EDMONTON — A virus best known for the damage it does to the liver can also damage brain cells, University of Alberta researchers report in a new study.
The research into the impact of hepatitis C on the brain is significant, they say, because it marks the first time scientists have been able to show that the virus can infect the brain.
"It has been a question for a long time," said Pornpun Vivithanaporn, a post-doctoral fellow in the U of A's Faculty of Medicine and Dentistry and first author of the hepatitis C study, which was published last week in the Public Library of Science One Journal.
"It proves the virus has implications on neurological disease," she said Tuesday.
Hepatitis C infects about 170 million people globally and about 300,000 in Canada. It targets the liver, causing inflammation and cirrhosis.
Researchers already knew that severe liver disease can affect a person's brain, but more recent research suggested that hepatitis C patients without serious liver problems also could suffer from brain-related issues such as memory loss, trouble concentrating, apathy and depression.
The new study allowed a team of researchers to show precisely how the hepatitis C virus can infect brain cells on its own.
"That had never been shown before," said lead researcher Dr. Christopher Power, a neurologist who works in the U of A's Faculty of Medicine and Dentistry. "It gets in there, it infects and it replicates. For a virologist, that's a really core observation. You can see infection of the cells and you can see replication."
To show how the hepatitis C virus infects brain cells, Power pointed to a computer screen in his U of A lab on Tuesday.
On one side of the screen, pictures of two healthy brain cells appeared in red. On the other side, those same cells appeared peppered with green dots. And in this picture, green is bad since it represents a buildup of viral proteins that eventually damage and kill the cell. In a way, Power explained, the virus can cause brain cells to drown in their own garbage.
The discovery is important, Power said for a couple of reasons.
First, he said, there are immediate clinical implications. "It tells us we need to be vigilant for neurological problems for people who have hepatitis C," he said.
That would mean taking such steps as ensuring patients have assess to a neurologist or psychologist on their team of physicians as well as a liver specialist.
"The second issue is it underscores the importance (of) developing new treatment for hepatitis C so we can prevent infection of the brain," said Power, whose research is funded by Alberta Innovates — Health Solutions and the Canadian Institutes of Health Research.
There is now no vaccine to prevent hepatitis C. Researchers have uncovered some treatments that work for a portion of patients infected with hepatitis C, but those also can have serious side effects for some people.
Michael Harmsworth, a hepatitis C sufferer who counts Power among his five doctors, said Tuesday he was extremely interested to learn about the research team's discovery. He said he hadn't realized that hepatitis C had the potential to affect the brain until Power showed him computer images of infected tissue samples.
Harmsworth, who was diagnosed about 13 years ago, said it all points toward progress.
"It's making me think, 'Hey, I may still have my time left here,'" Harmsworth said. "My little girl is nine years old and I want to be here when she turns 16 and goes to the prom."
I read yesterday and have decided it is my new "blame it on the brain fog" excuse for everything I do wrong. ;) Just trying to make light of yet another damn thing we have to deal with. So much that nobody really even knows yet how it does affect us to have this disease and why perhaps we don't get over it even after we are SVR - maybe not the interferon as everyone always assumes.
memory loss, trouble concentrating, apathy and depression.
Gosh, and I was wanting to blame it all on old age! It is nice to hve some confirmation on how many body systems are impacted by this virus. We already know it has a lot to do with the lungs. Now the brain. Isn't anything sacred?
I would venture to say that there is not a single cell in the body that Hep C does not infect.
Like it or not, there's nothing that can be done about "occult" infections. As long as the damage stops, that's fine with me. For some of us, the choices that brought us here were made long, long ago in a far away land. I for one ain't gonna worry my little gray head over it.
Interesting article. Yet another factor for the implications of treating sooner than later, at least to me.
This part makes me think:
""The second issue is it underscores the importance (of) developing new treatment for hepatitis C so we can prevent infection of the brain," said Power, whose research is funded by Alberta Innovates — Health Solutions and the Canadian Institutes of Health Research."
What happens once infection of the brain has occurred? Does eradicating the virus with SVR also cure the infection to the brain? Can they measure this? Makes me wonder.
I do believe that some years ago these were the same "theories and observations" that I raised on multiple occassions. Although my ideas seemed to be roundly rejected back then, they may just be revisited these days. And do we have any idea at all what effect the interferon has on the "brain" infection?? Could there also be other organs or cells that the virus also infects, and may remain within long term??? Questions that I no longer try to get answers to....the answers will come along on their own. Since our blood is now considered "virus free" (for the SVR's), does that mean that there is absolutely no virus acting on any systems or organs in our body? We don't have those answers yet....but we will in time.... Still SVR after 7 years....and working at getting back to "normal".... my brain often doesn't want to cooperate......and maybe there is a reason.... Anyway, I am going to make the best of whatever this SVR consists of....Hello to all my old friends and (not so friends) on the forum. I hope you are all doing well!
I totally believe that both the HCV and the 10 TX's have had a large impact on my brain. One of the reasons why I qualified for SSDI was due to the fact that I couldn't pass that psychologic/neurologic tests that their own psychiatrist did on me when he was evaluating me. In the state of Florida is did not qualify for SSDI based on my Hep C because I had not yet developed cirrhosis. It was based on the effect that all of this had on my functioning and not the Hep C. Anyhow, I don't expect many of you will understand why it is that I can't work. I did try to go back to work once, when I was in the waiting stage of trying to get the disability and it was a disaster. I totally could not absorb the instructions/directions that they were giving me when they were trying to train me and the very next day I had a melt down. This, I might add, was when I was NOT on treatment. Now, whether or not that would improve with SVR, I would be very interested to know. Because, believe it or not, I truly want to be cleared of this and be back to being a working person and a productive member of society. Take Care ya'll.
This thread also is pertinent to the recent thread on HCV Brain Damage, and would provide additional information to anyone curious about other organs that may be directly infected by the virus. Food for thought!!!
And i am not- even depressed anymore,i manage to dont see t-he ignorence of t-he docto-rs, who maby t-hing i deserve what i am suffering.There are st-ill many- things t-o be discovered about how HCV affects us .But i dont have any- hope it- will be soon.Here in t-he forum i found anot-her who had my simpt-oms (depresion,low libido) but in his last- post-s before 3 y-ears he was talking about- suicide.I really- hope i learn to- live wit-h my- disabiliti-es and never t-o th-ong or t-ry- suicide , like i did a y-ear ago,
There are obviously many things that hep c does to our bodies that is not yet understood, or the relationship is not understood. There is a long list of extra hepatic manifestations of hcv. We always hear that vl has no effect on liver damage, but it is not know how vl and how long someone has been infected effect the related conditions and other organs.
Here is a list of some of those extra hepatic manifestations. Most people do not get these types of issues unless they have been chronic for a long time.
Extrahepatic Manifestations of Chronic Hepatitis C
Roderick Remoroza, MD, and Herbert Bonkovsky, MD
(To see the figures and illustrations in this article, please download the pdf version.)
Although most patients with chronic hepatitis C are asymptomatic, an appreciable number will experience symptoms that are due to the liver disease and/or extrahepatic manifestations of HCV infection. Recognition of these symptoms will lead to early diagnosis and treatment of hepatitis C. Fatigue is the most common symptom of chronic hepatitis C and is most often mild. Intermittent right upper quadrant pain, anorexia and nausea occur less commonly.
Chronic hepatitis C infection predisposes patients to the development of diseases involving other organ systems including the kidneys, the skin, eyes, joints, immune system, and the nervous system. There are many extrahepatic manifestations of hepatitis C: some are relatively common (e.g., cryoglobulinemia), whereas others are infrequent and their association with hepatitis C has not been clearly defined. Only the common extrahepatic manifestations with clear association with hepatitis C will be discussed in this review.
Cryoglobulins are antibody complexes that precipitate as serum is cooled and that dissolve on rewarming (1). These complexes contain hepatitis C virus (HCV) particles and can precipitate in the walls of small and medium sized vessels. There are three types (I, II, III) of cryoglobulinemia .Type II or “mixed” cryoglobulinemia (MC) is the one most commonly associated with chronic hepatitis C infection. This type is called “mixed” because the antibodies that are found are of two kinds. One antibody is a polyclonal (i.e., from more than one group of cells) antibody (IgG), and the other antibody is a monoclonal (IgM) directed against the IgG. The frequency with which cryoglobulins are detectable in serum of patients with CHC depends on how carefully samples are handled and upon the methods used for detection of cryoglobulins. Because these proteins precipitate from serum as it is cooled, the blood must be kept at body temperature after it has been obtained until it has clotted and the serum has been drawn off. Then the serum is tested for the abnormal proteins. If this precaution is not observed, the test may be spuriously negative.
The skin, kidney, nerves and joints can be affected by cryoglobulins. Cutaneous leukocytoclastic vasculitis is a skin lesion that appears as palpable purpura (hemorrhages in the skin that result in the appearance of purplish spots or patches) that usually affects the lower extremities over the shins (Fig 1). These lesions are caused by plugging of the dermal capillaries (very small blood vessels in the skin). Successful treatment of the hepatitis C infection with interferon (+ ribavirin) usually results in resolution of the skin lesions.
Cryoglobulins also affect the nervous system in some HCV infected patients. The most frequent symptoms and signs are those of chronic sensory polyneuropathy, although acute or subacute encephalopathy has been reported as well (2,3). “Restless leg syndrome” and Guillain-Barré syndrome have also been reported (4). The mechanism of nerve involvement is thought to be MC-well-established related vasculitis of the small blood vessels that supply the nerves. There is no well-established treatment. Treatment with interferon, corticosteroids, or cyclophosphamide (cytoxan) has not shown any consistent results although some patients appear to respond to one or a combination of these drugs (5).
The kidneys are also affected in some patients with hepatitis C. The most common kidney disease related to hepatitis C infection is membranoproliferative glomerulonephritis (MPGN) (6). The prevalence of MPGN varies with geographical location. It is more common in Japan and is less frequently seen in France. Patients with MPGN usually complain of weakness, edema and have systemic arterial hypertension. Urine of such patients contains a lot of protein (>3.5 g/day), a condition called nephritic syndrome. Other abnormalities include low serum albumin (due to losses in the urine), decreased complement levels, and the presence of rheumatoid factor and cryoglobulins. MPGN may sometimes occur in the absence of cryoglobulinemia. Another kidney disease called membranous nephropathy (MN) is less common in HCV infected patients and is not associated with cryoglobulinemia or rheumatoid factor but is associated with heavy proteinuria (7). The mechanism of the disease is still unclear, but some studies suggest that it is caused by circulating complexes of antibodies and HCV particles directly causing damage to the kidneys as they are deposited in the glomerulus and tubules of the kidneys. Some authors recommend treatment of patients with HCV-related kidney disease even in the absence of active liver disease. The current treatment of choice for HCV infection is interferon and ribavirin. However, in patients with severe renal failure, only interferon monotherapy is recommended because ribavirin cannot be removed by dialysis. Thus, it accumulates and causes severe breakdown of red blood cells (hemolysis) and anemia.
Porphyria cutanea tarda (PCT) is the most common form of the porphyrias, a group of diseases characterized by defects in one or more of the enzymes involved in the production of heme. This results in the overproduction of porphyrins or its precursors. Patients with PCT often present with blisters and vesicles on the dorsal aspects of the hands, forearms, back of the neck and face. These lesions develop in areas that are exposed to the sun and that sustain minor trauma. Increased facial hair and pigmentation changes are also noted. In some patients, as the injury becomes chronic, scarring, alopecia and thickening of the skin may occur. The skin lesions may be further complicated by deposition of calcium and formation of non-healing ulcers. See Figure 2. Patients with PCT who are of northern European origin were also found to have increased prevalence of HFE gene mutation, the gene found to be responsible in most cases of hereditary hemochromatosis. In addition to iron, heavy alcohol use and use of estrogens are also major risk factors for the development of PCT. The treatment of PCT involves dietary restriction of foods rich in iron, and avoidance of alcohol and estrogen use. Phlebotomy to remove iron is the first treatment for most patients with PCT. In patients with PCT, we recommend iron depletion by phlebotomy before initiating antiviral therapy with interferon and ribavirin. Antimalarial drugs like chloroquine have been used in the treatment of PCT as well (8).
In a large case–control study of 34,204 veterans, lichen planus, vitiligo and PCT are the skin disorders that have been found to have significant association with HCV infection (9). Lichen planus is a disease of the skin and mucous membranes that appears as violaceous, scaling papules usually located on the limbs and white reticular lesions on the mucous membranes (See Fig 3). It is suggested that this is an autoimmune response to an antigen shared by HCV particles and the basal cell layer of the skin. Vitiligo is an acquired loss of pigmentation of the skin. The loss of pigmentation is usually found around body orifices like the mouth, eyes and nose and on the extensor surfaces of the elbows and knees as well as the wrists. Interferon has not been found to be uniformly effective in the treatment of lichen planus.
RHEUMATOLOGIC and AUTOIMMUNE MANIFESTATIONS
Myalgia (muscle pains), fatigue and arthralgias (joint pains) are common manifestations of HCV infection. HCV-related arthritis commonly presents as symmetrical inflammatory arthritis involving small joints. The joints involved in HCV-related arthritis are similar to rheumatoid arthritis (RA). This sometimes makes it difficult to differentiate true RA from HCV patients with positive rheumatoid factor but without RA. HCV-related arthritis is usually non-deforming and there are no bony erosions in the joints. A marker called anti-keratin antibodies has been studied to differentiate true RA from HCV related arthritis. In a recent study, 71 patients who were rheumatoid factor positive were tested for anti-keratin antibodies. Anti-keratin antibodies were detected in 20/33 (60.6%) patients with true RA and only 2/25 (8%) patients with HCV-related arthritis (10). Patients with HCV-related arthritis seldom respond to anti-inflammatory medications, and although there are no controlled trials to address this issue, it has been recommended to treat these patients with combination antiviral therapy of interferon and ribavirin (11).
Sjogren’s syndrome (SS), an autoimmune disease characterized by dry eyes and dry mouth has been found in some studies to be more common in HCV infected patients. They differ from primary SS in that they do not have lung and kidney involvment. Thus it is recommended to test for HCV infection in patients with SS or primary SS. A study by El-Serag of 34,000 veterans failed to show a significant association between HCV infection and diabetes, SS, or autoimmune thyroid disease (9).
Interferon therapy of HCV infection may also trigger the development of autoimmune diseases, the most frequent of which is autoimmune thyroiditis (Hashimoto’s thyroiditis). This may lead transiently to hyperthyroidism, but eventually to hypothyroidism (underactive thyroid) and to the need for life-long thyroid replacement therapy (Bonkovsky & Mehta).
B-cell non-Hodgkin’s lymphoma (NHL) has been linked to HCV infection. This is probably due to the long-standing stimulation of B cells caused by chronic HCV infection, although other factors must be important because most patients with CHC do not develop such lymphomas. A high prevalence of HCV was found in patients with immunocytomas, a low-grade type of lymphoma, which was associated with cryoglobulinemia. Another study linked HCV infection and splenic B-cell lymphomas. Seven of nine patients with splenic lymphoma were treated with interferon monotherapy. Two patients who had detectable HCV RNA after treatment received combination therapy of interferon and ribavirin. All nine patients had sustained virological responses and had remission of their lymphoma, as well. On the other hand, six control patients with splenic lymphoma without HCV infection did not respond to interferon treatment at all (12). It is therefore reasonable to screen for HCV infection in patients with splenic lymphoma as well as other low grade NHL.
HCV infection has been associated with several eye disorders. Keratoconjunctivitis sicca (dry eyes) is part of SS. Mooren’s ulcer is a rapidly progressive, painful ulceration of the cornea. The diagnosis is made by exclusion of other causes of corneal ulcer. A few cases of Mooren’s ulcer and HCV infection have been reported. In at least two of these patients, the ulcers did not respond to steroid and cyclosporine drops but did respond to interferon alfa-2b (13). Damage to the retina of the eye (retinopathy, which includes cotton-wool spot formation, hemorrhages and arteriolar occlusion) is a frequent complication of interferon therapy. Fortunately, the retinopathy is usually reversible once treatment is stopped and sometimes even improves despite continuation of therapy. However, patients receiving interferon who experience visual symptoms should hold treatment and undergo careful eye examinations by eye specialists.
In summary, extrahepatic manifestations of chronic hepatitis C are varied and involve a number of organ systems. Physicians and patients should be aware of these signs and symptoms, and testing for HCV should be done in patients who manifest these. This may lead to early diagnosis and successful treatment of chronic hepatitis C infection.
In summary, extrahepatic manifestations of chronic hepatitis C are varied and involve a number of organ systems. Physicians and patients should be aware of these signs and symptoms, and testing for HCV should be done in patients who manifest these. This may lead to early diagnosis and successful treatment of chronic hepatitis C infection. "
We should probably all copy this and take it to our doctors because from what I've read on here, many of them don't have a clue about this stuff.
Also please note additional thread, HCV, Brain Damage.....
Now that science is beginning to clarify some of the reasons for our cognitive and behavioral problems, maybe we will see a more multi-functional approach to the infection. ie: This virus is not just a "liver" virus, but it is a virus that directly infects, and probably directly impacts multiple organs and systems in humans. We now have proof that the brain is actually infected in many people, and I will guess that sometime soon they will also demonstrate the virus acting on connective tissues (joint problems), salivary tissues and glands (all the eye and dental issues, as well as SS complaints), skin, lungs, kidneys...etc. How about the cardio-vascular system...do we know yet why a much higher percentage of HCV+ individuals seem to suffer stroke and cerebral hemmorhage?....You have to also wonder if the virus, which runs rampant in the blood stream as we know so well, also damages the walls of the arteries and veins, or even heart tissues....and so on and so on....
I have always rankled at the term "a liver virus" when doctors refer to HCV. I have ALWAYS believed that the virus is a total system virus, that just happens to have a slightly larger propensity for the liver than maybe some other organs....maybe.
Many people with active HCV, and minimal liver damage have suffered from a wide range of "extra-hepatic" effects...usually with little explanation from the medical community as to "why". Now maybe we are finding that the "why" consists of HCV directly infecting and damaging various other organs and cells in the body. I have ALWAYS believed this, it only makes sense, especially if you have actually experienced these "extra-hepatic" symptoms over many years.....
Let's also hope that our SVR status also includes a termination of infection in all these other cells and organs as well....not just in the bloodstream! My biggest concern is how to insure that the brain infection is cleared on SVR, and maybe this is where brain scans and other lab testing will help us understand the long term outcome better as relates to our brains. There is still tons to be sorted out by researchers regarding just what is going on after SVR....which after-effects are due to all the interferon, which are from residual effects or changes from having had the virus for so many years, and finally which after-effects are possibly dure to still active HCV infection in isolated organs (the brain, lymph nodes, connective tissue, etc.). Possibly some forms of the infection, in certain cells, might not be capable of re-triggering the 'visible' HCV serum infection that we all originally treat. Could there be 'residual' HCV infection that continues on, in isolation, causing symptoms, and damage??? Only time, and good research, will tell.
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