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Originally published June 1, 2026
Last updated June 1, 2026
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When patients have an autoimmune liver disease, their immune cells attack one of their liver’s two main types of cells: hepatocytes and cholangiocytes. Hepatocytes perform most of the liver’s metabolic functions, while cholangiocytes modify and move bile from the liver to the small intestine.
The primary autoimmune disease that targets the hepatocytes is called autoimmune hepatitis (AIH). The diseases that strikes the cholangiocytes are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
AIH is more common among the three; PSC, though rare, occurs more commonly among patients with inflammatory bowel disease such as Crohn’s disease and ulcerative colitis. Some patients have features of two diseases at the same time, such as presenting with both AIH and PBC, or both AIH and PSC.
“In many patients, the immune cells don’t discriminate, and they attack both types of cells,” says Lily Dara, MD, a hepatologist with the USC Liver Health Center, part of the USC Digestive Health Institute and Keck Medicine of USC. She specializes in the clinical treatment and research of rare and complex liver diseases, including autoimmune liver diseases.
What causes the immune system to work against the liver is, unfortunately, unclear. “We don’t fully understand why some people get autoimmune liver disease, although there are certain genes that seem to predispose patients to autoimmunity,” Dara says, adding that there does seem to be a genetic association with AIH.
In these diseases, immune cells attack and destroy the liver cells, resulting in chronic inflammation. If uncontrolled, the inflammation can lead to fibrosis — which in turn can progress to chronic liver disease, cirrhosis, cancer, liver failure and the need for a liver transplant.
“It’s very important to diagnose and treat these chronic autoimmune liver diseases in a timely manner so the patient does not develop chronic liver disease,” says Dara, who treats patients at Keck Hospital of USC, USC Norris Cancer Hospital and Keck Medicine of USC’s new Pasadena location at 590 S. Fair Oaks Ave.
Often, people who have undiagnosed AIH or PBC experience nonspecific symptoms such as fatigue and itching. While roughly 20% to 25% of people with AIH present with an acute flare — involving nausea or abdominal pain, very elevated liver enzymes and even jaundice — the symptoms can be silent in most people with AIH. Strikingly, in AIH, for example, roughly one out of three patients, or 30%, are diagnosed when they are already cirrhotic.
To help diagnose AIH, PBC and PSC, primary care physicians should pay attention to their patients’ liver enzyme levels — specifically, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP).
“On annual labs, physicians should be on the lookout for abnormal liver enzyme results,” Dara advises. “More often than not, it’s the primary care physician who picks up on the disease with abnormal AST-ALT or ALP results.”
Sadly, many people’s elevated liver enzymes get ignored, even when they’re in the early stages of autoimmune liver disease. “Sometimes the abnormalities in the lab results are subtle,” Dara says. “However, abnormalities in AST-ALT and ALP, even if minor, should be taken seriously.”
When it comes to PBC, a test that identifies the presence of the antimitochondrial M2 antibody (AMA-M2) generally confirms the diagnosis. This antibody is present in about 85% to 90% of patients with this disease. If the AMA antibody is not present, but the suspicion for abnormality is high, special tests and often a liver biopsy are performed.
Because the diagnosis of AIH is more complicated, a liver biopsy is usually always required to confirm it. “It is very important to make sure the diagnosis is accurate before we put someone on high-dose, lifelong immunosuppression,” Dara says.
PSC is strongly associated with inflammatory bowel disease (IBD), but it is a rare disease that can manifest even in the absence of colitis. It is typically diagnosed by a special type of MRI called magnetic resonance cholangiopancreatography (MRCP) in patients who have elevated ALP enzymes. Although rarely, some patients may need a liver biopsy. These patients can be asymptomatic or present with fatigue, itching, jaundice and infection. The MRI shows a specific pattern called “beading” of the bile ducts, and this confirms the diagnosis.
“The concern for PSC is that it significantly increases the lifetime risk of bile duct and liver cancer,” Dara says. “This places a huge psychological burden on the patients on top of their symptoms.”
Autoimmune liver diseases are more common in women, but that reality isn’t specific to the liver. “AIH and PBC tend to occur more in women,” Dara says. The reason for the gender imbalance is unknown, though it may be related to hormones, she notes.
That said, PSC, which typically involves the large bile ducts, is more common in men than women. “Just because these diseases are rare in men doesn’t mean men don’t get them,” Dara points out.
Autoimmune liver diseases affect all ethnicities and races. These diseases also can happen at any age, with one caveat: unlike AIH and PSC, PBC doesn’t appear to occur in children.
Aside from gender, having other autoimmune disorders — such as hypothyroidism, lupus, rheumatoid arthritis, etc. — is also a risk factor for developing autoimmune liver disease. With PSC, it’s very common to also have inflammatory bowel disease.
For PBC, the first line of treatment is ursodeoxycholic acid (UDCA), which brings down ALP levels and inflammation, and has been clearly shown to improve patient survival. Still, about 40% of patients with PBC do not fully respond to UDCA. For these individuals, two newly FDA-approved medications, elafibranor and seladelpar, can bring down their ALP levels even further.
For AIH, the treatment is more limited: patients receive steroids along with some steroid-sparing immunosuppressive agents. “There’s been a lot of push from the hepatology community to get more research to find better steroid-sparing agents for people suffering from AIH,” Dara says.
PSC remains one of the most difficult diseases to treat as there are no known disease-modifying treatments. The PSC community, however, has been very influential in lobbying for therapies, and the good news is there seems to be some momentum and a number of drugs and clinical trials in development.
Last year, Keck Medicine opened its newest Pasadena location at 590 S. Fair Oaks Ave., where specialists treat a wide range of conditions, including autoimmune liver disease. Dara says this autoimmune liver clinic focuses on a multidisciplinary, collaborative approach involving specialists focused on immune disorders in various organs and their overlapping conditions. These include hepatology, gastroenterology — specifically for IBD like ulcerative colitis and Crohn’s disease — rheumatology, neurology, dermatology and allergies.
“When you have a rare disease, you really want to see a rare-disease specialist. And a lot of our patients have multiple autoimmune disorders, so coordinating their care and being on the same page about their immunosuppression is very important,” she concludes.
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