Can Cirrhosis Be Prevented?

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Can Cirrhosis Be Prevented?

By Marilyn Sterling, R.D.

 

Intelligent lifestyle and nutrition choices may thwart the liver

disease long considered unstoppable

 

The liver truly is remarkable—directly affected by nearly everything

a person eats, drinks and breathes, it is still durable and capable

of regeneration. Tucked away on the right side of the abdomen, the

liver is the human body's largest internal organ, serving as command

central for a variety of vital metabolic processes. Because of its

essential role, protecting the liver from the numerous lifestyle,

environmental and viral insults that can accumulate and destroy its

ability to function is paramount. Several types of liver disease can

result from the onslaught of life, including cancer, alcohol-related

liver disorders, viral hepatitis and cirrhosis.

 

Cirrhosis of the liver is the fourth most common cause of death among

people between the ages of 30 and 50, and the eighth most common

killer overall. A liver affected with this chronic degenerative

disease becomes hardened and scarred and eventually so damaged it

can't function because normal blood flow through it is blocked. The

degeneration process dramatically affects the organ's metabolic

processes and detoxification abilities.

 

The liver is the body's recycling center, where thousands of

compounds are taken apart and put together again as useful and

essential body chemicals. Its several detoxification techniques

include filtering large toxins from the blood, synthesizing and

secreting bile to carry many impurities out of the body, and

neutralizing unwanted chemical compounds in a two-step enzymatic

process generally referred to as Phase I and Phase II detoxification.

Toxins such as alcohol, urea from amino acid breakdown and

environmental invaders are turned into benign by-products that are

either used or excreted. Small wonder that when the liver fails, the

only effective treatment is a transplant.

 

With all that at stake, it is important to understand and avoid the

risk factors that contribute to cirrhosis. Whether a person is trying

to prevent cirrhosis or manage the condition, understanding the roles

of alcohol consumption, hepatitis and toxic exposure is critical.

 

Alcohol and cirrhosis are a roulette game—not all serious alcoholics

develop cirrhosis, though some social drinkers do. Women do not

process alcohol as efficiently as men and are thus more likely to

develop cirrhosis from drinking. Alcohol is a toxin that damages the

liver directly, and the two pathways for breaking down alcohol in the

liver also generate dangerous oxygen derivatives, or oxidants, that

lead to collagen scar-tissue formation.

 

Chronic hepatitis, a viral liver disease, is gaining on alcohol as

the leading cause of cirrhosis. Although hepatitis A, spread through

contaminated water and food and excreted in stools, does not cause

cirrhosis, other forms are not so benign. If a hepatitis B or C

infection is not completely eradicated through treatment, the chronic

hepatitis that remains can eventually lead to cirrhosis.

 

Hepatitis B, transferred through body fluids such as saliva and

blood, progresses to cirrhosis about 5 percent of the time. One in

every 250 people is a carrier of hepatitis B, and 30 to 40 percent of

them have no symptoms. It is estimated that one in every 20 people

will contract hepatitis B—one-third of them without symptoms. In

fact, A simple test can determine whether a person has hepatitis,

which is a good idea for those in doubt, because future problems are

just as likely even if no symptoms are present. The hepatitis B

vaccine is recommended for those at risk, including adolescents and

health care workers.

 

Hepatitis C is harder to contract. It is usually transmitted via

contaminated needles or transfusions of infected blood, and in some

cases it has been transmitted sexually. Hepatitis C becomes chronic

in 80 to 85 percent of patients, and up to 30 percent of them develop

cirrhosis. It is estimated that 4 million people have hepatitis C,

many of them silent carriers, and the number is growing rapidly. The

usual treatment is a course of interferon alpha, which enables

invaded cells to be more readily recognized and killed by T

lymphocytes and inhibits virus production within infected cells. This

treatment is often unsuccessful, however, and has unpleasant side

effects including flulike symptoms. Even those patients whose liver

enzymes normalize completely after the interferon treatment,

indicating they are cured, often relapse, meaning the disease was

quiescent for a time. Other antiviral drugs, when combined with

interferon, offer hope for more successful eradication of hepatitis C.

 

Toxic chemical exposure is yet another cause of cirrhosis. Many

commonly used chemicals and solvents are liver toxins. A seemingly

benign medication, if it triggers an allergic reaction, can also

cause cirrhosis. Although the liver is the primary site of

detoxification, the very process can poison it. Chemicals that cause

cirrhosis often do so by forming oxidants, which are by-products of

metabolic activity.

 

Toxins, which include environmental and normal body chemicals, are

detoxified in the liver by chemical neutralization. Briefly, Phase I

enzymes directly neutralize many of the chemicals or convert them to

substances that are then processed by Phase II enzymes. Sometimes

these intermediate substances are more toxic or more chemically

active than they were before, further underscoring the importance of

a fully functional liver. Phase I detoxification involves a group of

enzymes called the cytochrome P450 system. These myriad enzymes

metabolize many of the same chemicals to ensure all are neutralized.

 

Nourishing the Liver

Is there any way to prevent cirrhosis? Could nutrition help? With

hundreds of thousands of people at risk, these should be urgent

public health questions. The only " cure " for cirrhosis is a $400,000

liver transplant, so finding a way to prevent cirrhosis could save

many lives, not to mention billions of dollars. Unfortunately,

society invests most of its health care dollars in treatment rather

than research on prevention. On the bright side, there are some

intriguing clues about the development of cirrhosis. People who

already have liver damage, however, have complicated metabolic issues

and need personalized diet therapy from a registered dietitian. Here

are some avenues that may help heavy alcohol drinkers or people with

chronic hepatitis avert cirrhosis development:

 

Limit iron because hepatitis viruses thrive in iron-rich

environments. An iron surfeit impairs many aspects of immune function

including T lymphocyte proliferation and maturation. Also, iron

catalyzes damage by oxidants. While iron deficiency is common among

women who menstruate, older women and men often have an excess

because they don't excrete as much. Limiting iron intake weakens

hepatitis and increases the chance of successful interferon therapy.1

Patients with hepatitis C might want to avoid iron-enriched cereals,

food cooked in iron pots, multivitamins containing iron, molasses,

and liver and limit their intake of meat—all of which contribute

excess iron. Vitamin C increases iron absorption, so supplements or

foods high in vitamin C should not be taken with meals.

 

Supplement with choline, an amino acid that is part of the

phospholipid lecithin. Alcoholism causes a relative choline

deficiency in the liver by decreasing the enzyme methionine

synthetase, which is necessary for choline production. A choline

deficiency, which promotes liver damage, can be corrected with

lecithin supplements. Choline increases the activity of the enzyme

hepatic collagenase, which breaks down collagen, preventing

cirrhosis. In an experiment on primates, baboons were fed high-

alcohol diets for eight years. Most developed cirrhosis. However, no

members of a group provided with lecithin supplementation during the

experiment developed cirrhosis. Large-scale trials are now under way

to see if lecithin has the same protective effect in humans.2-5

 

Reduce fat intake because evidence from one study showed this helped

hepatitis C patients who drank alcohol. Those patients who ate high-

fat, low-protein and low-carbohydrate diets were more apt to progress

to cirrhosis.6 One reason could be that unsaturated fatty acids are

prone to oxidation, which is dangerous to a damaged liver. This might

also explain why one animal experiment found cirrhosis was reversed

in animals consuming saturated rather than unsaturated fats (i.e.,

butter rather than sunflower oil). While intriguing because cirrhosis

is often considered irreversible, no research has been conducted in

humans in regard to cirrhosis and fat-type consumption.

 

Limiting fat shouldn't be taken to extremes, however. People do need

to meet their intake requirement for essential fatty acids.7 In fact,

another experiment on monkeys showed that those with diets low in

essential fatty acids and low in antioxidants were more apt to

develop alcoholic cirrhosis.8

 

Vitamin E helps maintain high levels of glutathione in people with

hepatitis or with other liver problems.9,10 Glutathione (GSH), an

antioxidant present in the liver, is the body's key protector against

the oxidizing compounds that lead to cirrhosis. By maintaining GSH

levels, vitamin E supplementation may help protect against cirrhosis.

In one study, almost 50 percent of people with hepatitis C who did

not respond to interferon therapy improved dramatically with 800 IU

of vitamin E daily.11

 

Just because vitamin E helps protect the liver, however, does not

mean all antioxidants are equally helpful in liver-related problems.

Vitamin A, for example, can build to toxic levels in damaged livers.12

 

S-adenosyl-L-methionine and N-acetyl cysteine (NAC) also help

maintain glutathione. Scientists are interested in these amino acids

because they may counter the altered biochemistry found in patients

with liver disease, such as the glutathione decrease caused by

alcohol and hepatitis. S-adenosyl-L-methionine prevented alcohol-

induced glutathione depletion in a baboon study.13 It is now being

tested on humans but is quite expensive.

 

In a study of people with hepatitis C, 600 mg daily of NAC enhanced

the effectiveness of interferon therapy.14 However, another study did

not confirm this finding.15 Regardless, NAC protects against damaging

oxidant-producing immune factors called cytokines and chemokines

released in the liver in response to heavy-metal exposure.16 Some

researchers predict that future treatment of hepatitis C will depend

upon antioxidant therapies such as NAC.17

 

Eating cruciferous vegetables can enhance the liver's ability to

detoxify. Substances that harm the liver act synergistically.

Alcoholics, for example, are more susceptible than nonalcoholics to

other liver toxins, and people with hepatitis cannot tolerate

alcohol. Therefore, it is important for people who are at risk of

cirrhosis to avoid toxic chemicals and ensure their bodies' capacity

for detoxification is maximized.

 

Here is where the cabbage family shines. The cruciferous vegetables

activate the liver's cytochrome P450 detoxification chain. Even more

exciting, researchers have recently found that brussels sprouts

stimulate the liver's Phase II enzymes—the first dietary component

shown to affect this important detoxification system. The cruciferous

vegetable family includes broccoli, cauliflower, kale, mustard

greens, radish, bok choy and brussels sprouts.

 

Liver-Friendly Herbs

In addition to dietary modifications and nutritional supplements,

there are a variety of herbs with scientific evidence of liver-

supportive actions.

 

Milk thistle (Silybum marianum), also called St. Mary's thistle or

mariana thistle, is the best-known liver tonic, having been described

in herbals since the late 1600s. Its most active constituent,

silymarin, is a powerful antioxidant that inhibits harmful oxidants

and prevents formation of leukotrienes, one type of dangerous oxidant

produced by the immune system.

 

Silymarin not only prevents glutathione depletion but actually

increases quantities of it. As well, it has the ability to stimulate

protein synthesis in the liver.18-20 In recent experiments, silymarin

protected animals from radiation damage. A 100-mg/kg/day dose

protected rat livers from gamma radiation damage. Using 70 mg/kg

twice daily for two weeks or more repaired radiation damage.21

Another study found that animals supplemented with silymarin did not

show damage from carbon tetrachloride, a substance commonly used to

induce liver destruction.22

 

However, a recent double-blind, controlled study of 200 alcoholic and

hepatitis C cirrhotics did not show a benefit from silymarin

supplementation. The subjects were given either 450 mg silymarin or

placebo daily for two years. Both groups had comparable numbers of

deaths during this time period—14 of those taking silymarin and 15 of

those taking placebo died—so it was determined that silymarin

supplementation did not influence survival.23 The study patients were

very ill to begin with, so perhaps silymarin would be more effective

in preventing than treating cirrhosis in those with existing liver

damage and in hepatitis patients who are not alcoholics.23

 

Artichoke (Cynara scolymus) leaves are another liver remedy. Recent

animal tests show supplementation with artichoke prevented a liver

toxin from causing oxidation, thus preventing glutathione

destruction.24 The active compound, cynarin, is found in highest

concentrations in the leaves. Chlorogenic acid and other antioxidants

are also present.

 

Licorice root (Glycyrrhiza glabra), in the form of the injectable

active principle glycyrrhizin, a saponin glycoside, has been used for

liver problems in Japan for 20 years. Controlled trials have shown

that glycyrrhizin use in chronic hepatitis is associated with

improvement in liver enzymes. Liver biopsies confirmed that the liver

cells of those taking the compound vs. a placebo were healthier.25,26

 

Long-term supplementation with the Japanese glycyrrhizin medicine

Stronger Neo-Minophagen CTM (SNMC) has been found to prevent liver

cancer in people with hepatitis C. During a period of 10 years, the

control group had 2.5 times the liver-cancer rate as those treated

with the herb.27 Several mechanisms make glycyrrhizen efficacious

including stimulation of the cytochrome P450 system and disruption of

the hepatitis virus surface.28A similar compound called PotenliniTM,

used in China, is effective for cirrhosis caused by either hepatitis

or alcohol.29 The licorice extract is usually provided in an

injectable form, so it is not possible to compare these medicines

with oral licorice root consumption. Large amounts of licorice can

lead to hypertension and dangerous potassium depletion, so its use

should be supervised.

 

For decades we have accepted that cirrhosis is not preventable, but

by putting together what we now know about the liver, there is hope.

One thing is certain: Relying on costly, unpleasant interferon and

antiviral therapy followed by exorbitantly expensive, often

unsuccessful liver transplants is not a rational way to approach the

current and growing cirrhosis epidemic. Health care practitioners

should encourage cost-effective nutrition therapies to slow or

prevent cirrhosis in the first place.

 

Sidebars:

Diet For A Healthy Liver

 

 

 

Marilyn Sterling, R.D., is a freelance writer, consultant and

practicing nutritionist in northern California.

 

References

 

1. Hayashi H, et al. Improvement of serum aminotransferase levels

after phlebotomy in patients with chronic active hepatitis C and

excess hepatic iron. Am J Gastroenterol 1994;89:986-8.

 

2. Trotter JF, Brenner DA. Current and prospective therapies for

hepatic fibrosis. Compr Ther 1995 Jun;21(6):303-7.

 

3. Lieber CS. Alcohol and the liver: 1994 update. Gastroenterology

1994 Apr;106(4):1085-105.

 

4. Chawla RK, et al. Biochemistry and pharmacology of S-adenosyl-L-

methionine and rationale for its use in liver disease. Drugs 1990;40

(3 Suppl):98-110.

 

5. Cabre E, Gassull MA. Nutritional support in liver disease. Eur J

Gastroenterol Hepatol 1995;7(6):528-32.

 

6. Corrao G, Ferrari PA. Exploring the role of diet in modifying the

effect of known disease determinants: application to risk factors of

liver cirrhosis. Am J Epidemiol 1995 Dec 1;142(11):1136-46.

 

7. Nanji AA, et al. Dietary saturated fatty acids down-regulate

cyclooxygenase-2 and tumor necrosis factor alpha and reverse fibrosis

in alcohol-induced liver disease in the rat. Hepatology 1997 Dec;26

(6):1538-45.

 

8. Pawlosky RJ, et al. The effects of low dietary levels of

polyunsaturates on alcohol-induced liver disease in rhesus monkeys.

Hepatology 1997 Dec;26(6):1386-92.

 

9. Comporti M, et al. Glutathione depletion: its effects on other

antioxidant systems and hepatocellular damage. Xenobiotica 1991 Aug;21

(8):1067-76.

 

10. Houglum K, Venkataramani A. Pilot study of the effects of d-alpha-

tocopherol on hepatic stellate cell activation in chronic hepatitis

C. Gastroenterology 1997 Oct;113(4):1069-73.

 

11. von Herbay A, et al. Vitamin E improves the aminotransferase

status of patients suffering from viral hepatitis C: a randomized,

double-blind, placebo-controlled study. Free Radical Res 1997 Dec;27

(6):599-605.

 

12. Russell RM. The impact of disease states as a modifying factor

for nutrition toxicity. Nutr Rev 1997 Feb;55(2):50-3.

 

13. Lieber CS. Susceptibility to alcohol-related liver injury.

Alcohol 1994;2 Suppl:315-26.

 

14. Beloqui 0, et al. N-acetyl cysteine enhances the response to

interferon-alpha in chronic hepatitis C: a pilot study. J Interferon

Res 1993;13:279-82.

 

15. Cimino L. Effect of N-acetyl-cysteine on lymphomonocyte

glutathione and response to interferon treatment in C-virus chronic

hepatitis. Italian J Gastroenterol Hepatol 1998 Apr;30(2):189-93.

 

16. Dong W, et al. Toxic metals stimulate inflammatory cytokines in

hepatocytes through oxidative stress mechanisms. Toxicol Appl

Pharmacol 1998 Aug;151(2):359-66.

 

17. Bonkovsky HL. Therapy of hepatitis C: other options. Hepatology

1997 Sep;3(1 Suppl):143S-51S.

 

18. Flora K, et al. Milk thistle (Silybum marianum) for the therapy

of liver disease. Am J Gastroenterol 1998 Feb;93(2):139-43.

 

19. Salmi HA, Sarna S. Effect of silymarin on chemical, functional

and morphological alteration of the liver: a double-blind controlled

study. Scandinavian J Gastroenterol 1982;17:417-21.

 

20. Boari C, et al. Occupational toxic liver diseases. Therapeutic

effects of silymarin. Min Med 1985;72(2):679-88.

 

21. Kropacova K, et al. Protective and therapeutic effect of

silymarin on the development of latent liver damage. Radiat Biol

Radioecol 1998 May;38(3):411-5.

 

22. Favari L, Perez-Alvarez V. Comparative effects of colchicine and

silymarin on CCl4-chronic liver damage in rats. Arch Med Res 1997;28

(1):11-7.

 

23. Pares A, et al. Effects of silymarin in alcoholic patients with

cirrhosis of the liver: results of a controlled, double-blind,

randomized and multicenter trial. J Hepatol 1998 Apr;28(4):615-21.

 

24. Gebhardt R. Antioxidative and protective properties of extracts

from leaves of the artichoke (Cynara scolymus L.) against

hydroperoxide-induced oxidative stress in cultured rat hepatocytes.

Toxicol Appl Pharmacol 1997 Jun;144(2):279-86.

 

25. van Rossum TG, et al. Review article: glycyrrhizin as a potential

treatment for chronic hepatitis C. Ailment Pharmacol Ther 1998 Mar;12

(3):199-205.

 

26. Yamamura Y, et al. The relationship between pharmacokinetic

behaviour of glycyrrhizin and hepatic function in patients with acute

hepatitis and liver cirrhosis. Biopharm Drug Dispos 1995 Jan;16(1):13-

21.

 

27. Arase Y, et al. The long-term efficacy of glycyrrhizin in chronic

hepatitis C patients. Cancer 1997 Apr 15;79(8):1494-500.

 

28. Takahara T, et al. Effects of glycyrrhizin on hepatitis B surface

antigen: a biochemical and morphological study. J Hepatol 1994 Oct;21

(4):601-9.

 

29. Wang JY, et al. Inhibitory effect of glycyrrhizin on NF-kappaB

binding activity in CCl4 plus ethanol-induced liver cirrhosis in

rats. Liver 1998 Jun;18(3):180-5.