Primary Biliary
Cirrhosis
What is Primary Biliary Cirrhosis (PBC)?
Primary biliary cirrhosis is a slowly progressive disease of the bile
ducts inside the liver. In PBC 
the
bile ducts become inflamed and eventually scarring can occur in the
bile ducts which will block the excretion of bile. The bile will back
up into the liver and into the bloodstream, causing various symptoms.
If extensive scarring occurs, cirrhosis will eventuate.
What is the cause of PBC?
We do not know the cause of PBC. We have found, however, that in this
condition, the body’s immune system recognises a protein on the
bile duct lining as foreign and there is resultant inflammation in that
bile duct lining. It is thus one of the spectrum of so called auto-immune
diseases of which rheumatoid arthritis is another example.
What are the symptoms of PBC?
PBC occurs much more commonly in women (it is ten times more common
in women than in men). Early in the disease, most patients have no symptoms
and the only findings will be minor abnormalities in liver blood tests
e.g. a high level of the liver enzyme alkaline phosphatase.
Later in the disease, itching, fatigues and jaundice are common symptoms.
Other immune related problems can occur e.g. dryness of the eyes and
mouth. Softening and fragility of the bones can also occur and there
is an increased risk of fractures.
How is the diagnosis made?
PBC is diagnosed on several pieces of information. The doctor will
usually assess the symptoms e.g. itching, fatigue and jaundice and will
note the level of certain liver enzymes on blood tests.
The most important laboratory test is one for anti-mitochondrial antibodies.
For unknown reasons, a protein antibody develops against mitochondria
(energy sources within the cells) in about 95% of cases of PBC.
If there is doubt regarding the diagnosis, there will often be investigations
performed to image the bile ducts e.g. an ERCP where a light flexible
endoscope is inserted through the mouth, stomach and then into the small
intestine and a thin tube is passed through the scope into the bile
ducts with dye injected to highlight the bile ducts on X-ray. Magnetic
resonance cholangiography is an alternative mode of investigation which
can give similar information.
As the disease is progressive, a liver biopsy may be needed to determine
the severity of the damage.
What Treatment is there available?
Treatment is aimed at both controlling the symptoms and slowing down
the progression of the disease.
Itching can be controlled by drugs such as Questran or occasionally
antibiotics such as Rifampicin.
As patients often will develop thinning and fragility of the bones,
the patient is often encouraged to take a high calcium diet –
1200 mgs of calcium per day and to take supplemental Vitamin D.
Unfortunately there is no effective treatment for fatigue.
Recently, it has been shown that some drugs such as ursodeoxycholic
acid (Ursofalk) can improve the liver function blood tests and some
research studies have suggested that they will reduce the damage to
the liver.
When PBC progresses to a point where too much liver damage has occurred,
liver transplantation must be considered.
SUMMARY
Primary biliary cirrhosis is a slowly progressive disease which occurs
in 90% of cases in females. Once diagnosed, treatment is directed in
managing symptoms and slowing down liver damage.
Primary
Sclerosing Cholangitis
What is Primary Sclerosing Cholangitis?
Primary Sclerosing Cholangitis (PSC) is a disease which primarily involves
the bile ducts, either inside or outside the liver or both.
In this condition, the walls of the bile ducts become inflamed (cholangitis)
and the inflammation causes scarring and hardening (sclerosis). This
results usually in narrowing of the bile ducts.
The net result is usually a problem with drainage of bile and there
is eventual liver damage. 
After
usually a reasonable period of time, cirrhosis of the liver can develop
and the patient can become jaundiced.
The exact cause of PSC is unknown. It is probably, however, caused
by the body’s immune system incorrectly identifying a part of
the bile duct cell as being foreign and attacking that area.
Once considered a rare disease, recent studies have suggested it is
more common than previously thought. It appears to affect men more often
than women and approximately 70% of the patients have inflammatory bowel
disease (either ulcerative colitis or Crohn’s disease). There
are almost certainly genetic factors which link PSC and inflammatory
bowel disease.
What are the Symptoms?
PSC usually progresses very slowly and initially there are usually
no symptoms. Eventually the patient will become jaundiced and can get
recurrent episodes of liver infection (chills, fever and upper abdominal
tenderness).
Itching is common and as the disease progresses, chronic fatigue, loss
of appetite and jaundice (yellowing of skin and eyes) can occur.
In the advanced stages of cirrhosis, extensive swelling can occur in
the abdomen and feet.
Diagnosis
The liver enzyme tests usually show an elevation in alkaline phosphatase
or gamma GT. The bilirubin may also be elevated.
Your doctor may suspect PSC if you have a history of inflammatory bowel
disease and these abnormal blood tests.
The diagnosis is best made with cholangiography (imaging of the bile
ducts). These days this is done using either an ERCP or magnetic resonance
cholangiography (MRC).
An ERCP is done using an endoscope. In this examination, dye is passed
up through the bottom end of the bile duct. In a Magnetic Resonance
Cholangiogram, an endoscope is not necessary.
Liver biopsy occasionally is used to either diagnose the condition
or determine the presence or absence of cirrhosis.
Treatment
There is no cure for PSC. Patients are usually treated with ursodeoxycholic
acid (UrsofalkR). This medication appears to slow down the progression
of the disease and may help with the symptoms.
Itch can be often treated by using Cholestyramine (QuestranR) which
helps to eliminate some of the bile which passes to the intestine.
If an episode of infection develops, antibiotics can be used.
In some cases, endoscopic or surgical procedures may be used to open
major blockages in the bile ducts. Through an endoscope, a tiny tube
with a balloon is often passed into the narrowed bile duct and the balloon
is inflated to expand the duct. Sometimes stents (plastic or metal tubing)
can be placed in the narrowed ducts to keep them open.
Liver transplantation is often used in advanced cases. The outcome
for PSC patients after liver transplantation is excellent with survival
rates of well over 80% and a good quality of life after recovery.
Autoimmune
Hepatitis
What is Hepatitis?
Hepatitis is a term which literally means “inflammation of the
liver”. It is most often caused by viral infection but it can
be also caused by alcohol, certain drugs, chemicals, poisons or other
diseases.
Hepatitis is classified as being either acute or chronic. In acute
hepatitis, the inflammation develops quickly and lasts for only a short
period of time. The patient almost invariably recovers completely. If
a person fails to recover fully, an acute hepatitis can become chronic
i.e. it will continue on at a smouldering pace.
Chronic hepatitis can develop over a number of years without the patient
ever being acutely unwell. As the liver repairs itself, scarring (fibrous
tissue) develops in the same way that a scar will form after the skin
is cut. Advanced scarring is called cirrhosis and over time cirrhosis
will often end in liver failure.
What is Auto-Immune Hepatitis?
The immune system is designed to help protect the body against foreign
materials. Occasionally the immune system mistakenly recognises some
of the body’s own proteins as foreign and develops antibodies
against these proteins.
When the immune system attacks the liver in this way, it is a condition
called auto-immune hepatitis (AIH) ensues. The trigger which causes
the immune system to attack the liver is unknown. The AIH is not an
infectious disease and thus is not contagious.
Symptoms and Diagnosis
Auto-immune hepatitis occurs much more frequently in young females.
Early symptoms are non specific i.e. can have a lot of other causes
and include fatigue and aching joints.
When AIH becomes severe, there may be jaundice and when cirrhosis develops,
there can be marked swelling of the abdomen, intestinal bleeding or
mental confusion.
Patients who develop AIH will often have other auto-immune diseases
e.g. ulcerative colitis, diabetes mellitus, vitiligo (a patchy loss
of pigment in the skin), Sjogren’s disease (a condition causing
dry eyes and mouth).
Blood tests will often result in a presumptive diagnosis of auto-immune
hepatitis but liver biopsy is needed to confirm this. Two antibodies
that may develop in the blood are anti-nuclear antibody (ANA) and smooth
muscle antibody (SMA). In addition, a blood protein called gamma globulin
is usually elevated.
Treatment
The aim of treatment is to dampen down the immune response and thus
limit the damage to the liver cells.
Prednisone is usually the mainstay of treatment. Over 80% of patients
will respond (i.e. their liver enzyme tests – ALT, AST will settle
down) after 6-12 weeks of treatment. The dose of Prednisone is usually
tapered to the minimum necessary to control the symptoms.
Azathioprine (Imuran) is frequently used such that a lower dose of
Prednisone can be used for maintenance treatment. In the vast majority
of patients, treatment needs to be continued indefinitely.
Prednisone can cause significant side effects such as facial swelling,
fluid retention, weight gain and acne. Long-term treatment can result
in osteoporosis, hypertension, cataracts and even diabetes. It is thus
important that the minimum dose of Prednisone is used.
In patients who do not respond to the treatment and whose liver condition
deteriorates, liver transplantation often is considered. Survival rates
of over 80% with a good quality of life after recovery are found in
most liver units.
Liver
Cysts
What are Liver Cysts?
Liver cysts vary in size from as little as 2-3 mms to greater than
10cms. They are small, usually round, fluid filled cavities which form
within the liver. They are surrounded by normal liver tissue.
Approximately
1% of the population will develop liver cysts. The vast majority of
these liver cysts do not cause any symptoms at all.
Half the patients have more than one cyst with occasional patients
having multiple cysts.
They are slightly more frequent in males than females but surprisingly,
females tend to have more symptomatic cysts.
Symptoms and Diagnosis
The majority of patients do not develop any symptoms at all. Only
when the cysts become very large – usually larger than 7 or
8cms can they cause abdominal pain and discomfort. Very occasionally
the cysts can be felt in the right upper part of the abdomen.
The cysts are usually diagnosed on ultrasound and generally show a
circular or oval appearance.
While cysts themselves are only very rarely of any importance, certain
types of cysts can cause problems.
If there are unusual features on the ultrasound or the patient has
lived in an area where hydatid disease is common, blood tests are often
performed to exclude this possibility.
Very occasionally cancers from other organs can spread to the liver
and produce cyst-like deposits.
Very occasionally it may be important to distinguish a cyst from an
abscess or a benign tumour of the liver.
Treatment
Most cysts do not need any treatment. Only large cysts which are causing
symptoms need treatment. Unfortunately, removing the fluid in the cyst
does not cause any more than temporary improvement and excision of the
external part of the cyst is necessary.
Benign Liver Tumours
The liver is a common site for both benign and malignant liver tumours.
The patient will understandably become very concerned about a comment
that there is a lump in the liver. There are often features about a
“lump in the liver” which can quickly reassure us that the
lesion is benign i.e. non malignant.
There are many causes of benign liver tumours but the most common ones
we see are:
1. Liver cysts.
2. Haemangiomas.
3. Focal nodular hyperplasia.
4. Hepatic adenomas.
1. Liver cysts.
Liver cysts have a number of causes including parasitic infections
(hydatid disease), cystadenoma of the liver (a rare liver tumour which
has a strong tendency to recur and has the potential to turn malignant)
and Caroli’s Syndrome where there is dilatation of small bile
ducts with infection frequently occurring in these ducts (cholangitis).
The majority of cysts in the liver, however, are benign simple liver
cysts.
Asymptomatic liver simple cysts are found in about 1% of adults and
usually discovered accidentally on ultrasonography or CT scanning.
In the vast majority of patients are asymptomatic. The cysts vary
in size from as small as a few mms to as big as 20 cms although the
vast
majority are under 2 cms in size. A half of adults will have more than
1 cyst and occasionally there are multiple liver cysts. This can be
associated with polycystic kidney disease. In this condition, the kidney
disease is of clinical importance and the liver cysts only occasionally
will cause problems.
The vast majority of cysts cause no symptoms whatsoever. Very large
cysts can occasionally cause abdominal pain or discomfort. Interestingly,
very large cysts are almost exclusively seen in women.
The cysts can usually be diagnosed reliably on ultrasound and CT scanning.
It is important, however, to exclude hydatid disease (a parasitic infection
of the liver resulting in cysts), secondary cancers in the liver which
have become cystic and cystadenomas
Asymptomatic simple cysts, even when large, need no treatment. Removing
the fluid content of the cysts with a needle under ultrasound does not
provide definitive therapy and the cyst recurs usually rapidly. In the
occasional patient where the cyst is large and causing symptoms, it
can be removed surgically
2. Haemangioma
This is the commonest benign liver tumour and when it is over 2 cms
in diameter, there are often very specific appearances present on
imaging
of the liver with an isotope scan. In addition, fairly characteristic
changes can occur on CT scanning & Magnetic Resonance Imaging (MRI).
In this condition, liver tests are normal and usually there are no
symptoms. Niggling or sharp abdominal pains can occur and the lesions
may expand during pregnancy and in women taking oral contraceptive pills.
Simple pain relief is usually the only treatment required but very
large lesions sometimes require resection, especially if pain is a problem.
Complications such as rupture are very rare and these lesions
do not become malignant.
It is usual for the radiologist to be able to give a confident diagnosis
of haemangioma on imaging studies. Occasionally, however, this is not
possible and these lesions are often then just observed. Very occasionally,
liver biopsy is performed and in those instances often the radiologist
will find that blood is aspirated when the needle is in the lesion.
3. Focal nodular hyperplasia (FNH)
This lesion is probably caused by abnormalities in the vascular supply
to a part of the liver. Characteristically a central scar will occur
in an area of focal nodular hyperplasia and this can give characteristic
features on scanning.
It is uncommon for these lesions to cause symptoms unless large when
they can be associated with pain.
It has been thought in the past that enlargement may occur during pregnancy
or with the oral contraceptive pill or oestrogen treatment. This is
controversial, however, and it is now not routinely suggested that patients
stop the oral contraceptive pill if a confident diagnosis of FNH has
been made.
This lesion has no malignant potential and complications such as rupture
and bleeding are rare.
4. Hepatic adenomas
These rare benign tumours are sometimes difficult to distinguish from
focal nodular hyperplasia (FNH). They are very vascular and thus liver
biopsy can be dangerous i.e. significant bleeding can occur.
It is sometime difficult to distinguish an hepatic adenoma from a primary
liver cancer in a non cirrhotic liver and surgical resection is usually
recommended.
The risk of complications of this rare lesion is especially high during
pregnancy or in women taking oral contraceptives or oestrogen.
Gilberts Disease (The
Disease That Is Not A Disease)
What is it?
Gilbert’s Syndrome was named after a French gastroenterologist.
It is a common, often inherited disease, where the processing by the
liver of the pigment bilirubin is sluggish. This can lead to an abnormal
increase in bilirubin in the blood and a yellowish tinge to the skin
(jaundice).
The liver, however, remains normal and it is not a disease. It cannot
cause any problems.
Gilbert’s Syndrome is probably caused by a decrease in the activity
of an enzyme in the liver which processes bilirubin. It affects approximately
5% of the population and is thus very common. It is usually detected
when blood tests are performed.
What are the Clinical Features?
Usually there are no symptoms but sufferers can experience mild jaundice.
It is said by some that bouts of abdominal pain, loss of appetite and
fatigue can also occur although this has never been confirmed. When
someone with Gilbert’s Syndrome does not eat for a period of time,
they will often develop the yellowing of the skin and it can also occur
when they are unwell for other reasons e.g. a respiratory tract infection.
Vigorous exercise, a feverish illness or repeated vomiting can also
cause the yellowing to occur.
Investigations and Treatment
Simple blood tests are usually carried out and can almost invariably
make the diagnosis. Occasionally, there can be some confusion with conditions
which cause an excess breakdown of red blood cells (haemolysis).
There is no treatment required for Gilbert’s Syndrome.
People with Gilbert’s Syndrome have a normal life expectancy
and there is no evidence that the disorder is associated with other
serious liver diseases.
We do bother about Gilbert’s Syndrome because suddenly becoming
yellow can be very alarming to a person. Jaundice itself can be a sign
of a serious or infectious disease and rightly causes concern to doctors
and also to sufferers and their families.
Knowing about the diagnosis as a harmless Gilbert’s Syndrome,
therefore not only provides reassurance to the sufferer but also to
their care-givers.
