Prevalence of Hepatopathy in Type 1 Diabetic Children

Abstract

SUMMARY L iver 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 pediatric literature about type 1 diabetes related liver disease is scant and mostly limited to small case series or case reports for children presenting with symptomatic hepatic dysfunction during time of metabolic decompensation and ketosis. 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. Thus, there is a need to develop and validate non‐invasive tests that can accurately reflect the full spectrum of hepatic fibrosis and severity of liver diseases. One of those methods is 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. The aim of this study was 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. This cross sectional study was carried out on 100 type 1 diabetic patients; 39 males and 61 females. The mean age of patients was 13.8 ±1.9 years (range, 11-18 years) and their mean disease duration was 6.5 ± 1.7 years. None of the studied patients had micro- or macro-vascular complications. All the included patients were subjected to detailed medical history and thorough clinical examination. 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. In this study, thirty-one (31%) patients were found to have one or more abnormalities; - Clinical hepatomegaly in 8% (2 had AIH, 1 had HCV, 1 had Mauriac syndrome, 2 had NAFLD and 2 had NASH). - Elevated ALT in 10% (4 had AIH, 3 had HCV, 1 had Mauriac syndrome, 2 had NASH). - Autoimmune antibodies in 11% (10 were positive for ASMA and 2 were positive for ANA (titer 1/80) while anti-LKM antibodies were negative. - HCV in 6 %. The incidence of HCV infection by ELISA was 7% and as confirmed by PCR was 6% among the studied type 1 diabetic patients. - Abnormal hepatic ultrasound in 20% (5 had AIH, 2 had HCV, 1 had Mauriac syndrome, 9 had NAFLD and 3 had NASH). One of type 1 diabetic patients with NASH had also pigmentation and short stature with hepatosplenomegaly and elevated ALT which denotes a suspected case of H syndrome for confirmation by genotyping of SLC29A3 mutations.