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TOPIC: Hepatitis C and Neurological Damage

Hepatitis C and Neurological Damage 9 months 2 weeks ago #22500

The brain fog, fatigue and depression associated with Hep C are well known. Here is an in depth review about the how and the why.

Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders.

www.ncbi.nlm.nih.gov/pmc/articles/PMC4840160/
YMMV
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22503

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Thanks for this, Doc.

Do all the conditions the article refers to disappear after successful treatment?
Genotype 1a
Diagnosed in 2004, had HCV for all my adult life. Until 2016!!!!
Harvoni treatment, started 19 March 2016
4 week results Bilirubin 12 down from 14 pre treatment,
Gamma 25 down from 52, ALT 19 down from 63, AST 19 down from 47,
VL <15 down from a lazy 6 million or so

EOT Results
Bilirubin 10, GGT 18, ALT 19, AST 21, VL UND

12 Weeks post EOT
Bilirubin 11, GGT 16, ALT 22, AST 20, VL UND
Cured baby
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22508

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I have only 3 more days left of treatment. I lost most of the feeling in my right foot below the ankle about 6-7 years ago. The numbness is now 90-95% gone. It is still lingering around the ball of the foot.
I will amend this post if it disappears completely.
G4
F0-F1
diagnosed in 2006
Tx naive
Treatment started 8/12/16, Ledipasvir/ Sofosbuvir (Harvoni) supplied by Monkmed
8/1/16 ALT 36 AST 40
1/4/17 ALT 17 AST 21
7/13/17 ALT 17 AST 25
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22519

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I read that Vitamin B12 and D are helpful for neurological pain, interesting as these two supplements are the ones recommended to take during treatment, especially the B12 I believe.
GT1a Dec14 F2/8.7 VL 900000-2.5M
Jan16 Hepcivir-L MonkMed/Redemption
Baseline: VL 913575 Alt 76 Platelets low
Wk2 VL1157 Alt 23
DET Wk 8 VL 32 Alt19 'In the slow lane'
June16 Fibro 5.7 F0/1 LIF 1.5
Wk 11 VL<12 Alt 13 Det/Unq
Extending tx 12 wks Mylan Sofo/Dac MonkMed
Wk 14 VL <12 Det/Unq
Wk 16 VL UNDETECTED
Wk 22 + 4 Wks Sunprevir FixHepC
Wk 24 UNDETECTED Alt 13
Wk 12 post tx SVR12 Wk 26 SVR24
Thank-you Tim, Dr Debasis @ MonkMed & Dr Freeman @ Fix HepC
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22520

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Thanks for the article. With the focus on the actual virus the associated brain fog, fatigue and depression are not always given a lot of consideration despite the fact that they are very real and can have an enormous impact on all aspects of life, work and relationships.

The brain fog is one of the hardest things to explain to others. Just before my treatment I was describing it like operating with a brain full of pea soup. :cheer:
G1a probably early 1980's, Biopsy F1(2010), F2-F3(2015). VL 5+mill; 2+mill (2014) Tx naive. Accessed Sof/Led through Dr Freeman at GP2U and Buyers Club (lifesavers!!!)
Commenced tx 12/11/15. 9 wk: VL <15 Detected but LFT = Normal 12 week results: UND (Yay!) Due to slow response commenced Sof/Dac 4 Feb for 12 weeks. EOT @ 24 weeks 27 April 2016. (With thanks to Dr Freeman et al). SVR11 result: VL 1,950,000. It's back!
New tx 030916 (Viekira Pak, Solvadi, Ribavirin UND @ 111116. EOT 170217.
SVR12 UND Hooray...
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22526

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"The presence of multidrug resistance proteins such as the P glycoprotein in the BBB provide a protective niche for the replication of virus by restricting the access of antiviral drugs in patients treated for HCV infection[45]. "

Is this indicating longer period of treatment??

Similar to cirrhotic patients being harder to treat as the virus is harder for the DAAs to get at?

J.
GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 16 May 2016: 4 ref <11
6. AFP 11 June 2016: 4 ref< 11
7. VL 4th July 2016: DET
8. ultrasound 12th July 2016 - OK
9. Oct16 start treat - June UND
Last Edit: 9 months 2 weeks ago by sabrecat.
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22531

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Very interesting indeed SCat,
"multidrug resistant proteins" - are these the RAVS that are talked about?

As I responded slowly to the meds, but still responded (and now SVR12) this is of interest to me, could this be connected to Neurological and Cryoglobulin disorders? I had terrible back, hip and pelvic pain pre treatment, could hardly walk. Also I was losing weight and it appeared not absorbing proteins etc properly.

Blood tests flagged up very low triglycerides pre treatment. There was so little to read about low trigs. most articles focused on fatty liver and high trigs, very few articles on low ones and really had to search hard. Always in the minority me ! ;) These tests were flagged up in a private blood test under the cholesterol section, my hospital(s) didn't routinely test those. I always 'knew' there was something I didn't quite get to the bottom of, there was some discussion on this forum re this if I remember correctly. My feeling is this kind of info could indeed be helpful pre treatment with DAAs, but it seems a very complex area and no doubt NHS patients would need to pre test privately. I also instinctively feel VitB12 may could play a part in my own case.

One of my consultants had a full-time heamotologist in their liver clinic, handy I would say !

LG
GT1a Dec14 F2/8.7 VL 900000-2.5M
Jan16 Hepcivir-L MonkMed/Redemption
Baseline: VL 913575 Alt 76 Platelets low
Wk2 VL1157 Alt 23
DET Wk 8 VL 32 Alt19 'In the slow lane'
June16 Fibro 5.7 F0/1 LIF 1.5
Wk 11 VL<12 Alt 13 Det/Unq
Extending tx 12 wks Mylan Sofo/Dac MonkMed
Wk 14 VL <12 Det/Unq
Wk 16 VL UNDETECTED
Wk 22 + 4 Wks Sunprevir FixHepC
Wk 24 UNDETECTED Alt 13
Wk 12 post tx SVR12 Wk 26 SVR24
Thank-you Tim, Dr Debasis @ MonkMed & Dr Freeman @ Fix HepC
Last Edit: 9 months 2 weeks ago by LondonGirl.
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22533

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"multidrug resistant proteins" - are these the RAVS that are talked about?

Hi LG,

No, this isn't related to viral resistance to drugs (RAV or RAS) where the virus natively has or develops resistance to the drugs.

In simple terms, there are proteins in our bodies such as those found in the Blood Brain Barrier (BBB) which naturally prevent toxins (and sometimes also medicines) from entering our brains which is normally protective for us so is usually seen as a good thing. But in this case they are saying that if the HCV virus has made its way into a patient's central nervous system/brain and if it is replicating there, then the normal protective blocking processes of the BBB may make it harder for the DAAs to reach the virus and stop it replicating.

I've highlighted the two points above because they are the key to sabrecats question. The DAAs don't kill HCV but rather slow or stop it replicating and give our own immune system a chance to do its job properly. But currently we don't know if it replicates in the CNS/brain which it would need to do for the BBB to cause issues.

It is however unclear if the CNS itself supports the viral replication...(page 6)

So at the moment while we know that HCV causes neurological problems I think the jury is still out on whether this problem also contributes to some of the group that relapse.
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND!!! :cheer: :silly: :woohoo:
Last Edit: 9 months 2 weeks ago by Gaj.
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22535

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Thanks Gaj :+1:
But in this case they are saying that if the HCV virus has made its way into a patient's central nervous system/brain and if it is replicating there, then the normal protective blocking processes of the BBB may make it harder for the DAAs to reach the virus and stop it replicating.

Hmm .well, 'make it harder' could amount to a similar thing, no? Maybe not in a technical sense re cause, but with the possibility of a slower response outcome?

All v interesting, if rather complex! Not sure my brain has totally returned from the fog, although much improved :lol:
GT1a Dec14 F2/8.7 VL 900000-2.5M
Jan16 Hepcivir-L MonkMed/Redemption
Baseline: VL 913575 Alt 76 Platelets low
Wk2 VL1157 Alt 23
DET Wk 8 VL 32 Alt19 'In the slow lane'
June16 Fibro 5.7 F0/1 LIF 1.5
Wk 11 VL<12 Alt 13 Det/Unq
Extending tx 12 wks Mylan Sofo/Dac MonkMed
Wk 14 VL <12 Det/Unq
Wk 16 VL UNDETECTED
Wk 22 + 4 Wks Sunprevir FixHepC
Wk 24 UNDETECTED Alt 13
Wk 12 post tx SVR12 Wk 26 SVR24
Thank-you Tim, Dr Debasis @ MonkMed & Dr Freeman @ Fix HepC
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22547

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Supose the result would be similar (slower response /higher chances of recurrence ). It is just it would happen not due to virus being resistant to medication but because virus is hidden from medication in the brain. Hope it makes sense.
Diagnosed September 2016.
1b
ALAT in 40s.
VL 460 000
Fibroscan 12.5
Start of treatment 18/10/16
Wk 2 VL 145
Wk 4 VL detected unquantifiable
Wk 8 VL detected unquantifiable
Wk 12 undetected
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Hepatitis C and Neurological Damage 9 months 2 weeks ago #22549

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Hi countless,

another question may be if it passes the blood brain barrier, is it able to cross both ways? That is reinfect the rest of the UND body?

Still think the DAAs must get into the brain because the brain fog (for me) seems to go when under treatment. Hard to tell this time round though with being re-treated as I am using Ribavirin as it has some poo-ey side effects of its own.

Last time round I did not get viral load tests done until 12 weeks after EOT so I don't know whether the treatment failure was the virus making some heroic comeback after treatment, or had come back with a vengeance in the later stages of treatment. If after treatment, then I think if the scarring + BBB is making it harder for the DAAs to work, then even longer treatment (+ or - Ribavirn on the way through?) is indicated?

Maybe out of PBS guidelines, but then again there is generics?

yours

Jeff
GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 16 May 2016: 4 ref <11
6. AFP 11 June 2016: 4 ref< 11
7. VL 4th July 2016: DET
8. ultrasound 12th July 2016 - OK
9. Oct16 start treat - June UND
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