الفهرس 
Type 1 Diabetes MellitusOnly 14 pages are availabe for public view
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Abstract
Background: Liver disease among patients with type 1 diabetes mellitus (T1DM) may be attributed to diverse pathologies; fatty liver, hepatic glycogenosis, hepatitis C virus (HCV) infection or autoimmune hepatitis (AIH). The diagnosis of type 1 diabetes related hepatopathy is based on a combination of biochemical, immunological and histological features. FibroScan, or transient elastography (TE), non-invasively assesses liver fibrosis and presents comparable performance to liver biopsy to predict liver-related outcomes in patients with chronic liver diseases. Aim: To determine the prevalence of autoimmune hepatitis-related autoantibodies in children with T1DM and asses the relation between AIH and glycemic control as well as hepatic fibrosis. Methods: This cross sectional study was carried out on 100 patients with T1DM (aged <18 years with at least 5 years disease duration) attending the Pediatric Diabetes Clinic, Pediatric Hospital, Ain Shams University. None of the studied patients had micro- or macro-vascular complications. Laboratory investigations included mean fasting blood glucose (FBG) in the last 3 months prior to the study, liver function tests, fasting lipid profile, HbA1c and coagulation profile. HCV antibodies were tested by enzyme linked immunosorbent assay and patients with an anti-HCV antibody-positive sample were further confirmed by testing HCV-RNA in their sera using quantitative real-time reverse-transcription-polymerase chain reaction. Serum immunoglobulins were assessed and autoimmune antibodies; Anti-nuclear antibody (ANA), Anti-smooth muscle Antibody (ASMA), and Anti-Liver Kidney microsomal antibody (anti-LKM) were detected using indirect immunofluorescence methods. Pelvi-abdominal ultrasound was performed for all patients and TE was indicated for patients with elevated alanine transferase (ALT), HCV infection, positive AIH antibody and/ or abnormal ultrasound findings. A hyperechogenic liver and/or hepatomegaly on ultrasound were attributed most likely to excess glycogen or fat in the liver, after negative extensive work-up to rule out other underlying liver disease. Liver biopsy was done when indicated and when parental consent was obtained. Results: Thirty-one (31%) patients were found to have one or more abnormalities; clinical hepatomegaly in 8%, elevated ALT in 10%, HCV in 6 %, autoimmune hepatitis (AIH) in 11% (10 were positive for ASMA and 2 were positive for ANA while anti-LKM antibodies were negative) and abnormal hepatic ultrasound in 20% (5 had AIH, 2 had HCV, 1 had Mauriac Syndrome, 9 had non-alcoholic fatty liver disease and 3 had non-alcoholic steatohepatitis). The mean liver stiffness in those 31 patients was 7.0 ± 2.1 kPa (range, 3.1– 11.8 kPa); 24 were Metavir F0-F1 and 7 were F2-F3 while none were F4. Type 1 diabetic patients with abnormal ultrasound had significantly higher FBG, HbA1c and total cholesterol than those with normal-sized liver (p<0.05) with slightly higher transaminases (p>0.05). Patients with abnormal ultrasound findings had significantly higher incidence of AIH than those with normal liver. All patients with AIH were HCV-negative and had elevated serum immunoglobulin G. Patients with AIH had higher HbA1c than those with negative autoimmune antibodies (p=0.012). Liver stiffness index was significantly higher in patients with abnormal ultrasound compared with those with normal liver (p=0.039). Liver stiffness was also significantly higher among patients with AIH compared to those without (8.5 ± 2.79 kPa versus 5.71 ± 2.07 kPa; p=0.009) and 5 (45.5%) AIH patients were diagnosed as F2-F3. Conclusions: Hepatic abnormalities are prevalent in children and adolescents with T1DM and related to poor metabolic control. Liver stiffness by TE provides a reliable non-invasive method for detection of hepatopathy-induced fibrosis. The incidence of hepatopathy may be underestimated in patients with good glycemic control. ASMA is the most common autoantibody found while anti-LKM antibody is rarely found in young patient with T1DM. Screening for liver disease by pelviabdominal ultrasound together with biochemical analysis and serological tests is required as hepatopathy among patients with T1DM can be silent and asymptomatic.