well, really, because if they were fatigued before the treatment it would be much harder to interpret the results.