Liver Degenerative Disease
Symptoms that are indicative of reduced liver function or possible liver damage include general malaise, fatigue, digestive disturbances (eg, constipation), allergies and chemical sensitivities, weight loss, jaundice, edema, and mental confusion. Generalized pruritus (itching), nausea, and vomiting can also result from impaired liver function. Causes of liver damage are numerous and may include congenital defects (malformed or absent bile ducts), obstructed bile ducts (cholestasis), autoimmune disorders, metabolic disorders (hemochromatosis, Wilson's disease), tumors, toxins (drugs, overdoses, poisons), alcohol-related conditions (cirrhosis), bacterial and parasitic infections, and viral infections (hepatitis B and C). This section discusses several chronic disorders and diseases that can lead to degenerative liver damage without proper diagnosis and treatment.
Cholestasis is interruption or stagnation of bile flow in any part of the biliary system, beginning with the liver. Cholestasis has several causes, including obstruction of the bile ducts by the presence of gallstones or a tumor, drug and alcohol use, hepatitis, and existing liver disease (Glanze 1996). In the United States, an important cause of cholestasis and impaired liver function is the consumption of alcohol. Other common causes of cholestasis are viral hepatitis and drugs, particularly steroidal hormones (including estrogen and oral contraceptives).
Cholestasis can cause alterations of liver function tests, indicating cellular damage. In the initial stages of liver dysfunction, standard tests (serum bilirubin, alkaline phosphatase, SGOT, LDH, GGTP, etc.) may not be sensitive enough to be of value for complete, early diagnosis. However, measurement of serum bile acids is a safe, sensitive test to determine the functional capacity of the liver. Treatment for cholestasis includes surgery resulting in unobstructed bile flow from the liver. Drug-induced cholestasis will generally disappear if the causative drug is discontinued. There is no specific treatment for cholestasis caused by hepatitis. However, bile flow will improve slowly if inflammation of the liver can be resolved.
Wilson's disease is an inherited disorder characterized by the liver's inability to metabolize copper, resulting in the accumulation of excessive amounts of copper in the brain, liver, kidney, cornea, and other tissues. The resulting copper accumulation and toxicity result in liver disease and brain damage in some patients. Although deposits of copper begin at birth, it may be some time until symptoms of liver disease become evident. Patients, generally between the ages of 10-40 years, present symptoms of liver disease, a movement disorder associated with neurological disease, behavioral abnormalities, or often a combination of these. Blood testing will reveal elevated liver enzymes. Symptoms of hepatitis and cirrhosis may be evident. Secondary injury from an accumulation of copper in the body may include kidney damage, neurological disorders, hemolytic anemia, and osteoporosis.
Copper also accumulates in other organs (particularly the brain) and may result in difficulty with speech, trembling, writing problems, unsteady gait, depression, suicidal impulses, and loss of mental functions. Other organs may also be damaged by copper overload. Copper can accumulate in the cornea of the eye and cause a characteristic brown pigmentation called Kayser-Fleischer rings. Hemolytic anemia, a low blood count related to damaged red blood cells, may occur in patients with Wilson's disease. There may also be injury to the kidneys from copper overload. Finally, severe bone disease from osteoporosis can occur in patients with Wilson's disease.
If left untreated, Wilson’s disease will cause increasing damage to organs, especially in the liver and brain. D-penicillamine is a copper chelating agent administered to remove excess copper and prevent further accumulations. Trientine may also be used as a copper chelating agent. Both drugs are administered with vitamin B6 (see Life Extension’s Heavy Metal Detoxification protocol for additional information on chelation). Foods high in copper content such as shellfish, nuts, chocolate, liver, and mushrooms must be avoided.
Because Wilson's disease can be effectively treated, it is extremely important for physicians to learn to recognize and diagnose the disease. Treatment options have evolved rapidly in the last few years, with zinc now being an important choice in most situations. Researchers consider zinc to be so important in the treatment of Wilson's disease that they refer to it as being "the drug of choice" (Brewer 1999).
Wilson's disease requires management by a physician. Self-treating this condition with zinc is not recommended.
Autoimmune hepatitis is associated with an increase in circulating autoantibodies and gammaglobulin resulting in progressive inflammation of the liver. The symptoms of Type-I autoimmune hepatitis (the most common) are characterized by the presence of antinuclear antibodies and a resemblance to symptoms of systemic lupus erythematosus. The disease occurs most commonly in females during adolescence or early adulthood. Other autoimmune disorders may be present with autoimmune hepatitis including thyroiditis, ulcerative colitis, vitiligo (loss of skin pigmentation), and Sjogren's syndrome (characterized by dry mouth and eyes).
Fatigue, abdominal discomfort, aching joints, itching, jaundice, enlarged liver, and spider angiomas (blood vessels) on the skin are the most common symptoms. More severe complications of liver disease may occur as the disease progresses.
Up to 80% of patients have long-term survival with appropriate treatment. Prednisone and azathioprine are usually administered to treat immunosuppression. The treatment goal is to control rather than cure the disease.
In the United States and Europe, approximately 1.25 million people are chronically infected with the hepatitis B virus (HBV) (Malik 2000). About 5-10% of those with acute hepatitis B will develop chronic infection. The remainder will recover and develop antibodies to the virus that make them immune from further viral activity (Lammert 2000; Mayerat 1999). At least 1 million chronically infected individuals die each year of complications due to HBV-related diseases, especially liver cancer and cirrhosis. In the entire world, about 5% of the population (or 350 million people) have chronic hepatitis B (Gumina 2001).
Hepatitis B causes inflammation of the liver resulting from infection with a DNA-type virus. The infection is passed via blood products, as in transfusions or the sharing of contaminated needles. It may also be acquired by exposure to bodily fluids in addition to blood, during sexual intercourse, and in transmission from mother to fetus. About 5-10% of volunteer blood donors show evidence of having prior hepatitis B--meaning that they once had hepatitis B, and may or may not still be infected with the viral agent.
The incidence of hepatitis B is increased in dialysis patients, IV drug users, persons with AIDS, transplant recipients, and patients frequently receiving blood transfusions (eg, those with leukemia or lymphoma). When acute hepatitis occurs, symptoms include weakness, nausea, vomiting, body aches (myalgias), diarrhea, fever, joint pain (arthralgia), jaundice (yellow discoloration of the skin and whites of the eyes), loss of appetite, weight loss, loss of interest in tobacco products, and sometimes an itchy skin rash. The average duration of symptoms of acute hepatitis B is 1-3 months. During the final phase of symptoms, the body begins to build immunity against the hepatitis B infection and does become immune 90% of the time (Lammert 2000). In the other 10%, however, a state of persistent infection occurs for more than 6 months. These persons are designated as having chronic hepatitis B. A liver biopsy is done in those patients with chronic hepatitis B; about one-third have chronic active hepatitis and two-thirds have chronic persistent hepatitis. Of these two types, chronic active hepatitis is more aggressive with a more rapidly progressing course.
Two forms of therapy are now licensed for use in chronic hepatitis B infection: interferon-alpha and lamivudine (Epivir). A vaccine for hepatitis B now exists and is frequently given to newborns, oversea travelers, and other people at risk of exposure (refer to Life Extension’s Hepatitis B protocol for more information and specific therapies).
Hepatitis C can be transmitted by blood and blood product transfusion. Up to 170 million persons are infected worldwide. In the United States, more than 4 million people are infected with the hepatitis C virus (HCV). Most liver transplants in the United States are a result of hepatitis C. Hepatitis C has a frightening tendency to result in chronic hepatitis, resulting in cirrhosis (15-20% of those infected) or hepatocellular carcinoma (primary liver cancer) (Ou 2002).
HCV is an RNA virus, spherical and enveloped in a lipid (fatty) outer envelope, which can be transmitted by narcotics use, transfusion of blood products, and exposure of medical personnel to infected patients. In some cases, the reason one contracts hepatitis C cannot be determined. The HCV inflicts most of its damage by latching onto molecules of iron and generating free-radical damage to liver cells. These free radicals can induce liver inflammation, cirrhosis, and primary liver cancer via oxidative attacks on liver cells.
Successful eradication of the HCV from the body often requires that iron levels in the liver and blood be at very low levels. In many cases, high stores of iron in the liver preclude successful therapy against the HCV. It is desirable to reduce iron levels in the body before initiating treatment with conventional (interferon and ribavirin) therapy. Despite substantial scientific evidence, few physicians implement iron-depletion therapy when treating hepatitis C. This partially accounts for the high failure rate to eradicate the virus.
In patients with hepatitis C, particularly those who are HIV-positive, a systemic depletion of glutathione is present, especially in the liver. This depletion may be a factor underlying resistance to interferon therapy. This finding represents a biological basis for taking supplements that boost cellular glutathione levels. Glutathione is a critical factor in protecting liver cells against free-radical damage.
Standard therapy for hepatitis C has consisted of ribavirin combined with interferon. However, a combination therapy of peginterferon alpha-2b and ribavarin is currently the standard of care (refer to Life Extension’s Hepatitis C protocol for more information and specific therapies).
Hemochromatosis is a hereditary disorder in which too much iron is absorbed from the diet resulting in free-radical damage to the liver, heart, and pancreas. It is estimated that over 1 million Americans suffer from the disease. If diagnosed early, hemochromatosis can be controlled by phlebotomy (giving blood) until stored iron levels are reduced. High levels of antioxidants and herbal detoxifiers are usually recommended to neutralize free radicals generated by excess iron. Chelation therapy is an alternative treatment in which a synthetic amino acid is administered intravenously to bind and extract unwanted metals from the body. People with hemochromatosis must avoid iron-fortified foods, cast-iron cookware, and red meat. Symptoms may not appear until middle age, after multiple organ damage has occurred. Due to blood loss from menstruation and pregnancy, the disease is less prevalent in women than men (refer to Life Extension’s Hemochromatosis protocol for more information and specific therapies).
Steatosis, Steatohepatitis, and Cirrhosis
Steatosis (fatty liver) is a common finding in biopsy of the human liver. Fatty liver is a condition in which fat accumulates within the liver cells (hepatocytes) without causing any specific symptoms. Fatty liver is defined as either more than 5% of cells containing fat droplets or total lipid exceeding 5% of liver weight.
Fatty liver is usually a long-standing chronic condition, occurring in association with a wide range of causes--exposure to poisonous and toxic substances, taking certain drugs, and drug abuse (injecting recreational drugs) (Glanze 1996)--although in clinical practice, the majority of cases are the result of excessive alcohol, diabetes, and obesity. Less common are occurrences of acute fatty liver during pregnancy or in response to the administration of tetracyclines, acetaminophen, prescription drugs, and toxins.
Our understanding of fatty liver has advanced considerably. At one time, fatty liver was believed to be a benign, reversible condition. However, clinical studies now demonstrate that fatty liver, whether from alcoholic or nonalcoholic origin, can lead to inflammation, cell death, fibrosis (steatohepatitis), and perhaps progress to cirrhosis. Cirrhosis is the irreversible end result of fibrous scarring, a response by the liver to a variety of long-standing inflammatory, toxic, metabolic, and congestive damage processes (refer to Life Extension’s Cirrhosis and Liver Disease protocol for more information and specific therapies).
As stated earlier, in the Western world, alcohol is a common cause of fatty liver and the second most common cause of cirrhosis. However, there are considerable differences among individuals in the degree of liver damage produced by excessive alcohol intake. There seems to be no correlation between the incidence and severity of fatty liver and the amount, type, or duration of alcohol abuse. In some individuals, it is unclear why fatty liver, whatever its etiology, never progresses to steatohepatitis and cirrhosis.
Obesity is considered to be the most common cause of nonalcoholic steatohepatitis (NASH). There is evidence to suggest that liver disease can actually be considered to be a complication of obesity. However, no major prospective longitudinal studies of NASH have been carried out. Generally, it seems that the risk of progression to cirrhosis is low for non-obese individuals, but significant among obese individuals. Unfortunately, there is also no predictable correlation between symptoms, abnormality of liver function tests, and severity of liver tissue damage.
As early as 1985, a study of 50 unselected, obese subjects admitted to a hospital for weight reduction found that 10% had normal livers, 48% had fatty livers, 26% had steatohepatitis, 8% had fibrosis, and 8% had cirrhosis (Braillon 1985). Obesity was defined as being 21-130% above ideal body weight.
Among patients with fatty liver related to obesity, it has been observed that rapid weight loss caused by dieting and intestinal bypass surgery actually increased the risk for developing steatohepatitis. The resulting increase in the concentration of fatty acids and/or ketones within the liver severely augmented the generation of free radicals (Day 1994).
A study indicated that obesity also increases susceptibility to endotoxin-mediated liver injury (Yang 1997). Endotoxins are cell wall components produced by intestinal Gram-negative bacteria thought to play a role in liver injury induced by alcohol and other hepatotoxins. Under normal conditions, endotoxins are absorbed into portal venous circulation and detoxified by the liver. Hepatic dysfunction interferes with this clearing mechanism and amplifies the negative activities of endotoxin, such as lipid peroxidation, reduced P-450 function, and impairment of the immune system.
Researchers summarized the following insights on the mechanisms of steatohepatitis (Berson 1998):
- Its development requires a double hit, the first producing steatosis, the second a source of oxidative stress capable of initiating significant lipid peroxidation. This concept provides a rationale for both the treatment and prevention of disease progression in steatosis of alcoholic and non-alcoholic causes. Management strategies should ideally be directed at reducing the severity of steatosis and at avoiding and removing the triggers of inflammation and fibrosis. Specific treatment modalities for at-risk individuals might include sensible weight reduction, cessation of exposure to toxins and treatment with antioxidants and inhibitors of peroxisomal β-oxidation.
Toxic Damage to the Liver
The external environment contributes most to the load of toxins that the liver has to detoxify. Today, the burden on the liver is heavier than ever before. Additionally, nutritional deficiencies and imbalances from unhealthy eating habits add to the production of toxins, as do alcohol and many prescription drugs, further increasing stress on the liver and requiring a strong detoxification capacity. Surprisingly, even unprocessed organic foods can have naturally occurring toxic components that require an effective detoxification system.
Toxic chemicals are found in the food we eat, water we drink, and air we breathe, both outdoors and indoors. In a study by the Environmental Protection Agency (EPA), chemicals such as p-xylene, tetrachloroethylene, ethylbenzene, and benzene were documented as "everywhere present" in the air (Wallace 1989). Listed as "often present" were chloroform, carbon tetrachloride, styrene, and p-dichlorobenzene. A customary trip to a gas station or dry cleaner (as well as smoking) results in elevated levels of inhaled toxins.
The Food and Drug Administration (FDA) has found an alarming level of chlorinated pesticides in food. Dichlorodiphenyldichloroethylene (DDE) was found in 63% or more of 42 food samples, even though dichlorodiphenyltrichloroethane (DDT) and DDE have been banned in the United States since 1972. DDE is a breakdown product of DDT. Unfortunately, toxic chemicals used anywhere in the world can move easily around the globe (ie, they are carried by the wind). There is enough evidence of a connection between chemical exposure and chronic health problems for us to be aware that herbicides, pesticides, household chemicals, food additives, etc. pose serious health concerns.
When the liver's detoxification system is overloaded, the liver does not function properly; thus, toxins we are exposed to accumulate in the body. These toxins affect us in numerous ways, and have damaging effects on many bodily functions, particularly the immune system, causing chronic health problems. It is not surprising that an overburdened and undernourished liver can be a root cause of many chronic diseases.Cancers are also thought to be a result of the effects of environmental carcinogens (eg, cigarette smoke, chemical fumes, toxic exhaust, and airborne particulates), particularly if combined with deficiencies of nutrients required for optimal functioning of the detoxification and immune systems. A study of chemical plant workers in Turin, Italy analyzed the association of bladder cancer according to occupation (ie, textiles, leather, printing, dyestuffs, tire and rubber goods production). Highest risks were for the leather, dyestuffs, and tire production industries. An association was found for cancer and the aromatic amines, with the risk being estimated at 10% for those occupations consistently associated with bladder cancer. Researchers also found that there was a multiplicative effect of relative risks for persons in high-risk occupations who also smoked cigarettes (Vineis 1984).