Dr. Lee was born in Shanghai, China, and received his college and medical training in the United States. He is fluent in English and three Chinese dialects. He graduated with chemistry departmental honors from Harvey Mudd College. He was appointed president of AOA society at UCLA School of Medicine. He underwent internal medicine residency and gastroenterology fellowship training at Cedars Sinai Medical Center.
Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.
Alcohol is a very common
cause of cirrhosis, particularly in the Western world. The development of
cirrhosis depends upon the amount and regularity of alcohol intake. Chronic,
high levels of alcohol consumption injure liver cells. Thirty percent of
individuals who drink daily at least eight to sixteen ounces of hard liquor or
the equivalent for fifteen or more years will develop cirrhosis. Alcohol
causes a range of liver diseases; from simple and
uncomplicated fatty liver
(steatosis), to the more serious fatty liver with
inflammation (steatohepatitis or
alcoholic hepatitis), to cirrhosis.
Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver diseases that, like
alcoholic liver disease, ranges from simple steatosis, to nonalcoholic
steatohepatitis (NASH), to cirrhosis. All stages of NAFLD
have in common the
accumulation of fat in liver cells. The term nonalcoholic is used because
NAFLD occurs in individuals who do not consume excessive amounts of alcohol,
yet, in many respects, the microscopic picture of NAFLD is similar to what can
be seen in liver disease that is due to excessive alcohol. NAFLD is associated
with a condition called insulin resistance, which, in turn, is associated with
the metabolic syndrome and diabetes mellitus type 2. Obesity is the most
important cause of insulin resistance, metabolic syndrome, and type 2
diabetes. NAFLD is the most common liver disease in the United States and is
responsible for 24% of all liver disease. In fact, the number of livers that are
transplanted for NAFLD-related cirrhosis is on the rise. Public health officials
are worried that the current epidemic of obesity will
dramatically increase the development of NAFLD and cirrhosis in the
Cryptogenic cirrhosis(cirrhosis due to unidentified causes) is a common
reason for liver transplantation. It is termed cryptogenic cirrhosis because
for many years doctors have been unable to explain why a proportion of
patients developed cirrhosis. Doctors now believe that cryptogenic cirrhosis
is due to NASH (nonalcoholic steatohepatitis) caused by long standing obesity,
type 2 diabetes, and insulin resistance. The fat in the liver of patients with
NASH is believed to disappear with the onset of cirrhosis, and this has made it
difficult for doctors to make the connection between NASH and cryptogenic
cirrhosis for a long time. One important clue that NASH leads to cryptogenic
cirrhosis is the finding of a high occurrence of NASH in the new livers of
patients undergoing liver transplant for
cryptogenic cirrhosis. Finally, a study from France suggests that patients
with NASH have a similar risk of developing cirrhosis as patients with long
standing infection with hepatitis C virus. (See discussion that follows.)
However, the progression to cirrhosis from NASH is thought to be slow and the
diagnosis of cirrhosis typically is made in patients
in their sixties.
Chronic viral hepatitis
is a condition where hepatitis B or hepatitis C virus infects the liver for
years. Most patients with viral hepatitis will
not develop chronic hepatitis and cirrhosis. For example, the majority of
patients infected with hepatitis A recover completely within weeks, without
developing chronic infection. In contrast, some patients infected with
hepatitis B virus and most
patients infected with hepatitis C virus develop chronic hepatitis, which, in
turn, causes progressive liver damage and leads to cirrhosis, and, sometimes,
Inherited (genetic) disorders result in the accumulation of toxic substances in the liver
which lead to tissue damage and cirrhosis. Examples include the abnormal
accumulation of iron (hemochromatosis) or copper (Wilson's disease). In
hemochromatosis, patients inherit a tendency to absorb an excessive amount of
iron from food. Over time, iron accumulation in different organs throughout
the body causes cirrhosis, arthritis, heart muscle damage leading to heart failure, and
testicular dysfunction causing loss of sexual drive. Treatment is aimed at
preventing damage to organs by removing iron from the body through bloodletting
(removing blood). In Wilson disease, there is an inherited abnormality in one of
the proteins that controls copper in the body. Over time, copper accumulates in
the liver, eyes, and brain. Cirrhosis, tremor, psychiatric disturbances and
difficulties occur if the condition is not treated early. Treatment is with
oral medication that increases the amount of copper that is
eliminated from the body in the urine.
Primary biliary cirrhosis
(PBC) is a liver disease caused by an abnormality of the immune system
that is found predominantly in women. The abnormal immunity in PBC causes
chronic inflammation and destruction of the small bile ducts within the liver.
The bile ducts are passages within the liver through which bile travels to the
intestine. Bile is a fluid produced by the liver that contains substances
required for digestion and absorption of fat in the intestine, as well as
other compounds that are waste products, such as the pigment bilirubin.
(Bilirubin is produced by the breakdown of hemoglobin from old red blood
cells.). Along with the gallbladder, the bile ducts make up the biliary tract. In PBC, the destruction of the
small bile ducts blocks the normal flow of bile into the intestine. As the
inflammation continues to destroy more of the bile ducts, it also spreads to
destroy nearby liver cells. As the destruction of the hepatocytes proceeds,
scar tissue (fibrosis) forms and spreads throughout the areas of destruction.
The combined effects of progressive inflammation, scarring, and the toxic
effects of accumulating waste products culminates in
cholangitis (PSC) is an uncommon disease found frequently in patients with
ulcerative colitis . In PSC, the large bile ducts
outside of the liver become inflamed, narrowed, and obstructed. Obstruction to
the flow of bile leads to infections of the bile ducts and jaundice and
eventually causes cirrhosis. In some patients, injury to the bile ducts
(usually as a result of surgery) also can cause obstruction and cirrhosis
of the liver.
Autoimmune hepatitis is a liver disease caused by an abnormality of the immune
system that is found more commonly in women. The abnormal immune activity in
autoimmune hepatitis causes progressive inflammation and destruction of liver
cells (hepatocytes), leading ultimately to cirrhosis.
Infants can be born without bile ducts (biliary atresia)
and ultimately develop cirrhosis. Other infants are born lacking vital enzymes
for controlling sugars that leads to the accumulation of sugars and cirrhosis.
On rare occasions, the absence of a specific enzyme can cause cirrhosis and scarring of
the lung (alpha 1 antitrypsin deficiency).
Less common causes of
cirrhosis include unusual reactions to some drugs and prolonged exposure to
toxins, as well as chronic heart failure (cardiac
cirrhosis). In certain parts of the world (particularly Northern
Africa), infection of the liver with a parasite (schistosomiasis) is the most common
cause of liver disease and cirrhosis.