HepC BC
by Darlene Morrow, BSc
Background:
Many people tend to view bone as a static entity. However this is not the case. Bone is constantly being re- modelled in the body. Cells form new bone while different cells break down the old bone and recycling or re-use the components. This process is controlled by various feedback mechanisms that include hormones, alkaline phosphatase, and Vitamin D. And many of these are processed in the liver.
The initial step in bone metabolism occurs with the fat soluble Vitamin D. The body takes the inactive Vitamin D from food and supplements and converts it through a two step mechanism into its active form. The intermediary less active form is converted and stored within the liver. This is then further activated by the kidneys as needed. This final form acts as a hormone to promote intestinal absorption of calcium which causes the blood level of calcium to rise. The calcium is then used by the bone forming cells to lay down new bone. Too little Vitamin D causes a decreases in bone formation and too much causes an increase in bone breakdown.
Cirrhosis and the Bone:
Metabolic bone disease is well documented in cirrhosis.(1, 2, 5, 8, 9, 12) Osteoporosis (thinning of the bones) is commonly observed and results from decreases in bone formation and increases in bone breakdown.(4, 5) These problems can be due to a variety of problems in the feedback mechanisms that were mentioned earlier. Vitamin D metabolism (5,6,12) parathyroid hormone levels, and testosterone (6) are among those that are disturbed. Further complicating the issue is the iron overload that can also be seen in HCV. A connection between high levels of iron and osteoporosis has also been observed. (2)
It is not unreasonable to assume that these changes to the bone do not happen overnight. Sstudies that have looked at the various stages of cirrhosis (Child-Pugh's classifications A, B, and C) have found that the bone changes and osteoporosis worsened as the cirrhosis became more severe. (6)
Now let's go one step further. If the bone disorders increase as the cirrhosis increases, when does the problem begin? Will osteopenia (pre- osteoporosis) or osteoporosis show up in pre-cirrhotic individuals?
Chronic Liver Disease and the Bone:
And in fact studies have found that both osteopenia and osteoporosis began in pre-cirrhotic individuals. (4, 5) So a gradual thinning of the bone appears to occur in chronic HCV. And this problem is not gender specific. BMD is observed in both men and women. (3,6,8) and many of the studies include both men and women. (5,9,11)
The next question that comes up is can the BMD caused by HCV be further complicated in special conditions?
Special Situations:
Age- As we age there is a normal loss of bone. One study comparing normal women to cirrhotic women found that there was an increased loss of bone in the cirrhotic women after the age of sixty. (8)
Women- Some menopausal women are an increased risk of osteoporosis. As estrogen production decreases with loss of ovary function the rates of bone breakdown increases and the buildup decreases. And many women with chronic liver disease cannot take estrogen replacement therapy because the hormone is processed in the liver. This double whammy is bound to have an detrimental effect on bone integrity.
What Can We Do?
See your doctor. Bone density can be measured using dual-energy X-ray absorptiometry. This non-invasive procedure is painless. Low level gamma radiation is used to measure your lumbar spine and hip and these measurements are fed into a computer which compares your values with the normal population.
It is my personal opinion that osteopenia and osteoporosis are an under-reported complication of HCV. Women over 40 and particularly those women that have had HCV a long time and have a family history of osteoporosis should discuss the need for having this procedure with their doctors.
Sunshine- Vitamin D can be obtained by the direct action of the sun on the skin. It is particularly important to get some outdoor light during the winter.
Exercise- Weight bearing activity causes an increase in bone formation and an increase in calcium deposition (resulting in stronger bones). Energy is a limited resource for people with HCV. However you should consider 30 minutes a priority whenever possible. This exercise need not be vigorous and slow walking is perfectly acceptable. Weight training also has a positive affect.
Vitamin D and Calcium Supplementation- The studies do not agree on the correlation between Vitamin D levels and BMD. While they all found that there were lower levels of Vitamin D in chronic liver disease, some found that the low levels were associated with decreased bone density (3,10) but others did not. (5) Calcium supplementation is standard for aging women but again I urge you to see your doctor / specialist and discuss this with them.
References:
1. Idilman R, deMaria N, Uzunalimoglu O, va Thiel DH. Hepatitic Osteodystrophy: A Review. Hepatogastroenterology 1997 Mar;44(14):574-581.
2. Sinigaglia L, Fargion S, Fracanzani AL, Binelli L, Battafarano N, Varenna M, Pipero A, Fiorelli G. Bone and joint involvement in genetic hemochromatosis: role of cirrhosis and iron overload. Rheumatol 1997 Sep;24(9): 1809-1813
3. Monegal A, Navasa M, Guanabens N, Peris P, Pons F, Martinez de Osaba MJ, Rimola A, Rodes J, Munoz-Gomez J. Osteoporosis and Bone Mineral Metabolism in Cirrhotic Patients Referred for Orthotopic Liver Transplantation. Calcif Tissue Int 60(2):148-154 (Feb 1997).
4. Nakano A, Kanda T, Abe H. Bone changes and mineral disorders in rats with experimental liver cirrhosis. J Gastroenterol Hepatol 1996 Dec;11(12):1143-1154.
5. Tsuneoka K, Tameda Y, Takase K, Nakano T. Osteodystrophy in patients with chronic hepatitis and liver cirrhosis. J Gastroenterol 1996 Oct;31(5):669-678.
6. Chen CC, Wang SS, Jeng FS, Lee SD. Metabolic bone disease of liver cirrhosis: is it parallel to the clinical severity of cirrhosis? J Gastroenterol Hepatol 1996 May;11(5):417-421.
7. Kalef-Ezra JA, Merkouropoulos MH, Challa A, Hatzikonstantinou J, Karantanas AH, Tsianos EV. Amount and composition of bone minerals in chronic liver disease. Dig Dis Sci 1996 May;41(5):1008-1013.
8. Shiomi S, Kuroki T, Masaki K, Takeda T, Nishiguchi S, Nakajima S, Seki S, Kobayashi K, Okaamura T, Ochi H. Osteopenia in primary biliry cirrhosis and cirrhosis of the liver in women, evaluated by dual-energy X-ray absorptiometry. J Gastroenterol 1994 Oct;29(5):605-609.
9. Nakano A, Kanda T, Miyamoto T, Ishigami Y, sato T, Shimizu Y. A study of osteopenia in liver cirrhosis by dual energy X-ray absorptiometry. Nippon Shokakibyo Gakkai Azsshi 1993 Aug;90(8):1689-1694.
10. Sezai S, Herano M, Iwase T. Osteodystrophy in liver cirrhosis: detection and treatment evaluation using 99Tcm methylene diphosphonate bone scintigraphy. Clin Radiol 1991 Jan;43(1):32- 38.
11. Szalay F, Lakatos P, Nemeth J, Abonyi M, Buki B, Tarjan G, Hollo I. Decreased serum osteocalcin level in non-alcoholic and alcoholic chronic liver diseases. Orv Hetil 1991 Jun 16;132(24):1301-1305.
12. Pietschmann P, Resch H, Muller C, Woloszczuk W, Willvonseder R. Decreased serum osteocalcin levels in patients with liver cirrhosis. Bone Miner 1990 Feb;(2):103-108.
When I first started feeling sick with HepC lots of people would say to me: "Gee, you sure look tired!" My usual response was confusion and annoyance. I didn't feel tired, which I translated into feeling sleepy. Instead I felt woozy, cloudy, foggy, dizzy, and generally exhausted. And when I explained this to the doctors I was seeing (who told me that I had HepC, but that I shouldn't worry), the general consensus was that my symptoms were the psychosomatic projections of a mentally unbalanced individual. Well, for those of you who know me: "what can I say" J!
Fatigue, however, is very real for many sufferers of Hepatitis C. In fact, fatigue is one of the major clinical signs of this disease, sometimes the only one, that can render an individual completely incapable of normal functioning. The problem for the medical profession is that fatigue is subjective (see above) and that there is no objective way of evaluating it based on quantifiable biochemical parameters. Increasingly, however, doctors are coming to accept that the activity of chronic viral hepatitis is enough to explain the asthenia (i.e., weakness) which effectively prevents many sufferers of HepC from engaging in steady and gainful employment.
According to the article "Chronic Viral Hepatitis," in one of the most current textbooks on hepatology, "the major and most common symptom of chronic viral hepatitis is fatigue, which can be variously described as malaise, easy fatiguability, tiredness, lassitude, weakness, or lack of stamina. Patients may attribute the symptom to ageing or to stress or other factors. The fatigue may be subtle and only elicited by direct questioning. Typically the fatigue of chronic hepatitis is intermittent and is worse after prolonged activity, such as at the end of the day."1 But, depending on the individual, "fatigue may also occur at any time of day but is most common in the morning about an hour after awakening. By 9 a.m. one may already feel the exhaustion of a full workday. Others describe weakness and a lack of energy throughout the entire day. Their usual "pep" is now gone. Even little tasks become more trying and around 4 p.m., they simply must lie down to take a nap."2
The medical profession is increasingly coming to recognise that there is no direct relation between the severity of symptoms (i.e., fatigue) and the severity of the disease (i.e., height of enzyme levels, or even stage of liver damage), and perhaps this is one reason why doctors, who have relied upon blood tests and biopsies as the sole measures of liver disease, have been slow to acknowledge the reality of fatigue in the lives of those afflicted. The biochemical mechanism of hepatitis-related fatigue is still not clearly understood, but it is thought to be "related to production of inflammatory cytokines,"3 or to "an altered homeostatic mechanism which is deranged independent of the severity and aetiology of liver disease."4
What can you do? Not much. Rest when you need to, and cut down on any OTC medications you may be taking. Check with your physician about any other medications you may be currently taking, and if you smoke, STOP. Other than that, switch to sensible nutrition guidelines, such as those recommended in our very own hepcBC.bull, and reduce stress in your life. My own experience with stress is, frankly, that it makes me ill--and quickly too. In this respect, practising kindness, prayer and meditation can be very helpful.
Time for a nap!
1 Bisceglie & Hoofnagle, in Hepatology: A Textbook of Liver Disease, by
David Zakim and Thomas D. Boyer, vol. 2, 3rd. ed. (London: Saunders, 1995):
1300.
3 Bisceglie & Hoofnagle, 1300.
4 JN Plevris, JA Cossar et al., "Chronic Fatigue in Patients With Liver
Disease; A Preliminary Study" (Liver Research Laboratories University
Department of Medicine and Clinical Psychology, The Royal Infirmary Edinburgh)
HAVE YOU NOTIFIED THE RED CROSS?
The traceback process can work both ways
If you have tested positive for HepC and if you have given blood, it would be of great assistance to the Red Cross if you would call in and help them with their traceback program. Many of us do not know when or where got our hep. I know that I gave blood between 1978 and 1992 (about 10 pints). I never received notification from the Red Cross that my blood was tainted, but it has been suggested to me that I have had HepC for about 20 years. I have repeatedly asked for PCR tests (which are not free) to help me find out the approximate date that I acquired the virus. The medical profession has not been helpful in the least.
So: by notifying the Red Cross that you have given blood, you are doing 2 things: 1) helping those who have acquired the infection through blood products pinpoint the source of their infection; and 2) helping yourself pinpoint where, when, or how you received the virus.
For example: in my case, should the blood I donated in 1983 come back negative then I know that I did not get my infection "20 years ago." Also, if the Red Cross is thorough they should be able to find that pint in the ten I gave which reveals the time of infection.
I called the Canadian Red Cross traceback program to notify them that I was positive and to ask them to trace my blood donations. They thought this was an excellent idea and suggested that we get more persons infected with the virus to do the same.
I told them that I would pass on the request.
Dr. C. D. Mazoff
"Joan, they found a dollar-sized lump on my liver."
I received the long distance call from my internet pen pal a few days ago. She had just undergone a biopsy as a follow-up to her IFN/Ribavirin treatment, and the ultrasound was ominous. Six months ago, everything looked fine on her ultrasound. She had a CAT scan today, which made the doctors schedule her for another biopsy. (Strangely enough, the condition of her liver has improved—except for the lump.) In the meantime, my means of coping is to look up everything I can find—dare I say it?—about liver cancer.
My searches lead me to conclude that there are two types of cancer associated with hepatitis C: hepatocellular cancer (HCC), and non- Hodgkins lymphoma (NHL).
Hep C is well-known as a major risk factor for HCC, but it usually takes two or three decades of infection for the HCC to develop.5 Hepatocellular carcinoma is strongly associated with Hep B or C and cirrhosis, although only 60 to 90% of patients with HCC actually have cirrhosis. There are reports proving that one does not have to have cirrhosis to develop HCC. 6
Non-Hodgkin's lymphoma interests me because it is not usually associated with Hep C. Many specialists are not aware that NHL patients are often infected with Hep C. Studies were done in several research centers throughout northern Italy, and an article from Fukuoka, Japan, states: "Recently, cases of malignant B cell lymphoma associated with hepatitis C virus infection have been reported."7 In Trieste, researchers found that 28% of their NHL patients were suffering from Hep C,8 and in Pisa, the results were 34%.9 The Italian researchers concur with most specialists that Hep C is the principal cause of cryoglobulinemia, which can develop into more aggressive blood disorders, such as low-grade NHL. In fact, in Florence all the patients with both cryoglobulinemia and NHL had Hep C.10 Tests in 120 B- cell NHL patients in the US detected HCV in 23%, compared to 7% in a control group with malignant blood conditions, and 5% in a group with nonmalignant conditions.11
What can we do to avoid liver cancer? We can choose a healthy lifestyle. We can eliminate alcohol, one of the principal causes of HCC, other toxins, and mouldy foods. We can get yearly ultrasounds and alphafetoprotein tests done. We can request that these tests be done every six months, rather than annually. We can consider interferon treatment, which some studies suggest reduces the chance of liver cancer, even in non-responders.
Common treatments for liver cancer include removal of localized, small tumors, radiation therapy, and chemotherapy. Liver transplant ion is also used in some cases. Newer, experimental therapies, such as warming the body to kill the cancer cells, and therapies using the body's own immune system, are being studied. There are other novel methods, such as cryosurgery which attacks lethal liver tumors by freezing them with liquid nitrogen that is placed in the tumors with hollow steel probes, causing the cancer cells to freeze to death and explode.12 Other techniques include local ablation with ethanol, microwave therapy, hepatic artery, transarterial embolization and targeted radiotherapy. Promising experiments with polyprenoic acid are being done which could prevent additional tumors from forming.
Joan Diemecke
Postscript: I just received a call from my friend. The biopsy of the lump proved that it is a hemoangioma. It's not cancer, thank goodness!
1 Di Bisceglie AM, "Hepatitis C and hepatocellular carcinoma," Department
of Internal Medicine, St. Louis University School of Medicine. PMID;
9305661, MUID: 97449192.
2 Nzeako U, Goodman ZD, Ishak KG, "Hepatocellular carcinoma in cirhotic and
noncirrhotic livers," Am J Clin Pathol 105 (1996): 65-75.
3 K Hiroshige, "Primary splenic non-Hodgkins B-cell lymphoma in a patient
with chronic hepatitis C - case report," Journal of Gastroenterology and
Hepatology 11 (8) (1996 Aug):
724-727.
4 G Pozzato, "Hepatitis-C Virus and Non-Hodgkins-Lymphomas," British
Journal of Haematology 94 (3) (1996 SEP): 544-550.
5 C. Ferri, F. Caracciolo, A.L. Zignego, et. al., "Hepatitis C virus
infection in patients with non-Hodgkin's lymphoma," Br. J. Haematol. 88
(1994): 392-4.
6 Zignego Al, "HCV Infection in Cryoglobulinemia and B Cell Non-Hodgkins
Lymphoma," Archives of Virology 142 (3) (1997): 545-555.
7 Zuckerman E, "Hepatitis C virus infection in patients with B-cell
non-Hodgkin lymphoma," Annals of Internal Medicine 127 (6) (1997 Sep 15):
423-428.
8 SOURCE: Doctor's Guide to Medical News - September 9, 1997
Have you read something in the hepcBC.bull that you don't understand? Or have you read something that appears to contradict another article? Then this is the place for you! If you have any questions that you would like to ask the staff at the hepcBC.bull
phone: (250)388-4311, fax: (250)479-5290 (Victoria) OR (604)987- 7396 (Vancouver)
mail your questions to What the Heck? 1611 Quadra Street, Victoria, BC, V8W 2L5.
Question: The articles on transmission of HCV in the October 1997 Issue of the hepcBC.bull appear to disagree on the transmissibility of the hepatitis c virus and on the method that works best to kill the virus. Why is this so?
Answer: You have to remember that until very recently there was no animal model to infect with the hepatitis C virus and therefore no way to directly study the virus transmissibility. I say until very recently because they have now been able to infect a chimpanzee with HCV and that chimpanzee became ill with the disease. This is a very good move forward for all of us. And many of these apparent controversies may be resolved in the future.
So, until now, the researchers have in fact disagreed with one another. More studies must be done and these studies must be with larger numbers of participants. It is one thing to look at a small group of participants and make conclusions based on this group. But it is quite another thing to reproduce that study with a larger number of participants and also reproduce the conclusion and findings. What may have looked like a cause and effect relationship with a group of twenty becomes an unimportant blip in a larger group.
It is our opinion however, that based on both the small and large studies, that we must err on the side of caution. Remember— HCV is not well understood. If it is even remotely possible that chemical agents alone will not kill the hepatitis C virus, then when it is possible, other methods should be used ( heat ). It is not possible to do this in the home. So bleach used to clean up blood spills becomes our next best agent.
If you missed the Oct. 2nd airing of Tyabji's news presentation on Hepatitis C, you may want to borrow a taped copy of the program from the HepC library of the Hepatitis C Society - Victoria Chapter at our next monthly meeting.
The program which can be viewed daily at 1 o'clock on Channel 6 started with Tyabji informing viewers that Hepatitis C was an illness she knew very little about but along with viewers would be learning about during the forthcoming hour. The first 20 minutes of the show focused on a current description of the disease, and provided some background information about the Krever Commission. Events (from l981 to the present) were outlined. Events that now implicate the Red Cross in what has become known and referred to as "Canada's Tainted Blood Scandal". The program also addressed concerns about transmission and prevention.
The highlight of the show for me was how reassuring and reaffirming it was to see familiar faces. Dave Smith and Joan Diemecke, guests of the program, were the first people I had talked to when I received my diagnosis about one and a half years ago. After having been told by my family doctor that she knew nothing about this new disease, it was Dave Smith and Joan Diemecke that listened to my concerns and tried to answer my questions or direct me to appropriate information sources. As guests of the program, Joan and Dave responded to Tyabji's comments and helped with the numerous questions coming in from viewers.
Family members and I personally felt that the information the program provided was thorough and comprehensive. Because of this disease my life has truly been turned upside- down. Being one of the 15,000 diagnosed transfused victims (I was infected through a transfusion in l984), the challenge of this disease has, on more than one occasion, made me feel isolated, invisible and extremely vulnerable. Thank you Tyabji, Joan and Dave, for giving the dreaded disease, and the plight of those caught in its snares, some visibility. Currently on a medical leave, I find myself frequently tuning into channel 6 at 1:00 p.m. to see what is being covered. I now enjoy watching Tyabji. It is a very interesting and informative current affairs news show.
Joanne Balchin
On October 20, 1993, my life took a different path that the one I had previously been taking. Today, October 29th, 1997, I took a moment to reflect upon the path I came to find myself travelling. Atually, all my thought processes were imbued with thinking about it. It's always easier to look back than it is to look forward. Hindsight is 20/20 (far different from my own!) When I came out of intensive care, only to discover that my esophagus had burst, that I was in end stage liver disease, and that it had been caused by hepatitis C, I thought my life was over. In hindsight, I realize it was just beginning, although it took over two years and a liver transplant to get comfortable with the idea.
I realize now, in retrospect, that when one door closes, another one opens, and in my case, the one that opened did so very widely, and into a world that was vastly different from the one that slammed shut on that fateful day.
Oddly enough, one of the first things I thought about was whether or not there was a support group for people with HCV. I was not to find out for another year, and it took yet another year before I became actively involved in the Hep C Society, when Dr. Powell, our founder, asked me to.
This was 3 months after my transplant, and I was still trying to understand the grave new world I was unceremoniously tossed into. As a matter of fact, I'm still trying to figure it all out, because truth only reveals itself in small doses and occasional false starts, and sometimes when you're not expecting it.
Suffering is a by-product of this disease. We all suffer to a greater or lesser degree, depending how symptomatic we are. When I was waiting for my transplant, I didn't say, "Why me?" I said, "Why not me?" Why should I be exempt from suffering the slings and arrows that life hurls at anything or anyone living? In retrospect, this helped me a great deal because it reduced the sense of alienation that comes from having a chronic illness. I felt a sense of connectedness to life that I had never experienced before. Words cannot really express the feeling I had, but after my transplant, those feelings were further validated when I saw how other transplant recipients responded to their disease. so does that mean suffering is good? I can't answer that question for anyone else, but in the context of HCV and liver transplantation, for myself, it didn't do any harm. The word "suffering" never entered my vocabulary, as in, "Boy, am I suffering," but suffer, I did, and suffer, we all do. Enough on this for now.
Afterword: Last week, October 15-16, I took a trip up island to visit the Nala Paqu Chapter up there, of which Ted has already graciously written. It is being spearheaded by Ria and Ted, and the meeting I attended on Oct. 16 had 18 people. I was really inspired by this group, and I see them in approximately the same position that we were in 18 months ago. Hi, Ted, Ria, and all the great people up there.
I talked to Rae S. in Cumberland, who used to be Secretary of the Victoria Chapter, and she assures me that plans are underway to form a chapter in Courtenay-Comox area. In Campbell River, I talked to Kim C., and she is attempting to get a group going up there. Best of luck, and if there's anything we can do from down here, we'll be glad to help.