Baseline characteristics of cirrhosis and non-cirrhosis in AIH patients
A total of 196 patients with AIH were enrolled in the study, including 168 women and 28 men, all with an average age of 56 years. 43 patients with AIH were complicated with other autoimmune diseases, including 9 patients with Sjogren's syndrome, 14 patients with Hashimoto's thyroiditis, 10 patients with Rheumatoid arthritis, 5 patients with Systemic lupus erythematosus and 5 patients with Atopic dermatitis. In addition, there were 80 cirrhosis patients and 116 non-cirrhosis patients in total population. Table 1 showed the baseline characteristics of the two groups, including demographic, liver function, and lipid profiles. Patients with cirrhosis were older than those without cirrhosis. In addition, patients with cirrhosis also had higher levels of IgA, white blood cells, hemoglobin and INR. However, PTA, PLT and GGT levels were higher in non-cirrhotic group. We also analyzed the blood lipid levels of patients, including TG, TC, HDL-C and LDL-C, and the results showed that patients with cirrhosis had lower levels of TG, TC and LDL-C (P<0.05). The two groups were similar in gender, other autoimmune diseases and diabetes mellitus.
Factors associated with AIH-related cirrhosis
Univariate and multivariate binary Logistic regression analyses were used to evaluate the factors associated with AIH-related cirrhosis. Multivariate results in Table 2 showed that patients with cirrhosis were older (age>50 years) than non-cirrhotic group. Patients with cirrhosis had more abnormal IgA (>4.35 g/L) and PLT (<100*109/L) levels and lower ALT levels. We also included serum lipid metabolism indicators in the regression analysis and dichotomized them according to the optimal cut-off value. Univariate results showed lower serum TG (≤0.95 mmol/L), TC (<2.9 mmol/L), and LDL-C (≤1.48 mmol/L) levels in patients with cirrhosis. However, the results of multifactorial regression analysis demonstrated that only TG was associated with AIH cirrhosis.
Distribution of cirrhosis in subgroups
With the above results, we confirmed that TG is an important factor associated with cirrhosis, and then we continued to analyze the correlation between TG and cirrhosis among different subgroups. Figure 1 showed that there were more cirrhotic patients (65.9%) in the TG≤0.95 (n=85) group, compared with 21.6 percent in the TG > 0.95 group. We further divided age, PLT, IgA and ALT into different subgroups, and observed the distribution of cirrhosis in different TG levels. As the results shown in table 3, in older age group (>50), patients with low levels of TG had more cirrhosis. Regardless of PLT, IgA and ALT levels, there were consistently more cirrhosis patients in the lower TG level group.
Correlation of serum TG with the severity of AIH-related cirrhosis
Previous studies have suggested that lipid levels are related to the severity of cirrhosis, so we analyzed the relationship between serum TG and the severity of cirrhotic patients with AIH. We compared the expression levels of serum TG in patients with AIH cirrhosis at different stages of progression. Based on Child-pugh scores, we divided the patients into three groups, Child A (n=18), Child B (n=33) and Child C (n=29). As we can see in Figure 2A, TG levels showed a decreasing trend in A, B and C, with mean values of 1.029 mmol/L, 1.3 mmol/L and 1.8 mmol/L, respectively. Compared to group A, patients in group C had significantly lower TG levels (P<0.05). Next, TG levels were compared across the different Meld classifications (Figure 2B), and the results showed that TG levels were lower in the higher Meld score (≥9) group compared to the lower Meld(<9) group (0.810 mmol/L vs 1.063 mmol/L). The results concluded that the worse the liver function, the lower the TG level.
Effect of serum TG on survival of patients with AIH-related cirrhosis
We further analyzed the role of TG on the prognosis of AIH patients. During 60 months follow-up (mean 56.05 months), there were 22 deaths, including 18 in AIH cirrhosis patients. Figure 3 analyzed the 5-year survival rates of different TG levels in the total AIH population, which were lower in the group of patients with TG ≤ 0.95 (Log-rank P < 0.05) (HR=3.79, 95%CI: 1.528-9.423). However, in patients with AIH cirrhosis, there was no statistical difference in 5-year overall survival among the different TG levels. In Figure 4, we used restricted cubic splines to flexibly construct the model, and visualized the nonlinear relationship between predicted serum TG level and overall survival in patients with cirrhosis (p<0.001). By fitting the cox proportional risk model, there are five nodes at the 5th, 35th, 50th, 65th and 95th percentile of TG. Overall survival decreased gradually with increasing TG in the interval of TG of 0.5-0.8 mmol/L, and the probability of TG risk per standard deviation prediction was 0.97 (95%CI: 0.94-0.99). The risk decreased to a minimum at 0.8 mmol/L, and plateaued at approximately TG > 0.8 mmol/L(Figure.4A). Further, we observed the non-linear relationship between TG and overall survival in patients with decompensated cirrhosis. The results showed that lower TG still had lower survival in decompensated patients and the nonlinear p-value was 0.002. When TG was less than 0.6 mmol/L, the risk of death of patients was negatively correlated with TG level, and the probability of TG risk per standard deviation prediction was 1.49 (95%CI: 1.00-2.24) (Figure.4B). The results suggested that lower TG was a risk factor for death in patients with AIH regardless of whether in cirrhosis or decompensated cirrhosis.