Depression in HCV
Q Do you know whether hep C related depression is likely to improve after successful combination therapy? I have been clear for almost two years now and have suffered some moderate depressive episodes since. I had hoped they would get better. Maybe I need to give it more time.
A For the most part, depression which is directly attributable to the hepatitis C virus is reversible after successful treatment with pegylated interferon and ribavirin. It is very rare for depressive symptoms to continue 2 years after stopping treatment - usually everything has resolved after 6 months. There have been some case reports of persisting depression, but since depression is a problem with many underlying causes (not just hepatitis C), I think you have to be clear that there aren't any other contributory factors. Your GP might want to refer you to a psychiatrist to make sure nothing has been missed.
Q I am experiencing extreme depression six months after my treatment finished. I need to know if my treatment outcome will have been affected by the fact that I have had hepatitis A, B (about 15 years ago) and C, most recently.
A The short answer to your question is no, but I shall answer in more detail!
The hepatitis A, B and C viruses are all very different in their make-up and their effects on the body. There is evidence that the hepatitis C virus directly affects brain function, although the precise mechanisms for this are still an area of medical research. There is no evidence that the hepatitis B virus affects brain function as it only infects the liver (unlike the hepatitis C virus which can potentially get into all parts of the body as HCV can live in white cells in the blood which then travel to all body tissues). The hepatitis A virus has no lasting effects, since once the body has cleared the virus, there is no on going action or reaction by the body.
Q I've experienced much depression and emotional difficulties over many years. Most probably contracted Hep C around 30 years ago. What baffles me really is: how much of this has been due to the virus affecting my brain?
In fact once I was diagnosed 2 years ago it was a kind of relief to know that there was a reason for my difficulties. It may well be impossible to know how much it has affected my brain; it would however be interesting to know that had I not had Hep C would my life have been any different? Also is the damage reversible?
A Yes, the virus is significantly associated with depression and a constellation of symptoms which many people like to call "brain fog" including poor memory, lack of concentration and the like. This may be a direct effect of the virus on the brain, but could also in part be related to circulating chemicals which the virus provokes the body into producing (so called "cytokines").
Of course, there are many causes of depression, but hepatitis C is a big player in this. I cannot say whether your life would have been different without the virus, but I suspect so.
There is no evidence to suggest that the virus has an irreversible effect on the brain. This is an area of ongoing research with imaging studies of the brain (MRI magnetic resonance imaging) in patients with hepatitis C which we are conducting in the UK and are also being conducted in other countries such as Canada, Spain, Germany and India.
Q I have chronic depression and take nusak, an anti depressant, it does seem to help but there are times especially when I am sick when I feel very low. I saw a psychologist here in Cape Town who told me I would have to take them for the rest of my life due to hep c and being in recovery. I hope this isnt the case. I stopped unsuccessful treatment 18 months ago and looking back at journals I do seem to be better now regarding brain fog but feel as if I've lost 'my spark"
A Successful clearance of the virus from the body is the only sure way of stopping or reversing your symptoms. There are new antiviral treatments coming along which may be helpful in the longer term if you haven't been able to clear with pegylated interferon and ribavirin. However, the right dose of an antidepressant can at least restore the chemical imbalance in the brain. Different antidepressants work well in different people and it is a bit of trial and error ("cookery") to find the antidepressant which suits you as an individual - but please remember that most antidepressants do not have an immediate effect and take at least 6 weeks to "kick in" fully.
Q As I have cirrhosis and chronic hep C I often wonder whether the symptoms I attribute to 'brain fog' are in fact the first mild stage of encephalopathy, eg - 'Minimal hepatic encephalopathy - lack of detectable changes in personality or behavior, minimal changes in memory, concentration, intellectual function, and coordination.' Is it possible to tell the difference?
I have recently been prescribed amitriptyline as I find it so difficult to sleep and am depressed - is this a good drug? Although I have only been taking it for a week I do not like the side effects although it gives me more sleep.
A Actually minimal encephalopathy is quite different from brain fog. The first condition only occurs in people with established cirrhosis of the liver and is due to the fact that the failing liver does not filter out circulating toxins from the gut.
In hepatitis C, brain fog occurs without cirrhosis, even in people with minimal or absent liver disease. The liver is perfectly capable of filtering out circulating toxins from the gut, but the symptoms although seemingly similar, are due to the effects of the virus on the brain (either directly or indirectly, as I have described in other answers.
Amitriptyline is a good drug, but it has a series of unacceptable side effects in many patients, including dry mouth and blurred vision. Thus, for the most part, it is not used. It does take about 6 weeks to work.
SSRIs such as citalopram do not have these side effects. Mirtazepine is a drug which we use at St Mary's which does not have these side effects either, but it does have the sedative effect at night to help you sleep
Q Do you think there should there be a psychiatrist or psychiatric nurse attached to Hep C departments where anti-depressants are being prescribed to assist alongside treatments?
A I agree that psychiatric support is very helpful. In our unit at St Marys Hospital in Paddington, London, we have a dedicated psychiatric liaison service where patients can be assessed prior to treatment with pegylated interferon and ribavirin and started on suitable anti-depressants before treatment if they are thought to be at risk or referred over for psychiatric opinions if problems arise during therapy. It is important to have a close relationship with the psychiatric service, but I appreciate that this is not always possible in every centre for various local reasons, which differ in each hospital.
Q Before starting treatment on March 1st this year I had severe fatigue, crashing brain fog and feelings of hopelessness and depression. The fatigue would occur soon after getting up and last the whole day. Sleeping in the afternoon seemed to make it worse. After 2 weeks on treatment, I continued to feel very low, and accepted the anti-depressant Citalopram which was offered to me. The first 2 weeks on Citalopram I was desperately anxious, more so than before starting the AD, but I wasnt warned about this. I was told I would feel better within 3 weeks.
A Anxiety is a known side effect of citalopram which occurs in a small percentage of people. It can wear off with time, but often switching anti-depressants is helpful if these symptoms persist. It normally takes up to six weeks for the drug to be fully effective, but most people feel benefit much before that.
Q What can you recommend for someone on treatment who will not take anti-depressants or sleeping tablets (neither herbal nor prescribed) because of previous drug use/misuse
A I think that it is important to have a good supportive network around you. Many Hep C treatment groups have good liaison with psychiatric services that offer psychotherapy as a non-drug option - it is worth tapping into this in your local area. Different Health Authorities offer different facilities.
However, some relaxation treatments are effective (tai-chi, yoga, pilates) as are talking to people in your local hepatitis C support group.
Q Six months after a failed 48 wk treatment my depression took me to a critical level a few weeks ago, although I was on the anti-depressant citalopram. After this sad episode my depression is much worse but I am afraid to add any more chemical to my brain for fear of what I may do. Gp has tried me on anxiety Dothiepin for panic attacks but just after two nights I reacted adversely to them and my mood dropped again to crisis point. He now says I should try Mirtazapine, which I am reluctant to do. Do you think I should follow my instinct and allow time to balance my brain chemicals?
A Mirtazepine is a good drug which can also help you sleep (as a beneficial side-effect). It isn't addictive. However, I have already addressed the issues of psychotherapy and relaxation techniques. Some people find that acupuncture may help, although I cannot vouch for this (although from personal experience, it cured my painful neck when I had one!).
I think you need to give anti-depressants a fair time to kick in if you do try them - it is at least 6 weeks before they have maximal effect - there is no instant relief from them.
Q If the presence of 'genetic sequences of HCV' in post mortem brain tissue is used to validate fatigue/short-term memory loss etc, why should these symptoms persist when SVR has been achieved, as it appears to in many cases? Do you think that the persistence of 'riba-rage' and other symptoms may be related to the creation of neural links, or do you suspect that there may be another cause?
A The persistence of symptoms after successful clearance is due to the fact that the brain is slow to respond to change. We believe that the virus causes a population of cells in the brain called microglia to become active and secrete various chemicals which cause the imbalance in the brain which results in the symptoms. We are doing research at the moment with a technique called positron emission tomography (PET) which can look at the activity of these cells in the brain with a type of brain scan. It would appear from early results from this research and research into other brain conditions that these cells take quite a while to switch off and quieten down - why they remain active and on their guard for a lag phase of several months is really not known at the moment.
Q Since finding out about my hep c 10 years ago, I have declined from a confident, out-going, sociable person who has traveled the world to a semi-recluse who spends my time mostly on my own trawling the net finding supposedly liver-friendly products to eat, cosmetics, cleaning products etc, all stuff to keep the strain on my liver to a minimum.
We are told we can eat anything in our diets including red meat and dairy products, not too much fat. Although what we eat may not affect the progression of the disease, does it not affect how we feel on a day to day basis?
I love chocolate and cakes etc but am scared to eat them because I have read sugar can act like alcohol on the liver. How much damage would a bar of chocolate do to the liver? This may seem trivial but when you can't drink alcohol, smoke or the other, a bar of choc is like heaven. Is there any research on diet going on at the moment?
A Diet is important for liver disease in general. I think there is no harm in eating chocolate cake in moderation. There is some evidence that fish oils have an anti-inflammatory effect in the liver and ingestion of cod liver oil may have a beneficial effect. Professor Margaret Bassendine has just started a major study in Newcastle aimed at looking at the anti-viral effect of fish oils (funded by the British Medical Research Council). Eating fish twice per week is probably just as helpful (oily fish such as mackerel, herrings, sardines, tuna and salmon).
Q I'm now 12 months post treatment, which was successful. However, there are still ongoing problems with bad mood swings and depressive episodes. I didn't use anti-depressants during treatment due to a bad reaction to them in the past and the only medication I take are occasional beta blockers for anxiety. I am concerned about long term brain damage due to the therapy. Is there any evidence of this possibility?
A This is an area of ongoing research. There is no evidence of ongoing long term brain damage and for the most part, symptoms do settle in people after 6 months (and up to 12 months). I explained about the microglial cells taking a long time to switch off in a previous answer and it is possible that in different people, the "switch-off" effect takes a longer time - this is an area of active research.
There are other causes of depression and you have to be sure that there is no other reason (for example changes in the thyroid gland can cause depression and this can be upset by interferon treatment - I presume your doctors will have checked this, but it is worth enquiring).
Imaging studies on the brain are addressing the issue of longer term damage, but results are yet to be determined (Watch this space)!
Q I was wondering if you have an idea why depression associated with hepatitis C comes and goes so much what might be happening in the brain to cause the fluctuations? Do you think it might also have any connection to the immune system fighting the virus, or possibly the inflammation process in the liver, as well as being associated with the virus being in the brain? I find the depression can last for as little as a day or a few days and then other times for many weeks and descend out of the blue. Somehow being able to understand the mechanism, if its possible, helps! I have had hepatitis C for many years and have not had treatment.
A The simple answer is that it is not known why this is the case. What you describe is a very real phenomenon experienced by many.
We can postulate that the imbalance in chemicals (neurotransmitters) in the brain is an interplay between chemicals produced by the body in response to the liver and blood infection (circulating cytokines) and the direct effects of the virus on the brain and at any one moment these factors may differ - causing fluctuations which you and many other people experience.
This is an area which people are researching actively (including Dr Daniel Forton at St George's Hospital in London who pioneered this area of research and Dr Bob Grover at the Hammersmith Hospital in London who is doing the imaging studies). The results of some of these studies will start filtering out in the next 6-12 months and will be posted on this website.
Q I suffered terrible depression during the last phase of my treatment (24 weeks inf + riba) but would not take anti-depressants. I am still getting bad phases of depression though, this week has been awful for me, feeling really down (no reason at all), no urgency to do anything and loss of self interest. My treatment finished on Nov 9th 2006 and I got the all clear, SVR is due on 7th May. I realise that everyone suffers from depression, fatigue, lack of interest at times through their life and it is not a condition of any sort but just life in general.
My question is do you think that this sudden depression is due to the after effects of my treatment (as it turns on and off so quickly) or is this normal??
A It is not uncommon to get depression after treatment for several months. I have talked about the possible reasons for this in other answers. I think if symptoms persist, you need to be sure that there is no other cause (as I discussed in other answers).
With respect to your skin problems, these could make you feel depressed in their own right. I think if they are not healing, you need to see a dermatologist (skin doctor).
With respect to your symptoms compared to other people, your experience is not uncommon, but different people react differently and this is a complex interplay between the type of virus that you have and the genetic make up that you have (which governs the immunological response that your body mounts in order to fight the virus). The battleground is your body and where the various wars take place is individual - this is an area of immunology research. People such as Professor Salim Khakoo in Southampton are working on this question at the moment.
Q If, as stated, "Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease and now the recent detection of HCV genetic sequences in post-mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment." Would Dr Robinson agree with me that the response by this government and its agencies, such as the Department of Health, the DWP, and Medical Services is a disgrace, and that it amounts to little more than the denial of basic human and statutory rights to sufferers? Would the doctor care to comment on the failure of GPs, consultants, and PCTs to adequately address these issues, and the detrimental influence said negligent failure can have on patients?
A Thank you for raising this issue. I agree that there is a big lack of awareness of the effects of the hepatitis C virus on the brain and the poor quality of life that many people endure as a result. This is a problem at Governmental level with respect to the DOH and NHS in general, but also there is poor awareness amongst the medical fraternity (hepatitis C is seen solely as a liver disease, which it is not!).
Organisations such as the Hepatitis C Trust are doing their bit to raise awareness and hopefully the involvement of personalities such as Anita Roddick can capture the headlines, as it did with Pamela Anderson in the USA.
Q I have hep c geno type 1 and have done 48 weeks on treatment with lots of side effects. The virus was undectable after 12 wks and stayed so until my pcr 6 months after treatment when I was told I was still positive. This news was worse than finding out I had hep c in the first place. I understand this is very difficult to answer, but I was told I must wait for new cure to come on board. I am devastated. Can you please tell me what quality of life I can expect in the mean time? I am a 51 yr old male who works manually hard but right now I dont feel ill just a little tired.
A Actually, there are new drug treatments coming along. Professor Geoffrey Dusheiko is a world expert in this field and he is coming to answer your questions on the hepatitis C Trust website next week (May 1st - same time). He can detail the drugs that are around the corner and those that are on the more distant horizon.
You don't have to worry - many people with hepatitis C do not ever have any depression. If you just feel a bit tired, there is no reason why you should suddenly feel depressed, just because of the virus. In some people there is evidence that the virus may never infect the brain (again it is due to specific mutations in the virus and is an area of active research with Professor Howard Thomas and Dr Peter Karayiannis at Imperial College in London).
I would just have a positive attitude and eat healthily (fish is good as I said before in a previous answer). I would be glad you don't have depression!
Q I would like to ask the doctors that my mom (75 years) has been on treatment with pegasys and interferon for close to three months. However, I am very worried about her overall health....she looks drained and always exhausted. She is coughing often with back pains and her facial appearance is not good. I would like to know if these are all side effects of the treatment or should I take her to see the specialist who is treating her. I am worried because I do not want to delay in case things become complicated. She is seeing a specialist in South Africa as we live in Zambia and there are no facilities here with regard to this disease.
A I am not able to answer your question confidently without seeing your mother, but it sounds to me as if she needs to be checked out by a doctor, either locally in Lusaka, Ndola or Livingstone or else going back to see the prescribing physician in South Africa. I would think she needs to be seen by a local Zambian doctor first, to ensure that there is nothing else going on (treatment with pegylated interferon can cause all sorts of issues such as anaemia, thyroid problems and this may be more evident in a 75 year old lady).
Q Where can I get info on new treatments, I live in Cape Town where the cost is ridiculous and info is minimal.
A The British Liver Trust and the Hepatitis C Trust have reliable websites with validated information on liver disease. However, new treatments are not always updated on some websites. The Hepatitis C Trust does have a section on new treatments which is regularly updated, particularly after big medical conferences.
Professor Dusheiko is coming in to the Hepatitis C Trust next week to talk with you all on new drug treatments - so this should answer most of your questions (May 1st 2007 - same time).
Q When my doctor here in Cape Town mentioned brain fog as a possible symptom to expect to experience during my treatment I wasnt sure what to expect...I soon learnt what he meant.! My brain already felt pretty mashed as I'd just done 9 months treatment so it wasnt a great idea to have started so soon in recovery..looking back..
I found and still do it really hard to remember anything, conversations, films, names, phone numbers even my own.. my short term memory is mashed and I do think I'm going senile. I have to write everything down so cant go anywhere unless armed with a list. I find cell food helps, a brain food.. I'm also interested in ibogaine it is supposed to help with viral load and is an anti depressant, Im going to try it as my husband treats addicts using ibogaine and received a load of info on how it helps with hep c...it would be great to get out of the fog! Have you heard anything regarding ibogaine and hep c??
A I have replied about the general issues surrounding brain fog in another reply to another question, but ibogaine (which is a plant extract from the root bark of the African plant, Tabenathe iboga) is an unlicensed and unproven treatment in many countries. I know that there has been an American study that has suggested its use in this context as an antiviral agent, but there is no scientific evidence to advocate its use at the moment from proper, large scale clinical trials. While the preparation may work and I have no evidence to say that it doesn't, plant extracts in general (be they ibogaine or Chinese herbs, for example) have problems in the sense that there is no control over how much active ingredient is in the preparation, nor is there any control over potential impurities that could cause harm. There is a website on ibogaine (www.ibogaine.org and www.ibogaine.co.uk), but I cannot vouch for the validity of what is said on the websites.
Q What actually causes the discomfort around the liver area, because the liver itself has no nerves I believe?
It can be intermittent; discomfort for several days or weeks then it goes for a while. Could diet have a role to play in this or is it the viral load increasing and decreasing or could it be the bile ducts clogging up in the liver or something?
It is hard to put this hep c to the back of the mind while there is a reminder there all of the time (discomfort) saying,' I'm here, I've not gone anywhere, I'm continuing to do damage to your precious liver'. It can have a profound affect on how you deal with this thing thinking like that, so maybe trying to understand what is happening would help and rather than thinking of it as a time bomb ticking away I could avoid things that would give the discomfort?
A You are correct that the body of the liver has no nerves, but the liver is surrounded by a capsule (a bit like a sausage skin). The capsule has nerves in it which are sensitive to stretching and to inflammation and thus some people can occasionally experience pain if the liver becomes enlarged or inflamed. However, there are other causes for pain in that area. The brain is not very good at distinguishing pain from different organs. Liver pain is comparatively rare and usually the pain is actually from the large bowel (colon) as it squeezes bowel contents around (it acts like a wriggling worm and is always active) - thus most of the activity that the brain receives is from the colon which can "tie itself in figurative knots" sometimes with trapped wind and increased contractions. There are other organs that also lie in close proximity to the liver and could be responsible for discomfort including the gall bladder and the pancreas and the bile ducts. However for the most part the issues are often with the colon, but the liver, even in people without liver disease, can be uncomfortable if the colon is hyperactive.
I would not worry about it overly - but it is worth getting your doctor to do an ultrasound if you have not had one as it excludes other things such as gallstones.
Q Since some level of depression is inevitable with long term chronic illness, and since SSRIs have only ever been demonstrated to be effective with genuine manic depressives and suicidals, is the large scale treatment of hepatitis C sufferers with anti-depressants to be advised? [Although a crude cudgel, if one asks a depressive what they would do if the symptoms were removed tomorrow, most fail to find an answer ... if you ask the same question of a hep C sufferer they are likely to give you an extensive list].
A You are right that mass treatment with SSRIs is something that needs to be addressed. This is something that is being addressed in a meeting in Prague in June (EISH 8-10th June) as many experts think that this question needs serious attention. You are also right that SSRIs may not be the optimal treatment because there is a cascade of different chemical changes in the brain related to the hepatitis C virus and SSRIs only correct one (albeit major) pathway.
Q I had hep c, genotype 3 for approximately 23 years before being diagnosed and subsequently successfully treated (I am now 3 years post-treatment). I have recently had a general health check and everything was found to be normal and in general I feel well, although physical tiredness and general aches have also been an ongoing problem since treatment.
I noticed since treatment that my cognitive skills are deteriorating I now frequently make silly mistakes, like spelling their when I mean there when I am writing/typing and sometimes I seem to have complete blank spots where I cannot seem to concentrate on a single thought but instead get hit with a torrent of half-thoughts completely unrelated to what I am actually doing.I also sometimes find it extremely hard in conversation to come up with a word I am looking for, and often have to settle for more basic or simple words which is frustrating when I want to express myself well.
Fortunately it is not for prolonged periods of time but it is frustrating and definitely not something I experienced previous to treatment. I am 44 so hopefully it is not just down to getting older! I do have worries that it is getting progressively worse and wondered whether you have done/or known anyone who has monitored people who did interferon back in the early 90s to see if they are currently experiencing problems like this, or if they did, have they resolved over time.
Lastly, would you agree that it is vital to carry out more research in this area? I think a lot of patients are put off doing treatment because of uncertainty about the short and long term side effects.
A These are very distressing symptoms. There has been no research on the long term follow-up from patients treated with interferon as yet, with respect to their brain function. The symptoms so long after treatment are unusual, and you have to be sure that there is no other cause. However, research is being carried out in the UK and particularly in Canada on this issue, but it will be a while before the answers are known.
Q I have 3 questions if it is possible for the Prof to answer. They are in regard to my partner who has chronic HCV Virus and advanced liver cirrhosis. He has appt at Edinburgh Liver Unit in May, has had one unsuccessful HCV combination therapy and is alcohol free for over one year. He has ascites, edema and hepatic encephalopathy and has required hospitalization on approx 4x last year. He has also been treated on 3x occasions for thrombo-phlebitis.
1. Joint Pain becoming increasingly worse in ankles, knees, elbows and wrists. Is HCV the cause and how can this symptom be relieved?
2. Cramps in hands, legs and feet, mainly at night but can occur anytime without warning. Hands appear to have contractures, big toe sticks up involuntary for hours and calfs distort? Analgesics ineffective and cant be prescribed Quinine. Are there any medicines or alternative remedies to help relieve the pain?
3. Brain fog- My partner describes a feeling of things closing in on him, hears voices echoing and is intolerant of people, noise and light. Is this brain fog or can you describe for me please?
A These are very important questions.
1. Joint pain is associated with hepatitis C and is usually treated effectively with pain killers. However, an opinion of a rheumatologist (joint doctor) is sometimes helpful as pain killers aren't always effective.
2. Cramps are very distressing and are commonly caused by imbalances in the salts in the blood. Quinine is usually effective and I cannot think of any reason why your husband should not have a small dose. However, it is important to have a balanced diet with a decent amount of good quality protein (dietary supplements are helpful which the hospital dietician should be able to advise you with, but Ensure and other supplements contain the right balance of minerals to keep things on track. Excess salt is bad though as your husband has ascites).
3. It sounds as if your husband has been suffering from something called "hepatic encephalopathy" which is where the brain is exposed to toxins which are normally filtered out by the liver. This usually only occurs in bad cirrhosis and is not related to the "brain fog" which we have been discussing. It is not specific to hepatitis C, but occurs in all causes of severe cirrhosis. It is treatable with drugs such as lactulose and L-ornithine L-aspartate (very different from the brain fog in hepatitis C which occurs without cirrhosis and is related to the virus, not the liver damage). It responds to liver transplantation.
