Fatigue and Liver Disease

In this article, which is excerpted from my book “ Dr. Melissa Palmer’s Guide to Hepatitis and Liver Disease” I will discuss one of the most common and debilitating symptoms among individuals with liver disease - fatigue. Fatigue is a symptom characterized by a diminished ability to exert oneself, usually associated with a feeling of being tired, bored, weak, and/or irritable. It is universal to all types of liver diseases, and does not necessarily correlate with the severity of liver disease. In fact, fatigue may be just as debilitating to an individual in the early stages of liver disease, as in an individual with advanced cirrhosis.

In some people, fatigue begins several years after the diagnosis of liver disease has been made. In others, it is the primary reason for seeking medical attention in the first place. Oftentimes, multiple visits are made to a variety of different types of doctors in search of a cause of fatigue before it is connected with liver disease. Some people even seek psychiatric evaluation since depression often accompanies fatigue. 

Fatigue may occur at any time of day, but it is most common in the morning. Often, little more than an hour after awakening, a person may already feel the exhaustion of having worked an entire day. Others describe weakness and lack of energy throughout the whole day. Their usual “pep” is now gone. Even little tasks become more trying, and around 3:00 P.M. they simply must lie down to take a nap. 

Fatigue can be caused by the liver disease itself, from other disorders- such as a thyroid disease or vitamin deficiencies- often associated with liver disease, or from medication used to treat the liver disease - such as interferon. Thus, the successful treatment of fatigue can be multifactorial, and a challenge. The patient’s doctor must carefully look at all of the factors possibly contributing to his or her feeling of fatigue, as some factors can be corrected easily.

Anemia is a common cause of fatigue. The primary source of anemia should be carefully sought, as there are many different potential causes. Iron deficiency anemia may be due to blood loss from internal bleeding. Thus, an extensive gastrointestinal evaluation may need to be done. Simply taking iron supplements, however, is not always a wise move, and may, in fact, be dangerous. Both iron deficiency and iron overload may both cause fatigue. Excessive iron in the body of a liver patient can be extremely dangerous. In excess, iron is toxic to the liver and can lead to cirrhosis, liver failure and liver cancer. Furthermore, there is growing evidence that even mildly increased (or sometimes even normal) amounts of iron may cause or enhance the amount of injury to the liver in the presence of other liver diseases. This applies especially to individuals with alcoholic liver disease and chronic hepatitis C. In fact, iron overload is commonly seen in people with alcoholic liver disease and chronic hepatitis C, and has been found to worsen the outcome and to decrease the responsiveness to treatment. Liver scarring and liver cell damage are directly related to the iron content of the liver cell. Since a person’s body is unable to eliminate an overabundance of iron, neither iron supplements nor vitamins containing iron should be included in the diet of an individual with liver disease, unless it has been determined that there is an iron deficiency.

Interferon and/or ribavirin - medications used to treat chronic hepatitis C, may also result in anemia. Interferon has been shown to suppress red blood cell production, and ribavirin may cause red blood cells to burst open and be destroyed– hemolysis. In fact, more than half of patients on interferon and ribavirin combination therapy have been shown to decrease their red blood cell count (hemoglobin) and become anemic. Erythropoietin is a hormone made by predominately by the kidneys. This hormone stimulates the bone marrow to produce red blood cells. Recombinant human erythropoietin was first cloned in 1985, and subsequently became FDA approved in 1989 - Epoetin alfa, Procrit. Preliminary studies demonstrate increases in hemoglobin levels following the subcutaneous administration of Epoetin alfa for anemia due to interferon/ribavirin therapy.

Vitamin B 12 and folate are both crucial to the formation of red blood cells. Therefore, a deficiency of these vitamins often leads to anemia and associated fatigue. This explains why individuals with liver disease who suffer from excessive fatigue, often ask about vitamin B12 injections. However, their expectation that such an injection will provide an “extra boost ” of energy is misguided. Since vitamin B12 is commonly found in animal food products such as meat, fish, milk and eggs, a vitamin B12 deficiency is a very uncommon cause of fatigue in individuals with liver disease. A few exceptions must be made to this statement. One exception applies to individuals with alcoholic liver disease for whom the bulk of nutrients are obtained from alcohol. A vitamin B12 deficiency may develop among these individuals. Furthermore, since alcohol interferes with the absorption of vitamin B12, a vitamin B12 deficiency may develop if a person consumes an excessive amount of alcohol even if he or she maintains a well-balanced diet. A vitamin B 12 deficiency may also occur in individuals with chronic liver disease who maintain a strict vegetarian diet for a long period of time, such as is the case for those suffering with chronic encephalopathy. Finally, the older a person is, the more likely a B12 deficiency is to develop. This is because stomach acid is needed to absorb this vitamin from food, and, as a person ages, the amount of acid in the stomach diminishes. Therefore, individuals with liver disease who are over the age of sixty, or individuals with liver disease who are chronically on medications that block stomach acid - such as H2 blockers (for example Pepcid, Axid, Tagamet, and Zantac) or proton-pump inhibitors (for example, Prilosec, Nexium, Prevacid, Aciphex and Protonix) should be checked for a vitamin B 12 deficiency. As with vitamin B12, a folate deficiency can also produce anemia. In fact, vitamin B 12 must be present in order to activate folate, which accounts for the fact that a deficiency of one tends to simultaneously cause a deficiency of the other.

Thyroid disease commonly coexists with liver disease and may also cause fatigue. Furthermore, thyroid abnormalities may occur while on interferon therapy. People who are prone to autoimmune disorders are more likely to develop a thyroid disorder than people without this propensity. A patient may develop either a slow-functioning thyroid (hypothyroidism) or a fast-functioning thyroid (hyperthyroidism). Thyroid disorders are readily diagnosed by obtaining a thyroid profile from blood tests. Both hypothyroidism and hyperthyroidism may be easily treatable with thyroid medication. Thyroid abnormalities that develope while an individual is on interferon commonly resolve after interferon is discontinued.

People with liver disease often suffer from sleep disturbances which is a common cause of fatigue. In fact, approximately thirty-five to fifty percent of individuals with cirrhosis report having sleep-related difficulties. Some people have trouble falling asleep, whereas others have difficulty staying asleep. Many people complain of being tired all day, yet awake all night. Others complain of erratic sleeping habits characterized by days of excessive sleep (hypersomnia) alternating with days of lack of sleep (insomnia). Still others state that they experience delays of their usual bedtimes and wake-up times. For most people suffering from these sleep disorders, the sleep they do get is not refreshing. And, all of these forms of sleep disturbances may cause fatigue.

The cause of sleeping disorders in individuals with liver disease is unclear, but most likely relates to alterations in the body’s production of melatonin (a substance produced by the pineal gland and is involved in the sleep cycle). Sometimes, sleep disturbances stem from medications used in the treatment of liver disease. For example, interferon, ribavirin, prednisone and propanolol are all associated with insomnia. Also, caffeine, nicotine and alcohol consumption may contribute to disturbed sleep habits and, as such, abstinence from these substances will likely assist in the quest for a good night’s sleep. It should be noted that sleep disturbances may be a sign of impending encephalopathy.

Treatment of sleeping disorders associated with liver disease consists of both behavioral modification and medical management. People should use their beds only for sleeping and never for other activities such as reading, watching television, or eating. These activities should be performed in other areas of the home. If an individual is unable to fall asleep within twenty minutes of retiring, he or she should get out of bed and read a book or perform another relaxing activity in another room. Lights should be kept low and the television turned off. Only after becoming tired should he or she return to bed. Also, people should make an effort to wake up at the same time each day - regardless of the amount of time he or she spent sleeping during the night. Although long naps of two to three hours during the day are not recommended, a twenty- to -thirty minute nap in the early afternoon, if it can be arranged, may have a salutary effect. In no circumstances should alcohol should not be used as a sleeping aide. Also, as most prescription and over-the-counter sleeping pills are broken down by the liver, they should be avoided unless their use in low doses and only for short periods of time, is okayed by a liver specialist. Individuals with liver damage may be at increased risk of prolonged sedative effects if these medications are used at their generally prescribed dosages. Although used primarily for the treatment of depression, selective serotonin re-uptake inhibitors (SSRIs) such as Paxil, Zoloft, Celexa and Prozac are generally safe for most individuals with liver disease, and may be of some benefit in treating insomnia. Patients may also try Tylenol PM which contains benadryl prior to retiring. Supplemental melatonin (1-2mg/day), taken a half hour before going to bed, may also be helpful, although one must remember that this supplement is not regulated by the FDA, and therefore the amount of active ingredient per pill may vary from one bottle to the next. The herb valerian has been purported to help sleep disorders. However, this herb may cause serious liver disease and should always be avoided.

Disorders of other organs, such as the heart or the brain, may also cause or contribute to fatigue. These potential sources must be searched for as well. Nutritional deficiencies, such as a lack of protein, as well as disturbances in fluid and electrolyte balance, such as a low sodium level, also contribute to exhaustion. Depression may lead to fatigue and may require pharmacological control. All medications and drugs that the patient is taking, both prescription, as well as over-the-counter, must be reviewed by the patient’s physician. All unnecessary ones should be eliminated, as some medications may also cause fatigue. Excessive use of caffeine and lack of exercise are all causes of fatigue which may be rectified via a lifestyle adjustment.

Finally, fatigue may be due to excessive and/or emotional stress. The demands of a hectic job or harried home life may need to be modified, as overwhelming stress may cause fatigue even in a person not suffering from liver disease. Therefore, it is important that the patient’s family and friends be aware of the increased needs that the patient suffering from fatigue may have, and attempt to reduce any excessive or unnecessary obligations or expectations that they may normally have of the individual. Fatigue may be due to working too many hours. In fact, some individuals suffer from the physical and mental effects of overwork without even realizing.

If fatigue continues to persist after ruling out or correcting any medical conditions, there are a few lifestyle changes that may be helpful. For example, eating a healthy, low fat, well- balanced diet, quitting smoking, refraining from all alcohol consumption, and exercising daily, are all lifestyle changes that can have a beneficial effect on fatigue. Drinking plenty of water and limitation of caffeine- containing beverages to one- to -two cups per day are also recommended. Any excess weight should be eliminated via a sound weight -reducing diet (never lose more than one-to-two pounds per week). If possible, a thirty-to-forty-minute daytime nap should be taken daily. This can help rejuvenate a person with liver disease. In some cases, it may be necessary to incorporate naps into the daily schedule. Often, a doctor’s letter to the patient’s employer or supervisor may be in order. A person with fatigue should feel free to ask his or her doctor for such a note.

Finally, one must remember that the treatment for fatigue cannot be found in a pill. Be especially wary of any product that boasts, “improved energy levels” on its label. Because the liver is in charge of breaking down supplements and medications, more harm than good may result from taking such a product. And, taking excessive amounts of vitamins and minerals in an attempt to treat fatigue, especially vitamin A, niacin or iron, can lead to worsening of liver disease. It is essential that a person with liver disease consult a hepatologist prior to taking supplements or any products that promise to cure fatigue.

By reading this article, you have acquired some useful knowledge about some causes and treatments of fatigue. For additional information on fatigue you may wish to consult my book. Until next time - continue to keep up the fight for a healthy liver.

Portions of this article were reprinted with permission of the author Melissa Palmer, MD from the book "Dr. Melissa Palmer's Guide To Hepatitis and Liver Disease".

http://liverdisease.com 

Combatting HCV Fatigue 

Alan Franciscus, Editor-in-Chief

and Fran Carey

http://www.hcvadvocate.org/news/newsLetter/2005/advocate0405.html#2

One of the most vivid memories I have from running a support group is of a

woman who came to one of our support group meetings complaining of fatigue

and depression. When we started our check-in, she expressed her frustration

with the increased bouts of fatigue and the effect they were having on her

life. This person's story is not that much different from others who suffer

from fatigue, but I think that she was able to verbalize what many of us go

through when we are fatigued. She is a single parent of two children. In

order to put food on the table for her family and a roof over their heads,

she is required to work long days and devote all of her precious energy to

work. In the evening when she came home from work she would basically

collapse in front of the TV and would be unable to perform many of the

functions needed to care for herself and her children. She became isolated

and started to become depressed. In addition, she was unable to spend the

necessary time to cook nutritious meals for herself and her children. The

thought of exercise never occurred to her because she was so tired all of

the time. For this person, life became a downward spiral and she saw no way

out. Luckily, she came to a support group. Throughout the evening we were

able to give her words of encouragement - she was not alone. We were also

able to help her develop strategies to combat her fatigue. It was one of

those incredible support group moments when you can start to see a ray of

hope in someone's eye.

One of the most common symptoms that people with hepatitis C experience is

fatigue. In fact, in one study 67% of people living with hepatitis C

reported fatigue as a symptom. Fatigue can range from mild to severe and can

affect every area of life. Fatigue is a difficult symptom to quantify since

it affects everyone differently. Some people with hepatitis C have constant

fatigue while others may have fatigue cycles - sometimes they feel energetic

and at other times they may feel so tired that they might not be able to

perform basic daily functions, such as going to work, cleaning the house or

joining in on social events.

It is important to keep in mind that when living with a chronic illness such

as hepatitis C, energy management should be a top priority. When we push

ourselves beyond our physical capacity, good judgment declines and accidents

occur more frequently. In addition, when fatigue sets in, it is easy to

become depressed or anxious about the future.

One of the most important strategies HCV positive people can adopt is to

pace themselves and focus on techniques that may decrease the time spent

doing certain activities and increase the amount of rest. As well,

activities should be prioritized according to their importance. If the house

needs to be cleaned but you have a dinner date that evening, think about

saving your energy for the evening and doing the house cleaning later in the

week. You don't want to sacrifice needless energy at the expense of more

important areas that will provide more of a balance in your life.

Causes of Fatigue

Fatigue can be caused by many factors including depression, anemia, poor

diet, and lack of exercise, or by more serious ailments. It is important to

talk with your medical provider if you are constantly fatigued. If you feel

too tired to get out of bed for more than 24 hours or if you feel confused,

dizzy, or have a problem waking up you should notify your health care

provider as soon as possible.

Medical Treatment for Fatigue

There are no approved medications to treat HCV-related fatigue, but some

physicians are experimenting with a variety of drugs including Ritalin and

Provigil. However, there is concern about the potential for abuse of these

drugs - especially Ritalin since it is known to exacerbate substance use

disorders. Studies are needed to determine the safety and effectiveness of

these drugs in HCV positive individuals before they are used to treat

HCV-related fatigue.

Rest When Tired

It is important to rest when you get tired or when you have time. Taking

short naps or rest periods during the day helps most people. Try not to

sleep too much during the day because this could affect how well you sleep

at night. Also, too much rest may make you even more tired so try to find a

balance. Many people report that even just taking a few minutes to close

down, mediate, pray, listen to music, reading or thinking about a happy or

positive experience revitalizes them within a very short period of time. If

you are having trouble sleeping or experience insomnia for more than a few

days, talk to your medical provider about medicines to help you sleep.

Plan Activity and Rest

Make a plan for the day, week, and month. Try to alternate activities so

that you can balance the more difficult activities with the lighter

activities. People normally have certain times during the day or night when

they have more energy. Save the more difficult tasks for when you are more

likely to have the energy to perform them. Alternate the difficult with the

easy tasks. Many people with hepatitis C and other chronic illnesses report

that they have more energy in the evening. However, be careful that you don't

overdo it or stay up too late since this can affect how well you sleep in

the evening and how you will feel the next day.

Breathe

Incorrect breathing can lead to fatigue. When people are stressed out or

fatigued they have a tendency to hold their breath. Try deep breathing

exercises and concentrate on how the air goes in and out of your body.

Massage

People report that massage helps to improve their energy and general

wellbeing. Try massage that uses techniques to encourage lymphatic flow and

regain energy.

Acupuncture

Acupuncture is based on the idea that "qi" flows through the body in

channels called meridians; each organ system has a set of channels.

Acupuncture has been found to be helpful in relieving pain, overcoming

addictions and in decreasing fatigue.

Exercise

It may seem counterintuitive, but regular exercise is one of the best

strategies for combating fatigue. Try to stay as active as possible but don't

overdo it. Exercise comes in many forms and walking is one of the best

exercises for relieving fatigue. Other forms of exercise include Pilates,

yoga, swimming, light weight resistance or any other activity that will

re-energize, but do not exercise to the point of becoming overly fatigued.

Listen to your body and let it guide you. Start slowly with a 2- or 3-minute

walk and work your way up to 30 minutes of activity 5 days a week. It is

also recommended that you check-in with your healthcare provider or an

exercise physiologist to determine what level of activity is right for you.

Diet

A healthy and nutritious diet based on the recommendations from health

experts includes finding a balance between the quantities of food you eat

with the amount of energy expended. Try to stay away from foods that are

high in fat, sugar and sodium. Eat larger portions of fruits and vegetables

and drink plenty of water. If possible, consult with a registered dietician

or nutritionist.

Vitamins & Nutritional Supplement

A well-balanced diet should contain all the essential vitamins and minerals

you need, but some people also take vitamin supplements. Taking a

megavitamin supplement may be harmful to the liver. Instead choose a

multi-vitamin supplement without iron that meets the daily requirements.

Is It Important?

Ask yourself -is this task really necessary? Will the benefit outweigh the

chance that you will become overly fatigued? There are many alternatives to

common chores, such as to allow dishes to drip dry, to buy permanent press

or fabrics that need little attention beyond laundering, and to use frozen

or pre-cut vegetables instead of peeling and cutting.

Ask for Help

Don't be afraid to ask for help from family members or friends. Many times

people are willing to help but may not want to interfere with your life. It

never hurts to ask for help and you might be surprised to find that your

family and friends will be more than happy to help you out. However, you may

need to set limits so that it doesn't turn into a social exercise that could

deplete your energy even more. If you have the resources available, it might

be worth considering using a laundry or house cleaning service. The key is

to simplify when possible.

Educate Family and Friends

Talk to your friends about what it means for you to be fatigued. Tell them

that at times you may not be able to participate in social functions or that

you may need to leave early because of fatigue. Learn to say "no" to family

and friends who have unrealistic expectations of your energy level.

Organize

Staying organized is sometimes difficult, but it is the key for putting to

use the limited energy one has. Have organized work centers, with all

supplies for each task stored together:

Keep all of the dry ingredients together including the mixing bowls; keep

measuring tools together.

Put all of the cleaning supplies in a pail.

Store the can opener in the cupboard with the canned goods.

Store pots & pans near the stove.

Keep items within easy reach.

Avoid bending & reaching.

Eliminate unnecessary clutter.

Utilize organizing equipment such as revolving shelves, stacking bins,

lazy-susans, etc.

Use wheels to transport: laundry cart, grocery basket, kitchen cart - to

convey equipment & supplies in one trip. Load the cart with all the goods

needed to set the table in one trip rather than several.

Use a wagon to transport groceries from car to the house, a cart to

transport the laundry, foods from the fridge to the counter, etc.

There are a lot of strategies that can help conserve energy and reduce the

likelihood of fatigue induced injuries.

Try some of these simple tips:

Sit whenever possible. Use a tall stool at the sink to wash & prepare

food, use an adjustable ironing board as a work surface to sit at, wipe down

the bathtub while still sitting in it, or use a shower stool and hand held

shower for bathing.

Bathe before going to bed rather than in the morning. It takes less energy

to put on nightwear since there is much less of it and you will have less to

attend to in the morning. Always sit down while dressing and undressing.

Use good posture and comfortable work heights. While standing, the working

surface should be between waist & hips, while sitting, the surface should be

no more than 3 inches below your elbows. Don't work at a low counter that

causes you to bend over it. If the kitchen sink is low, place a pan under

the dishpan to raise it closer to you.

Stand & sit with spine erect.

While you are working avoid stretching & bending. Keep most commonly used

items within easy reach. Have long handles on the dustpan, bath brush, and

use tongs to reach for something on the floor.

Work in a well-lighted environment that is at a comfortable temperature

and has good ventilation. Wear supportive and comfortable shoes.

Use both hands for activities: setting the table, dusting, holding pots.

Avoid stress and rushing. Frustration and irritation increase fatigue.

Pace yourself; rushing leads to mistakes and accidents which then require

extra energy to clean up or resolve, not to mention the potential for

injury.

Flare-ups of symptoms including fatigue are a common experience for people

with HCV, which can drastically reduce your energy level and quality of

life. Prepare for these times by storing dried, canned and frozen

foods/meals available for the times when you are not able to get to the

store. Keep healthy snacks around the house and remember to eat small

frequent healthy meals. Skip unimportant tasks until a better time.

One of the most important strategies is to listen to your body. It is

important that you allow yourself to rest - pushing yourself unnecessarily

could prolong your "flare-up" and make you feel worse. We all know that

fatigue can cause depression and anxiety. Be prepared to indulge yourself in

enjoyable activities that require little energy, such as meditating,

reading, watching a video, knitting, etc.

It is 'ok' to recognize that you are depressed. It is not healthy to put a

positive spin on everything. Talk to family and friends - a friendly ear can

help with anxiety and depression. Talk to professionals and seek guidance.

Consider antidepressants - they can help with depression and energy. One of

the most important strategies people living with hepatitis C can adopt for

themselves is to join a support group.

Everyone experiences physical, mental and emotional changes throughout their

lives and must adapt accordingly in order to safely maintain their ability

to function. By practicing some of the above techniques you will reduce your

risk for injuries and conserve your energy for the things in life that are

most important to you.

Sources:

Arthritis Foundation website:

http://www.arthritis.org 

Fatty Liver (Steatosis)

The Role of Steatosis in the Progression of Chronic Hepatitis C

The relationship between HCV infection and steatosis is only incompletely understood. In particular, it remains to be determined if steatosis contributes to fibrosis, cirrhosis and ultimately to hepatocellular carcinoma in individuals of hepatitis C virus infection.

In the March 2004 issue of The Journal of Hepatology, Dr. Francesco Negro reviews what is currently known about the relationship between hepatitis C infection and steatosis. Following is an edited version of his commentary:

The progression of chronic hepatitis C towards cirrhosis is a relentless process that may evolve over a period of decades. Several factors may accelerate the rate of progression of liver fibrosis. Many such factors, like male gender, prolonged alcohol abuse, co-infection with the immunodeficiency virus, and obesity are now well recognized.

Others, like smoke and, possibly, some genetic polymorphisms, are slowly being unravelled. In this context, the role played by the liver steatosis as a disease modifier is suggested by an increasing number of observations. Indeed, judging from the number of papers appeared on this subject in recent years, steatosis is viewed as taking an increasingly important role in many aspects of the hepatitis C virus (HCV) infection: not only is it a diagnostic tool, but it may also significantly affect both liver disease progression and response to antiviral treatment.

The diagnostic significance of steatosis in chronic hepatitis C was proposed by early works, and later confirmed by several authors, especially when it became clear that in many patients steatosis is a histological hallmark of a direct toxic effect of HCV on the hepatocyte.

The evidence in favour of this comes from three observations: (1) steatosis is more frequent and severe in patients infected with the genotype 3 of HCV, suggesting the existence of specific ‘steatogenic’ sequences proper to this genotype; (2) the degree of fat infiltration (especially in patients with the genotype 3) is correlated with the level of HCV replication and protein expression, as measured both in serum and in liver tissue, and 3) there is a close correlation, at least in some patients (again, especially among patients with genotype 3) between the disappearance of fat from the liver and the response to antiviral therapy. In addition, the recurrence of HCV infection after an initially successful treatment is accompanied by the reappearance of steatosis.

That steatosis may correlate with fibrosis was first reported by Hourigan et al. and then confirmed by several authors. However, recent data suggest that this interaction is far more complex than previously thought. Furthermore, it is less and less clear whether steatosis, that may negatively influence liver disease progression, is due to HCV or rather to concomitant conditions unrelated to the virus.

This issue is highly relevant, since understanding the histological findings in pathogenetic terms has always been critical to proper clinical management. So, we need to address the question: is steatosis seen in chronic hepatitis C always due to HCV? And, if not, what are the alternative mechanisms?

Several studies have provided good evidence in favour of the existence of multiple factors independently underlying the fatty liver in chronic hepatitis C. There is a ‘viral’ steatosis, i.e. directly linked to HCV replication and mostly (but not exclusively) seen in patients with genotype 3, that disappears upon successful antiviral therapy.

Then, there is a so-called metabolic steatosis. The severity of fat accumulation, in these cases, is proportional to the body mass index (BMI), and is not responsive to antiviral therapy. Since obesity increases with age and patients with genotype 3 are usually younger, the metabolic type of steatosis is likely to affect more frequently patients infected with non-3 genotypes. A third, well known component of steatosis is alcohol abuse, but its contribution to the published series is variable.

Diabetes and dyslipidemias may also contribute to steatosis of the liver, and, finally, it is not unexpected that a variable proportion of patients present with a mixed type steatosis, i.e. where viral and one or more metabolic factors overlap. This is more likely to occur in populations where overweight is highly prevalent and tends to affect younger generations.

As said above, the association between steatosis and fibrosis in HCV infection has been reported by many authors, including Patton and co-workers. However, recent data seems to suggest a more complex interaction. In one study, the association was denied, while in others it seemed to hold true for only some patients' subgroups. As a matter of fact, Patton et al. found an association between steatosis and fibrosis only among patients with genotype 1 infection, i.e. those more likely to suffer from metabolic steatosis, unresponsive to antiviral therapy.

A relationship between fatty liver and advanced fibrosis in genotype 3-infected patients is also suggested by other studies.

Dr. Negro concludes, “In conclusion, steatosis appears another factor in affecting chronic hepatitis C progression. Whether it affects all patients or only some subgroups of them, as a function of pathogenesis, remains to be elucidated.”

“While prospective studies may address this question, measures aiming at reducing risk factors of fatty liver seem now an established acquisition in the clinical management of chronic hepatitis C patients.”

06/18/04

Reference

F Negro. Hepatitis C virus and liver steatosis: when fat is not beautiful. Journal of Hepatology 40(3): 533-535. March 2004.

Link to Index of all HCV articles

http://www.hivandhepatitis.com/hep_c/news/2004/061804b.html

HEPATOLOGY WATCH®

Timely Information for Practicing Physicians

May 2001

Hepatitis C Virus (HCV)

Steatosis and chronic HCV infection. Steatosis is associated with hepatic fibrosis and is a frequent finding in chronic HCV. Andrew Clouston and coworkers studied 80 consecutive patients with untreated chronic HCV for whom a liver biopsy was available for review to determine the contribution of steatosis to fibrosis. Steatosis was present in 56 patients (70%) and subsinusoidal fibrosis (SSF) and/or central vein fibrosis was found in 52 of these patients. The fibrosis had a chicken-wire appearance similar to that seen in steatohepatitis. There was an association between more severe grades of steatosis and the finding of SSF. In addition, the mean body mass index of patients with focal or extensive SSF was higher (within the overweight range) than that of patients without SSF. These findings demonstrate that the occurrence of hepatic SSF during the course of chronic HCV infection is correlated with steatosis, which in turn is associated with being overweight. Thus, weight reduction may be an important therapeutic maneuver for patients with chronic HCV. (Clouston AD, et al. J Hepatol 2001;34:314-320)

http://www.hepwatch.com/May2001.htm

All the below links are found at Imkindlys support forum

(a wealth of information awaits you)

Images - Pictures 

Obesity-Related Steatohepatitis

Steatosis/Non- Alcoholic Steatohepatitis

A Genomic Variation and NASH

NASH and Insulin Resistance 

More Support

NASH - its Significance and Management 

Biopsy pictures (microscopic) 

What is Fatty liver,.... what's NASH?

Fatty Liver - Symptoms and Diagnosis

NON-ALCOHOLIC STEATOHEPATITIS

NASH - Clinical Features  

Conditions associated with NASH

Studies

What is Steatohepatitis?

Fatty Liver - Causes

Metformin may be a cure

Treatment

Fibrosis, Cirrhosis, and Steatosis

by Liz Highleyman

http://www.hepatitis-c-advocate.org/ 

Although many people with chronic hepatitis have few or no symptoms and minimal liver disease progression, others will go on to develop serious liver damage. This typically takes several years or decades. It is estimated that 10-25% people with chronic hepatitis C will develop cirrhosis after 20-30 years; for people with chronic hepatitis B infection, the estimated rate is 20-30%.

Advanced liver damage may include fibrosis, cirrhosis, and steatosis. These conditions can result from various types of liver injury, ranging from viral infection to exposure to alcohol or other toxic substances. The hepatitis C and B viruses (HCV and HBV) attack liver cells (hepatocytes), where they multiply, or replicate. HCV and HBV cause liver inflammation and kill liver cells (necrosis). Inflammation is an immune response to infection or injury characterized by the infiltration of white blood cells. The degree of liver inflammation is often reported in terms of grades—from 0 to 4—or may be described as mild, moderate, or severe.

Fibrosis

Fibrosis refers to the development of fibrous scar tissue within the liver and occurs when the normal processes involved in tissue repair get out of control. The death of hepatocytes stimulates inflammatory cells to release cytokines and other chemicals, which cause cells known as fibroblasts to form around injured hepatocytes and synthesize fibrous tissue, a process called fibrogenesis. Hepatic stellate cells have been shown to play a key role in this process. Collagen, various glycoproteins, and other components are deposited within the liver. This connective tissue makes up the extracellular matrix (the structure between cells) in healthy livers, but it proliferates excessively in people with fibrosis. In addition, the liver’s normal ability to break down matrix tissue (fibrolysis) may be impaired, leading to further collagen build-up. Fibrosis can obstruct blood flow in the liver, lead to further hepatocyte atrophy and death.

Bridging fibrosis occurs when new linking blood vessels form in an attempt to restore circulation and fibrotic tissue extends beyond one area (or portal) of the liver. Over time, fibrosis may progress to cirrhosis.

Cirrhosis

Cirrhosis is a process in which the normal liver architecture (structure) is altered by the formation of regenerative nodules surrounded by scar tissue and fibrous membranes (septa), in an attempt to repair the damaged organ. Liver cirrhosis may be classified by the size of the nodules: micronodular (small nodules less than 3 mm in diameter), macronodular (large nodules over 3 mm), or mixed. The build-up of scar tissue usually progresses over time as long as the source of liver injury remains. Eventually, abnormal cell proliferation may lead to hepatocellular carcinoma, a type of liver cancer.

Compensated cirrhosis occurs when the liver is scarred but can still work relatively normally; people with compensated cirrhosis typically exhibit few or no serious symptoms. Decompensated cirrhosis occurs when the liver is so damaged that it cannot function properly. The Child-Pugh scoring system is used to grade the severity of cirrhosis on the basis of symptoms.

Because the liver is responsible for so many important functions, liver damage can have wide-ranging effects. Extensive scarring can impair the circulation of blood through the liver, leading to portal hypertension, or high blood pressure in the vessels that serve the liver. This in turn can lead to the development of varices (stretched and weakened blood vessels) in the esophagus and stomach, which may burst and bleed. If the damaged liver is unable to synthesize adequate albumin (a blood protein), fluid may accumulate in the abdomen, a condition known as ascites. Inadequate production of clotting factor by the liver can lead to prolonged bleeding and easy bruising. If the liver’s filtering and processing ability is impaired, metabolic by-products, hormones, and other substances may accumulate in the body. Some people with decompensated cirrhosis experience jaundice (yellowing of the skin and whites of the eyes), dark urine, and pale-colored stools as bilirubin levels increase. The build-up of bile acids in the body can cause pruritis (itching). An accumulation of estrogen can lead to spider angiomas (clusters of dilated blood vessels in the skin) and gynecomastia (breast enlargement in men). The build-up of toxic substances such as ammonia can affect the brain causing hepatic encephalopathy, characterized by mental impairment, confusion, lethargy, personality changes, mood swings, and even coma. In the most severe cases, frank liver failure may occur, necessitating a transplant.

Steatosis

Steatosis ­refers to the accumulation of fat within liver cells. It is often associated with heavy alcohol consumption, but also occurs in people who drink little or no alcohol (nonalcoholic steatosis). Studies have shown that steatosis occurs in 30-70% of people with chronic hepatitis C, although it is not yet known whether HCV infection itself is directly responsible. The relationship between liver steatosis and conditions such as obesity, high blood fat levels (hyperlipidemia), insulin resistance, and diabetes is not well understood, but is currently under study. Recent research indicates that people with steatosis are at risk for more rapid development of fibrosis and cirrhosis.

Several factors impact the rate of liver disease progression, including alcohol consumption (which accelerates progression), sex (men develop liver damage more rapidly than women, possibly due to a protective effect of estrogen), age (younger people progress less rapidly than older people, especially those over age 50), duration of infection, and possibly HCV genotype shown in only a few small trials.

Assessing Liver Damage

Liver damage and dysfunction may be indicated by clinical symptoms and by abnormal lab test results, including elevated levels of certain liver enzymes (especially alanine aminotransferase, or ALT), reduced levels of serum albumin, and prolonged prothrombin time (a measure of blood clotting efficiency). However, some people with liver damage experience few symptoms and have persistently normal lab results. New, noninvasive methods for assessing liver disease progression are under study, including tests that measure levels of collagen byproducts and cytokines in the blood that may be markers for fibrotic activity.

The “gold standard” for assessing liver disease status is biopsy, in which a small sample of liver tissue is withdrawn, stained, and examined under a microscope for evidence of tissue damage. Liver biopsy results are reported in terms of histological stages (alternative staging and scoring systems, such as the Knodell Histological Activity Index, also may be used). Unlike the established inflammation score—which reflects current disease activity—these stages reflect degree of liver damage. Stage I refers to liver inflammation without fibrosis. Stage II is inflammation plus fibrosis confined to one portal of the liver. Stage III indicates that fibrosis extends over adjacent portals (bridging fibrosis), but nodules are not yet present. Stage IV is cirrhosis with loss of normal liver architecture. People progress through these stages at different rates; often people have early or moderate fibrosis for many years without developing cirrhosis.

Treatment and Future Prospects

Research indicates that effective treatment with interferon and ribavirin as well as lamivudine for HBV can slow or halt liver disease progression, and may actually allow for some degree of repair and reversal of existing damage, especially if it is not yet advanced. Ongoing research may lead to the development of therapies that directly inhibit the fibrotic process. Experts traditionally have discouraged treatment of people with decompensated cirrhosis—because interferon, in particular, can lead to a worsening of liver inflammation—but some studies suggest that treatment of such people may in fact be beneficial. New combination regimens and drugs in the development pipeline (such as adefovir for chronic HBV) show promise. At this time, participation in a clinical trial may be the best option for people with advanced liver disease.

Fatty Liver Disease, ALT, & Overweight

Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States
Background & Aims: In the absence of other causes, overweight and obesity increase the risk of liver disease. We examined whether central adiposity and metabolic markers explain the association of body mass index (BMI as kg/m2) with abnormal serum alanine aminotransferase (ALT) activity in a national, population-based study.
 
Methods: Adult participants (5724) in the third U.S. National Health and Nutrition Examination Survey (1988-1994) underwent anthropometric measures and phlebotomy after an overnight fast. Participants with excessive alcohol consumption, hepatitis B, hepatitis C, iron overload, or known diabetes were excluded.
 
Results: Elevated ALT levels were found in 2.8% of the population. In univariate analysis, factors associated with elevated ALT levels (P < 0.05) included younger age, male sex, Mexican-American ethnicity, and higher BMI, waist-to-hip circumference ratio (WHR), and fasting serum leptin, triglyceride, insulin, and glucose concentrations. The proportion of elevated ALT activity due to overweight and obesity (BMI 25 kg/m2) was 65%. In multivariate logistic regression analysis, control for WHR, demographic factors, and glucose concentration diminished but did not eliminate the association of higher BMI with elevated ALT activity. After adding leptin and insulin concentrations, abnormal ALT activity was most strongly associated with higher WHR (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.12-1.56) and leptin (OR, 1.12; 95% CI, 1.01-1.24) and insulin (OR, 1.27; 95% CI, 1.01-1.60) concentrations, whereas BMI was not independently related. Conclusions: In this large, national, population-based study, central adiposity, hyperleptinemia, and hyperinsulinemia were the major determinants of the association of overweight with elevated serum ALT activity.
 
Gastroenterology Jan 2003;124:71-79. Constance E. Ruhl, James E. Everhart
 
Editorials

Defining nonalcoholic fatty liver disease: Implications for epidemiologic studies
 
Jeanne M. Clark, Anna Mae Diehl
 
In the United States, chronic liver disease and cirrhosis are the 10th leading cause of death overall, and among the top 7 leading causes of death in men and women ages 45-64. Despite recent advances in technology, physicians must still rely on the liver biopsy for diagnosing and particularly for staging liver disease. Liver function tests including serum transaminases and -glutamyltransferase are often used as screening tests among both low- and high-risk populations. However, there is ample evidence that these tests lack sensitivity and specificity for liver disease and cirrhosis. Thus, despite increased interest in a broad array of liver diseases, medical research has been hampered by a significant referral bias because of the need for liver biopsy for accurate diagnosis and staging.
 
In this issue of GASTROENTEROLOGY, Ruhl and Everhart6 attempt to expand our understanding of liver disease in the United States population, by presenting an analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III). Using this data, they examine the prevalence of an abnormal alanine aminotransferase (ALT), defined as an ALT>43 U/L for men or women. By eliminating individuals with moderate-to-high alcohol consumption, hepatitis B or C, elevated transferrin saturation or a history of diabetes mellitus, the authors use the elevated ALT as a surrogate for nonalcoholic fatty liver disease (NAFLD).
 
After these exclusions, they found that 2.8% of the population had an elevated ALT. Elevated ALT was associated with younger age, male sex, Mexican-American ethnicity, impaired glucose metabolism and insulin resistance, obesity, and measures of central adiposity, as well as higher leptin, triglycerides, and C-peptide. In multivariate analyses central adiposity, insulin, and leptin concentrations were the most highly associated factors. They conclude that these factors are the major determinants of the association between elevated ALT concentration and higher body weight.
 
As with any good research, this article leaves the reader with more questions than answers. The first major question is how to study the epidemiology and risk factors of a disease for which the gold standard diagnostic test is an invasive procedure. Ruhl and other investigators conducting epidemiologic research have used serum aminotransferases. However, this has not been universally accepted, despite the lack of a superior alternative. Accepting that aminotransferases are the best, widely available serum markers of liver disease, it is unclear if ALT should be used alone, as in this article, or whether aspartate aminotransferase (AST) and ALT7,8 or other combinations of liver tests should be used. Furthermore, the level of elevation that is considered abnormal varies widely and has recently been brought into question.10 There is also debate as to whether or not different cutoffs are indicated for men and women. In fact, gender-specific norms for ALT were defined in the NHANES III manuals.11 Given all the controversy, it is clear that more acceptable and accurate means of noninvasively diagnosing liver disease in general, and NAFLD in particular, are needed.
 
The article by Ruhl and Everhart highlights the impact the current uncertainty in noninvasive diagnosis can have on epidemiological studies. Using ALT alone, they estimate the prevalence of NAFLD in the United States is 2.8%. This estimate is much lower than general population estimates of NAFLD in other countries, which range from 16%-20% based at least in part on ultrasound evidence for hepatic steatosis. It is also substantially lower than that predicted by a recent population-based study of seemingly healthy Italian blood donors.10 Moreover, using recently suggested lower normal values for ALT (>30 U/L for men and >19 U/L for women), Ruhl and Everhart found elevated levels in 12.4% of men and 13.9% of women, estimates significantly higher than their original 2.8%.
 
There are several reasons why Ruhl and Everhart may have arrived at a lower estimate of NAFLD than other population studies. First is their decision to use ALT alone as a marker for occult liver disease. Although many have suggested that ALT is higher that AST in NAFLD, an elevated ALT/AST ratio may be true only of early disease. Furthermore, in NAFLD, as in most other types of chronic hepatitis, ALT values fluctuate over time. Thus, diagnostic criteria that rely solely on a single elevated ALT value could underestimate disease prevalence. In addition, the authors used a higher cutoff value for normal ALT than many suggest (and one that is higher than published in the National Center for Health Statistics NHANES III manuals). Naturally, this would lower the estimated prevalence of occult liver disease. Furthermore, as the authors themselves acknowledge, ALT testing in NHANES III was conducted on serum that had been frozen. Freeze-thawing of samples may affect enzyme activity and artifactually lower ALT values, leading to an underestimation of disease burden in the population. Finally, the authors excluded people with known diabetes, a group who are at high risk for NAFLD. This eliminated a relatively large subpopulation that is likely to be enriched with fatty liver disease, and may have biased their conclusions. However, although several common causes of liver disease were excluded from this study, it is likely that not all of the remaining elevated ALT values were due to NAFLD. Some were probably caused by other conditions, such as autoimmune hepatitis. This possibility is supported by a recent biopsy study that demonstrated histologic proof of NAFLD or NASH in only about 65%-90% of patients with "cryptogenic" hepatitis. Nevertheless, Drs. Ruhl and Everhart's estimate of NAFLD prevalence and the associations they found are likely to be more indicative of the burden of NAFLD in the general population than information obtained from patients who are selected for further study based on referral to gastroenterology clinics. Even if the true prevalence of NAFLD in the United States population is merely 2.8%, fatty liver disease would be twice a common as chronic hepatitis C (1.3%).
 
This leads to the second question: what does a diagnosis of NAFLD really mean? Stated another way, is this condition merely NAFL, or is it truly NAFLD? Fatty liver is often considered to be an incidental condition with a benign prognosis. However, a growing body of literature contests this idea, indicating that the natural history of NAFLD, at least for some, includes progression to cirrhosis and to hepatocellular carcinoma. The latter data defy conventional wisdom, which suggests that most people with this condition remain asymptomatic for decades. Indeed, the preponderance of asymptomatic individuals with fatty liver has tempted some to conclude that fatty liver alone may be a variant of normalcy, rather than a true disease. However, applying similar logic would force one to conclude that asymptomatic individuals with a blood pressure of 180/100 mm Hg, a fasting blood sugar of 180 mg/dL, or low density lipoproteins of 200 mg/dL, while abnormal, do not have a disease state. Fortunately, epidemiological studies of hypertension, diabetes, and dyslipidemia have taught us that each of these diseases is indolently progressive, leading to clinically significantly morbidity and mortality in a subset of afflicted individuals decades after disease onset. The knowledge of subsequent serious outcomes drives the current practice of early therapeutic intervention in individuals with those diseases.
 
Certainly, before NAFLD is dismissed as quirk of nature, more studies are required to clarify its genuine, health-related outcomes. In addition to elucidating the natural history of portal hypertension-related morbidity and mortality, these should assess more subtle symptoms that may affect an individual's quality of life. Our own analysis of NHANES III data, as well as a recent prospective survey of NAFLD patients who were referred to the Mayo Clinic, suggest that individuals with NAFLD may not be truly asymptomatic because they describe their health status as significantly below average. In addition, if NAFLD is part of the metabolic syndrome, as these authors and others suggest, then it will be important to determine what pathogenic role fatty liver plays, relative to the other components of the syndrome. It will also be important to determine whether or not treatment of NAFLD improves the other aspects of the metabolic syndrome, and vice versa. Finally, more work is needed to identify which patients with fatty livers are most likely to progress from steatosis to steatohepatitis and cirrhosis. A better understanding of the factors that modulate liver disease progression is critical, so that we can target selected patients for more aggressive monitoring, lifestyle interventions, and pharmacotherapy.
 
In summary, it is important to emphasize that epidemiological studies are crucial to further our understanding of many diseases, particularly those that are indolently progressive over decades, like NAFLD. Ruhl and Everhart6 have made a major advance toward clarifying the burden of liver disease in the United States population. Their findings suggest that occult liver disease may be much more common in the general adult population than we previously suspected, affecting 4 to 5 million people. Moreover, evidence that such ALT abnormalities associate with other components of the metabolic syndrome supports the authors' conclusion that most of the abnormalities are probably due to NAFLD. Given the increasing prevalence of obesity in children, as well as adults, this has potentially important public health implications. The cynics among us will argue that these interpretations are premature without definitive histologic proof of fatty liver. Others remain skeptical that, even if valid, the diagnosis of NAFLD rarely portends a real risk for clinically significant adverse health outcomes. The debate is likely to smolder until better, noninvasive tests to diagnose and stage NAFLD are developed and used to identify and track afflicted individuals over time. Until then, it seems prudent to place NAFLD in the same health risk category as other components of the metabolic syndrome, and to consider it no more or less worthy of medical attention than its "bed fellows," i.e., obesity, diabetes, hypertension, and dyslipidemia. Sometimes, "still waters run deep."

NEW YORK (Reuters Health) Jul 02 - Hepatic steatosis appears to be a risk factor for hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection, according to a recent report by Japanese investigators.

Multiple factors, including cirrhosis, HCV genotype, and total alcohol intake, have been tied to the risk of developing HCV-associated HCC. Although hepatic steatosis is a common finding in patients with chronic HCV infection, it remains unclear whether this liver abnormality is also risk factor for HCC.

The new findings, which are published in the June 15th issue of Cancer, are based on a study of 161 patients who were diagnosed with chronic HCV infection between 1980 and 1999 at Nagasaki University Hospital. All of the patients had no detectable HCC at enrollment. The average follow-up period was 6.4 years.

The cumulative incidence rates of HCC at 5, 10, and 15 years after HCV diagnosis were 24%, 51%, and 63%, respectively, senior author Dr. Katsumi Eguchi, from Nagasaki University School of Medicine, and colleagues note.

In agreement with previous reports, older age, cirrhosis, and not receiving interferon therapy were identified as independent risk factors for HCC, the authors note.

In addition, Dr. Eguchi's team found that hepatic steatosis was independently linked to an increased risk of HCC (p = 0.0135). Further analysis revealed that this liver abnormality correlated with body mass index and with serum ALT and triglyceride levels.

"Our data emphasize the need for the careful monitoring of patients with chronic HCV and hepatic steatosis for the development of HCC," the researchers state.

It is possible that the effects of steatosis on cancer risk may persist even after achieving HCV clearance, Dr. Andrew X. Zhu and Dr. Raymond T. Chung, from Massachusetts General Hospital in Boston, note in a related editorial.

"However, before contemplate targeting steatosis as a strategy to decrease the risk of HCC development in patients with chronic HCV infection, it will be important to demonstrate that steatosis is a critical step in the hepatocarcinogenesis pathway," they add.

Cancer 2003;97:3036-3043,2948-2949.

Related Links

Fibromyalgia

By Lucinda Porter, RN

Lucinda K. Porter, RN is a research nurse and patient educator at Stanford in the area of hepatology. She co-facilitates a support group and is active in many aspects of hepatitis C education. In addition to being HCV+, she has a life which include her husband and teenaged daughter.

The most common complaints of patients with chronic hepatitis C are fatigue and muscle or joint aches. These same symptoms also occur in patients with fibromyalgia. Although most patients with hepatitis C who have muscle aches do not have fibromyalgia, some patients may have both conditions.

Fibromyalgia is believed to affect two to six percent of the U.S. population.The term fibromyalgia means "pain in the muscles and fibrous connective tissue". Muscle pain and fatigue are two of the hallmark characteristics of fibromyalgia syndrome, but these two symptoms can also be associated with a host of other medical conditions.

For this reason, and because there is no specific test to confirm this condition, fibromyalgia can be difficult to diagnose. In the past, fibromyalgia was sometimes dismissed or overlooked by physicians. Some patients were treated for psychological problems.

However, over the past 10 years, fibromyalgia has become better understood and the symptoms that constitute an accurate diagnosis are better defined.

Symptoms
Pain is the most common symptom. The location and description of the pain can be key in helping a doctor make an accurate diagnosis. In 1990, the American College of Rheumatology developed criteria for diagnosing fibromyalgia syndrome. These include:
¥ At least 3 months of widespread pain in all 4 quadrants of the body.
¥ Bilateral pain in 11 of 18 specific trigger points. The trigger points are located along the neck, shoulder, ribs, collarbone, hip and knee.
The pain associated with fibromyalgia has been described as burning, gnawing, or aching. Pain is almost always present. Some say it feels like having the flu. Sleep disturbances, fatigue, morning stiffness and headaches sometimes accompany fibromyalgia syndrome.
Difficulty concentrating and mood changes may also be reported, although this may be due to sleep disturbances commonly occurring with fibromyalgia. Some patients complain of depression, but it is believed that depression is more often a result of the symptoms caused by the fibromyalgia.

Causes
Although there is a great deal of research being conducted on the causes and triggers of fibromyalgia, the cause is still unknown. Studies have shown that people with fibromyalgia syndrome have decreased circulation to the affected areas. They also have more substance P, a neuropeptide that acts as a pain transmitter. There is speculation that inappropriate exercise or poor posture may contribute to the condition. Trauma, infection, sleep disturbances, stress, and hormonal imbalances have all been suggested as possible causes.

Treatment
Trial and error is one of the ways that patients learn how to manage fibromyalgia. Knowing what triggers exacerbations and what bring relief is key.
Lack of sleep, strenuous exercise, and stress may act as triggers, while relaxation techniques and moderate exercise may offer relief. Here are some further treatment options:

¥ Physical therapy
¥ Stretching
¥ Moderate exercise (start very gradually)
¥ Massage (some people say certain types of massage worsens their condition)
¥ Hot baths
¥ Meditation
¥ Medication (Discuss this with your doctor. There are a number of options to try, such as nonsteroidal anti-inflammatory or anti-depressant drugs.)

If you feel that you might have fibromyalgia, talk to your physician. Although there may be similarities between the symptoms related to hepatitis C and those of fibromyalgia, these two conditions are quite different. Further, there are many other disorders that may cause similar symptoms.

A well informed primary care doctor, a physiatrist or rheumatologist can evaluate your situation and make recommendations. If your physician lacks knowledge on the subject, or does not take your symptoms seriously, find another doctor.

For More Information
¥ If you need more information contact the Arthritis Foundation at (800) 283-7800 or http:/ www.arthritis.org

¥ Send a business-sized SASE to the National Chronic Fatigue Syndrome and Fibromyalgia Association, P.O. Box 18426, Kansas City, MO 64133

¥ An excellent Internet site that offers quite a bit of information can be found at: http://members.bellatlantic.net/~clotho/fibro.htm

¥ For support, there are Internet chat groups. Keep in mind that the Internet is a tool, but unless you know how to use it, you can do as much harm as good.

Sources for this article:
Patrice Cacoub, Thierry Poynard, Pascale Ghillani, Frederic Charlotte, Martine Olivi, Jean Charles Piette, Pierre Opolon October 1999. Extrahepatic Manifestations in 1614 Patients with Chronic Hepatitis C. Hepatology Vol. 30, No. 4 (Supplement) (Abstract No. 805)

Brandy Coward October 1999. Fibromyalgia. American Journal of Nursing. Vol.99, No 10

Fibromyalgia, Hepatitis C Infection and the Cytokine Connection

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculo-skeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints.

This review by researchers in the Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years. Other cytokine alterations discussed include

• increased gp130, which is a neutrophil cytokine transducing protein;
• increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and
• IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia.

In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively.

The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.

09/05/03

Reference
ME Thompson and Abarkhuizen. Fibromyalgia, hepatitis C infection, and the cytokine connection. Current Pain and Headache Reports 7(5): 342-347. October 2003.

Gallbladder

TITLE: The prevalence of gallstones in chronic liver disease is related to degree of liver dysfunction.

BACKGROUND/AIMS: Earlier studies have indicated an elevated risk for gallstone disease in patients with cirrhosis. This study aimed to evaluate the prevalence of gallstones in patients with chronic liver disease (CLD) with respect to sex, etiology, and severity of liver disease.

METHODOLOGY: Four hundred and thirteen adults (176 women), mean age 51.2+/-14 years, with CLD, who had undergone liver biopsy during 1978-1993, and from whom sera were available, were investigated retrospectively. The results were compared with a population-based ultrasonography study of 556 healthy men and women, in their 40s and 60s.

RESULTS: The prevalence of gallstones in patients with CLD did not differ from that in the control population. An increased frequency was observed in patients with CLD initially classified as cryptogenic, of whom the majority (60%) later were reclassified as chronic hepatitis C. The frequency of gallstones was also high in PiZ-heterozygotes for alpha1-antitrypsin deficiency (5/21, 24%) compared to non-PiZ-carriers (17/389, 4.8%), (p less than 0.001). In 67 patients with histologic evidence of cirrhosis, 30% (20/67) had gallstones (vs. 15% in the general population, p less than 0.01). The prevalence of gallstones increased significantly from Child's class A (16%) to C (56.2%). The difference was significant in males (18.2% vs. 62.5%, p=0.033), but not in females. Fifty percent of the patients with gallstones were symptomatic.

CONCLUSIONS: Progressive liver dysfunction is a risk factor for gallstones particularly in males. HCV infection and PiZ carriership may further increase biliary lithogenesis.

AUTHOR: Elzouki AN, Nilsson S, Nilsson P, Verbaan H, Simanaitis M, Lindgren S Department of Medicine, University Hospital, Malmo, Sweden.
SOURCE: Hepatogastroenterology 1999 Sep-Oct;46(29):2946-50

Know Your Body: The Gallbladder

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