Primary biliary cholangitis and primary sclerosing cholangitis: Clinical sciences

Primary biliary cholangitis, or PBC, and primary sclerosing cholangitis, or PSC, are immune-mediated cholestatic liver diseases associated with inflammation and destruction of bile ducts.

Although these disorders present with common clinical features, PBC affects biological females more and targets small intrahepatic bile ducts; whereas PSC occurs more frequently in biological males and is characterized by damage of medium to large extrahepatic and intrahepatic bile ducts.

Ultimately, both conditions can lead to subsequent bile leakage into the liver parenchyma. Over time, this can result in liver complications, such as liver fibrosis and cirrhosis. Now, primary biliary cholangitis and primary sclerosing cholangitis can be differentiated based on right upper quadrant imaging findings.

Okay, if a patient presents with chief concerns suggesting primary biliary cholangitis or primary sclerosing cholangitis, your first step is to perform a focused history and physical exam. History typically reveals symptoms such as severe fatigue and pruritus, but some individuals might also report right upper quadrant pain. Additionally, there might be a history of autoimmune conditions like inflammatory bowel disease or Sjögren syndrome.

The physical examination might reveal jaundice and skin excoriations due to severe pruritus; as well as yellowish skin deposits of cholesterol called xanthomas, which, when present around the eyelids, are called xanthelasmas. In advanced cases, you might find hepatomegaly, splenomegaly, and, if the synthetic function of the liver is severely compromised, you might notice ascites and peripheral edema!

With these findings, you should suspect liver disease, so your next step is to order labs to differentiate hepatocellular disease and cholestatic liver disease. However, it’s important to note that it’s not all black and white, and some liver diseases can have mixed features of both hepatocellular and cholestatic disease.

Okay, so your labs should include liver function tests, like aspartate aminotransferase or AST, alanine transaminase or ALT, alkaline phosphatase or ALP, and bilirubin, to assess for hepatocellular damage; as well as albumin levels, and coagulation studies checking PT and INR to assess the synthetic function of the liver.

Hepatocellular disease is typically characterized by elevated AST and ALT out of proportion to the ALP, and may lead to elevated bilirubin, and in some cases, there may be low albumin levels; and decreased coagulation factors leading to elevated PT and INR. In such cases, consider an alternative diagnosis. Examples include viral hepatitis, alcoholic hepatitis, non-alcoholic fatty liver disease, hemochromatosis, or even cirrhosis.

On the other hand, cholestatic liver disease is characterized by elevated ALP out of proportion to the AST and ALT, as well as elevated bilirubin levels. In addition, cholestatic liver disease can also impair bile flow within the liver, so albumin and coagulation studies might also be affected. If that’s the case, you should suspect cholestatic liver disease and obtain a right upper quadrant abdominal ultrasound.

Now, here’s a high-yield fact! Elevated serum ALP can also indicate other factors like bone disease. To determine the source, you can obtain a serum gamma-glutamyl transpeptidase, or GGTP, which is mainly produced in the liver. If both GGTP and ALP are elevated, then the most likely source of the elevated ALP is the liver.

Now, let’s look at the results of the right upper quadrant ultrasound. If the ultrasound shows extrahepatic biliary obstruction with no intrahepatic involvement, consider an alternative diagnosis. Including pancreatic mass or obstructive cholelithiasis, also known as choledocholithiasis, which is specifically the presence of gallstones in the common bile duct.

Now, let’s look at the opposite scenario. If you see a normal ultrasound, and there is no extrahepatic biliary obstruction, this suggests destruction of the small intrahepatic bile ducts; you should suspect primary biliary cholangitis.

Now, keep in mind that conditions other than PBC can also present with an increased ALP and a normal ultrasound. These conditions include sarcoidosis, autoimmune hepatitis, and medication side effects, such as phenothiazines and trimethoprim-sulfamethoxazole. So, to confirm the diagnosis, you should obtain a serum antimitochondrial antibody or AMA for short. If it is positive, diagnose primary biliary cholangitis!

Here’s a clinical pearl to keep in mind! Serum AMA is positive in most cases of PBC and is considered diagnostic of this condition. However, if AMA is negative but there’s still a high clinical suspicion of PBC, consider performing a liver biopsy. In early PBC, liver biopsy results show lymphocytic infiltration and destruction of small or medium-sized bile ducts.

And another high-yield fact! PBC is often linked with CREST syndrome, which stands for Calcinosis, Raynaud phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasias. PBC can also be associated with other autoimmune conditions, such as Sjögren syndrome, scleroderma, and Hashimoto thyroiditis.

Now, let’s take a look at the management of PBC. This primarily relies on medications that help slow down the progression of the disease, like ursodeoxycholic acid. If your patient doesn’t respond well to this medication or can’t tolerate it, you can give obeticholic acid, which works by decreasing bile acid synthesis.

Next, add symptomatic treatment for pruritus, such as antihistamines or cholestyramine; and don't forget osteoporosis prevention with calcium and vitamin D supplementation.