Elevated levels of the antibody immunoglobulin G (IgG) in patients newly diagnosed with primary biliary cholangitis (PBC) were associated with a higher risk of cirrhosis and liver-related death, making early monitoring and intervention critical, according to a study published recently in Liver International.
This recent study of 675 patients with PBC, including 592 without cirrhosis, found that individuals with increased levels of IgG at the time of diagnosis had worse disease progression compared to those with normal levels of IgG. However, normalizing levels of IgG through treatment with ursodeoxycholic acid (UDCA) was linked to improved outcomes, suggesting that patients with increased IgG could benefit from closer follow-up and early add-on treatments.
Among the non-cirrhotic patients, 97 had increased levels of IgG. This group was more often female and had a higher incidence of other autoimmune diseases. They also had higher frequencies of specific autoantibodies, including PBC-specific ANA, sp100 and gp210, compared to the 495 patients with normal IgG. Patients with increased IgG were diagnosed at an older age and had lower albumin levels, along with elevated markers of liver inflammation, including AST, ALT, ALP, γGT, and IgM.
“[T]his long-term follow-up study demonstrated that increased IgG levels at baseline characterize a subgroup of non-cirrhotic PBC patients with faster disease progression and increased probability of liver-related death (the higher the IgG level the worse outcome),” explained the authors of this study. “These patients could benefit from stricter follow-up and earlier administration of second-line treatments, as normalization of IgG levels during UDCA treatment in the present study seems to improve prognosis, even though future large-scale studies are needed to definitely address this point.”
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Over time, patients with increased IgG were significantly more likely to develop cirrhosis and face liver-related death. Those with levels of IgG exceeding 1.5 times the upper limit of normal had the highest risk, with a hazard ratio of 9.5 for cirrhosis and 27.1 for liver-related death. However, patients who saw their IgG levels normalize after a year of treatment with UDCA had a much better prognosis. These individuals had outcomes similar to those with normal IgG, including a lower risk of the development of cirrhosis.
Long-term analysis also revealed differences in liver stiffness between the groups. Patients with normal IgG had a greater likelihood of regression of liver stiffness, indicating a potential slowing of disease progression. In contrast, fibrosis progression was more common in those with persistent increased IgG. This suggests that levels of IgG may serve as an important biomarker for tracking severity of disease and response to treatment.
Despite these findings, there was no significant difference in the percentage of patients receiving UDCA between the two groups, nor in the use of fibrates as an add-on therapy. The study also found no notable variations in the presence of other chronic liver diseases (such as viral hepatitis or metabolic dysfunction-associated fatty liver disease) between the normal IgG and increased IgG groups.
These results highlight the need for more personalized treatment strategies in PBC. Patients with elevated IgG at diagnosis may require earlier intervention and additional therapies to slow progression of disease. For those undergoing treatment with UDCA, monitoring levels of IgG over time could help identify individuals at higher risk, ensuring they receive timely and appropriate care.
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