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The“Hidden” Liver Disease

February 2004

By Penelope Hamil


Can NAFLD Be Treated or Prevented?
Conventional medicine does not yet have one specific pharmacological treatment that truly works to control NAFLD. People who are at high risk of developing NAFLD, particularly those who are obese or have diabetes or metabolic syndrome conditions, may want to consider talking to their doctor about taking the soybean extract polyenylphosphatidylcholine (PPC). Research suggests that the supplement may stop liver damage in its tracks and even accelerate its regression.26

Phosphatidylcholine (the main component of lecithin) is an integral part of cell membranes, essential for their structural and functional integrity. Cell membranes act like gatekeepers, allowing nutrients into the cells but blocking damaging toxins from gaining entrance. PPC has been shown to enhance cell membrane function throughout the body.

The History of NAFLD

The spectrum of NAFLD came to light as an ailment separate from alcohol-induced fatty liver disease just over 30 years ago. The condition was not named until 10 years later, when in 1980 Dr. J. Ludwig and colleagues at the Mayo Clinic noticed that certain people who shared some common conditions (obesity, diabetes, and elevated cholesterol) had a liver disease that bore a remarkable resemblance to alcoholic liver disease, though none of the individuals drank alcohol. Hence, Dr. Ludwig coined the term nonalcoholic steatohepatitis.3 It took another decade for doctors to finally realize that nonalcoholic steatohepatitis is not a harmless condition, but rather a dangerous one. Since then, scientists, hepatologists (liver specialists), endocrinologists (hormone specialists), and nutritionists have joined forces, scrambling to learn more about the disease that is now known as NAFLD (nonalcoholic fatty liver disease).

PPC already is approved for the treatment of chronic liver diseases in many European countries and is being investigated for treatment of hepatitis (see sidebar on p. 55, “PPC in Viral Hepatitis”). PPC is listed in the Physician’s Desk Reference (PDR) commonly used by US physicians. An accumulating body of research suggests that PPC’s umbrella of protection may extend from the liver to the stomach, pancreas, and cardiovascular system. PPC is well absorbed in humans and animals when taken orally and has no known contraindications, side effects, or interactions with other drugs, even when consumed in large quantities. In one pilot study, researchers found that daily doses of PPC halted the progression of liver fibrosis,27 and a Czech study showed that taking the supplement every day (along with low doses of fatty acids, B vitamins, and vitamin E) reduced fatty-liver symptoms within six months in more than half of the study participants.28 PPC also appears to increase the breakdown of collagen, the connective-tissue protein that tends to accumulate in liver disease, promoting the scarring behind fibrosis and cirrhosis.29

PPC’s protective effect is believed to be the result of its ability to be incorporated in normal and damaged cell membranes. Animal studies have indicated that PPC, which is a polyunsaturated phosphatidylcholine, becomes incorporated in the membranes of liver cells as a substitute for native saturated phosphatidylcholine molecules.30 This substitution is shown to result in an increase in membrane fluidity and active transport activity across the membrane. Similarly, PPC is incorporated in blood lipoproteins such as cholesterol, leading to lipid-lowering properties. In one Russian clinical trial, the supplement lowered total and LDL (“bad”) cholesterol by about 15%, decreased triglyceride levels by 32%, and raised levels of “good” HDL cholesterol by 10%.31

PPC also appears to have antioxidant properties, which means it may effectively reduce the oxidative stress (cellular changes that generate cell-damaging free radicals) shown to be a contributing factor in the inflammation and scarring of nonalcoholic steatohepatitis.32

Experts point out that simply losing weight often will result in a significant reduction of excess fat in the liver. But they add that it is best to lose weight slowly—at a rate of no more than 1 to 2 pounds a week—because rapid weight loss has been shown to exacerbate a fatty liver condition, causing inflammation and even resulting in liver failure.33-35

Keeping high glucose levels under control also is critical for NAFLD patients, as research has shown that a fatty liver improves as glucose levels are controlled.36 A preliminary study found that a drug called metformin (Glucophage®), which improves insulin sensitivity and is used to treat type II diabetes, also significantly lowered liver enzyme levels and decreased fatty deposits in the liver in people with NAFLD.7 Additional studies are now under way.

Doctors say that NAFLD can probably be largely prevented and even eliminated in the future by encouraging the adoption of healthy eating habits and more-active lifestyles. For those who already have nonalcoholic fatty liver disease, encouraging discoveries show that the use of natural products may potentially alter the course of this serious consequence of aging and unhealthful lifestyles.

Electron micrograph of hepatitis B virus particles. Hepatitis B causes an inflammation of the liver.
PPC in Viral Hepatitis

PPC (polyenylphosphatidylcholine) has been found to decrease serum aminotransferases in experimental hepatitis. In 1998, Niederau and colleagues conducted a multicenter, randomized, placebo-controlled clinical study evaluating the effects of polyenylphosphatidylcholine (PPC) in combination with interferon alpha (IFN) in patients suffering from hepatitis B and hepatitis C. Although IFN is the standard treatment for these diseases, only 50% of patients with hepatitis B and 20-30% of patients with hepatitis C respond to this antiviral drug with long-term normalization of serum aminotransferases. Of patients with hepatitis C who do respond to IFN while under treatment, at least 50% relapse, which indicates a need for more-effective treatment.

In this study, all 176 patients were given the same amount of interferon during the 24-week test period. In addition, patients were randomly assigned to receive either 1.8 grams per day of PPC or placebo for those 24 weeks. A biochemical response to therapy was defined as a minimum 50% reduction of alanine aminotransferase (ALT) compared to pretreatment values.

The results show that PPC increased the response rate to IFN in chronic viral hepatitis C (71% versus 51% in the placebo group). Prolonged PPC therapy given to responders 24 weeks beyond the cessation of interferon therapy tended to increase the rate of sustained responses in patients with hepatitis C (41% vs. 15%). Hepatitis B patients, however, did not have an improved biochemical response to interferon from PPC.

PPC’s beneficial effect in hepatitis C has been the subject of further investigation. Very recently, it was determined that steatosis (fatty liver) is present in a high percentage of patients with chronic hepatitis C. Furthermore, studies have now shown that steatosis is a predictive factor in patients with chronic hepatitis C regardless of viral genotype or body mass index. The studies concluded that hepatitic steatosis—whether mild, moderate or severe—appears to be an independent predictor of poor response to therapy.37-39

The PPC-interferon study suggests that PPC can be a valuable adjunct to IFN treatment of hepatitis C, and can also be of benefit after cessation of IFN therapy to increase the chance of sustained response to therapy.


The Liver’s Role

The largest organ in the body, the liver has its work cut out for it— performing a wide range of tasks, including processing fats, sugars, proteins, and vitamins, and regulating blood clotting. This vital organ also plays a major role in the body’s defense system, filtering and removing toxins and invading microbes from the blood.40

The Syndrome X Connection

Because abdominal obesity, insulin resistance, and elevated triglyceride levels all appear to be strongly linked to NAFLD, some researchers advocate classifying NAFLD as an additional feature of the cluster of abnormalities called metabolic syndrome (or Syndrome X).41 Syndrome X is characterized by the National Institutes of Health as having at least three of the following health concerns: abdominal obesity; high triglyceride levels (150 mg/dL or higher); low HDL (“good”) cholesterol levels (less than 50 for women and less than 40 for men); moderately elevated or high blood pressure (130/85 or higher); and moderately elevated or high blood sugar levels (a fasting glucose of 110 or higher).

According to the American Medical Association, one in five American adults, or about 47 million, are afflicted with the syndrome, which can more than double one’s risk of heart attack, stroke, and diabetes. One study of people with NAFLD found that 88% of those with nonalcoholic steatohepatitis had metabolic syndrome, compared to 55% of patients with simple fatty liver. The researchers concluded that the presence of the syndrome increased the risk of a person with benign fatty liver disease progressing to nonalcoholic steatohepatitis.42

No cure and no single specific treatment are available for metabolic syndrome; today doctors can only treat the various conditions—such as obesity, hypertension, high cholesterol, and diabetes—that are components of the disease.

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