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 early identification of
severe liver scarring, or cirrhosis, in NASH patients is of clinical importance
because of the prognostic (outcome) information it conveys. This fact has led to
several studies attempting to identify factors that predict severe liver
scarring in patients with NASH and/or obesity. These studies found that patients
at risk for severe scarring are most often age 50 or older, significantly obese
(BMI greater than 30 kg/m2), and have DM2. Also, they often show an increase in
liver enzymes (AST greater than ALT) despite the absence of alcohol use.
As
already mentioned, some iron deposits in the liver (iron overload) may be
associated with NAFLD or NASH. This appears to be more common at the stage of
severe, irreversible liver scarring (cirrhosis). Testing for serum iron markers,
however, turns out to be of little use in predicting any degree of liver
scarring (fibrosis). Moreover, the predictive role of genetic markers (HFE mutations) of
hemochromatosis (hereditary iron overload) appears questionable.
In order to diagnose
NASH with precision and characterize its severity, there is still no substitute
for performing a liver biopsy. To date, however, no consensus exists for a
precise microscopic (pathological) definition of NASH or for a system to grade
its severity.
The initial descriptions defined NASH, as its name would suggest, as the
association of a fatty liver and inflammation, regardless of the presence of
associated liver abnormalities. Such abnormalities can include destroyed liver
cells (hepatocellular necrosis), scarring in different areas of the liver
(sinusoidal or portal fibrosis), abnormal proteins (Mallory bodies) that deposit
inside the liver cells, presumably due to peroxidation, and complex sugars that
deposit in the nuclei of the liver cells (glycogenated nuclei, often seen in
diabetes).
So, the initial studies on NASH included patients with simple criteria (just
fatty liver and inflammation) for the diagnosis. Later, it was suggested that a
fatty liver with inflammation alone (steatohepatitis) was not specific and that
some degree of liver cell death (steatonecrosis) was required to diagnose NASH.
The idea was that only a fatty liver with accompanying inflammation along with
liver cell death represented significant disease, based on the biochemical
findings and the potential to form cirrhosis.
Given these uncertainties as to what is or is not NASH, specialists in the
field are now suggesting that a more descriptive approach be used. The trend is
now to use a simple criterion (fatty liver) to establish the diagnosis of NAFLD,
and then grade the severity of the disease according to inflammation,
destruction of liver cells, scarring, and abnormal liver proteins.
Still, specialists do not agree as to when a liver biopsy should be
performed. Since, as will be discussed below, no specific treatment is available
for NAFLD or NASH, the result of a biopsy would not impact the patient's
treatment. In other words, if an individual is obese and/or diabetic, he or she
will be encouraged to lose weight by diet and exercise, regardless of the biopsy
result.
On the other hand, it may be important to know whether an individual has
severe NASH, especially if she or he is young. Severe NASH would indicate that
the risk of developing cirrhosis later on is high. Therefore, a liver biopsy can
provide important information about outcome (prognosis). It also can exclude the
presence of other liver diseases. In research protocols, a liver biopsy may be
required to qualify a patient for an investigational drug. Otherwise, the
decision as to whether or not to biopsy the liver to diagnosis NASH in clinical
practice should be made on a case-by-case basis.
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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