Bile duct damage, loss may be sign of liver disease in sarcoidosis
Patients with liver complications more likely to have bile duct disease
Damage to and the loss of bile ducts, which are the tubes that carry the digestive fluid bile from the liver to the intestines, may be a sign of progressive liver disease among people with sarcoidosis, a study found.
Such abnormalities appeared independent of inflammation related to granulomas, the clusters of immune cells that cause sarcoidosis.
These findings were based on the examination of liver biopsy samples from sarcoidosis patients under a microscope.
“Biliary abnormalities may occur independently of granulomatous inflammation and can thus identify a subset of patients at risk for progressive liver disease,” the researchers wrote.
The study, “The Varying Histology of Hepatic Sarcoidosis and the Relation of Bile Duct Damage and Loss to the Presence of Portal Hypertension and Cirrhosis,” was published in the journal Gastro Hep Advances.
Biopsies from 53 patients used to help identify risk of liver problems
The liver is one of the organs affected by sarcoidosis, a disease characterized by the formation of clumps of activated immune cells called granulomas, which have the potential to disrupt function. Over time, granulomas can harden and cause permanent organ damage.
Liver involvement in sarcoidosis is often asymptomatic or discovered by accident, but when symptoms do emerge, patients usually have abdominal pain, itching, fever, night sweats, and weight loss. In more severe cases, patients may develop high blood pressure in the veins that pass through the liver, called portal hypertension, as well as cirrhosis (severe scarring) or liver failure.
Identifying sarcoidosis of the liver, or hepatic sarcoidosis, can be challenging but may involve looking for abnormal liver function tests, an enlarged liver, liver nodules, or swollen lymph nodes. In those with suspected sarcoidosis and abnormal liver function tests, a liver biopsy can often confirm the presence of granulomas and establish a hepatic sarcoidosis diagnosis.
Still, few studies have compared liver tissue samples examined under a microscope, known as histology, with complications related to hepatic sarcoidosis.
“Our study aimed to examine liver histology to assess disease severity better and help identify patients potentially at risk for developing portal [hypertension] and cirrhosis,” the researchers wrote.
The team at the Icahn School of Medicine at Mount Sinai, in New York, examined histology samples from 53 people with hepatic sarcoidosis who had undergone a liver biopsy. Patients were divided into two groups: 33 with portal hypertension and/or cirrhosis and 20 without either of these complications.
Bile duct damage seen in 85% of sarcoidosis patients with liver complications
The most common other organs involved in patients with and without portal hypertension included the lungs (73% vs. 75%), lymph nodes (36% vs. 35%), and skin (18% vs. 15%). Spleen involvement was seen in 21% of those with portal hypertension/cirrhosis, whereas granulomas affected the eyes of 15% of patients without these complications.
When examined under a microscope, certain disease-related features — including the location, type, and number of granulomas in the liver — were similar between the two groups.
In contrast, more severe scarring, or fibrosis, of liver tissue occurred significantly more often in patients with portal hypertension or cirrhosis, alongside mild inflammation in certain regions of the liver.
Twice as many patients with hypertension/cirrhosis had nodular regenerative hyperplasia, or the growth of nodules within the liver (42.2% vs. 20%), and venous outflow obstruction (18.2% vs. 10%), a blockage of blood flowing out of the liver, than those without complications.
Researchers then examined the bile ducts, a series of tubes that carry bile from the liver to the small intestines to aid in digestion.
Significantly more patients with portal hypertension/cirrhosis had signs of bile duct disease than those without. Nearly half of patients with these complications had bile duct loss, while 85% had biliary damage. Among those without, loss of bile ducts was seen in 15% and damage in 55%.
Ductular reaction, or the excessive growth of bile duct cells due to advanced chronic liver disease, was also significantly more common among those with complications, affecting 82% of this group and 50% of those without complications.
The presence of bile duct loss or damage on liver biopsy might identify patients with a greater risk of progression of their liver disease.
Researchers pointed out that one in four patients had some degree of steatosis, the abnormal buildup of fat in the liver, which in some cases “could [influence] the typical abnormal liver biochemistries noted in patients having hepatic sarcoidosis.”
A thorough examination of liver samples from patients with complications revealed seven cases of cirrhosis. All except one showed evidence of biliary cirrhosis, or the formation of scar tissue in the liver due to prolonged obstruction or damage to the bile ducts. Although the extent of biliary fibrosis was greater in samples showing advanced fibrosis and cirrhosis than in those with minimal fibrosis, the number of granulomas was similar across all samples.
In blood tests, markers for liver damage, called alkaline phosphatase, and granulomas, known as angiotensin-converting enzyme, were elevated in patients with portal hypertension/cirrhosis. At the same time, platelet counts and levels of albumin, a protein produced by the liver, were lower in this group.
Finally, an examination of liver samples from seven patients who underwent multiple biopsies revealed granulomas changed locations across different regions of the liver over time and showed worsening ductular reactions.
“Our findings demonstrate that patients with hepatic sarcoidosis had [nodular regenerative hyperplasia], outflow obstruction, and advanced biliary fibrosis as the [cause] for their portal [hypertension],” the scientists wrote. “There was no correlation with the degree or extent of granulomatous inflammation.”
While “the presence of bile duct loss or damage on liver biopsy might identify patients with a greater risk of progression of their liver disease,” more studies are needed on the role of liver biopsies in sarcoidosis, the team concluded.
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