Primary sclerosing cholangitis (PSC) is a chronic hepatobiliary disorder characterized by continuous cholestasis, inflammation, and fibrosis of the intra- and extrahepatic bile ducts. This inflammation is believed to be autoimmune in nature. Chronic PSC can cause liver cirrhosis, portal hypertension and ESLD generally through natural progression of the disease. 

First and foremost, there is a link between PSC and IBD, specifically, ulcerative colitis. PSC also increases the susceptibility of cholangiocarcinoma (bile duct cancer). Cancer risk is increased significantly higher in the patients having both ulcerative colitis and PSC which would mean that cancer surveillance is imperative in such patient’s management 

The condition has become more frequently diagnosed now that techniques such as endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) are available. Serological markers that may be used in the diagnosis of PSC include serum level of alkaline phosphatase, gamma-glutamyl transpeptidase, and serum aminotransferase as well as hypergammaglobulinemia. 

The goal of treatment is to control the symptoms and manage the associated complications. Liver transplantation is the only therapy now that can reverse the natural history of the disease, or alter its course, and primary sclerosing cholangitis is among the top indications for adult liver transplantation. 

Primary sclerosing cholangitis (PSC) is a rare cholangiography pattern of idiopathic liver disease with an estimated annual incidence of 0–1.3 per 100,000 inhabitants and point prevalence between 0 and 16.2 per 100,000 people. PSC is observed more often in North America and Northern Europe than in Asia. Its most common presentation is late, a third of patients receiving their diagnosis between 30 and 40 years of age, with a median age at diagnosis of 41 years. The condition is more common in men by a ratio of 2: 1 and males are estimated to represent 65- 70% of all individuals with PSC. First-degree relatives of PSC sufferers are in 9–39 times higher risk for developing PSC as compared to normal population. However, it is worth noting that PSC occurs more frequently in non-smoking patients. 

Primary-sclerosing-cholangitis (PSC) is a chronic hepatic disorder, described by inflammatory stenosis and cholestasis. This is an autosomal dominant polygenic trait and both genetic and environmental factors are implicated including human leukocyte antigens (HLA). This condition advances with obstruction of the bile ducts and inflammation of the liver and cholangitis, in addition to the development of portal hypertension. PSC is predisposing factor to cholangiocarcinoma which affects 10-20% of patients with the condition probably due to chronic inflammation and bile toxicity. There is also a genetic and immune system basis for the elevated cancer risk. 

The actual etiology has thus not been determined but they are widely accepted that there are both genetic and some environmental predisposing factors that contribute to the onset of PSC. Primary sclerosing cholangitis is associated with an increased incidence of inflammatory bowel disease and is seen in 60-80% of the patients. Of all these, about 80% are diagnosed with ulcerative colitis, while 20% with Crohn’s disease. On the other hand, 5-10% of patients with ulcerative colitis are likely to also have PSC. 

It is believed that PSC is an autoimmune disease. The laboratory findings include altered plasma levels in some patients, including antineutrophilic cytoplasmic antibodies, antinuclear antibodies, and anticardiolipin antibodies. Also, those with HLA B8 and HLA DR3 gene are have a higher chance of being affected by PSC. 

Primary sclerosing cholangitis is an inflammatory liver disease, in which the bile ducts are progressively narrowed and scarred. It is expressed by both genetic and environmental factors, and highly associated with specific HLA variants. The disease advances to involve the bile ducts, liver cirrhosis, cholangitis and portal hypertension. PSC is widely regarded as a cholangiocarcinoma precursor because 10%-20% of PSC patients are diagnosed with this cancer most likely attributable to long-standing inflammation and bile insult. Other causes include genetic and immune systems that may also influence the decision making on high risk cancers. 

Age group 

PSC is normally diagnosed at a median age of 30–40 years, although it can affect any age group, including pediatric populations and geriatric populations. The age at which patients are likely to be diagnosed with the condition is average, approximately at the age of 41 years. The incidence rate also varies according to the gender with the male gender accounting for 65 – 70 percent of the total cases. 

The early physical examination of a PSC patient usually remains quite normal until advanced stages when features of cholestasis, including jaundice, or hepatomegaly can manifest. There are features of portal hypertension seen in later stages, the basic of which include splenomegaly, ascites, and spider angiomas. The pruritis may result to excoriations on the skin. Late stages might also present symptoms of liver failure including muscle wasting or peripheral oedema. 

Inflammatory Bowel Disease (IBD) 

Autoimmune Conditions 

Increased Risk of Cholangiocarcinoma 

Increased Risk of Colorectal Cancer 

PSC often presents with mild, or no symptoms and the disease can progress silently for years. 

When symptoms appear, they include: 

Fatigue (chronic, non-specific). 

Pruritus (itching) due to cholestasis. 

Jaundice (yellowing of skin and eyes), a result of bile duct obstruction. 

Right upper quadrant abdominal pain (mild to moderate). 

Symptomatic Management:  

Pruritus: Before treating cholestyramine or rifampin is often employed to lower bile acids that induce itching. For this purpose, antihistamines may be administered in addition.  

Management of Cholestasis: 

Ursodeoxycholic acid: Despite its use being justified for enhancing the conduction of bile, this agent’s ability to alter the disease course is still in doubt.  

Endoscopic intervention: For using in dilation of dominant bile duct strictures or placing stents in cases of severe pathology.  

Treatment of Infections (Cholangitis): Given in cases of bacterial cholangitis, tends to cover Gram-negative organisms.  

Management of Complications:  

Portal Hypertension: They received beta-blockers to prevent variceal bleed and diuretics in case of ascites.  

Cirrhosis: Hepatorenal syndrome, infections, refractory ascites and spontaneous bacterial peritonitis management.  

Osteoporosis: Because these patients have impaired absorption of fat-soluble vitamins (A, D, E, K), vitamin replacement and bisphosphonates may become necessary to avoid bone disorders.  

Surveillance for Cancer: The – MRI or MRCP- and CA 19-9 levels blood test to track the signs and development of bile duct cancer. Every 1-2 years in patients with both PSC and IBD because the risk of Cholangiocarcinoma is much higher. 

Gastroenterology

Dietary Adjustments: A high fat and calcium complement is necessary because fat-soluble vitamins (A, D, E, K) and calcium are resistant to reduced bile flow. They may also avoid the use of alcohol to minimize the risk of harm caused to the liver.  

Sunlight Exposure: Taking vitamin D rich foods or getting as much sunshine as possible might help avert osteoporosis, which is not uncommon in PSC patients.  

Infection Control: As such, refraining from exposure to circumstances in which the probabilities for bacterial infection, such as cholangitis, tend to rise is vital, especially after procedures such as ERCP.  

Low-Sodium Diet: For patients with portal hypertension or ascites, it is always advisable to prescribed low salt diets to avoid cases of fluid consumption and related problems.

Gastroenterology

Azathioprine: It functions through altering the process of purine synthesis and thus reducing the formation of DNA, RNA and proteins. This helps to reduce the abundance of immune cells, which in turn would suppress autoimmune processes in the body.  

Cyclosporine: It turns out to be a cyclic polypeptide which acts mainly as an immunosuppressive agent by inhibiting cell mediated immunity – delayed hypersensitivity and allograft rejection and certain humoral immunity. Separately it is utilized in organ rejection prevention and some autoimmune disorders. Both adult and children’s doses are based on the ideal body weight.  

Prednisone: This is an immunosuppressive drug which is widely used to control auto immune disorders. It decreases inflammation by stabilising lysosomal membranes, decreasing the capillary permeability, and by inhibiting the function of polymorphonuclear cells. It also modulates the activity of lymphocyte and restricts the synthesis of antibodies as well. Methotrexate: This is an antimetabolite which is active in cancer treatment, severe psoriasis and rheumatoid arthritis. It interferes with the activity of dihydrofolate reductase, reducing the transformation of dihydrofolates to tetrahydrofolates which are crucial information of DNA and cell division. This disruption inhibits growth and repair of these cells. 

Gastroenterology

Penicillamine: It is an antidote, utilized mostly for Wilson’s disease to remove copper out of the body. This drug decreases the level of IgM rheumatoid factor and suppresses T- lymphocyte activity but has little effect on B- lymphocyte activity.

Gastroenterology

Ursodiol: It operates by lowering cholesterol formulation and release by the liver as well as decreasing the liver formation and release of cholesterol and the soaking up of cholesterol in the intestines. It might also replace toxic and endogenous BAs in the enterohepatic circulation and have a protective effect on hepatic cells. It can also decrease cholestasis and enhance the function of the liver in general, as well as assist with the proper circulation of the blood. 

Gastroenterology

Cholestyramine: It forms a complex with bile acids in the intestine which does not allow return to the hepatic circulation. In patients with partial biliary obstruction, this reduces the steep rise of serum bile acid concentration and thus reduces the amount of excess bile acids that mobilize in skin leading to pruritus.

Gastroenterology

Endoscopic Retrograde Cholangiopancreatography (ERCP):  

Stricture Management: Strictures in the bile ducts can be diagnosed and treated through the aid of ERCP. During the procedure, the use of a balloon or placing a stent can also assist in the clearance of the obstruction, enhancing the flow of bile and mitigating the occurrence of cholangitis. 

Cholangiography: ERCP also enables imaging of the bile duct pathology to determine further management plans.  

Biliary Stenting: However, when the patient has a lot of obstruction in the bile duct, stenting can ensure the patency of the ducts and encourage bile drainage and hence allow the reduction of complications including cholangitis and symptoms such as jaundice.  

Liver Transplantation: Therefore, for patients with E LSD or with severe complications for PSC, the liver transplantation is the only definitive treatment. It can increase the chances of living and the level of functioning with the chronic illness.  

Surgical Interventions: For patients with strictures that cannot be endoscopically treated, reconstructions of the bile duct may be performed for strictures in certain cases

Gastroenterology

There are several phases in the management of Primary Sclerosing Cholangitis or PSC. After first consultation the emphasis is made of X-rays, blood test and, finally, discussion of the disease with a patient. During the symptomatic management approach, therapy is focused on managing symptoms such as itching with drugs such as cholestyramine, adequate nutrition being provided. An important characteristic of the treatment process is frequent follow-ups to evaluate hepatic function and detect malignancies frequently associated with cirrhosis. These forms of treatment involve the intervention phase where the treatment plan involves ERCP for strictures as well as the liver transplant for patients with ELS. Finally, the maintenance phase which involves post-transplant follow-up health care and various supportive measures meant to enhance the overall well-being of PSC patients.