Elevated serum IL-34 is correlated with disease severity in patients with biliary atresia following Kasai portoenterostomy.

BACKGROUND: Biliary atresia (BA) is a severe congenital disorder with progressive obstructive cholangiopathy in young children. The inflammatory process has been recognized as one of the pathological mechanisms driving bile duct injury. Since interleukin-34 (IL-34) has been reportedly linked to several pathological liver disorders, including inflammation, the current study aimed to analyze circulating IL-34 and the association of circulating IL-34 with hepatic deterioration and clinical outcomes in post-Kasai BA children. METHODS: Circulating IL-34 levels were analyzed in 89 post-Kasai BA subjects and 45 healthy individuals using an ELISA. Liver stiffness (hardness) was measured by ultrasound elastography. RESULTS: Circulating IL-34 was substantially higher in BA children than in control individuals, particularly those with unfavorable outcomes including hepatic dysfunction, jaundice, and portal hypertension. In BA group, circulating IL-34 was positively correlated with liver stiffness (r = 0.515, p < 0.001), AST (r = 0.403, p < 0.001), ALT (r = 0.279, p = 0.008), total bilirubin (r = 0.224, p = 0.03), ALP (r = 0.255, p = 0.016), and serum IL-6 (r = 0.590, p < 0.001) but inversely correlated with albumin (r = -0.417, p < 0.001). Kaplan-Meier survival analysis showed that higher circulating IL-34 levels were significantly associated with reduced survival rates in BA subjects (p = 0.002). CONCLUSION: Higher circulating IL-34 values were directly associated with hepatic impairment and the BA severity, implicating thatserum IL-34 could be applied as a noninvasive marker for the monitoring of the severity in BA subjects following Kasai portoenterostomy and therapeutic efficacy.

Increased serum glypican-3 is associated with liver stiffness and hepatic dysfunction in children with biliary atresia.

AIM OF THE STUDY: Biliary atresia (BA) is an uncommon disorder of the liver and bile ducts affecting infants and is characterized by progressive fibrosclerosing obstruction of the extrahepatic biliary tree leading to end-stage liver failure. The purpose of this study was to determine serum glypican-3 (GPC3) levels and liver stiffness in children with BA and the correlation of glypican-3 with clinical parameters. MATERIAL AND METHODS: Seventy-five post-Kasai BA patients and 28 healthy age-matched controls were registered. Serum GPC3 levels were examined by enzyme-linked immunosorbent assay. Liver stiffness measurement was analyzed by transient elastography. RESULTS: BA patients had significantly greater serum GPC3 and liver stiffness values than controls (p < 0.001). Serum GPC3 and liver stiffness values were significantly higher in jaundiced BA patients than in non-jaundiced BA patients (p < 0.001). Additionally, serum glypican-3 was associated with liver stiffness and serum total bilirubin (p < 0.001, respectively). CONCLUSIONS: Elevated serum GPC3 levels were associated with hepatic dysfunction and the severity of BA. As a result, serum GPC3 and liver stiffness might serve as biomarkers reflecting the deterioration of hepatic function and the outcome in post-Kasai BA.

Alu hypermethylation and high oxidative stress in patients with musculoskeletal tumors.

BACKGROUND: Alu is one of the non-autonomous element retrotransposons, constituting nearly 11% of the human DNA. Methylation changes of the Alu element can cause genomic instability, a hallmark of cancer development, ultimately leading to the development of cancer. Epigenetic factors may induce the aberrant methylation of Alu and also oxidative stress. However, current knowledge of Alu methylation and oxidative stress is limited. There are few studies that have evaluated Alu methylation and oxidative stress on musculoskeletal tumor progression. Therefore, the present study evaluated the status of Alu methylation in musculoskeletal (MS) tumor, adjacent tissues, and blood leukocytes from MS tumor subjects, as well as unaffected participants. Moreover, we also investigated the oxidative stress status in MS tumor subjects and the control participants and determined the correlation between Alu methylation in MS tumors and that in blood leukocytes. METHODS: Musculoskeletal tumors from musculoskeletal tumor patients (n = 40) were compared to adjacent tissues (n = 40). The blood leukocytes from musculoskeletal tumor patients were compared to the blood leukocytes from controls (n = 107). Alu methylation status was analyzed using quantitative combined bisulfite restriction analysis (COBRA). In addition, 8-hydroxy 2'-deoxyguanosine (8-OHdG) values were determined using enzyme-linked immunosorbent assay. RESULTS: Alu methylation values in MS tumors were statistically significantly higher than those in adjacent tissues (P = 0.035). Similarly, Alu methylation statuses in the blood leukocytes of MS tumor subjects were statistically greater than those of control participants (P < 0.001). Moreover, there was a positive association between Alu methylation levels in MS tumors and blood leukocytes (r = 0.765, P < 0.001). In addition, the highest tertile was significantly associated with the risk of MS tumors (OR = 14.17, 95% CI [5.08-39.51]; P < 0.001). The 8-OHdG values in MS tumors were statistically higher than in adjacent tissues (P < 0.001) and circulating 8-OHdG levels were substantially greater in MS tumor subjects than in the control participants (P < 0.001). DISCUSSION: These findings suggest that Alu methylation in blood leukocytes and plasma 8-OHdG might represent non-invasive biomarkers to help diagnose MS tumors. Therefore, Alu hypermethylation and high oxidative stress might be involved in the pathogenesis of the musculoskeletal tumors.