Poor primary biliary cholangitis outcomes tied to two antibodies
Testing positive for both could be used with PBC-specific GLOBE risk score
Testing positive for the self-reactive anti-gp210 and anti-centromeric antibodies significantly increases the risk of poor liver-related outcomes for people with primary biliary cholangitis (PBC), a study shows.
The antibodies could be used alongside the PBC-specific GLOBE risk score to better understand the likelihood of poor liver-related outcomes.
Testing positive for both self-reactive antibodies “was an independent prognostic marker that could predict a poor prognosis in patients with PBC at diagnosis and may further optimize risk stratification in combination with the GLOBE scoring system,” the researchers wrote.
The study, “The prognostic value of anti-gp210 and anti-centromere antibodies in patients with primary biliary cholangitis: Enhancing the prognostic utility on the GLOBE scoring system,” was published in Digestive and Liver Disease.
Cholangitis refers to inflammation of the bile ducts, the tubes that carry the digestive fluid bile from the liver to the intestines. This causes bile to accumulate to toxic levels in the liver, damaging the organ. Left untreated, the disease can lead to cirrhosis, or irreversible liver scarring, and liver failure.
PBC is a chronic, autoimmune form of cholangitis that occurs when the immune system attacks healthy cells in or around bile ducts. The disease is mostly associated with the presence of self-reactive antimitochondrial antibodies (AMAs), which target molecules in mitochondria, the cell’s powerhouses. However, a large proportion of PBC patients also test positive for antibodies that target molecules inside the cells’ nucleus, where genetic information is stored. One such antibody targets the gp210 protein and is associated with poor outcomes in PBC.
Anti-centromeric antibodies (ACAs), which target a specialized region on chromosomes — the thread-like structure made up of DNA that’s located in the nucleus — have also been detected in PBC patients, but its prognostic value remains controversial.
The GLOBE scoring system classifies PBC patients as low-, medium-, and high-risk of needing a liver transplant or dying based on patient age and markers of disease severity in the blood.
Self-reactive antibodies may aid in determining prognosis
Still, “the potential of anti-gp210 antibody and ACA status to enhance the prognostic value of the risk-scoring system… remains to be determined,” wrote researchers in China who evaluated both antibodies’ prognostic role in PBC progression and if their status could boost the GLOBE score system’s ability to predict outcomes.
The researchers analyzed data from 1,412 Chinese people with PBC (85% women) who were a mean age of 53 and were followed for a mean of six years.
About 1 in 10 patients (11%) needed a liver transplant or had a liver-related death, 9% had variceal hemorrhage, a sign of liver disease marked by bleeding from the veins in the gastrointestinal tract, and 24% showed disease progression, based on liver tissue analysis.
A total of 439 patients (31.1%) tested positive for anti-gp210 antibodies, 266 (18.8%) for ACAs, and 69 (4.9%) had both.
Having anti-gp210 antibodies was a significant risk factor for needing a liver transplant or liver-related death, while testing positive for ACAs was a significant risk factor for variceal hemorrhage, statistical analyses showed.
Patients with both anti-gp210 antibodies and ACAs showed higher rates of several poor liver-related outcomes, including variceal hemorrhage, cirrhosis (irreversible liver scarring), and liver-related death or liver transplant.
This double antibody status was found to be a significant risk factor for liver transplant/liver-related death, regardless of GLOBE scores, and combining antibody status with the score system could more accurately predict such outcomes.
When patients were classified into low-, medium-, and high-risk groups on the basis of their GLOBE scores, the PBC patients that tested positive for both self-reactive antibodies had worse outcomes relative to those who were positive for anti-gp210 antibodies alone and those who were negative for anti-gp210 antibodies.
Specifically, over five years, double antibody status was significantly associated with a 1.5 to two times greater likelihood of needing a liver transplant or having a liver-related death among the high-risk group and a three times higher risk of those outcomes in the medium-risk group. Testing positive for both antibodies was a risk factor for liver failure over those who only tested positive for anti-gp210 antibodies.
“These findings may inform future recommendations for PBC treatment to integrate anti-gp210 antibody and ACA status assessments into decision-making algorithms,” the researchers wrote.
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