AUTOIMMUNE HEPATITIS-PRIMARY SCLEROSING CHOLANGEITIS
Autoimmune hepatitis, formerly called lupoid hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body’s immune system attacks liver cells causing the liver to be inflamed. Common initial symptoms include fatigue or muscle aches or signs of acute liver inflammation including fever, jaundice, and right upper quadrant abdominal pain. Individuals with autoimmune hepatitis often have no initial symptoms and the disease is detected by abnormal liver function tests.
Anomalous presentation of human leukocyte antigen (HLA) class II on the surface of liver cells, possibly due to genetic predisposition or acute liver infection, causes a cell-mediated immune response against the body’s own liver, resulting in autoimmune hepatitis. This abnormal immune response results in inflammation of the liver, which can lead to further symptoms and complications such as fatigue and cirrhosis. The disease may occur in any ethnic group and at any age, but is most often diagnosed in patients between age 40 and 50.
Though there is a strong female predominance, men are also at risk for the disease. Patients may present with signs of chronic liver disease (abnormal liver function tests, fatigue, aches) or acute hepatitis (fever, jaundice, right upper quadrant abdominal pain).
“Autoimmune hepatitis usually occurs in women (70 %) between the ages of 15 and 40. Although the term “lupoid” hepatitis was originally used to describe this disease, patients with systemic lupus erythematosus do not have an increased incidence of autoimmune hepatitis and the two diseases are distinct entities. Patients usually present with evidence of moderate to severe hepatitis with elevated serum ALT and AST activities in the setting of normal to marginally elevated alkaline phosphatase and gamma-glutamyltranspeptidase activities. The patient will sometimes present with jaundice, fever and right upper quadrant pain and occasionally systemic symptoms such as arthralgias, myalgias, polyserositis and thrombocytopenia. Some patients will present with mild liver dysfunction and have only laboratory abnormalities as their initial presentation. Others will present with severe hepatic dysfunction.”[
The diagnosis of autoimmune hepatitis is best achieved with a combination of clinical, laboratory and histological findings after excluding other etiological factors (e.g. viral, hereditary, metabolic, cholestatic, and drug-induced diseases).
A number of specific antibodies found in the blood (antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), liver/kidney microsomal antibody (LKM-1, LKM-2, LKM-3), anti soluble liver antigen and liver–pancreas antigen (SLA/LP) and anti-mitochondrial antibody (AMA)) are of use, as is finding an increased Immunoglobulin G level. However, the diagnosis of autoimmune hepatitis always requires a liver biopsy.
Expert opinion has been summarized by the International Autoimmune Hepatitis Group, which has published criteria which utilize clinical and laboratory data that can be used to help determine if a patient has autoimmune hepatitis. A calculator based on those criteria is available online.]
Overlapping presentation with primary biliary cirrhosis and primary sclerosing cholangitis has been observed.
Primary sclerosing cholangitis (PSC) is a disease of the bile ducts that causes inflammation and obliterative fibrosis of bile ducts inside and/or outside of the liver. This pathological process impedes the flow of bile to the intestines and can lead to cirrhosis of the liver, liver failure, and other complications, including bile duct and liver cancer. The underlying cause of the inflammation remains unknown, but elements of autoimmunity and microbial dysbiosis have been described and are suggested by the observation that approximately 75% of individuals with PSC also have inflammatory bowel disease (IBD), most often ulcerative colitis. The most defPrimary sclerosing cholangitis (PSC) is a disease of the bile ducts that causes inflammation and obliterative fibrosis of bile ducts inside and/or outside of the liver. This pathological process impedes the flow of bile to the intestines and can lead to cirrhosis of the liver, liver failure, and other complications, including bile duct and liver cancer. The underlying cause of the inflammation remains unknown, but elements of autoimmunity and microbial dysbiosis have been described and are suggested by the observation that approximately 75% of individuals with PSC also have inflammatory bowel disease (IBD), most often ulcerative colitis. The most definitive treatment for PSC is liver transplantation, though only a fraction of individuals with PSC will ultimately require it.
Many patients with PSC are asymptomatic, but a substantial proportion will have debilitating signs and symptoms of the disease. These may include:
- Pruritus (itching), which may be severe.
- Severe fatigue (a non-specific symptom often present in liver disease)
- Jaundice and scleral icterus (yellowing of the white of the eyes)
- Episodes of acute cholangitis (infection within the bile ducts), which can be life-threatening
- Dark urine due to excess conjugated bilirubin, which is water-soluble and excreted by the kidneys (i.e. choluria)
- Malabsorption (especially of fat) and steatorrhea (fatty stool) due to an inadequate amount of bile reaching the small intestine, leading to decreased levels of the fat-soluble vitamins, A, D, E and K.
- Hepatomegaly (enlarged liver due to portal hypertension caused by compression of portal veins by the proximate sclerosed intrahepatic bile ducts) and right upper quadrant abdominal pain
- Portal hypertension, a complication of Cirrhosis, which can manifest with esophageal and parastomal varices as well as hepatic encephalopathy (mental status alteration/disturbance caused by liver dysfunction and shunting of blood away from the scarred liver; such that ammonia detoxification is reduced with concomitant encephalopathy)
- PSC is generally diagnosed on the basis of having at least two of three clinical: serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal, cholangiography demonstrating biliary strictures or irregularity consistent with PSC, and liver histology (if available). Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals “beading” (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its non-invasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.
- Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear anti-neutrophil cytoplasmic antibodies; however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20%-50% of PSC patients and, likewise, are not specific for the disease but may identify a subgroup of PSC patients who also have auotimmune hepatitis (i.e. PSC-AIH overlap syndrome)
- Other markers which may be measured and monitored are a complete blood count, serum liver enzymes, bilirubin levels (usually grossly elevated), kidney function, and electrolytes. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea) are prominent.
- The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation non-anastomotic biliary strictures, and HIV-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease response to treatment, and risks of disease progression.