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.
The exact cause of NASH is still unknown. Strong
evidence, however, supports the concept that the process common to all stages of
primary fatty liver disease (NAFLD) is insulin-resistance. A number of other
factors may be involved as well in causing NAFLD and NASH and in progressing
through the stages of NAFLD.
Insulin
resistance is a state wherein normal signaling pathways that convey biochemical
messages between insulin and its target cells are disrupted. As a result, the
insulin does not exert its normal or full effects. Put another way, the body is
resistant to the effects of insulin.
What does insulin normally do? Well, the pancreas secretes varying amounts of
insulin during the day in response to food intake. Insulin works to maintain
blood sugar (glucose) at normal levels. Thus, insulin prevents blood glucose
from becoming too elevated. If insulin does not work in this way, high blood
sugars and diabetes would occur. Insulin is a hormone that acts on the receptors
of cells to trigger the complex biochemical reactions that control blood sugar.
The cells targeted by insulin are mainly the fat cells (adipocytes), muscle
cells (striated myocytes), and the liver cells (hepatocytes).
In insulin resistance, a defect in these insulin receptors causes insulin to
be less effective than it normally would be. Thus, the pancreas must produce
more insulin than normal in order to maintain normal blood glucose levels.
Initially in this process, the increased insulin levels are sufficient to
maintain normal blood glucose. In these patients, however, although the blood
glucose is normal, the condition of being overweight or obesity are still clues
that they are insulin resistant. At this juncture, only sophisticated blood
tests (such as the euglycemic clamp test) can detect insulin resistance at the
biochemical level.
As the insulin resistance progresses, even very high levels of insulin become
ineffective. This degree of insulin resistance leads to elevated blood sugars
and diabetes mellitus, type 2 (DM2). DM2 is usually managed by diet, exercise,
and medication (see treatment section) that increases insulin sensitivity (the
opposite of insulin resistance). If the process proceeds unchecked, however, the
pancreas can no longer secrete insulin. Then, the patients require insulin
injections, which condition is referred to as insulin-dependent DM2. Insulin
resistance and DM2 are very different from diabetes mellitus type 1 (DM1), which
is also called juvenile-onset diabetes. In DM1, a defect in insulin secretion
occurs early on in life and requires immediate and ongoing treatment with
insulin.
Insulin resistance can also surface early in life when it is due to
congenital genetic abnormalities in the insulin receptors. More often, however,
as described above, it becomes evident later in life as a result of acquired
obesity. A sedentary lifestyle and a diet rich in carbohydrates, sugars, and
fats also promote insulin resistance. Moreover, the degree of insulin resistance
increases with a greater BMI and abdominal fat (that is, big waists). Elevated
lipids (LDL cholesterol and triglycerides) are also associated with insulin
resistance.
Insulin resistance leads to changes in the processing (metabolism) of sugar
(glucose) and fat (lipid) in the liver, muscles, and fat cells (adipocytes). The
result of these changes is an increased uptake (infiltration and accumulation)
of triglyceride fat into the liver cells. The triglycerides are absorbed from
the diet as well as channeled from abdominal fat and peripheral muscles. These
large quantities of triglyceride fat are then stored in tiny sacs (vesicles)
inside the liver cells.
So, this is how a fatty liver develops. In fact, it has been shown that as
the BMI increases, so does the amount of fat in the liver.
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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