Before you learn about PSC, let’s learn a few basics about the liver…
The Liver and the Bile Ducts
PSC affects the bile ducts of the liver. The liver is one of the largest organs of the body, weighing roughly 1.5kg in an adult. It is located within the upper right side of the abdomen. The liver carries out many vital roles such as filtering toxins, synthesising blood clotting factors, assisting the immune system, and producing bile to help digest food.
The cells of the liver produce a substance called bile. Bile is a yellow-green solution that breaks down fats in food. Bile flows through the bile ducts of the liver, eventually flowing through the larger bile ducts as it leaves the liver, and heads towards the small intestine.
When discussing PSC and the bile ducts you will quite often hear the term intrahepatic bile ducts and extrahepatic bile ducts. Intrahepatic ducts describe the bile ducts that are inside the liver. Extra-Hepatic bile ducts describe the ducts that lie just outside the liver.
The extra-hepatic ducts are composed of a Right and Left hepatic duct, a common hepatic duct, cystic duct, and the common bile duct. The gallbladder is a small muscular sac that sits just underneath the liver, and its function is to store some of the bile leaving the liver that does not need to be used straight away.
PSC is strongly linked to IBD (Inflammatory Bowel Disease). Around two-thirds of patients diagnosed with PSC will also have an IBD diagnosis such as Ulcerative Colitis or Crohn’s disease.
Since the late 1900’s there has been increasing recognition, as well as exciting research carried out in the area of PSC. These studies include theories on possible causes and the development of potential new medications for PSC through lab research and clinical trials.
PSC Cases in Australia and Worldwide
PSC is considered a rare disease. Consequently, there is limited data collected on PSC in general and most of it is retrospective in nature. In a 2012 Australian publication on various conditions, it was estimated that there were only 872 reported cases of people with a PSC diagnosis in Australia. A conservative estimate in this publication suggested that by the year 2030 Australia will have just over 1,100 people with PSC. An incredibly small number of our population indeed.
It is possible, however, that these estimates are slightly below the actual true prevalence of PSC in Australia. A recent study of patients with PSC in NSW identified 208 patients living with PSC, and this study was by no means exhaustive in finding all cases within the state. Further studies are being conducted in other states. In any case, it is a rare disease and for this reason we partner with Rare Voices Australia in a bid to overcome the issues that are associated with rare diseases.
Worldwide, PSC is commonly found in Northern Europe and North America with a rate of between 0.4 and 2.0 cases per 100,000 per year. Although PSC can affect any age or gender, it is frequently found in younger males aged between 30-40 years old. PSC seems to be less common in Southern Europe and South-east Asia, although there have not been as many studies carried out in these countries. Studies of PSC in children are scarce, although studies show the overall number of children with PSC seems to be very low.
What causes PSC?
The exact cause of PSC remains unknown. However, recent studies have shown a combination of genetics, the environment, and the body’s own immune response may play a role in the development of PSC. PSC is not contagious, and so cannot be “caught” or transmitted to another person. Nor is it caused by alcohol, diet or other lifestyle factors.
The genetic component is slowly becoming better understood, though remains complex. There have been 22 genes identified which make an individual susceptible to PSC, however, just having some of the genes does not mean you will get the disease. It has been suggested by some that there may be an increased risk of first degree relatives also having PSC. The risk is poorly defined, bit does remain low. More commonly seen are other autoimmune diseases in both the patient and their family. has been suggested by some that there may be an increased risk of first degree relatives also having PSC.
Although some sort of autoimmune response is suggested, due to strong immune genetic associations and also the close relations with IBD, the term “autoimmune” means the body’s immune system is reacting against itself. There is some doubt, however, whether PSC is a true autoimmune disease , largely because of it’s lack of response to immune suppressant medications. Often it is referred to as an “immune-mediated” disease, meaning that the immune system is playing a role and is being overactive, but whether this is due to a reaction against itself or to some external source is not clear.
To date, there has been no definitive cause identified, but there is growing interest in the liver-gut axis and theories are being formed on the basis of the findings. The field of microbiome is one that is currently being heavily researched in IBD, and we are also seeing some research into the role it may play with PSC. The leaky gut theory suggests that pre-existing IBD causes the bowel wall to become more permeable, and therefore the bile ducts become exposed to gut bacteria, and toxins that ‘leak out’ of the gut. These toxins may damage the bile duct lining, and as a result, the ducts become susceptible to the toxic bile acid.
How do you find out you have PSC?
To diagnose PSC, an evaluation of your symptoms, medical history, blood tests, and imaging tests of your liver will be carried out. Once PSC is suspected, other causes for PSC type illnesses will need to be excluded by your Doctor. This includes illnesses such as autoimmune hepatitis, bacterial infection, cancers, and gallstone issues. Anyone with consistently elevated liver enzymes, particularly in a specific pattern called a cholestatic pattern”, should be considered as to whether they have PSC. In cases of early stage PSC most people have no symptoms. In fact, the first sign of PSC may be found through a blood test ordered by the doctor while being checked for something unrelated, particularly in a patient with coexisting IBD.
The Gold standard for diagnosis is MRCP (Magnetic Resonance Cholangiography). In most cases, this has replaced the need for ERCP ( Endoscopic Retrograde CholangioPancreatography) which is now reserved as a therapy mode instead of a diagnostic tool as it is more invasive and has additional risks.
In some cases, a liver biopsy will also be done. This tends to be where small duct PSC is suspected or to establish or eliminate other diagnoses such as Autoimmune Hepatitis or Primary Biliary Cirrhosis – two other immune-mediated liver diseases.
For more on tests take a look at our ‘tests and procedures’ section.
Understanding your diagnosis:
While PSC can have some typical symptoms and have similar markers, everyone’s PSC journey is unique. It’s important to talk with your doctors about your disease, how advanced your liver damage is, how it might impact with other illnesses you may have, and a range of other factors.
Some questions you might like to ask your doctors over the first months include:
- How well is my liver currently working?
- Do I have any fibrosis or cirrhosis?
- What further tests do I need and how often should I have them? Including surveillance tests.
- What should I do if I have issues or symptoms between appointments?
- Are there any dietary considerations I should follow? Is it ok to drink alcohol?
- Do I need to take any supplements?
- If you have known IBD – Do I need to see a gastroenterologist and Hepatologist or can you manage both at the moment?
- What follow up for my IBD do you recommend?
Remember that while your doctor should give you time and be attentive in your appointments, not all questions can be answered at one appointment and more pressing issues may take priority. If you feel you have more questions at the end of your appointment ask if you can be reviewed sooner to enable to spend time learning about PSC and how it is affecting you.
In the early stages of PSC, there are often no signs or symptoms. Other than higher than normal liver enzymes found in blood tests, many patients do not know they have the disease. For patients who do show symptoms, they are often non-specific, such as fatigue and tiredness. As the disease progresses other symptoms that present themselves include:
- Right Upper Quadrant Pain (Pain in the top right corner of the abdomen)
- Weight Loss
- Itchy skin (Pruritis)
- Chills and Fevers
- Spider Angiomas or Spider Neavi (swollen blood vessels beneath the skin – there are many causes for these and they are not an issue in themselves, however, treatments for cosmetic purposes are available).
- Jaundice (a yellow tinge to the skin and whites of the eyes)
In some cases, patients may develop frequent infections of the bile ducts. This normally causes fever, chills and upper right quadrant pain. Infection of the bile ducts, known as Acute Cholangitis, needs to be treated as early as possible with antibiotics as it can be serious.
Complications and symptoms of Later Stage PSC
In the late stages of PSC complications such as Cirrhosis of the liver may develop. A patient with late stage PSC may develop a range of symptoms such as:
- Fluid build-up in the abdomen (ascites),
- Varices – Enlarged blood vessels that can rupture and cause bleeding. Most commonly found in the oesophagus, but also common around stomas where these are present. (Bleeding varices are a medical emergency and an ambulance should be called if this occurs).
- Increasing weight loss, and loss of muscle mass.
- An enlarged liver and enlarged spleen.
- Hepatic Encephalopathy- forgetfulness, confusion, and ‘brain fog’. In serious cases can lead to coma. Usually seen in advanced stages of cirrhosis, however, can occur in earlier stages.
- Poor clotting due to reduction in Vit K production and reduced platelets in the bloodstream
Recent years have brought about promising theories and studies for the treatment of PSC. Clinical trials are occurring and it is always worth asking your doctor if there are any available to you that may be helpful. At this stage though, there are no proven medical treatments that halt or reverse liver damage caused by PSC, and we are still hoping for a cure. There are still medications and procedures that can be used to manage your symptoms and monitor any progression in an effort to be able to better predict it’s behaviour.
Not all patients will progress to end stage liver disease, and even for those who do, it tends to take 10 or more years from when you’re diagnosed. For those who do, a liver transplant is often a very successful treatment option.
For more information on transplants, see our ‘liver transplantation’ section on our Living with PSC page.
Ursodeoxycholic acid (UDCA or URSO)
The most widely used medication for PSC is called Ursodeoxycholic acid (UDCA or URSO). URSO is a type of bile acid that may have protective effects against the toxic bile salts within the liver. It has shown to greatly improve liver enzymes on blood tests, although studies have shown URSO does not prolong the amount of time between diagnosis and needing a liver transplant.
Medications such as Cholestyramine can be given to patients who suffer severe itching of the skin. It is wise to inform your doctor if this symptom appears as taking medication to help the itching will prevent scratching, and therefore open wounds and skin infections.
Medications such as Propranolol might be used to reduced portal hypertension if it is causing adverse effects such as varices, ascites, Hepatic encephalopathy, reduced platelets etc. These are not appropriate for everyone but can be helpful for some.
Hepatic Encephalopathy (HE) can become a life-threatening condition. Management of HE can often be achieved with the use of Lactulose and/or Rifaxamin.
Many patients with PSC are low on vitamins D, A, E, and K. These levels are monitored via blood tests, and vitamin supplements are prescribed by your Doctor as needed.
New and Trial Medication
There are promising studies underway into the effect of a new medication called NorURSO. NorURSO is a chemically chain-shortened version of URSO. It is currently undergoing trials, and so far has shown significant reductions in liver blood test results. Studies have shown that NorURSO also seems to demonstrate protective effects against damage within the bile ducts.
This strong antibiotic is also showing some promising results in some people, though is not currently PBS subsidised for use in PSC in Australia.
Please see our blog or Facebook page for up to date information on clinical trials.
Tests and Procedures
- Alanine aminotransferase (ALT) – an enzyme mainly found in the liver; high levels indicate active inflammation.
- Alkaline phosphatase (ALP) – elevated levels may indicate blockages in the bile ducts. In children and adolescents elevated levels are also seen at times of rapid growth as this enzyme is also produced in bones.
- Aspartate aminotransferase (AST) – elevated levels may indicate liver injury, but this protein can also be manufactured in other organs so is not liver specific.
- Bilirubin – indicates bile duct blockage or liver damage, but not PSC specific. This level is rarely elevated in early PSC and is directly related to jaundice or “yellowing” of the skin and eyes in later stages or acute cholangitis episodes.
- Albumin and Total Protein – measures the proteins made by the liver and tells whether or not the liver is making an adequate amount. It is an indicator of the liver’s ability to perform its functions.
- Gamma-glutamyl transferase (GGT) – Increases in this level generally indicate a liver damage issue. This indicator is often particularly high in paediatric patients, but not always elevated in the adult population.
A variety of other blood tests may be done, including your body’s ability to clot, full blood count, other antibody markers and vitamin and mineral levels. These are non specific to PSC but can help build a profile towards diagnosis and state of your liver health.
Magnetic Resonance Cholangiopancreatography (MRCP)
MRCP (Magnetic Resonance Cholangiopancreatography) is a high tech, magnetic scan of the upper abdomen and is considered the ‘gold standard’ in PSC diagnosis. An MRCP can provide a detailed picture of the liver, and show strictures and dilations of the bile ducts. In PSC, these strictures and dilations may cause the bile ducts to take on a ‘beaded appearance’ on the MRCP scan commonly seen in PSC patients. The MRCP is non-invasive and has a higher sensitivity then other methods of imaging such as Ultrasounds and Computer Tomography (CT) scans and provides accuracy consistent with the higher risk ERCP procedure. These are often done as a monitoring tool at regular intervals on people with known PSC, and can also be used when a non-invasive look at the bile ducts is prompted by symptoms or changes in liver enzymes.
Endoscopic Retrograde Cholangio Pancreatography (ERCP)
ERCP stands for Endoscopic Retrograde CholangioPancreatography and is a procedure that uses a long, slender camera tube that passes through the mouth, stomach, duodenum, and eventually into the bile ducts so that they can be viewed. The ERCP is not frequently used to diagnose PSC these days, due to risks associated with it such as pancreatitis, bleeding, and introducing bacteria into the bile ducts. However it is still a widely used therapeutic tool where bile duct dilatation is required. It can also be used to provide scrapings of bile ducts to investigate potential cancer where this is suspected.
An abdominal ultrasound can show some non specific, but tell-tale signs of liver disease. This is an easy, relatively non-invasive test that can show the size and texture of the liver, as well as look at the blood flow of the liver and examine the size of the nearby spleen. It is not generally used diagnostically, however, it can still provide useful information to the doctor. As it is much more accessible than MRCP, some doctors will use this intermittently as a monitoring tool.
Fibroscan is a new technology that is beginning to be used in PSC. The more it is used the more we will be able to understand what helpful information it can give us. This is a tool to monitor progression on liver stiffness, that is, detect progression to fibrosis or cirrhosis.
Liver biopsy is a procedure where a fine needle is passed through the abdominal wall and a tiny piece of liver is taken for examination under the microscope. This procedure does carry a risk of bleeding and infection, however, your centre will take great care to avoid these things occurring. For children, this procedure is often done under a general anaesthetic, unlike in adults where it is better done while awake and using local anaesthetic.
Liver biopsy is generally not required for the diagnosis of PSC alone, especially where there is a clear indication from imaging along with pathology and clinical picture. It can be useful in diagnosing some of the variants of PSC (IgG4 Sclerosing Cholangitis and Small duct PSC), as well as overlap syndrome or differential diagnosis of Autoimmune Hepatitis.
The biopsy results cannot necessarily distinguish PSC from other biliary diseases where the bile ducts are damaged (eg. Primary Biliary Cirrhosis and Secondary Sclerosing Cholangitis).
Gastroscopy (with/without banding)
A gastroscopy is a procedure usually done under light sedation so the patient is not aware of what is happening. A flexible camera is passed down into the oesophagus, stomach and beginning of the small intestine. If varices are seen they can be treated by way of “banding”. This involves the vessel being pulled into the endoscope using suction and an elastic band is wrapped around it, essentially strangling the vein so it cannot bleed.
This is a procedure where a camera on a flexible long thin tube with a camera on the end is passed through the anus while the patient is usually sedated. Inflammation and/or ulceration of inflammatory bowel disease can be seen, and tissue biopsies can be taken to give more specific microscopic information.
It is generally accepted that a person with PSC should have a colonoscopy every 2 years even in the absence of known IBD or abdominal symptoms. In those with known IBD annual colonoscopies are recommended.
This is a low dose x-ray scan that scans the body and gives results about bone density. People with liver disease, as well as those with IBD, are at risk of osteoporosis and its effects. Those with both are at increased risks. Talk to your doctor about how often you should have these scans.
See “associated conditions and complications of PSC” for more on bone health.
Transjugular intrahepatic portosystemic shunt (TIPS)
TIPS is a procedure performed by a radiologist that can be effective in reducing portal hypertension and it’s complications such as varices. This is a complex procedure and can increase the risk of hepatic encephalopathy. It is therefore often reserved for cases that cannot be managed by more conservative means.
Associated Conditions and Complications of PSC
Inflammatory Bowel Disease
Inflammatory Bowel Disease is an umbrella term that takes in several immune-mediated conditions of the bowel, the most common being Ulcerative Colitis and Crohn’s disease. Because approximately 80% of people with PSC also have IBD we wanted to provide just a little information about it here. However, we do also encourage you to use other reputable sights and talk with your doctor to learn what you can about these conditions. Usually, the IBD presents before PSC, though it’s not unusual for people to receive a dual diagnosis of both conditions at one time. It can also appear years after the PSC diagnosis has been made, but this is much less common.
More typically, when present in PSC, the person will have Ulcerative Colitis (UC), though sometimes they will be diagnosed with Crohn’s disease (CD), Indeterminant Colitis, or PSC Colitis.
Ulcerative Colitis only affects the colon. The inflammatory process is superficial in that it always involves the first layer, called the mucosa, and in more severe cases, the next layer down, called the submucosa. It tends to be continuous rather than patchy. In PSC patients the symptoms are often mild but usually extend along the entire colon. They often have a superficial inflammatory reaction in the last part of the small bowel where this meets the colon (backwash ileitis) together with variable inflammatory changes to the ileoceacal valve that separates the small and large bowel segments . It is common to see rectal sparing (no inflammation in the rectum) in these patients. Given these differences, an alternative term, PSC Colitis, has gained popularity in the medical literature after first being described nearly 15 years ago.
Crohn’s disease affects any part of the digestive tract. However, in the Caucasian population it most commonly involved the last (terminal) part of the small bowel or ileum, with or without patchy inflammation of the colon. Crohn’s disease exclusively limited to the large bowel is less common and care needs to be taken to ensure that this is not confused with Ulcerative Colitis or PSC Colitis. This is especially the case for people with PSC colitis given the presence of backwash ileitis and and rectal sparing in this sub group. The inflammation in Crohn’s disease can affect all layers of the intestinal wall (called transmural inflammation), seen more commonly in the ileal bowel segment as compared to colonic segments. The distribution of the inflammation tends to be patchy and not continuous as compared to Ulcerative colitis.
Management of IBD
There are a number of medications used in IBD that are very successful. Some people might be prescribed enemas or suppositories. Try not to be to put off by these. If they are effective in your case, it is a great way to manage your disease and minimise your systemic medication intake at the same time.
The initial class of oral medication used are known as 5ASA’s. Examples of these are Mesalazine and Sulfasalazine. These dampen down the inflammatory process in the bowel and allow the mucosa of the bowel to heal. They work by direction action on the colonoc mucosa (lining) and are usually delivered within a capsule that is resistant to break down as it passes through the stomach and the small bowel.
A second line of medications are the immunomodulators. These include things like Azathioprine, 6 Mercaptopurine and Methotrexate. These work through the patient’s bloodstream by reducing factors that drive inflammation.
In an acute episode, steroids are used, but these are not a good long term option because of the multiple side effects, particularly of long term use. They can be, however, a great way to get a severe flare under control.
The next level are the biologic agents. These target specific components of the immune system using a technology known as monoclonal antibodies. These agents are expensive and supported by the Federal Government’s Pharmaceutical Benefit’s Scheme (PBS). They are used when other medications fail. In fact, it’s a requirement of Medicare that you try the other medications before resorting to these. The biologics that have been used for many years now are Infliximab and Adalimumab. New biologics recently added to the PBS include Vedolizumab, Ustekinumab and Golimumab.
It’s important to talk with your specialist and find the best medication option for you. It’s not a one size fits all, and ongoing management is extremely important to monitor any condition changes and required changes to treatments.
It is generally recommended that if you have IBD and PSC, even if your IBD is controlled, that you have annual surveillance colonoscopies as there is a higher incidence of colon cancer in this setting.
Surgical management may also be recommended in some cases. In UC this would see the entire colon removed. This means you will require a temporary stoma followed by the additional surgery and the construction of an “artificial rectum” that is made from the last part of your small bowel (ileum). This is most commonly a “J” Pouch which relates to the technique of the surgery. The stoma is reversed so you can defecate through your anus. Alternatively, you and/or you surgeon may prefer the option of a permanent stoma. It is important to be aware that people with PSC who under J Pouch surgery are likely to have recurrence of gut inflammation in the new pouch , a condition called Pouchitis.
Surgery for a person with Crohn’s disease may look different due to the nature of the inflammation , and it is unlikely that a J Pouch or similar will be an option for you. Hence, it is important to be as clear as possible about the diagnosis of the co-existent IBD.
PSC causes inflammation to the liver. If this inflammation is ongoing it will lead to fibrosis and eventual cirrhosis. While PSC itself doesn’t have universally accepted staged classifications, liver disease that progresses into fibrosis can be staged as below.
- Stage 1 – A small amount of fibrosis limited primarily to regions in the liver called portal areas.
- Stage 2 – Fibrosis begins to appear outside the portal areas. The strands of fibrosis are not yet connected to each other.
- Stage 3 – Areas of fibrosis connecting to each other.
- Stage 4 – Widespread, honeycomb-like scarring known as cirrhosis.
Fibrosis is early scarring of the liver. The liver is a remarkable organ in that, if the underlying cause of fibrosis is removed, damaged cells can be restored unless cirrhosis has already occurred. Unfortunately in PSC we do not have any provem medications that allows this to occurr, however, there are some promising clinical trials currently occurring.
Cirrhosis is permanent and hard scarring. This cannot be reversed.
Cirrhosis can be classified as
- Compensated: where the liver is continuing to function relatively well and not causing significant issues with portal hypertension.
- Decompensated: where the liver is no longer performing its functions and any of the issues of portal hypertension are present.
Portal hypertension occurs in PSC where fibrosis or cirrhosis has developed. The scar tissue blocks the flow of the blood into the liver causing increased pressure in the blood vessel. The body tries to compensate much like we do when we’re in a traffic jam – when we can’t go the main route we try to find alternative routes – our body creates additional vessels for the blood to flow, but they are not as strong and flexible as our regular vessels, and they also direct the blood around the liver instead of through it, giving even less opportunity for the liver to perform its functions.
There are many possible issues with portal hypertension, but the two most common and dangerous are;
Hepatic Encephalopathy (HE): This can occur at any stage of liver disease, but is most commonly seen in the later stages. It is a complex disorder that affects the brain, causing symptoms from mild memory loss and personality changes through to loss of consciousness. This condition can develop gradually over time or have a sudden onset. It is important to tell your doctor if you or your family are concerned about HE symptoms as early treatment is ideal. We encourage you to listen to your family or trusted friends as part of this condition also produces a lack of insight into your capability, so if a friend is concerned, even if you feel fine, you should seek assistance. If someone you know with PSC is showing significant signs of reduced mental function you should call an ambulance. Medications such as Lactulose and/or Rifaxamin are commonly used to successfully manage HE.
Varices: Varices can occur in several areas. One common area where they present risk is in the oesophagus. Caused by the liver blocking the normal blood flow pathways, these vessels are not designed to carry the higher volume and pressures of blood and can rupture. If someone with PSC vomits blood or has black, tarry or bloody stools urgent care should be sought. In most instances, you should call an ambulance.
Another area where varices can cause bleeding issues is around a stoma if a person has one. These can be identified by the typical purple ring around the stoma. These too are also life threatening emergencies and immediate treatment should be sought if they bleed. In some of these cases, the varices bleed at superficial levels and manual pressure can also be applied to stop the bleeding. Even in these cases, if the amount of blood loss is high or unknown, the person should still be medically evaluated.
Liver disease, Inflammatory Bowel disease and use of steroids all increase the risk of Osteoporosis. In the longer term, it is thought that up to 90% of those with PSC will develop reduced bone mineral density.
Osteoporosis is a term used to define the significant loss of bone minerals, resulting in loss of bone thickness or density. This loss leads to weaker bones and increased risk of fracture. The first symptom of osteoporosis is usually a fracture, making it important to have regular Dexa scans to check for reducing bone mass. The best management for osteoporosis is ensuring adequate Vit D and calcium intake and undertaking regular exercise. Other medications are available if osteoporosis continues and specialist care from an endocrinologist will provide the best management plan.
The risk of developing a liver cancer of some sort when you have PSC and associated IBD is estimated to be over 400 times more likely than someone without these conditions. The most common of these is Cholangiocarcinoma (CCC).
CCA can be difficult to detect and there is currently no universally accepted surveillance model. However, many centres will perform annual MRI imaging correlated with the blood tumor marker carbohydrate antigen 19 – 9 (CA 19 – 9). These do have limitations and not all centres will perform these tests regularly. Early detection of CCA does bring about improved outcomes, and survival rates are improving with better surgical and medical treatments available.
PSC Phenotypes and Overlaps
International collaboration amongst researchers has helped us understand some different subgroups of PSC.
As we understand more about the variants below we may better be able to predict the course and find treatments that better target the different groups. Already patterns are beginning to emerge within the groups that provide some level of guidance and possible treatment options.
Large Duct Variants
This is the classic form of PSC, and as it is the most common, it is where we used to derive most of our statistics. The medium and large ducts are affected and the associated IBD is often mild. The natural history of this phenotype ranges from aggressive disease to indolent, that is, it is not presenting symptoms and is not progressing, or progressing extremely slowly. The typical beading pattern can be seen on MRCP.
In about 50% of these large duct cases, dominant strictures develop in either the common bile duct or the hepatic duct.
Non-IBD Large Duct PSC:
This phenotype tends to be diagnosed evenly among men and women and at an older average age. There is some evidence to support a better prognosis in this group.
High IgG4 PSC:
Still under the large duct banner is the IgG4 PSC, with only moderately elevated IgG4 levels (rarely greater than 2.8g/l, or twice the upper limit of normal). This is distinguished further from IgG4 sclerosing cholangitis discussed below.
PSC-Autoimmune Hepatitis Overlap (AIH)
The diagnostic criteria for this phenotype remain varied, leaving statistics on its frequency unreliable. These patients can at times present with typical AIH finding and progress to cholestatic disease. More often though, they present with extremely high elevations in their liver enzymes but have typical cholestatic histology findings. Even imaging can provide pictures that give mixed signals.
This rare phenotype tends to share many features of adult phenotypes, however, it does seem to be much more responsive to therapies and have a high frequency of AIH overlap. Sometimes termed Autoimmune Sclerosing cholangitis, this group reports a higher success rate with immunosuppressive medication as well as with Vancomycin.
Small Duct PSC
We still have a way to go in understanding this phenotype, and whether it is, in fact, a separate entity or actually just early stages of PSC. About 20% of these cases do progress to the classic large duct PSC and follow a similar pathway. Diagnosis for small duct PSC is made with liver biopsy, with raised Alkaline Phosphate levels for more than 6 months in the absence of radiological findings.
IgG4 Sclerosing Cholangitis
This is now recognised as a separate disorder to PSC, though diagnosis can take on challenges to differentiate it from the High IgG4 PSC phenotype. The differential diagnosis comes from a combination of histology, response to steroids, imaging, the involvement of other organs and serology (with a level of over 2.8g/l being suggestive of IgG4 sclerosing cholangitis).