Shahar Rosenstock

Background: Serum immunoglobulin G (IgG) levels are central to the diagnosis and monitoring of autoimmune hepatitis (AIH), yet the clinical implications of markedly elevated IgG remain incompletely characterized. We examined whether higher maximal serum IgG levels are associated with a biochemical phenotype of more severe hepatic injury, impaired hepatic synthetic function, and adverse clinical outcomes in patients with AIH. Methods: We conducted a retrospective cohort study of 80 adults with AIH treated at Sheba Medical Center. Patients were categorized into low, intermediate, and high IgG strata according to tertiles of maximal documented serum IgG. Demographic characteristics, comorbidities, treatments, admission laboratory values, hepatic synthetic function markers, and mortality outcomes were compared across strata. Primary outcomes were serum albumin, international normalized ratio (INR), hypoalbuminemia and the INR-to-albumin ratio. Secondary outcomes included hepatocellular and cholestatic pathophysiology surrogate markers, hospital length of stay, all-cause mortality during follow-up, and one- and five-year mortality. Results: Among 80 patients, maximal IgG differed significantly across strata (overall median, 2030 [IQR, 1545–2802.5]; low, 1320 [1105–1520]; intermediate, 2040 [1845–2215]; and high, 3310 [2827.5–3747.5]; p < 0.001). Compared with the low-IgG group, the high-IgG group had more frequent hypoalbuminemia (53.8% vs. 11.1%; p = 0.002), more frequent elevated INR values (34.6% vs. 7.4%; p = 0.035), and a higher INR-to-albumin ratio (median, 0.45 vs. 0.30; p < 0.001). Mortality did not differ significantly across IgG strata, including all-cause mortality during follow-up (15.4%, 14.8%, and 14.8%; p = 1.00), one-year mortality (p = 0.49), and five-year mortality (p = 0.72). After adjustment for age, recorded cirrhosis, ALT and corticosteroid exposure, each 1000 mg/dL increase in maximal IgG was associated with 0.248 g/dL lower albumin, 9.5% higher INR and an 18.5% higher INR-to-albumin ratio (all p < 0.001). Conclusions: Higher serum IgG levels in AIH patients were associated with impaired hepatic synthetic function, reflected by lower albumin, higher INR, and a higher INR-to-albumin ratio, without a corresponding increase in short- or intermediate-term mortality in this cohort. Markedly elevated IgG may help identify patients who warrant closer assessment of their synthetic hepatic reserve.