Liver diseases which need liver transplant
Basically a liver transplant may be recommended for:
1. Birth defects of the liver or bile ducts (such as biliary atresia)
2. Hepatic vein clot (thrombosis)
3. Liver damage (such as cirrhosis or primary biliary cirrhosis)
4. Long-term active infection (hepatitis)
5. Metabolic disorders associated with liver failure (such as Wilson's disease)
Thus, I focus on the diseases which its treatment mentions about liver transplant and then I look up
for its population. By that, we can possibly know how big and where the market is.
1. Biliary atresia:
Biliary atresia is characterized by obliteration or discontinuity of the extrahepatic biliary system,
resulting in obstruction to bile flow. The disorder represents the most common surgically treatable
cause of cholestasis encountered during the newborn period. If not surgically corrected, secondary
biliary cirrhosis invariably results. Patients with biliary atresia can be subdivided into 2 distinct groups:
those with isolated biliary atresia (postnatal form), which accounts for 65-90% of cases, and patients
with associated situs inversus or polysplenia/asplenia with or without other congenital anomalies
(fetal/embryonic form), comprising 10-35% of cases.
Biliary atresia is a serious but rare disease of the liver that affects newborn infants. It occurs in about
one in 10,000 children and is more common in girls than in boys and in Asian and African-American
newborns than in Caucasian newborns. The cause of biliary atresia is not known, and treatments are
only partially successful. Biliary atresia is the most common reason for liver transplantation in children
in the United States and most of the Western world.
The liver damage incurred from biliary atresia is caused by injury and loss (atresia) of the bile ducts
that are responsible for draining bile from the liver. Bile is made by the liver and passes through the bile
ducts and into the intestines where it helps digest food, fats, and cholesterol. The loss of bile ducts
causes bile to remain in the liver. When bile builds up it can damage the liver, causing scarring and loss
of liver tissue. Eventually the liver will not be able to work properly and cirrhosis will occur. Once the
liver fails, a liver transplant becomes necessary. Biliary atresia can lead to liver failure and the need for
liver transplant within the first 1 to 2 years of life.
In the United States, individual studies suggest an overall incidence of 1 per 10,000 - 15,000 live
births. And of international, the incidence of biliary atresia is highest in Asian populations, and it may
be more common in Chinese infants compared with Japanese infants.
2. Cirrhosis:
In adults, the most common reason for liver transplantation is cirrhosis.
Cirrhosis represents the final common histologic pathway for a wide variety of chronic liver diseases.
The term cirrhosis was first introduced by Laennec in 1826. It is derived from the Greek term scirrhus
and is used to describe the orange or tawny surface of the liver seen at autopsy.
Many forms of liver injury are marked by fibrosis. Fibrosis is defined as an excess deposition of the
components of extracellular matrix (ie, collagens, glycoproteins, proteoglycans) within the liver. This
response to liver injury potentially is reversible. In contrast, in most patients, cirrhosis is not a reversible
process.
Cirrhosis is defined histologically as a diffuse hepatic process characterized by fibrosis and the
conversion of normal liver architecture into structurally abnormal nodules. The progression of liver
injury to cirrhosis may occur over weeks to years. Indeed, patients with hepatitis C may have chronic
hepatitis for as long as 40 years before progressing to cirrhosis.
Often a poor correlation exists between histologic findings and the clinical picture. Some patients
with cirrhosis are completely asymptomatic and have a reasonably normal life expectancy. Other
individuals have a multitude of the most severe symptoms of end-stage liver disease and have a limited
chance for survival. Common signs and symptoms may stem from decreased hepatic synthetic function
(eg, coagulopathy), decreased detoxification capabilities of the liver (eg, hepatic encephalopathy), or
portal hypertension (eg, variceal bleeding).
Chronic liver disease and cirrhosis result in about 35,000 deaths each year in the United States.
Cirrhosis is the ninth leading cause of death in the United States and is responsible for 1.2% of all US
deaths. Many patients die from the disease in their fifth or sixth decade of life. Each year, 2000
additional deaths are attributed to fulminant hepatic failure (FHF). FHF may be caused viral hepatitis (eg,
hepatitis A and B), drugs (eg, acetaminophen), toxins (eg, Amanita phalloides, the yellow death-cap
mushroom), autoimmune hepatitis, Wilson disease, and a variety of less common etiologies.
Cryptogenic causes are responsible for one third of fulminant cases. Patients with the syndrome of FHF
have a 50-80% mortality rate unless they are salvaged by liver transplantation. The condition affects
men slightly more often than women.
In the United States, though the statistics from 1976-1980 is used, the National Digestive Diseases
Information Clearinghouse (NDDIC) quotes a prevalence of 400,000 persons in the United States who
have cirrhosis or some other type of chronic liver disease. And talking about the incurrence worldwidely,
cirrhosis is among the leading causes of death, and a disturbing epidemic of hepatitis has contributed
to a rising incidence of HCCA, a serious complication of chronic hepatitis and cirrhosis. Using official
death certification data from 1955-1990, derived from the World Health Organization (WHO) database,
an analysis was made of cirrhosis-related trends in mortality rates in 38 countries. The study found that
the highest reported death rates occurred in Chile and Mexico (60 deaths per 100,000 males; 15 deaths
per 100,000 females) during the late 1980s.
In Canada, the United States, and Latin America, mortality rates from cirrhosis ranged from 5-17
deaths per 100,000 for males and 3-5 deaths per 100,000 for females over the same calendar period,
with similar trends. In 1990, mortality rates in Japan were 13.6 deaths per 100,000 males. Appreciable
downward trends were observed in Hong Kong and Singapore, whereas Thailand's cirrhosis-related
mortality rate increased.
3. Hepatitis B:
Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus. It is a major
global health problem and the most serious type of viral hepatitis. It can cause chronic liver disease and
puts people at high risk of death from cirrhosis of the liver and liver cancer. Worldwide, an estimated
two billion people have been infected with the hepatitis B virus (HBV), and more than 350 million have
chronic (long-term) liver infections.
A vaccine against hepatitis B has been available since 1982. Hepatitis B vaccine is 95% effective in
preventing HBV infection and its chronic consequences, and is the first vaccine against a major human
cancer.
About 2 billion people worldwide have been infected with the virus and about 350 million live with
chronic infection. An estimated 600 000 persons die each year due to the acute or chronic
consequences of hepatitis B. About 25% of adults who become chronically infected during childhood
later die from liver cancer or cirrhosis (scarring of the liver) caused by the chronic infection.
In the United States, an estimated 200,000 new cases of hepatitis B virus (HBV) occur
annually, and 1-1.25 million people are carriers. The prevalence of the disease is higher among blacks
and persons of Hispanic or Asian origin. In addition, a higher carrier rate exists among certain
subpopulations such as the Alaskan Eskimos, Asian Pacific islanders, and Australian aborigines. Hepatitis
B virus (HBV) accounts for 5-10% of cases of chronic end stage liver disease and 10-15% of cases of HCC.
The hepatitis B virus (HBV) carrier rate variation is 1-20% worldwide. Basically, the prevalence of the
disease in different geographic areas can be characterized as follows:
1. Low-prevalence areas (rate of 0.1-2%) include Canada, Western Europe, Australia, and New Zealand.
2. Intermediate-prevalence areas (rate of 3-5%) include eastern and northern Europe, Japan, the
Mediterranean basin, the Middle East, Latin and South America, and central Asia.
3. High-prevalence areas (rate of 10-20%) include China, Indonesia, sub-Saharan Africa, the Pacific
Islands, and Southeast Asia. Vaccination programs implemented in highly endemic areas such as
Taiwan seem to change the prevalence of hepatitis B virus (HBV) infection. In Taiwan, seroprevalence
declined from 10% in 1984 (before vaccination programs) to less than 1% in 1994 after the
implementation of vaccination programs, and the incidence of HCC declined from 0.52% to 0.13%.
Hepatitis B is endemic in China and other parts of Asia. Most people in the region become infected
with HBV during childhood. In these regions, 8% to 10% of the adult population are chronically
infected. Liver cancer caused by HBV is among the first three causes of death from cancer in men,
and a major cause of cancer in women. High rates of chronic infections are also found in the Amazon
and the southern parts of eastern and central Europe. In the Middle East and Indian sub continent,
an estimated 2% to 5% of the general population is chronically infected. Less than 1% of the
population in western Europe and North American is chronically infected.
4. Hepatocellular carcinoma:
Only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer
cannot be completely removed, the disease is usually deadly within 3 to 6 months.
HCC is one of the most common tumors worldwide. The epidemiology of HCC exhibits two main
patterns, one in North America and Western Europe and another in non-Western countries, such as
those in sub-Saharan Africa, central and Southeast Asia, and the Amazon basin. Males are affected
more than females usually and it is most common between the age of 30 to 50. Hepatocellular
carcinoma causes 662,000 deaths worldwide per year, about half of them in China.
In North America and Western Europe, most malignant tumors of the liver discovered in Western
patients are metastases (spread) from tumors elsewhere. In the West, HCC is generally seen as a rare
cancer, normally of those with pre-existing liver disease. It is often detected by ultrasound screening,
and so can be discovered by health-care facilities much earlier than in developing regions such as
Sub-Saharan Africa.
And in Non-Western Countries, such as sub-Saharan Africa and Southeast Asia, HCC is the most
common cancer, generally affecting men more than women, and with an age of onset between late
teens and 30s. This variability is in part due to the different patterns of hepatitis B transmission in
different populations - infection at or around birth predispose to earlier cancers than if people are
infected later. The time between hepatitis B infection and development into HCC can be years, even
decades, but from diagnosis of HCC to death the average survival period is only 5.9 months according to
one Chinese study during the 1970-80s, or 3 months (median survival time) in Sub-Saharan Africa
according to Manson's textbook of tropical diseases. HCC is one of the deadliest cancers in China. Food
infected with Aspergillus flavus (especially peanuts and corns stored during prolonged wet seasons)
which produces aflatoxin poses another risk factor for HCC.
5. Primary biliary cirrhosis:
Primary biliary cirrhosis is a liver disease that slowly destroys the bile ducts in the liver. When the
ducts are damaged, bile builds up in the liver and damages liver tissue. Over time, the disease can cause
cirrhosis and may make the liver stop working. The etiology is unknown, although it is presumed to be
autoimmune in nature. The disease affects women more often than men, and usually occurs between
the ages of 30 and 60 years.
In the United States, the incidence of the disease has been estimated as 4.5 cases for women and 0.7
cases for men per 100,000 population. And in the world, the disease is reported to be more prevalent in
the United Kingdom and Scandinavia. The prevalence of the disease has been estimated as 24 cases per
100,000 population in Newcastle, United Kingdom; 12.9 cases per 100,000 population in Northeast
England; 1.9 cases per 100,000 population in Victoria, Australia; 2.2 cases per 100,000 population in
Ontario, Canada; 2.7 cases per 100,000 population in Estonia; 9.2 cases per 100,000 in Malmo, Sweden;
and 15.1 cases per 100,000 population in Umea, Sweden.
6. Sclerosing cholangitis:
Primary sclerosing cholangitis (PSC) is a chronic liver disease caused by progressive inflammation and
scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can
ultimately lead to liver cirrhosis and liver failure. The underlying cause of the inflammation is believed
to be autoimmunity. It is more prevalent in men than in women. The disease normally starts from age
30 to 60, though may begin in childhood. PSC progresses slowly, so the disease can be active for a long
time before it is noticed or diagnosed. The definitive treatment is liver transplantation.
In the United States, the prevalence is estimated at 6.3 cases per 100,000 population. Western
Europe is thought to have approximately the same prevalence rate as the United States, though
Scandinavian countries report a somewhat higher rate. In many developing countries with limited
access to advanced health care, the prevalence of PSC is probably underestimated, since the diagnosis
cannot be confirmed without ERCP (endoscopic retrograde cholangiopancreatography).
Liver transplantation is the only proven long-term treatment of PSC. Indications for transplantation
include recurrent bacterial cholangitis, jaundice refractory to medical and endoscopic treatment,
decompensated cirrhosis and complications of portal hypertension. In one series, 1, 2, and 5 year
survival following liver transplantation for PSC was 90%, 86% and 85% respectively.
7. Wilson's disease:
Wilson's disease causes the body to retain copper. The liver of a person who has Wilson's disease
does not release copper into bile as it should. The copper builds up in the liver and injures liver tissue.
Eventually, the damage causes the liver to release the copper directly into the bloodstream, which
carries the copper throughout the body. The copper buildup leads to damage in the kidneys, brain, and
eyes. If not treated, Wilson's disease can cause severe brain damage, liver failure, and death.
Wilson's disease is hereditary. Symptoms usually appear between the ages of 6 and 20 years, but can
begin as late as age 40. The disease is treated with lifelong use of D-penicillamine or trientine
hydrochloride, drugs that help remove copper from tissue, or zinc acetate, which stops the intestines
from absorbing copper and promotes copper excretion. Patients will also need to take vitamin B6 and
follow a low-copper diet, which means avoiding mushrooms, nuts, chocolate, dried fruit, liver, and
shellfish. Liver transplantation is the only cure for Wilson's disease, but is used only in particular
scenarios because of the numerous risks and complications associated with the procedure. It is used
mainly in patients with fulminant liver failure who fail to respond to medical treatment, or in patients
with advanced chronic liver disease. Liver transplantation is avoided in severe neuropsychiatric illness,
in which its benefit has not been demonstrated.
In the United States, the carrier frequency is 1 per 90 individuals. The prevalence of Wilson disease is
1 per 30,000 individuals. The worldwide incidence rate is 10-30 million cases, with increased rates in
areas of consanguinity. The heterozygote carrier rate is 1 case per 100 persons, corresponding to a gene
frequency varying between 0.3-0.7%. The frequency ranges worldwide from 1 case per 30,000
population in Japan to 1 case per 100,000 population in Australia. The increased frequency in certain
countries is due to high rates of consanguinity.
8. Budd-Chiari syndrome:
In medicine (gastroenterology and hepatology), Budd-Chiari syndrome is the clinical picture caused
by occlusion of the hepatic veins. The syndrome can be fulminant, acute, chronic, or asymptomatic. It
occurs in 1 out of 100,000 individuals and is more common in females. Some 10-20% also have
obstruction of the portal vein.
A minority of patients can be treated medically with sodium restriction, diuretics to control ascites,
anticoagulants such as heparin and warfarin, and general symptomatic management. The majority of
patients require further intervention. Milder forms of Budd-Chiari may be treated with surgical shunts
to divert blood flow around the obstruction or the liver itself. The transjugular intrahepatic
portosystemic shunt (TIPS) is similar to a surgical shunt. It accomplishes the same goal but has a lower
procedure-related mortality, which has led to a growth in its popularity. Liver transplantation is an
effective treatment for Budd-Chiari. It is generally reserved for patients with fulminant hepatic failure,
failure of shunts, or progression of cirrhosis that reduces the life expectancy to 1 year. Long-term
survival after transplantation ranges from 69-87%. The most common complications of transplant
include rejection, arterial or venous thromboses, and bleeding due to anticoagulation. Up to 10% of
patients may have a recurrence of Budd-Chiari syndrome after the transplant.
The disease occurs in 1 out of 100,000 individuals and is more common in females. Some 10-20%
also have obstruction of the portal vein. Budd-Chiari syndrome is extremely rare, and the incidence is
not well reported in the literature; however, membranous (or congenital) forms of Budd-Chiari
syndrome are the most common cause of Budd-Chiari syndrome worldwide, particularly in Asia. One
study in Sweden reports an incidence of about 1 case per million population per year.
Still other liver diseases or medication-caused liver failure or trauma-caused liver failure that are severe
enough and need a liver transplant to maintain patients’ living. However, regarding so small amount of
available livers and still the immune-problem afterwards, If we can develop a technology that can produce
every needy whose own liver, we can make life quality much better.