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.