High IgG levels at diagnosis tied to worse PBC outcomes: Study
Treatment with UDCA shown to have favorable effects among patients
High blood levels of the antibody immunoglobulin G, or IgG, at diagnosis are linked to a more severe disease course among people with primary biliary cholangitis (PBC) who do not have irreversible liver scarring, known as cirrhosis.
That’s according to a new study from Greece that showed that IgG levels more than 1.5 times the normal upper limit were significantly linked to a 9.5 times greater chance of cirrhosis in this subgroup of patients. Further, these patients were found to have a 27 times greater likelihood of liver-related death.
IgG is an antibody type commonly linked to autoimmune diseases. Here, researchers examined the effected of increased IgG in people with PBC.
“This long-term study demonstrates that I-IgG [increased IgG] levels characterise a subgroup of non-cirrhotic PBC patients with faster disease progression and increased probability of liver-related death,” the researchers wrote, adding that “these patients could benefit from stricter follow-up” and earlier treatment with additional therapies.
The researchers noted that IgG normalization with first-line ursodeoxycholic acid (UDCA) treatment was found to have “a favourable effect on disease outcome” in this group of patients.
The study, “Increased IgG Levels at Diagnosis Are Associated With Worse Prognosis of Patients With Primary Biliary Cholangitis,” was published in the journal Liver International.
Investigating the impact of high IgG levels in PBC patients at diagnosis
Cholangitis refers to inflammation in the bile ducts, the tubes that carry bile, a digestive fluid, from the liver to the intestines, resulting in bile accumulation in the liver. This causes liver damage that may progress to cirrhosis and liver failure.
PBC is an autoimmune form of cholangitis that occurs when the immune system wrongly attacks healthy cells around bile ducts.
The disease is mostly associated with the presence of self-reactive antimitochondrial antibodies (AMAs), which target molecules in mitochondria, which serve as the powerhouses of cells. However, a large proportion of PBC patients also test positive for self-reactive antibodies that target molecules inside the cells’ nucleus, where genetic information is stored.
Self-reactive antibodies that drive autoimmune diseases are frequently of the IgG type. While a proportion of PBC patients have elevated amounts of blood IgG at diagnosis, “no data exist on the significance of increased IgG (I-IgG) levels on disease progression in PBC patients,” the researchers wrote.
To learn more, a team from the General University Hospital of Larissa in Greece retrospectively analyzed the medical records of PBC patients with available blood IgG levels at first evaluation, or diagnosis.
To ensure that cirrhosis was not contributing to elevated IgG, 592 patients who did not have cirrhosis at diagnosis were included in the analysis. Among them were 495 individuals with normal IgG and 97 who had increased levels at diagnosis.
Compared with patients with normal IgG, those with increased amounts were more often women (93.8% vs. 86.7%). They also were older at disease onset (median of 58 vs. 51 years) and diagnosis (60 vs. 54 years), and more frequently had other autoimmune diseases (36.1% vs. 23.6%).
The group with increased IgG also had higher blood levels of liver damage markers, and a higher proportion of these patients had PBC-specific antibodies targeting nucleus proteins (33.7% vs. 14.7%).
Higher levels linked to increased risk of cirrhosis, liver-related death
When analyzing outcome data from 514 patients who were followed for more than one year — 429 with normal IgG levels and 85 with high levels — those with increased IgG were more likely to develop cirrhosis and liver-related death, the data showed.
A total of 504 patients (85.1%) were given UDCA, the first-line therapy for PBC. Of them, 422 had normal IgG and 82 had increased amounts of the antibody. Among those with high levels, 43 experienced a normalization of antibody levels with treatment, while 39 continued to show elevated levels.
Patients who experienced a normalization of IgG levels with UDCA were also more likely to show a normalization of liver damage markers than those who maintained high IgG levels, the researchers found.
An analysis of 445 patients treated with UDCA and followed for over one year — with mean follow-up of about 6.5 years — demonstrated that a significantly higher proportion of patients with high IgG were estimated to develop cirrhosis at five years (7.2% vs. 1.8%). Accordingly, patients with higher IgG levels were less likely to experience a reversion of liver scarring.
The high IgG group also showed significantly elevated rates of overall death (14.1% vs. 5.6%) and liver-related death (5.6% vs. 1.3%). After five years, 1.5% of patients with high IgG and 0.4% of those with normal amounts were estimated to die due to liver-related causes, the study found.
We found a statistically significant correlation of higher IgG levels with the outcome of patients. … The higher the IgG level above the [upper limit of normal] the more severe the disease course was.
Further statistical analyses showed patients with IgG greater than 1.5 times the upper limit of normal (ULN) had a significantly increased risk of cirrhosis and liver-related death compared with those with lower IgG. The risk of cirrhosis was 9.5 times higher, while the risk of liver-related death was 27 times higher, per the data.
“We found a statistically significant correlation of higher IgG levels with the outcome of patients,” the team wrote, noting “the higher the IgG level above the ULN the more severe the disease course was.”
According to the team, this “large PBC cohort study” show that elevated IgG levels at a PBC diagnosis or initial evaluation is linked to a worse prognosis for patients, “as attested by increased frequency of disease progression and liver-related death during follow-up.” Further, among individuals with PBC who do not have cirrhosis, high IgG levels “were associated with a lower probability of response to UDCA treatment.”
The researchers noted that “normalisation of IgG levels during UDCA treatment seems to improve prognosis,” and suggested this subgroup of patients would be better served with close follow-up and “earlier administration of second-line treatments.”
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