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Primary Sclerosing Cholangitis (PSC)

The liver which is the largest, solid, internal organ consists mainly of hepatocytes (liver cells) and bile ducts. Primary Sclerosing Cholangitis (PSC) is a slowly progressive and therefore chronic form of liver disease which attacks the bile ducts within the liver. Bile ducts are channels through which bile produced in the liver flows. PSC is an autoimmune condition – the body’s own immune system attacks the bile ducts. Specifically, it is the cells which line these ducts which are targeted by the immune system. PSC targets both ducts inside and outside the liver. This causes inflammation of these vessels with eventual scar tissue formation, thickening (sclerosis) and narrowing. Flow of bile becomes hindered and obstructed (cholestasis). This results in symptoms such as abdominal pain, itching, jaundice and infection of the bile ducts. Infection of bile ducts is called cholangitis. This whole process causes further scarring of liver tissue with the development of cirrhosis and finally liver failure. This whole process usually takes around 10 years.

What Is Bile?

Bile is a greenish acidic fluid produced by liver cells. It is then excreted by these cells into a system of tiny vessels within the structure of the liver. These are bile ducts. Bile ducts within the liver are known as intrahepatic bile ducts. Those that exist outside the liver (e.g. those connecting the gallbladder and pancreas) are known as extrahepatic bile ducts. The smaller intrahepatic bile ducts merge to form larger ducts which also merge to form the common bile duct. This extrahepatic duct leads to the gallbladder which stores bile. This fluid is excreted into the small intestines to help digest fatty foods and also aids in the absorption of vitamins A, D, E and K from the gut. Because bile is acidic, it is irritating to tissues which are not designed to be in contact with it. The process of cholestasis which causes leakage of bile into liver tissues therefore causes an inflammatory response in the liver.

Who Gets Primary Sclerosing Cholangitis?

Overall, PSC is a rare condition. Strangely for autoimmune diseases, men are twice as likely to develop PSC as women. There is a strong association between PSC and inflammatory bowel diseases, especially Ulcerative Colitis (UC) and less so Crohn’s Disease. There may also be an association with a disease called Coeliac Disease which reduces absorption of food from the small intestine.

The exact cause for PSC is not understood. Most patients have a slowly progressive condition which may last several years before any serious complications arise. But a small group of sufferers develop a rapid form of this disease – acute form. These patients have abdominal pain, itching and other symptoms which develop quickly. However, they seem to respond well to steroid tablets such as prednisolone.

Symptoms And Signs Of Primary Sclerosing Cholangitis

The majority of patients with PSC have no symptoms and may be unaware of their condition. It may only come to light because of a routine blood test for liver function tests. This may reveal a high level alkaline phosphatase (AP) which indicates bile flow obstruction. The full potential list of symptoms and signs includes the following;

none: liver disease may be found incidentally,
a feeling of being unwell,
fatigue,
nausea,
vomiting,
diarrhoea,
weight loss,
dry eyes and mouth,
red or pink, blotchy, mottled patches on the palms of hands (palmer erythema),
abnormal small blood vessels on the surface of the skin, mainly on the face, chest and arms (spider naevi),
abdominal pain or discomfort,
itching of skin,
enlargement of the liver (hepatomegaly),
jaundice: yellowing of the skin and whites of the eyes,
passing dark urine: associated with jaundice,
passing pale or clay coloured stools: associated with jaundice,
bruising,
bleeding from any site e.g. gums, nose, wounds, rectum, vagina,
abdominal distension from fluid collecting in the abdomen (ascites),
vomiting of blood (haematemesis), from oesophageal varices,
confusion and an altered level of consciousness (hepatic encephalopathy),
coma,
death.

How Is Primary Sclerosing Cholangitis Diagnosed?

PSC can be suspected on the basis of symptoms. However many conditions affect the biliary tract and can display similar symptoms. Examples of these include;

primary biliary cirrhosis (PBC)
gallstones in the bile ducts
bile duct strictures
cancer of the bile ducts.

Further tests are therefore always needed to confirm the diagnosis. These tests include;

1. Blood Tests

The key liver marker for cholestatic liver conditions is alkaline phosphatase (AP). This will usually be elevated. Other liver enzymes tests will also be raised such as AST and ALT. PSC can be distinguished from PBC by the lack of the autoimmune antibody called anti-mitochondrial antibody (AMA). This is usually present in PBC.

2. Ultrasound Scan

Although an ultrasound scan of the liver may be normal in up to half of all patients with PSC, it can sometimes show dilatation of intra and extrahepatic bile ducts as well as cirrhotic liver changes, fluid in the abdomen (ascites) and other changes.

3. MRI scan

Useful to visualise the liver and surrounding organs and exclude other conditions.

4. Endoscopic Retrograde Cholangio-pancreatography (ERCP)

ERCP is an invasive test similar to endoscopy. A long endoscope is passed through the mouth, gullet and stomach into the upper small intestine. The common bile duct is located and can be visualised. Dye can be inserted into the bile duct and photographed by X-ray to reveal the “biliary tree”. Samples of bile duct tissues can be taken for analysis. Doctors can also insert stents and other devices to open up blocked ducts. This relieves obstruction and reduces the risk of infection. However, ECRP does carry a risk of causing acute pancreatitis and injury to the bile ducts.

5. Magnetic Resonance Cholangio-pancreatography (MRCP)

This is a specialised scan which is non-invasive and safe. It can visualise both intrahepatic and extrahepatic ducts. PSC produces a classic “beaded” pattern to the bile ducts which can be identified. This is caused by areas of constriction and widening of the ducts. This tends not to occur in PBC.

6. Colonoscopy

As suffers of both PSC and UC are predisposed to developing cancer of the colon, it is wise to have colonoscopies done to visualise the large intestines and detect any precancerous changes early.

7. Liver Biopsy

Liver biopsies tend to be required at multiple sites as PSC may not be spread through the liver equally. Therefore, they are not always useful and are frequently reported as normal even in the presence of PSC. Generally, liver biopsies can be done in one of three ways;

1. Percutaneous Liver Biopsy

This can be done unguided or guided by ultrasound. After the position of the liver has been established, a local anaesthetic is injected into the skin. This is usually done over the upper right side abdomen or between the lower ribs. After the skin is numb, the doctor makes a small incision into the skin and inserts a needle (sometimes called a Trucut) into the wound. This is inserted into the liver and removed. It will contain a small sample of liver tissue.

2. Laparoscopic Liver Biopsy

This is usually done under general anaesthetic. With this approach, a small thin tube containing a light and camera is inserted into the abdomen. Through a separate small incision, another instrument is used to target specific areas of the liver to collect samples which are then removed.

3. Transjugular Liver Biopsy

This approach is sometimes used when a patient has severe clotting problems or when there is fluid in the abdomen. It is done in an X-ray unit. A catheter is inserted into a vein in the neck. This is then guided to the liver. A biopsy needle is then passed through the catheter until it travels down to the liver. A sample of liver tissue is then obtained and removed. This is generally a less risky approach compared to the percutaneous approach.

Treatment of Primary Sclerosing Cholangitis

Treatment of PSC aims to reduce the symptoms of cholestasis and reduce the progress of the disease itself. Options for treatment therefore include the following;

cholestyramine (Questran): this is commonly used to reduce the symptom of itching. However, it can cause a disturbance of bowel function and bloating.

rifampicin: an antibiotic which also can help with itching.

antibiotics: for bile duct infections (cholangitis).

ursodeoxycholic acid: this helps to reduce cholestasis – it improves the flow of bile acid through the ducts, thereby reducing leakage and damage to surrounding liver cells.

Endoscopic Retrograde Cholangio-pancreatography (ERCP): this procedure with balloon dilatation and/or stenting helps bile flow through extrahepatic bile ducts by stretching out narrowed portions due to strictures.

liver transplantation: for those with liver failure due to severe disease. This is usually very successful. However, the donated liver may also eventually develop PSC and succumb but this may again take many years.

other surgical procedures are rarely used but may include surgical removal of strictures followed by the creation of another channel so that bile can flow directly into the small intestine.

Complications of Primary Sclerosing Cholangitis

The main problems associated the long standing PSC are as follows;

1. Cirrhosis

As PSC progresses, irreversible scarring and destruction of liver cells continues. This eventually causes hepatic cirrhosis and may then lead to liver failure. PSC is a common reason for liver transplantation even though it is a rare condition itself.

2. Cholangitis

This is infection of the bile ducts and is caused by the sluggish flow of bile which occurs with PSC. Cholangitis is a serious infection and left untreated will invariable be fatal. Symptoms include fever, upper abdominal pain, nausea, vomiting, shaking (rigours) and jaundice. Eventually, infection localised to the bile ducts will spread to the rest of the liver and to other organs through the blood stream. This is called sepsis. It can cause death by multiple organ failure or by septic shock.

3. Cholangiocarcinoma

Longer standing PSC predisposes individuals to develop cholangiocarcinoma. This is cancer of the bile ducts. Approximately 10-15% of chronic PSC patients will develop this cancer. It carries a poor outlook as it spreads rapidly. Patients who are at highest risk are those with longer standing illness and who have cirrhosis and ulcerative colitis.

4. Cancer of the Colon

Both PSC and ulcerative colitis (UC) are factors which increase the chances of patients developing cancer of the colon. But, having both conditions together increases the chances further.