What is Pericholangitis?
Primary sclerosing cholangitis (PSC) is a rare type of liver disease that causes inflammation and scarring in the bile ducts within and outside the liver. This condition isn’t very common, with about one in every 100,000 people in the United States affected.
Medical techniques like endoscopic retrograde cholangiopancreatography (ERCP), first used in the 1970s, revealed that typical PSC shows up as multiple blockages or “strictures” in these bile ducts. However, ERCP cannot always detect smaller blockages within the liver’s bile ducts. This led to the question in 1985, of whether smaller bile ducts might also be affected in PSC.
Following further studies in 1991, a new term was introduced: small duct PSC (SDPSC). SDPSC came to refer to patients who have a type of bowel disease (inflammatory bowel disease) and long-lasting bile obstruction or “chronic cholestasis”, but with normal ERCP results. The diagnosis for these patients is confirmed through a liver biopsy, a procedure where a small piece of liver tissue is taken for examination.
What Causes Pericholangitis?
Small duct primary sclerosing cholangitis (SDPSC), also known as ‘pericholangitis,’ is a condition that affects the liver. The exact cause of this condition is not known, but it could be due to things like diet, infections, toxins, or an immune system response. This condition is considered a sub-type of primary sclerosing cholangitis (PSC), a disease that causes inflammation and scarring in the bile ducts of the liver.
Scientists have also looked into the possible genetic links between patients with SDPSC and those with LDPSC. They found that certain types of genes – specifically, those known as HLA-DRB1*13:01 and B*08 – were notably present in patients with SDPSC.
Additionally, it was found that SDPSC was genetically similar to LDPSC when it was associated with inflammatory bowel disease (IBD), suggesting SDPSC could be a milder version of LDPSC or its early stages. However, if SDPSC did not occur in tandem with IBD, then there were significant genetic differences between it and LDPSC.
Risk Factors and Frequency for Pericholangitis
Research has shown that males are more likely to have large and small duct issues, particularly if they also have inflammatory bowel disease (IBD). However, in those without IBD, it’s females who are mainly affected. In one study of 83 patients with small-duct primary sclerosing cholangitis (PSC), 61.5% were male, and 38.5% were female. The average age at diagnosis was 38.
Another study with 25 participants presented similar results. The average age of the patients was also around 37, and the number of males and females was almost equal, with a male to female ratio of 13:12.
- In patients with IBD, the occurrence of primary sclerosing cholangitis (PSC) was found to be around 11%.
- Among these IBD patients, 11.5% specifically had the small-duct variant of PSC.
Lastly, it’s been observed that within adult PSC patients, 75% show signs of both small and large ducts affected. The others were divided between those with only small ducts (15%) and those with only large ducts (10%). It’s worth mentioning that small duct PSC often emerges subtly and may only be detected once liver disease is advanced.
Signs and Symptoms of Pericholangitis
Small duct Primary Sclerosing Cholangitis (PSC) is a medical condition that scientists and doctors are still trying to understand completely. One question is whether having Inflammatory Bowel Disease (IBD) should be a requirement for making the diagnosis. Different studies have given varied definitions, although generally, IBD isn’t considered a necessity for diagnosing small duct PSC. The diagnosis usually involves signs of chronic cholestasis, a medical term meaning disruption in bile flow, with unknown cause, a normal cholangiogram (an imaging test checking bile ducts), and liver tissue changes that match PSC.
Large-duct PSC has similar diagnostic criteria to small-duct PSC, with the difference being that in large-duct PSC, there are abnormal structures and expansions in the bile ducts, often described as a “string of beads”.
These conditions routinely come to notice due to abnormal liver function tests, though they also often present with noticeable symptoms such as:
- Abdominal pain
- Fatigue
- Itching
- Weight loss
A study by Bjornsson et al. indicated a strong link between small duct PSC and IBD. Out of 83 patients with small duct PSC, about 81% also had colitis, which includes conditions like ulcerative colitis, Crohn’s colitis, and collagenous colitis. Still, the study concluded that the results, measured as death or needing a liver transplant, didn’t vary significantly whether small duct PSC patients had ulcerative colitis or Crohn’s colitis. They also noticed that Crohn’s colitis seemed to correlate with small-duct PSC more than large-duct PSC.
Testing for Pericholangitis
When diagnosing a liver condition called primary sclerosing cholangitis (PSC), several lab tests and examinations are helpful. Most patients with PSC show higher than normal levels of a substance called serum alkaline phosphatase in their bloodstream, detected through liver biochemical tests. The level of other substances called serum aminotransferases in the blood are generally less than 300 international units per litre. A test for blood protein, serum albumin, can help detect active inflammatory bowel disease, but it often shows normal levels in the early stages of PSC. Higher levels of serum immunoglobulin G4 (IgG4), a marker of a condition called autoimmune pancreatitis, has also been noticed in PSC patients.
Other tests should be used to rule out similar conditions such as autoimmune hepatitis, primary biliary cirrhosis, drug-induced liver disease, chronic viral liver disease, alcoholic hepatitis, HIV infection and pancreatic disease or gallstones.
Cholangiography, an imaging test of the bile ducts, is helpful for evaluating bile ducts larger than 100 micromillimeters. There are several ways to perform this test. Options include Endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP), or percutaneous transhepatic cholangiography (PTC). However, MRCP is often preferred as it is less invasive and more accurate. Small duct PSC affects smaller bile ducts that appear normal in standard cholangiography but can develop into large duct PSC over time.
A liver biopsy can also be used for diagnosis, and a frequent finding is an “onion skin” pattern; a concentric layering of fibrous tissue replacing connective tissue in small bile ducts. However, this alone will not confirm a diagnosis of PSC.
Lastly, a liver ultrasound can rule out other causes for chronic cholestasis, a condition where the flow of bile from the liver is blocked, such as issues with the pancreas and gallbladder.
Treatment Options for Pericholangitis
There isn’t much data available on specific treatments for Small Duct Primary Sclerosing Cholangitis (SDPSC). A study by Charatcharoenwitthaya and colleagues investigated the impact of a medication called ursodeoxycholic acid (UDCA) on 42 patients with SDPSC. They monitored the patients’ liver health and key markers in the blood, known as liver biochemistries, for nearly 25 years.
The study found that while UDCA did improve the results of liver tests, it didn’t appear to slow down the worsening of the disease. However, interestingly, the study did note that patients with SDPSC who eventually needed a liver transplant actually had a longer survival rate without needing a transplant as compared to those with a different type of liver disease called Large Duct Primary Sclerosing Cholangitis (13 years vs. 10 years, respectively).
What else can Pericholangitis be?
Certain conditions can cause pressure on the bile ducts from the inside or outside, including:
- Bile duct cancer
- Mirizzi syndrome
- Enlarged lymph nodes
- Portal hypertension
- Liver cancers spreading throughout the liver
- Narrowing of the bile ducts after surgery
- Long-term inflammation of the pancreas
Some infections can also affect the bile ducts, such as:
- AIDS-related bile duct diseases caused by Cryptosporidium parvum or cytomegalovirus
- Recurrent inflammation and infection of the bile ducts
- Parasitic infections such as Clonorchis, Opisthorchis, Ascaris
Damage to the bile ducts can also result from reduced blood flow, which can happen due to:
- Narrowing of the bile ducts after a liver transplant not related to the connection site
- After chemotherapy delivered directly into the arteries of the liver
- Following radiation therapy
Immune system diseases can also affect the bile ducts:
- IgG4-related disease affecting the bile ducts
- Eosinophilic cholangitis
- Mast cell cholangiopathy
- Histiocytosis X
- Systemic vasculitis
- Liver transplant rejection
- Primary biliary cholangitis
Finally, some people are born with conditions that affect the bile ducts, or the cause may be unknown:
- Choledochal cysts
- Progressive familial intrahepatic cholestasis
What to expect with Pericholangitis
Small duct PSC (Primary Sclerosing Cholangitis) is a type of liver disease less known than Large duct PSC and hasn’t been extensively studied. Usually, research compares their prognoses. Large duct PSC can lead to worse liver conditions such as cirrhosis (severe liver damage), end-stage liver disease, and the need for a liver transplant. It could also increase the risk of different types of cancers.
One study indicated that PSC patients with Inflammatory Bowel Disease (IBD) have a five times higher risk of colorectal cancer (CRC, a cancer affecting the colon and rectum) compared to those with IBD alone. Additionally, cholangiocarcinoma, a cancer affecting the bile ducts, is also a medical concern for PSC patients. Approximately 1% of PSC patients are diagnosed with it every year, and 15% of PSC patients might develop it in their lifetime.
On the other hand, Small duct PSC seems to be more benign or less harmful. A study observed 33 patients with Small duct PSC and 260 patients with Large duct PSC over approximately nine years. Only 12% of the Small duct PSC patients died or needed liver transplantation compared to 47% of the Large duct PSC patients. A separate study at the Mayo Clinic further confirmed these findings.
However, some people with Small duct PSC eventually develop Large duct PSC. In these cases, noticeable changes can be seen in the bile ducts inside or outside the liver.
Over a period, about 23% of the Small duct PSC patients progressed to Large duct PSC after approximately 7.4 years. And no progression to cholangiocarcinoma was reported except one patient who first developed Large duct PSC. This study also indicated that Small duct PSC patients have a longer period of living without needing a transplant as compared to Large duct PSC patients.
Interestingly, patients with a combination of Small duct PSC and IBD seem to have a better prognosis compared to those with just Small duct PSC. Also, they found that IBD associated with Small duct PSC had a lower prevalence of pancolitis, a condition where the entire colon gets inflamed, compared to IBD in patients with Large-duct PSC.
Possible Complications When Diagnosed with Pericholangitis
- Progression to a more severe type of primary sclerosing cholangitis (LDPSC), which may increase the risk of a type of cancer known as cholangiocarcinoma. However, there is no reported cholangiocarcinoma in the less severe variant of primary sclerosing cholangitis (SDPSC).
- Deficiencies in fat-soluble vitamins like A, D, E, and K.
- Development of metabolic bone disease, which usually manifests as weakened bones (osteopenia/osteoporosis) instead of the softening of bones (osteomalacia).
- Progression to liver cirrhosis, a disease that causes scarring of the liver, and portal hypertension, a condition marked by high blood pressure in the main vein to the liver.
- Hepatocellular carcinoma, a type of liver cancer, in patients with cirrhosis.
- Recurrence of the disease even after liver transplant.
Preventing Pericholangitis
Small duct primary sclerosing cholangitis (SDPSC) is a long-term liver disease that involves inflammation and scarring of small bile ducts that are less than 100 micrometers in diameter. It’s not very common and the exact number of people affected by it isn’t certain due to limited research. More often, it’s seen in men, typically diagnosed around the age of 38. It’s also notably linked (about 81% cases) with another condition called inflammatory bowel disease.
Most people with SDPSC don’t show any symptoms; the disease is usually picked up due to irregularities noted in liver tests. In some cases where symptoms do occur, the most common ones include abdominal pain, fatigue, itching, and weight loss. To diagnose SDPSC, several tests are needed: abnormal liver enzyme tests where the cause isn’t known, a normal cholangiogram (an imaging test of the bile ducts), and a liver biopsy showing characteristics of PSC (an inflammation and scarring of liver’s bile ducts).
The future health standpoint or prognosis for SDPSC isn’t as clear as for the version of the disease that affects larger bile ducts. However, some research suggests that people with SDPSC may have a longer time before needing a liver transplant. Common health complications associated with SDPSC include inflammatory bowel disease, deficiencies of essential vitamins (A, D, E, and K), metabolic bone disease causing thinning of the bones, cirrhosis of the liver, liver cancer in people with cirrhosis, and recurrence of the disease after a liver transplant.
Currently, there is no specific treatment for SDPSC. One study found that a therapy using a medicine called ursodeoxycholic acid may not slow the progression of the disease, but it could help to improve the health of the liver.