Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver disease characterized by fibrosis and inflammation of intra- and extrahepatic biliary ducts. The course of the disease varies from person to person, and may lead to liver cirrhosis and associated complications.
The course of the disease varies from person to person. When symptomatic, most of the patients present with pain in the upper right quadrant, jaundice, fatigue and pruritus. Symptoms undergo remission and exacerbations. Symptoms resemble acute cases of hepatitis in some. Some not so common symptoms include hyperpigmentation, xanthomas, and xantelasma . Around 10-15% of the patients show febrile episodes that disappear spontaneously without any specific treatment, a typical symptom of bacterial cholangitis. Those with portal hypertension and cirrhosis present with esophageal varices, encephalopathy and ascites.
Fever, gallbladder and biliary stones, abdominal pain, biliary tract strictures and cholangiocarcinoma are some of the complications associated with PSC. About one third of the patients with PSC have gallstones . About 15%-20% of the patients present with dominant strictures in common bile duct or common hepatic duct . Acute onset of jaundice, fever and pruritus are the clinical manifestations of strictures. PSC also increases the risk of cholangiocarcinoma .
Liver function tests are the most important diagnostic tests for PSC. Levels of serum alkaline phosphatase, serum aminotransferase, and hypergammaglobulinemia are confirmatory measures in this condition. Serum alkaline phosphatase levels tend to increase 3-5 times than normal. Gamma-glutamyl transpeptidase levels also rise simultaneously and help to differentiate PSC from bone disease. Patients with IBD present with hypoalbuminemia. About half of the patients with this disease have elevated levels of IgM. Antinuetrophil cytoplasmic antibodies and anticardiolipin measures also show an increase in most of them.
Endoscopic retrograde cholangiopancreatography (ERCP) is the imaging technique used in confirmatory diagnosis of PSC. Strictures and hepatic duct dilations can also be located and defined through ERCP. When ERCP is unsuccessful in diagnosis, transhepatic cholangiography is recommended. Magnetic resonance cholangiopancreatography is also being used in the diagnosis of PSC.
Histological features of liver are not always diagnostic for PSC. Some of the early histological features are ‘onion skin’ fibrosis, portal edema and expansion of portal ducts. Necrosis and portal phlebitis may also be seen in some.
There is no effective, standard cure for PSC. Treatment methods normally used aim at improving the symptoms and to manage complications associated with the condition. Any treatment modality used depends on the stage of the disease. Patient often needs to be monitored frequently for complications. Pruritus is controlled by cholestyramine with gradual increase in the dose until the symptoms are relieved. Rifampicin and naltrexone are used as next line treatment. Those with jaundice should be given replenishment of fat soluble vitamins, calcium, and vitamin D3.
For acute cholangitis, broad spectrum antibiotics are suggested. Endoscopic dilation of the duct is considered when well defined obstruction is located. For prominent strictures, stenting may be helpful. Biliary stones and biliary sludge are two complications often associated with PSC. Endoscopic sphincterotomy with duct extraction leads to improvement in the symptoms.
Ursodeoxycholic acid when used in combination with endoscopic stenting or dilation has shown to improve the survival rate . Patients with variceal bleeding and portal gastropathy are considered for liver transplantation. Other indications include hepatic encephalopathy, recurrent cholangitis, and ascites. Survival rate for liver transplantation ranges from 69.8% to 93.7%, with the highest for transplantation done within a year. Recurrence is noted in 20% patients after one year of transplantation. But recurrence has not been found to cause liver decompensation to the extent of going for another transplantation. Patients with ulcerative colitis may opt for proctocolectomy. Good outcome is also seen for resection of extrahepatic biliary tree followed by stenting. Patients with PSC and ulcerative colitis are at an increased risk of developing colon cancer and hence should undergo colonoscopy every year.
PSC is a progressive disease that results in portal hypertension and liver cirrhosis. Median length of survival from diagnosis is reported to be 12 years. Liver transplantation is a treatment modality that has a good prognosis. If symptoms are present at the time of diagnosis, prognosis is poor. Factors that affect prognosis in a patient include age, serum bilirubin and albumin, and history of variceal bleeding . Severity of disease is based on levels of bilirubin and albumin and prothrombin time. Presence of ascites, and grade of encephalopathy also influence outcome of the disease .
The actual etiology of the disease is not defined yet, but many factors are presumed to be responsible for the development of PSC. Some of the causative factors include absorption of toxins from the colon, ischemic injury, portal bacteremia, viral infections, and genetic predisposition. Autoimmunity is the accepted factor as the most common underlying cause of PSC. This is supported by the fact that about 75%-80% of the patients with PSC have IBD. Most of the patients present with hypergammaglobulinemia, while smooth muscle antibodies and antinuclear factors are also elevated, but at low titers.
Theories suggest that recurrent bacterial infection in the portal circulation and exposure to toxic components trigger an inflammatory response . HLA-B8, HLA-DR3, and HLA-Drw52a alleles have an increased prevalence in patients with PSC, suggesting a genetic predisposition . A number of susceptible loci have been identified that increases the risk of this disease. Exposure of genetically susceptible individuals to environmental triggers like infection and toxins, elicits an autoimmune reaction that leads to the development of this chronic condition.
Prevalence of PSC in many countries is not known. The condition is found to be closely associated with another inflammatory disease, IBD. The prevalence of PSC in patients with IBD is found to vary in different studies. Prevalence of IBD in patients with PSC ranges from 23% to 100% in different countries . Onset of the disease happens usually around the age of 20-30 years, but reports of childhood occurrence are also present. It is a progressive disease and may remain undiagnosed for a long period of time.
One of the studies shows that the prevalence of PSC is 2 to 4 times higher among Jewish population. About 70% of the patients with PSC are men with mean age of onset or diagnosis as 40 years. But, PSC without IBD is found to be more common in women with the mean age of diagnosis higher than that of men.
PSC is characterized by thickening and induration of the bile duct. As the disease progresses, the liver may become nodular in appearance. In the first stage of pathogenesis, epithelial cells of the bile duct degenerate forming the primary lesion. This is followed by infiltration of bile duct by lymphocytes and neutrophils. This progresses into inflammation, scarring and enlargement of the portal triad. In the next stage, inflammation and fibrosis spread to the periportal parenchyma resulting in destruction of periportal hepatocytes and necrosis of liver. Enlargement of portal triads is characteristic in this phase of the disease. Portal to portal fibrous septa formation ensues enlargement and bile ducts undergo degenerative changes. In the last stage cirrhosis is prominent.
Patients with PSC show a significant increase in the circulating immune complexes in the serum and bile. These complexes are associated with activation of complement system resulting in autoimmune response. T-suppressor cells reduce in the serum leading to altered T-helper to T-suppressor ratio. Activated-lymphocytes leads the infiltration into portal ducts. Immune complex increase may result from any of the environmental triggers in a genetically susceptible person.
Bacterial infection, as per another theory, leads to production of tumor necrosis factors and endotoxins through reaction with bacterial cell wall products. IBD is presumed to increase the risk of this reaction. Increased levels of cytokines activate neutrophils, fibroblasts, T cells and macrophages. Fibrosis result in atrophy of biliary epithelial cells leading to cholestasis, fibrosis and secondary biliary cirrhosis.
As the etiology of the disease is not defined, preventive measures are not known.
Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver disease characterized by fibrosis and inflammation of intra- and extrahepatic biliary ducts. The course of the disease varies and it may lead to liver cirrhosis and other complications. It is commonly associated with inflammatory bowel disease (IBD), particularly ulcerative colitis.
The etiology of the disease is not clearly defined, but autoimmune responses are presumed to be an important factor. Diagnosis of PSC is based on clinical, biochemical and radiological features. Beaded appearance of the bile ducts on cholangiography is indicative of PSC . It is more commonly seen among men and the mean age at diagnosis is around 40 years. It is less common than alcoholic liver disease, but is one of the leading cause for liver transplantation in the US. As an effective treatment modality is yet to be worked out, symptomatic treatment and management of complications are the steps in therapy now. Liver transplantation is the only method that gives a good prognosis.
Primary sclerosing cholangitis (PSC) is a chronic liver disease in which the bile ducts progressively undergo scarring and inflammation, narrowing the lumen. It may be seen alone or in association with ulcerative colitis. The disease progresses gradually and may lead to liver failure, infections of the liver, and tumors in the organ. The actual cause of PSC is not known yet. It is presumed that in people who are susceptible to the disease, infections or exposure to toxins trigger PSC. Some factors like age, gender, and inflammatory bowel disease, increase the risk of developing this disease. It is more prevalent in the age group of 30 to 50 years and occurs more frequently in men when compared to women. A major proportion of people with inflammatory bowel disease also have PSC.
Many patients remain asymptomatic for several years. Sometime it is diagnosed during a laboratory test or imaging indicated for the diagnosis of some other condition. Some of the early symptoms of the disease include fatigue, pain in the upper right part of the abdomen. Enlarged liver, weight loss and jaundice are also commonly seen. Some of the complications of PSC include liver failure, repeated infections, hypertension in portal veins, thinning of bones, cancer of bile duct, and colon cancer.
Liver function tests are the major tests used in the diagnosis of PSC. Magnetic resonance cholangiopancreatography is used to obtain images of the bile ducts and liver. This non-invasive procedure helps in identifying and defining the problem. Endoscopic retrograde cholangiopancreatography is the imaging method of choice to get an image of the ducts and liver. Biopsy of liver tissue is used to assess the extent of damage to the liver.
There are no known standard, effective treatments for PSC. Any method suggested aims at monitoring the health of liver and to control the complications. As the bile duct narrows due to fibrosis and inflammation, bile backs up and this may result in repeated infections. Antibiotics are recommended in case of repeated infections. Absorption of vitamins are affected in this condition and hence replenishing vitamins through supplementation is very important. If bone thinning is one of the symptoms, vitamin D and calcium supplementation are also needed. Block in the bile ducts can be cleared by balloon dilation or stenting. The only treatment known to cure and give a good prognosis is liver transplantation. This is usually recommended for people with liver failure or other severe complications. In some rare cases, PSC may recur in patients after liver transplantation.