Dr. Schoenfield served as associate professor of medicine and consultant in gastroenterology on the faculty of the Mayo Clinic for seven years. He became a professor of medicine in residence at UCLA from 1972 to 1999 (now emeritus). He was the director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles for 25 years, where he received the chief resident's teaching award, the president's award, and the pioneer of medicine award.
While the natural clinical history and the
processes involved in the development of NAFLD are beginning to slowly unravel,
no single truly effective treatment has been found to date. However, common
sense dictates that weight loss, if overweight, and correcting elevated
cholesterol, triglycerides, and blood sugar should be beneficial in NAFLD.
Yet, very little data exist on the effects of weight loss and exercise on the
progression of fatty liver disease. One retrospective study (looking back in
time) showed that in obese individuals with initially elevated transaminases,
weight gain lead to a further increase in the liver enzymes. In contrast, a 10%
weight loss lead to a significant decrease in the enzymes and even normal
transaminases in some patients. The enzyme decrease occurred at the rate of 8%
per 1% loss of body weight.
In studies of patients undergoing stomach (gastric) reduction operations for
morbid obesity, substantial weight loss is accompanied by a marked reduction in
transaminases and a regression of fatty liver. However, rapid weight loss in
this situation can also induce the occurrence of a fatty liver with liver
inflammation. Perhaps inflammatory cytokines (the small hormones mentioned
earlier) and the fat that produce the fatty liver and inflammation come from the
body fat (adipose tissue), especially the remaining abdominal fat.
There are
little published data on the use of glucose lowering (hypoglycemic) agents or
lipid lowering agents in the treatment of NASH. Troglitazone (Rezulin) is a
PPARg (peroxisome proliferator activating receptor gamma) compound that, as
indicated above, enhances the effects of insulin. The FDA, however, withdrew
this drug from the market because it caused cases of severe liver injury
(hepatotoxicity). Before the drug was withdrawn, however, a small trial of
troglitazone in patients with NASH was conducted for 6 months. The study showed
a significant decrease in transaminases, but only moderate improvement in
microscopic (histological) severity in the liver biopsies.
Troglitazone, as does
other medications in its class (thiazolidinediones), increases insulin
sensitivity and perhaps decreases inflammation and scarring in the liver. A
short trial with gemfibrozil (Lopid), a drug that lowers blood fats
(antilipidemic agent), showed some positive effects. It lowered transaminases
and serum triglycerides, but follow-up liver biopsies were not performed. A
one-year trial of clofibrate (Atromid-S), another drug that lowers blood fats,
however, had no positive effect whatsoever. Metformin (Glucophage),
is an insulin-enhancing (sensitizing) agent used extensively to treat DM2. The
drug was studied in a small series of NASH
patients and showed beneficial effects on transaminases and decreased fatty
infiltration in the liver. A larger trial is ongoing. Recent data also suggest that
lowering cholesterol and triglycerides using medications such as statins help decrease fatty
liver.
In one published trial, a one-year course of ursodiol (Actigall,
Urso) in patients with NASH decreased transaminases and improved the liver
biopsies. The way
that this bile acid molecule works in NASH remains unclear, but
it may involve effects on the immune system that decrease inflammation. But recent data
cannot confirm efficacy of Actigall in treating fatty liver.
In view of the multiple processes involved in causing
NASH, it may well be that many different classes of medications, as well as
weight loss, will have beneficial effects. These drugs could conceivably
include:
Insulin-sensitizing agents, such as the two new thiazolidinediones, pioglitazone
(Actos) and rosiglitazone
(Avandia), and metformin (Glucophage)
Medications that lower lipids such as statin drugs and
Lopid
Drugs that improve blood flow, such as pentoxifylline
(Trental)
Presumably, weight loss through exercise and diet modification along with
insulin-sensitizing agents will help reverse fatty infiltration of the liver.
The other therapies might be beneficial in slowing the processes of inflammation
and scarring. A combination of therapies will probably be the most
beneficial.
Fatty Liver - How Was Diagnosis EstablishedQuestion: The symptoms of fatty liver can vary greatly from patient to patient. What were your symptoms at the onset of your disease?
Abdominal pain is pain in the belly and can be acute or chronic. Causes include inflammation, distention of an organ, and loss of the blood supply to an organ. Abdominal pain can reflect a major problem with one of the organs in the abdomen such as the appendix, gallbladder, large and small intestine, pancreas, liver, colon, duodenum, and spleen.
Liver cancer is the fifth most common cancer in the world and the majority of patients with liver cancer will die within one year as a result. Patients with associated cirrhosis caused by chronic hepatitis B or C infections, alcohol, and hemochromatosis are at the greatest risk of developing liver cancer. Many patients with liver cancer do not develop symptoms until the advanced stages of the tumor which usually makes prognosis poor. The combination of an imaging study (ultrasound, CT, or MRI scans) and an elevated blood level of alpha-fetoprotein will most effectively diagnose liver cancer, while a liver biopsy can make a definitive diagnosis. Medical treatments, including chemotherapy, chemoembolization, ablation, and proton beam therapy, are not very effective. Surgical removal of the tumor or a liver transplant may be most effective in certain cases.
Cirrhosis of the liver refers to a disease in which normal liver cells are replaced by scar tissue caused by alcohol and viral hepatitis B and C. This disease leads to abnormalities in the liver's ability to handle toxins and blood flow, causing internal bleeding, kidney failure, mental confusion, coma, body fluid accumulation, and frequent infections. Symptoms include yellowing of the skin, itching, and fatigue.
Diabetes mellitus is a chronic condition characterized by high levels of sugar (glucose) in the blood. The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent). Symptoms of diabetes include increased urine output, thirst, hunger, and fatigue. Treatment of diabetes depends on the type.
Liver disease can be cause by a variety of things including infection (hepatitis), diseases such as gallstones, high cholesterol or triglycerides, blood flow obstruction to the liver, and toxins (medications and chemicals). Symptoms of liver disease depends upon the cause; however, common symptoms may include nausea, vomiting, upper right abdominal pain, and jaundice. Treatment depends upon the cause of the liver disease.
Hepatitis C is an inflammation of the liver due to the hepatitis C virus (HCV), which is usually spread by
blood transfusion, hemodialysis, and needle sticks, especially with intravenous
drug abuse. Chronic hepatitis C may be treated with interferon, usually in combination with anti-virals.
Cholesterol is naturally produced by the body, and is a building block for cell membranes and hormones. Low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol, conversely, high-density lipoprotein (HDL) cholesterol is the "good" cholesterol. High cholesterol treatment includes lifestyle changes (diet and exercise), and medications such as statins, bile acid resins, and fibric acid derivatives.
Alcoholism is a disease that includes alcohol craving and continued drinking despite repeated alcohol-related problems, such as losing a job or getting into trouble with the law.
Polycystic ovarian syndrome (PCOS), also known by the name Stein-Leventhal syndrome, is a hormonal problem that causes women to have a variety of symptoms including irregular or no menstrual periods, acne, obesity, and excess hair growth. Treatment of PCOS depends partially on the woman's stage of life and the symptoms of PCOS.
The hepatitis B virus is a unique, coated DNA virus belonging to the Hepadnaviridae family of viruses. The course of the virus is determined primarily by the age at which the infection is acquired and the interaction between the virus and the body's immune system. Successful treatment is associated with a reduction in liver injury and fibrosis (scarring), a decreased likelihood of developing cirrhosis and its complications, including liver cancer, and a prolonged survival.
Insulin resistance is the diminished ability of cells to respond to the action of insulin in transporting glucose (sugar) from the bloodstream into muscle and other tissues. Causes of insulin can include conditions such as stress, obesity, metabolic syndrome, and steroid use. Some of the risk factors for insulin resistance include fatty liver, heart disease, strokes, peripheral vascular disease, high cholesterol, and smoking. Treatment for insulin resistance are lifestyle changes and if necessary, medication.
The main features of metabolic syndrome include insulin resistance, hypertension (high blood pressure), cholesterol abnormalities, and an increased risk for clotting. Patients are most often overweight or obese. Lifestyle modification such as the Mediterranean diet, exercise, and quitting smoking are the preferred treatment of metabolic syndrome.
The liver is the largest solid organ in the body, and is actually an gland. The liver has a wide variety of critical functions such as manufacturing proteins and metabolizing fats and carbohydrates. The liver also eliminates harmful biochemical waste products from the body (alcohol, drugs, toxins). The liver secretes bile that aids in digestion. Examples of diseases of the liver include cirrhosis, hepatitis, cancer, and fatty liver. Symptoms of liver disease include bleeding, easy bruising, edema, fatigue, and jaundice.
Digestion is the complex process of turning food you eat into the energy you need to survive. The digestive process also involves creating waste to be eliminated, and is made of a series of muscles that coordinate the movement of food.
Reye's syndrome (RS, or Reye syndrome) is a sudden, sometimes fatal, disease of the brain with degeneration of the liver. Reye syndrome occurs in children and comes after the chickenpox or an influenza-type illness, is also associated with taking medications containing aspirin. Symptoms include vomiting, listlessness, irritability or combativeness, confusion, delirium, delusions, convulsions, and loss of consciousness. Treatment depends on early diagnosis and focuses on protecting the brain against irreversible damage by reducing brain swelling, reversing the metabolic injury, preventing complications in the lungs, and anticipating cardiac arrest.
Fast food consumption and lack of exercise are just a couple of causes of childhood obesity. Health effects of childhood obesity include type 2 diabetes, heart attack, stroke, high cholesterol, asthma, sleep apnea, gallstones, fatty liver disease, GERD, depression, and eating disorders.
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