الفهرس 
? Type 1 Diabetes MellitusOnly 14 pages are availabe for public view
 |  | from | 16 |  |  |
| | | from | 16 | | |
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. Liver biopsy is currently considered the gold standard for assessing hepatic fibrosis. However, it is an invasive procedure with rare but potential life threatening complications, limiting its acceptance and repetition in usually asymptomatic patients. 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 identify the effect induced by hepatopathies of different etiologies among children and adolescents with T1DM using liver stiffness by TE as a non-invasive assessment tool and its relation to clinical and laboratory parameters including glycemic control. 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. 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). All patients with AIH were HCV-negative and had high serum IgG. Patients with AIH had higher HbA1c than those with negative autoimmune antibodies (p=0.012). All patients were exposed to repeated hospitalization, frequent insulin injection and self-monitoring of blood glucose level. Patients with HCV infection had higher FBG and ALT. Liver stiffness index was significantly higher in patients with abnormal ultrasound compared with those with normal liver (7.7 ± 2.37 kPa versus 5.78 ± 2.38 kPa; p=0.039). Although liver stiffness was elevated in HCV-positive patients compared with HCV-negative group, the difference was non-significant. Liver stiffness was 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. Significant positive correlations were found between liver stiffness and HbA1c as well as ALT. Conclusions: Hepatic abnormalities are prevalent in young patients with T1DM and related to poor metabolic control. Liver stiffness by TE provides a reliable non-invasive method for detection of hepatopathy-induced fibrosis and its positive correlation with HbA1c highlights the importance of proper glycemic control in reversing the progression of liver disease. 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.