It is a disease in which the body's
immune system attacks liver cells. This causes the
liver to become inflamed (hepatitis). About 70 percent
of those with autoimmune hepatitis are women, most
between the ages of 15 and 40. The disease may start
at any age, but is most common in adolescence or early
Autoimmune hepatitis or autoimmune chronic hepatitis
is a progressive inflammation of the liver that has
been identified by a number of different names, including
autoimmune chronic active hepatitis (CAH), idiopathic
chronic active hepatitis, and lupoid hepatitis.
Autoimmune hepatitis was first described in 1950 as
a disease of young women, associated with increased
gamma globulin in the blood and chronic hepatitis
on liver biopsy. The presence of antinuclear antibodies
(ANA) and the resemblance of some symptoms to "systemic
lupus erythematosus" (SLE) led to the label "lupoid
hepatitis." It later became evident that this
disease was not related to SLE. The disease is now
called autoimmune hepatitis.
The disease is usually quite serious and, if not treated,
gets worse over time. It's usually chronic, meaning
it can last for years, and can lead to cirrhosis (scarring
and hardening) of the liver and eventually liver failure.
Autoimmune hepatitis is classified as either type
I or II. It occurs at any age and is more common among
women than men. About half of those with type I have
other autoimmune disorders, such as type 1 diabetes,
proliferative glomerulonephritis, thyroiditis, Graves'
disease, Sjögren's syndrome, autoimmune anemia,
and ulcerative colitis. Type II autoimmune hepatitis
is less common, typically affecting girls ages 2 to
14, although adults can have it too.
The reason for this inflammation is not certain, but
it is associated with an abnormality of the body's
immune system and is often related to the production
of antibodies that can be detected by blood tests.
Researchers think a genetic factor may predispose
some people to autoimmune diseases.
The most common symptoms of autoimmune
hepatitis are fatigue, abdominal discomfort, aching
joints, itching, jaundice, enlarged liver, and spider
angiomas (tumors) on the skin. Patients may also have
complications of more advanced chronic hepatitis with
cirrhosis, such as ascites (abdominal fluid) or mental
confusion called encephalopathy.
Blood tests identify antinuclear antibodies (ANA)
or smooth muscle antibodies (SMA) in the majority
of patients (60 percent). More than 80 percent of
affected individuals have increased gamma globulin
in the blood. Some patients have other autoimmune
disorders such as thyroiditis, ulcerative colitis,
diabetes mellitus, vitiligo (patchy loss of skin pigmentation),
or Sjogren's syndrome (a syndrome that causes dry
eyes and dry mouth).
A liver biopsy is important to confirm the diagnosis
and provide a prognosis. Liver biopsy may show mild
chronic active hepatitis, more advanced chronic active
hepatitis with scarring (fibrosis), or a fully developed
The treatment of autoimmune hepatitis is immunosuppression
with prednisone alone or prednisone and azathioprine.
This medical therapy has been shown to decrease symptoms,
improve liver tests, and prolong survival in the majority
of patients. Therapy is usually begun with prednisone
30 to 40 mg per day and then this dosage is reduced
after a response is achieved.
The standard dosage used in the majority of patients
is prednisone 10-15 mg per day, either alone or with
azathioprine 50 mg per day. Higher doses of prednisone
given long-term are associated with an increase in
serious side effects including hypertension, diabetes,
peptic ulcer, bone thinning, and cataracts. Lower
doses of prednisone may be used when combined with
The goal of treatment of autoimmune hepatitis is to
cure or control the disease. In two thirds to three
quarters of the patients, liver tests fall to within
the normal range. Long-term follow-up studies show
that autoimmune hepatitis appears more often to be
a controllable rather than a curable disease, because
the majority of patients relapse within six months
after therapy is ended. Therefore, most patients need
long-term maintenance therapy.
Not all patients with autoimmune hepatitis respond
to prednisone treatment. Approximately 15-20 percent
of patients with severe disease continue to deteriorate
despite initiation of appropriate therapy. This is
most common in patients with advanced cirrhosis on
initial liver biopsy. Such patients are unlikely to
respond to further medical therapy, and liver transplantation
should be considered.
Life expectancy and
Quality of Life
The 10-year survival rate in untreated patients is
approximately 10 percent.
This is the commonest liver disease
in India. It is caused by excessive consumption of
alcohol generally beyond safe dose. It is a preventable
disease. The three primary types of alcohol-induced
liver injuries are fatty liver, alcoholic hepatitis
and liver cirrhosis.
This is the commonest alcohol induced liver injury.
Fatty liver is excessive accumulation of fat inside
the liver cells. The liver is enlarged, causing upper
abdominal discomfort on the right side. Liver tests
are generally normal. This can be observed on ultrasonography
Alcoholic hepatitis is an inflammation
of the liver, accompanied by the destruction of individual
liver cells and scarring. Symptoms may include fever,
jaundice, and enlarged, tender liver and spider-like
veins in the skin. If consumption is not controlled
it leads to cirrhosis which is end-stage liver disease.
Severe alcoholic is associated with significant mortality.
Alcoholic cirrhosis is the permanent
destruction of normal liver tissue, leaving non-functioning
scar tissue. The severity of liver disease depends
on duration and quantity of alcohol the patient consumes.
Pain in right upper side of abdomen, fever, yellowing
of the skin and eyes, spider-like veins in the skin
are common features of alcohol related liver damage.
Some other serious symptoms may include
hemetemesis i.e. vomiting of blood along with passage
of tarry black stools; lump or heaviness in left upper
side of abdomen because of enlarged spleen, ascites
i.e. fluid build-up in the abdominal cavity leading
to abdominal distension along with swelling on feet,
kidney failure and in more severe situation confusion,
drowsiness, stupor, coma can be seen.
Consumption of alcohol also accelerates preexisting
damage due to other causes like hepatitis C infection.
A complete medical history and physical
examination are required along with few other tests.
Liver function tests include a series
of special blood tests that can determine liver function.
Abdominal sonography is useful to detect changes in
liver, spleen, fluid in abdomen. Gastroscopy is an
endoscopic procedure to look for enlarged veins in
esophagus and stomach due liver damage and it also
helps to treat in the form of injection or rubber-band
application on bleeding vessels.
If patient has never bled, some
medicines can be given to reduce the pressure and
there by prevent the bleeding from these enlarged
vessels. This procedure is life saving when there
is severe hemetemesis i.e. passage of blood in vomiting
or in stool due to bleeding from these esophageal
abstinence from alcohol.
nutrition including anti-oxidants to reduce liver
medicines to reduce the fluid in abdomen by increasing
the urine output.
another drug to reduce effects on to kidneys in patients
with alcoholic hepatitis.
another drug to reduce effects on to kidneys in patients
with alcoholic hepatitis.
intervention for bloody vomiting.
to prevent bleeding from esophageal vessels.
Differentiation between alcoholic hepatitis and alcoholic cirrhosis
HOW TO DIFFERENTIATE ALCOHOLIC HEPATITIS FROM ALCOHOLIC CIRRHOSIS AND IS THE DIFFERENTIATION IMPORTANT?
The association of alcohol abuse and liver damage is known since the times of ancient Greeks and is also recognised in Ayurveda. The clinical spectrum of alcoholic liver injury varies from asymptomatic hepatomegaly to profound hepatocellular failure with portal hypertension. The clinical picture tends to be more florid in individuals with more advanced liver injury. Alcoholic liver injury appears to progress from fatty changes through alcoholic hepatitis to cirrhosis. Majority of the individuals who abuse alcohol will develop fatty changes in their liver at some stage of their drinking career. However only 20% of such individuals will develop cirrhosis. The apparent predisposition of certain people to develop alcoholic cirrhosis is unknown. Fatty liver, though indicating a profound metabolic disturbance within the liver, is not necessarily harmful. Certainly, cirrhosis may develop in an alcoholic who has never had fatty change and isolated fatty change has not been shown to proceed directly to cirrhosis. Alcoholic hepatitis develops in only a proportion of drinkers even after decades of abuse and is assumed to be a precirrhotic lesion, although its natural history is not well understood. Thus in approximately 50% of individuals alcoholic hepatitis may persist for several years and in 10% of individuals the lesion may heal despite continued alcohol abuse. It has therefore been suggested that although alcoholic hepatitis may contribute, when present, to the evolution towards cirrhosis, it is not a sine qua non of such progression. Though most of the alcoholics may have a combination of alcoholic hepatitis and cirrhosis on biopsy and more or less similar clinical and biochemical features, there are certain features which may help in differentiating the two conditions as given in the Table 1 below.
Since alcoholic hepatitis is reversible and hepatic function improves over a period of time with abstinence, management consists predominantly of abstinence from alcohol and supportive care; whereas alcoholic cirrhosis once established is irreversible and hepatic function may not improve over time, management consists of abstinence from alcohol, treatment of complications and liver transplantation may be a viable option in carefully selected patients. Liver transplantation should not be done in patients with pure alcoholic hepatitis. Hence it is very essential to differentiate a patient having alcoholic from the one having alcoholic cirrhosis as the management and prognosis is different.
Differentiation between alcoholic hepatitis and alcoholic cirrhosis
|Patients with alcoholic hepatitis have been abusing alcohol till the time of presentation; they look more ill and being symptomatic present to a physician.
||Patients with alcoholic cirrhosis may not have abused alcohol for many years prior to presentation; most of them are well compensated, with only one-third being symptomatic.
|Jaundice is usually one of the most common symptom. Some common mode of presentations are: jaundice - 50% of the patients, ascites in 30 - 60% and splenomegaly - 15% of the patients.
||Ascites is usually the common symptom. Some common mode of presentations are: 40%, dilated abdominal wall veins - 60% and splenomegaly - 25% of the patients.
|Fever (even high grade) is seen in upto 50% of the subjects.
||High grade fever is not seen (unless there is superadded infection).
|Symptoms of variceal bleeding and hepatic encephalopathy are uncommon.
||Variceal bleeding and hepatic encephalopathy are quite common.
|Spider naevi and palmar erythema may be florid.8
||Spider naevi and palmar erythema though seen, may not be florid.
|Features of portal hypertension - Ascites, dilated abdominal wall veins, splenomegaly and oesophageal varices are not a prominent features of pure alcoholic hepatitis.
||Features of portal hypertension are a prominent feature of alcoholic cirrhosis
|Liver is very large and tender on palpation; its surface is smooth and consistency is soft to firm.
||Liver is mild to moderately enlarged or may not be palpable in advance cirrhosis and when palpable it is nontender, irregular with palpable nodules and firm in consistency.
|Arterial bruit may be heard over the liver area.
||Unless there is superadded hepatocellular Unless there is superadded hepatocellular
|Polymorphonuclear leucocytosis (upto) 20,000/mm3) is quite common.
||Polymorphonuclear leucocytosis though seen may not be as high as in alcoholic hepatitis.
|Platelet function is depressed, but there may not be thrombocytopenia. There is no evidence of hypersplenism.
||Both platelet function and number are reduced and there is evidence of hypersplenism.
|SGOT and SGPT are elevated upto 300 to 400 IU with SGOT/SGPT ratio > 2.
||SGOT and SGPT are usually normal.
|Highest levels of rise of gamma glutamyl transpeptidase, glutamate dehydrogenase and tumour necrosis factor are seen in alcoholic hepatitis.
||There is mild to moderate rise of gamma glutamyl transpeptidase and glutamate dehydrogenase in alcoholic cirrhosis.
|Most of the elevated enzymes fall back to normal level within 1 week of abstinence.
||No significant fall in enzyme levels are seen over a period of time, even if abstinent.
|Isotope liver scan may show total absence of radiotracer uptake by the hepatic parenchyma ("Medical hepatectomy") with avid uptake by the spleen and the bone marrow of vertebrae and the ribs. After a period of recovery, the liver scan may show normal tracer uptake.
||Isotope liver scan show inhomogeneous tracer distribution in the liver, with left lobe uptake greater than the right lobe, colloid shift to the spleen ("Hot spleen") and visualisation of the bone marrow of the vertebrae. Liver scan picture does not show improvement over time.
|Liver biopsy histology
||Liver biopsy histology
|Three obligatory features for the histologic diagnosis are -
||On liver biopsy the following features are seen-
ballooning degeneration of hepatocytes, with areas of necrosis.
inflammatory cell infiltrates, predominantly
|fibrosis, both pericellular (producing a lattice-like or chicken wire appearance) and perivenular (centrolobular).
|20% of alcoholics show features of hepatitis on 18.3% of alcoholics show features of cirrhosis (6.7%) or in combination with cirrhosis (13.4%).8 Alcoholic hepatitis rarely is seen as an isolated pathology on liver biopsy. On most occasions it is seen in combination with either fatty liver or cirrhosis.
||18.3% of alcoholics show features of cirrhosis on biopsy; 5% as only cirrhosis and 13.4% in combination with alcoholic hepatitis. Thus alcoholic cirrhosis may be the only pathology alcoholic cirrhosis may be the only pathology
|Alcoholic hepatitis is usually reversible on Alcoholic cirrhosis is generally considered to
||Alcoholic cirrhosis is generally considered to be an irreversible lesion once it is established
|Treatment consists of abstinence and proper nutritional support. Liver transplantation is not recommended at this stage.
||Apart from abstinence and treatment of complications, liver transplantation may be a viable option.
|Though high initial in hospital mortality of about 50%, long term prognosis of those who abstain from alcohol is very good.
||Though initial in hospital mortality may not be high (but depends on the mode of decompensation), long term prognosis is presentation and degree of hepatic dismal with nearly 50% 5 year mortality
|The Maddrey discrimination function is a simple equation in which the serum bilirubin and prothrombin time are used to indicate the presence of severe alcoholic hepatitis (4.6 x (PT in secs - control time) + serum bilirubin in mg/dl). A score greater than 32 indicates severe alcoholic hepatitis with poor prognosis.
||Child-Pugh score is used to determine the prognosis using the following parameters - ascites, encephalopathy, bilirubin, albumin and prothrombin time. Child class A has the best prognosis and child class C has the worst
Acute debauch, continued alcohol consumption
Probably a past drinker
|Ill patient (may be febrile)
Relatively well preserved (unless severely decompensated)
Presents usually with jaundice which may be deep (Cholestatic!)
Presents usually with ascites or GI bleeding
Tender, large and smooth hepatomegaly
Non tender, firm, irregular and nodular liver
|Florid spider angioma and palmar erythema
||Spider angioma and palmar erythema present
No major signs of portal hypertension
Signs of portal hypertension present
|Arterial bruit over the liver
Arterial bruit over liver only with hepatoma
Minimal polymorphonuclear leucocytosis
GGT, SGOT and SGPT elevated - usually upto 300 IU/L
|Liver enzymes usually in normal range
Gold standard for diagnosis is liver biopsy
Gold standard for diagnosis is liver biopsy
|Poor prognosis for Maddrey’s score > 32.
||Poor prognosis for Child class C.
Alagille syndrome is an inherited
disorder that mimics other forms of prolonged liver
disease seen in infants and young children. However,
a group of unusual features in other organ systems
distinguishes Alagille syndrome from other liver and
bile duct diseases in infants.
Children with Alagille Syndrome
usually have a liver disease characterized by a progressive
loss of the bile ducts within the liver over the first
year of life and narrowing of bile ducts outside the
liver. This leads to a buildup of bile in the liver,
causing damage to liver cells. Scarring may occur
and lead to cirrhosis in about 30 to 50 percent of
Although Alagille Syndrome was first
described in the English medical literature in 1975,
it is now becoming recognized more frequently among
children with chronic forms of liver disease.
Alagille Syndrome is generally inherited only from
one parent and there is a 50 percent chance that each
child will develop the syndrome. Each affected adult
or child may have all or only a few of the features
of the syndrome. Frequently a parent or brother or
sister of the affected child will share the facial
appearance, heart murmur or butterfly vertebrae, but
have a completely normal liver and bile ducts.
Symptoms of the illness are jaundice,
pale, loose stools and poor growth within the first
three months of life. Later there is persistent jaundice,
itching, fatty deposits in the skin and stunted growth
and development during early childhood. Frequently,
the disease stabilizes between ages 4 and 10 with
an improvement in symptoms.
Other features which help establish
the diagnosis include abnormalities in the cardiovascular
system, the spinal column, the eye and the kidneys.
Narrowing of the blood vessel connecting the heart
to the lungs (pulmonary artery) leads to extra heart
sounds but rarely to problems in heart function. The
shape of the bones of the spinal column may look like
a butterfly's wings on X-ray but almost never cause
problems with function of the nerves in the spinal
More than 90 percent of children
with Alagille Syndrome have an unusual abnormality
of the eyes. An extra, circular line on the surface
of the eye requires specialized eye examination to
detect and does not lead to any disturbances in vision.
In addition, some children have various abnormalities
in their kidneys that may lead to minor changes in
Many physicians believe that there
is a specific facial appearance shared by most of
the children with Alagille Syndrome that makes them
easily recognizable. The features include a prominent,
broad forehead, deep-set eyes, a straight nose and
a small pointed chin.
Diagnosis can be established by
microscopic examination of liver biopsy specimens,
a stethoscope examination of the child's heart and
chest, a slip-lamp eye examination, an X-ray of the
spinal column and an ultrasound (sonogram) examination
of the abdomen.
Treatment of Alagille Syndrome is
based on trying to increase the flow of bile from
the liver, maintain normal growth and development
and prevent or correct any of the specific nutritional
deficiencies that often develop.
Because bile flow from the liver
to the intestine is slow in Alagille Syndrome, medications
designed to increase the flow of bile are frequently
prescribed, including Phenobarbital and Cholestyramine
or Colistipol. This may decrease the damage in the
liver and improve the digestion of fat in foods that
Also, itching caused by the buildup of bile in the
blood and skin may be relieved. Other drugs are also
used to relieve itching, like Diphenhydramine hydrochloride
Elevations in blood cholesterol also respond to the
medications used to increase bile flow. Elevated blood
cholesterol levels can lead to small yellow deposits
of cholesterol on the skin of knees, elbows, palms,
eyelids and other surfaces that are frequently rubbed.
Lowering blood cholesterol usually causes the cholesterol
skin deposits to improve; although these are unsightly,
they are almost never associated with any dangerous
Although reduced flow of bile into the intestine leads
to poor digestion of dietary fat, a specific type
of fat can still be well digested and therefore infant
formulas containing high levels of medium-chain triglycerides
(MCT) are usually substituted for conventional formulas.
Problems with fat digestion and absorption may lead
to deficiency of fat-soluble vitamins--A, D, E and
K. Vitamin A deficiency causes night blindness and
red eyes. Vitamin D deficiency causes softening and
fractures of the bones and teeth (rickets). Vitamin
E deficiency causes a disabling disease of the nervous
system and muscles, and vitamin K deficiency causes
bleeding problems. Deficiencies of these vitamins
can be diagnosed by blood tests and usually can be
corrected by large oral doses. If the child's system
cannot absorb vitamins given by mouth, vitamin injections
into the muscle are necessary.
Sometimes surgery is necessary during infancy to help
establish the diagnosis of Alagille Syndrome by direct
examination of the bile duct system. However, surgical
reconstruction of the bile duct system is not recommended
because bile can still flow from the liver and there
is presently no procedure that can correct for the
loss of the bile ducts within the liver. Occasionally
liver cirrhosis advances to a stage where the liver
fails to perform its functions. Liver transplantation
is then considered.
Life expectancy and
Quality of Life
The overall life expectancy for children with Alagille
Syndrome is unknown, but depends on several factors:
the severity of scarring in the liver, whether heart
or lung problems develop because of the narrowing
in the pulmonary artery, and the presence of infections
or other problems related to poor nutrition. Many
adults with Alagille Syndrome lead normal lives.
Treatment is primarily medical and not surgical. Patients
generally have a much better outcome than children
with some of the other liver diseases that may present
at the same age.
Alpha-1 - antitrypsin deficiency is a hereditary disease
that may lead to hepatitis and cirrhosis. It is the
most common genetic cause of liver disease in children.
Adults are also affected and may have lung involvement
with emphysema as well as liver disease. The protein
alpha-1 - antitrypsin is a substance made in the liver.
It plays an important role preventing the breakdown
of enzymes in various organs of the body.
A child must inherit
the tendency from both parents to develop the disease,
alpha-1 -antitrypsin deficiency. The incidence of
the disease in the United States is approximately
1:2000 live births. Fortunately, for reasons that
are not understood, only 10-20 percent of the babies
born with the deficiency will have liver disease.
Decreased levels of the serum protein, alpha-1 - antitrypsin,
lead to liver damage with scarring and abnormal liver
The disease most
often appears in the newborn period with jaundice,
swelling of the abdomen, and poor feeding. It may
also appear in late childhood or adulthood and be
detected because of fatigue, poor appetite, swelling
of the abdomen and legs or abnormal liver tests.
Patients who develop
cirrhosis (scarring of the liver) have changes in
blood flow through the liver which produce other complications:
nosebleeds, bruising, excess body fluid, enlarged
veins in the inside of the stomach and esophagus (varices).
Occasionally, increases in pressure in these veins
make them leak, and internal bleeding may result.
Increased sleepiness after eating protein (due to
increased blood ammonia levels) and increased risk
of infection may be late complications.
The diagnosis is
made by blood tests when the serum level of alpha-1
- antitrypsin is low and standard liver function tests
are abnormal. Other tests such as urine collection,
ultrasound examination, or tests using specialized
X-ray techniques may be necessary. A biopsy of the
liver (sampling liver tissue with a needle or by operation)
is usually performed to look for liver injury. Relatives
who are carriers but do not have the disease can also
be diagnosed by blood tests.
The Diagnosis of Alpha 1 - Antitrypsin Deficiency
is also carried out by using Arterial blood gases.
Blood gases measure the pH (acidity), oxygen content,
and carbon dioxide content of the blood. Usually,
blood gases are used to analyze the arterial blood.
In rarer cases, venous blood may be used.
The test is performed by collecting a sample of blood
from an artery. Using a small needle, the sample may
be collected from the radial artery in the wrist,
the femoral artery in the groin, or the brachial artery
in the arm.
Before blood is drawn, the circulation to the hand
may be tested (if the wrist is the site). After the
blood is drawn, pressure is applied to the puncture
site for at least 5 minutes to completely stop the
The test must be sent to the laboratory for analysis
immediately, or the accuracy of the results cannot
is no cure for this disease. However, certain abnormalities
can be treated or controlled. Treatment is designed
to maintain normal nutrition, to provide the liver
and the body with essential nutrients, and to identify
complications early in order to treat them better.
Multiple vitamins and vitamins E, D and K are often
When jaundice is severe or itching appears, phenobarbital
or cholestyramine may be used. If the disease progresses,
excess body fluid may occur and can be treated with
can be done when liver failure develops and interferes
with normal functioning at school, work or in the
Life expectancy and
Quality of Life
The long-term outcome of the disease is variable.
Approximately 25 percent of affected patients develop
cirrhosis and its complications, but 75 percent of
individuals will not have any significant liver disease
after the newborn period. Some patients with cirrhosis
lead relatively normal lives for relatively long periods
of time. The reason for this difference is not known.