The Liver

The liver is the largest organ (about the size of a football and averaging about 3.5 pounds) and has more functions than any other human organ. A person's entire blood supply passes through the liver several times a day, and at any given time there is about a pint of blood there. The liver produces and secretes bile (to be stored in the gallbladder until needed) that is used to break down and digest fatty acids. It also produces prothrombin and fibrinogen, both blood-clotting factors, and heparin, a mucopolysaccharide sulfuric acid ester that helps keep blood from clotting within the circulatory system.

The liver converts sugar into glycogen, which it stores until the muscles need energy and it is secreted into the blood stream as glucose. The liver synthesizes proteins and cholesterol and converts carbohydrates and proteins into fats, which are stored for later use. It also produces blood protein and hundreds of enzymes needed for digestion and other bodily functions. As it breaks down proteins, the liver also produces urea, which it synthesizes from carbon dioxide and ammonia. (Urea, the primary solid component of urine, is eventually excreted by the kidneys.) The liver also stores critical trace elements such as iron and copper, as well as vitamins A, D, and B12.

Cirrhosis

Cirrhosis of the liver is a chronic, diffuse (widely spread throughout the organ), degenerative liver disease in which the parenchyma (the functional organ tissue) degenerates, the lobules are infiltrated with fat and structurally altered, dense perilobular connective tissue forms, and areas of regeneration often develop. The first scientist known to have diagnosed the disease was Gianbattista Morgagni, who published 500 autopsies in 1761. Laennec named the disease in 1826, using the Greek word for orange color because cirrhotic livers turn a yellowish to tan color.

Cirrhosis is the seventh leading cause of death by disease in the United States, with about 25,000 dying from it each year (down from 50,000 in 1979). About a third of the cases are compensated, meaning there are no clinical symptoms. Such cases are usually discovered during routine tests for other problems, or during surgery or autopsy. In most cases, though, there is a loss of liver cell function, and an increased resistance to blood flow through the damaged liver tissue (a condition known as portal hypertension) leading to esophageal varices (enlarged, swollen veins at the lower end of the esophagus). Severe cirrhosis leads to ammonia toxicity, hepatic coma, gastrointestinal hemorrhage, and kidney failure. As liver cells are destroyed, they are systematically replaced by scar tissue.

Symptoms

Symptoms of cirrhosis include nausea or indigestion and vomiting, constipation or diarrhea, flatulence, anorexia, weight loss, ascites (the accumulation of serous fluids in the peritoneal cavity), light-colored stools, weakness or chronic dyspepsia, dull abdominal aching, varicosities, nosebleeds, bleeding gums, other internal and external bleeding, easy bruising, extreme dryness of skin, and spider angiomas. Psychotic mental changes such as extreme paranoia can occur in cases of advanced cirrhosis. Other symptoms are testicular atrophy, gynecomastia (enlargement of the male breast), and loss of chest and armpit hair.

Complications

When blood flow in the cirrhotic liver is restricted, blood can "back up" in the spleen, causing enlarged spleen and sequestered blood cells. In this condition the platelet count typically falls, and abnormal bleeding can result. In extreme cases blood can actually flow backward from portal circulation to systemic circulation, leading to varicose veins in the stomach (gastric varices), esophagus (esophageal varices), and rectum (hemorrhoids). Ruptured varices bleed massively and are often fatal. Bilirubin levels may build up in the blood, causing jaundice and bright yellow to dark brown urine. Cirrhosis can also cause insulin resistance and diabetes mellitus. Brain injury can result from inadequate filtering of blood toxins. Such brain damage can have symptoms that range from poor concentration to coma, swelling of the brain, stupor, and even death. Cirrhosis is often associated with osteomalacia (the adult form of rickets, a softening of the bones that often leaves them brittle) and osteoporosis (a reduction in bone mass).

The Alcohol Factor

The most common cause of cirrhosis is believed to be alcohol (ethanol) abuse (about 10% of American men and about 3% of American women chronically abuse alcohol). Though it affects many organs, alcohol is especially harmful to the central nervous system and the liver, and is a factor in about three-fourths of the cases of cirrhosis in the United States. Alcohol must be metabolized, and the liver performs most of that job, suffering serious damage in the process. Not only does alcohol destroy liver cells, it also robs them of their ability to regenerate.

Such cofactors as hepatitis C virus can increase the risk of cirrhosis in those whose intake of alcohol is excessive. Alcohol-induced cirrhosis is among the ten leading causes of death in the United States. Women are at much higher risk for drinking-related cirrhosis than are men. This may be true because less of the alcohol consumed is metabolized in the stomach in women before being absorbed into the blood stream. Autopsies indicate that from 10 to 15% of American alcoholics suffer from cirrhosis at the time of death. About a third of those consuming one cup to one pint (8 to 16 ounces) of hard liquor a day (or the equivalent in other drinks) over a 15-year period will develop cirrhosis.

In addition to cirrhosis, alcohol abuse can lead to fatty liver, which can lead to stearohepatitis (or steatohepatitis, the older term), scarring of the liver, and eventually to cirrhosis. Overuse of alcohol can also lead to acute, chronic hepatitis. Complications can include liver dysfunction, abnormal blood clotting, jaundice, and hepatic encephalopathy (neurological dysfunction brought on by failure of the liver). Chronic abusers of alcohol often need significant vitamin supplementation to correct vitamin deficiencies caused as much by neglect and poor eating habits as by damage from the alcohol. An acute thiamin (vitamin B1) deficiency is typical.

Other Risk Factors and Causes

Cirrhosis patients are at high risk for obesity, fatal bacterial infections, stomach ulcers, kidney problems, gallstones, and diabetes mellitus. They are also at increased risk for liver cancer. Risk factors for cirrhosis include nutritional deficiencies (lack of proteins, vitamins, choline, trace elements, or methionine), hepatitis (B, C, or D) and other bacterial and viral infections, and severe reactions to prescription or "recreational" drugs. Vitamin B1 (thiamin) deficiency may directly cause alcoholic cirrhosis. One study concluded that vitamin B1 deficiency is a greater risk factor for liver cell death than heavy alcohol consumption.

Congestive heart failure and poisons (including alcohol, phosphorus, and carbon tetrachloride) pose a serious threat to the liver and can lead to cirrhosis. Genetic disorders, inherited metabolic diseases such as hemochromatosis (marked by excessive iron absorption and accumulation) and Wilson's disease (in which the liver stores too much copper), advanced syphilis, exposure to blood flukes, other parasitic infections (such as schistosomiasis), and blocking of the common bile duct are all factors that can lead to cirrhosis. Liver injury from an accident or from cystic fibrosis can also bring on cirrhosis.

Diagnosis

Positive diagnosis of cirrhosis must be made by liver biopsy, but X-ray, blood tests, and physical examination are all used in diagnosis, as is observation of the symptoms mentioned earlier. CAT (computerized axial tomography) scans, radioisotope liver scans, and ultrasound can all be used to diagnose cirrhosis. Early diagnosis is critical in order to establish the cause of the disease and determine the amount of damage to the liver.

Two symptoms of cirrhosis are the loss of healthy, functioning liver cells and the scarring and distortion of the liver that eventually take place. As fewer cells function, less albumin (a protein) is manufactured. Lowered albumin levels permit water retention (edema) in the legs and abdomen (ascites). Easy bruising and bleeding result, and, in some cases, vomiting of blood. Intense skin itching can also result from excessive bile product deposits in the skin, often accompanied by jaundice or yellow skin.

Gallstones are more likely to form in cirrhosis patients because there is not enough bile reaching the gallbladder. Toxins that the liver would normally remove build up in the blood, dulling mental functions and bringing on personality changes. Drugs the patient is taking, normally filtered out and disposed of in urine, may remain in the bloodstream for a much longer period and act longer than expected or even build up in body tissue. A liver with cirrhosis is usually much larger than a healthy liver.

Precautions and Prevention

Once cirrhosis has been diagnosed, sodium and fluids should be restricted, and all alcohol consumption must cease. Antiemetics, diuretics, and supplemental vitamins are prescribed. Cirrhosis patients should avoid straining at the bowel, violent sneezing and coughing, and nose blowing, and should use stool softeners as prescribed by a qualified medical caregiver. Untreated cirrhosis can be fatal; patients should avoid exposure to infections and eat small but frequent meals of nutritious foods, carefully following caregiver instructions. The liver is the only organ that can generate healthy, new tissue in response to injury or disease. It is therefore possible to regenerate a cirrhosis-damaged liver if extraordinary therapies are followed and the underlying cause of the cirrhosis is eliminated.

More than half of all liver disease could be prevented if we acted on the knowledge we already have. Avoiding or limiting the use of alcoholic beverages is a good place to start, because it is well documented that alcohol destroys liver cells. Man-made chemicals also pose an extreme threat to the liver, so take recommended precautions. Remember that all ingested, inhaled, and absorbed toxins must be processed by the liver. When working with hazardous chemicals use adequate ventilation; follow product instructions; do not mix chemicals; wear protective clothing and breathing equipment; avoid inhalation and ingestion of hazardous materials; avoid skin contact and flush (wash) affected areas immediately; if necessary, call your poison control center or your emergency number (such as 911). A complete listing of toll-free poison control center numbers can be obtained online at MediciNet.com.

Treatments

When varices result, they can be treated with a reduction of salt intake and with diuretics, which help eliminate excess salts and fluids from the body. Coma and encephalopathy are treated by a reduction of protein intake, and hemorrhage from varices can be stopped by sclerotherapy (injection of a scarring chemical into the bleeding vein). Varices can also be compressed by the use of a special balloon that is inflated around the enlarged vein, squeezing it as the balloon is inflated. There is a new procedure (using radiology)-transjugular intrahepatic protosystemic shunt (TIPS)-that shows some promise.

Interferon-alpha, a powerful antiviral, may reduce the risk of cancer in some cirrhosis patients. In cases of total liver failure, transplantation has been successful. Over 80% of liver transplant patients are still alive 5 years after the surgery. Japanese researchers found evidence that malotilate prevented both damage to liver cells and cirrhosis they attempted to induce in rats.

Natural Therapies

The liver can often perform its essential functions in spite of serious damage. It also has more ability to self-repair than do most other organs. It is important to give the liver the nutrients it needs to function and to regenerate and detoxify itself. Research done at the Center for Biomedical Research at the Hospital of St. Joan in Reus, Spain, in 1992 shows that supplementation of zinc lessens the effects of fibrogenesis in rats with induced cirrhosis. German research shows that zinc deficiencies are implicated in liver cirrhosis and concludes that zinc substitution should be provided to all cirrhosis patients when deficiency and corresponding symptoms are found. (Long-term supplementation of zinc should not exceed 90 mg a day.) Selenium deficiencies have also been found in the blood of cirrhosis patients, leading to recommendations for selenium supplementation. Ursodeoxycholic acid, a widely tested bile acid, has been found effective in slowing the progress of cirrhosis, preventing gallstone formation, and preventing the formation of varices.

Research has shown decreased blood serum levels of vitamins E and K1, and increased levels of vitamin A and iron in some cirrhosis patients. These patients should not directly supplement vitamin A or beta carotene, and should also avoid niacin (vitamin B3) and supplements containing extracts from the chaparral shrub. (Some research found absolutely no correlation between cirrhosis and vitamin A levels in the liver and concluded that cirrhosis patients were not at increased risk from vitamin A supplementation, while other studies showed decreased vitamin A levels in cirrhosis patients. More research is needed, but cirrhosis patients should consider vitamin A supplementation only under direct medical supervision.) Japanese studies showed that moderate intake of caffeine (in coffee) helped to counteract some of the negative effects of alcohol on the liver. Consumption of caffeine in green tea showed no such effect.

In Russian studies, supplementation with ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) improved the liver function of chronic liver disease patients. In a 1998 American study it was found that a high level of supplementation of vitamins B2 (riboflavin) and B12 (cyanocobalamin and hydroxycobalamin, associated with folate metabolism) reduced the risk of cirrhosis associated with alcohol consumption above 50 grams (1.75 ounces) a day.

Recommended supplements for a seriously damaged liver are the amino acids acetyl-L-carnitine (2000 mg a day), N-acetylcysteine (600 mg twice a day), L-arginine (5 to 10 grams a day), leucine (1200 mg a day), isoleucine (600 mg a day), and valine (600 mg a day). Silymarin (at about 600 mg a day) is effective in cirrhosis patients, even in alcoholic liver cirrhosis. It is especially helpful for diabetics with cirrhosis because it reduces the lipoperoxidation of cell membranes and insulin resistance, decreasing the need for insulin supplementation. L-Arginine (up to 5 to 10 grams a day) and glutamine (2000 mg a day) are only effective when there is still at least 20% liver function remaining. (L-arginine should be taken under a doctor's supervision.)

Because ethanol damages the liver at least in part by the generation of free radicals, and because it depresses an enzyme needed to convert methionine into SAMe (S-adenosylmethionine), SAMe supplementation can help regenerate normal liver function. Periodic blood testing is required to monitor the effectiveness of patient therapy. Doses of 400 to 800 mg twice a day have shown promise in reversing alcoholic cirrhosis. A less expensive alternative is twice-a-day supplementation with 500 mg of TMG (trimethylglycine, or betaine), folic acid (800 mcg), and vitamin B12 (500 mcg per day). Supplementation with phosphatidylcholine (2000 mg per day) may provide protection against alcohol-induced septal fibrosis, cirrhosis, and lipid peroxidation.

Because anemia is a common complication in cirrhosis patients, iron deficiency is a possibility. Iron supplementation should only be used under direct medical supervision with close monitoring because excessive iron can cause severe liver damage, especially when combined with alcohol, porphyrogenic drugs, or chronic viral hepatitis. Iron can also enhance the disease-producing abilities of viruses, adversely affect immune function, and enhance fibrogenic pathways, all of which may increase liver injury. Iron may also be implicated as a cocarcinogen or promoter of hepatocellular carcinoma, even in patients without hepatitis C or cirrhosis.

Ongoing Research

There is a large amount of research and study into causes and cures of cirrhosis of the liver. Patients and healthcare providers should stay abreast of research findings for the latest developments in cirrhosis treatment and therapy.

Summary
Cirrhosis of the liver can be caused by excessive alcohol consumption, accidental, bacterial, or viral liver damage, exposure to toxic chemicals, and severe reaction to prescription or "recreational" drugs. Supplementation of antioxidants, branched chain amino acids, and all except B3 (niacin) of the B complex of vitamins has been shown to be beneficial. For specific antiviral therapies to help eradicate hepatitis B or C, refer to our Hepatitis B  and Hepatitis C protocols.

1. Drink alcohol in moderation if at all. If diagnosed with cirrhosis, do not drink.
2. Studies on alcoholic cirrhosis patients have shown benefits from supplementing valine, leucine, and isoleucine. These branched-chain amino acids can enhance protein synthesis in liver and muscle cells and are used by body builders to produce an anabolic effect. Four capsules of Branch Chain Amino Acids (free form) provide 200 mg of L-leucine, 600 mg of L-isoleucine, 600 mg of L-valine, and 10 mg of vitamin B6 (pyridoxine). The suggested dose is 2 to 4 capsules per day between meals with fruit juice or before eating.

WARNING: These capsules are only to be used by adults who are fully grown, and not by anyone afflicted with pellagra.

3. Patients with depleted SAMe levels should take from two to four 200-mg tablets a day of SAMe, spread throughout the day. Patients must adhere to physician-prescribed blood testing schedules to assess the effectiveness of this therapy. A cost-effective alternative to SAMe supplementation is TMG (trimethylglycine). The suggested dose is two 500-mg tablets after meals, twice a day, or as directed by a physician.
4. The vitamin B complex is extremely important for liver health. Therefore, daily supplementation of vitamins B1 (500 mg), B2 (75 mg), B5 (1500 mg), and B6 (200 mg) is strongly recommended (though vitamin B3 [niacin] should be avoided by cirrhosis patients).
5. Other recommended daily supplements are 1500 mg of choline, 1600 mg of folic acid, 500 mg of vitamin C, 800 IU of vitamin E, 300 micrograms of selenium, and 100 mg of coenzyme Q10 (for its antioxidant and blood flow-enhancing properties).
6. 5. Acetyl-L-carnitine should be taken in two daily doses of 1000 mg each. Take two 600 mg doses per day of N-acetylcysteine. Drink green tea, or take 4 to 10 standardized 100 mg capsules of green tea extract a day to lower toxic levels of iron (which may exacerbate free radical damage to the liver).
7. 5 to 10 grams of L-arginine and 2000 mg a day of glutamine may help lower blood levels of toxic ammonia permitted to build up by a damaged liver. L-arginine can help facilitate liver regeneration if the liver still has at least 20% functional reserve capacity.
8. Silymarin treatment (about 600 mg a day) is appropriate for all alcoholic liver disease patients, and has reduced insulin resistance in diabetic patients with cirrhosis.
9. Zinc should be supplemented in cirrhosis patients at a rate of at least 30 mg per day (not to exceed 90 mg a day), while selenium should be supplemented according to your doctor's instructions.

For more information. Contact the American Liver Foundation, (800) 223-0179.