The course of NAFLD secondary to familial heterozygous hypobetalipoproteinemia (FHBL), a definite etiology of secondary nonalcoholic fatty liver disease (NAFLD) [1–3] featuring low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) plasma levels less than fifth percentile [4], is unknown. We report on a case with FHBL due to compound heterozygosity and apoB non-detectable in serum in which a long-term follow-up and paired liver biopsies were available. A 58 year-old obese woman with FHBL was observed in June 2007 for abdominal pain and poorly controlled type 2 diabetes (T2D). The T2D began at the age of 40. It was complicated by peripheral neuropathy of the legs, and a chronic vascular encephalopathy that was documented by computed tomography. The patient was initially treated with a combination therapy (i.e., metformin plus glibenclamide plus insulin). Additional medications used were gabapentin for the peripheral neuropathy, thiamazole for multinodular hyperthyroidism, and escitalopram for mild psychodepressive disorder. The patient’s alcohol consumption was nil. Laparoscopic cholecystectomy had been performed in 1998 for acute biliary pancreatitis. At that time, intraoperative wedge liver biopsy disclosed NAFLD type 1–2 according to Matteoni et al. with thin fibrous septa [5] (Fig. 1). BMI was 30 Kg/m. An abdominal ultrasound imaging (US scan) suggested steatosis. Plasma lipid values compatible with FHBL had been noted since 1998 (total Cholesterol 61 mg/dl, LDL-C 21 mg/dl, HDL-C 28 mg/ dl, Triglycerides 50 mg/dl, ApoA1 83 mg/dl, ApoB \ 40 mg/dl). The apoB gene molecular analysis confirmed a severe form of FHBL in 2005. The patient is a double heterozygote for two mutations both with pathologic effect. The first one is a non-sense mutation (G?A), in hexon 19, resulting in a truncated apoB (apoB-20.6), not secreted in plasma. The second one is a nucleotidic substitution (T?A) in intron 14 (IVS 14 -4T/A) whose translation product would be a small-size truncated apoB, and so not secreted. In June 2007, the patient’s BMI was 41 Kg/m. Glycemic control was poor (fasting glucose 464 mg/dl at admission, hemoglobin A1c 11%). The liver chemistry tests were substantially normal (AST 28 U/l, ALT 25 U/l, GGT 32 U/l, ALP 53 U/l, bilirubin 0.6 mg/dl, albumin 3.2 g/dl, INR 0.83). Thyroid function tests were normal too (TSH 0.36 lIU/ml, FT4 9.9 pg/ml, FT3 2.3 pg/ml). A repeat liver biopsy showed advanced fibrosing-NASH in the pre-cirrhotic stage with marked steatosis (Fig. 2). The antinuclear antibody test, extractable nuclear antigens, antimitochondrial antibodies, anti-HCV antibodies, and HbsAg and Lupus Anticoagulant studies were all negative. The HBsAb ([22 mIU/ml) and anti-smooth muscle antibody (1:80) were positive. The US scan confirmed hepatomegaly, with hyperechoic structure and mild hypertrophy of the spleen. S. Ballestri A. Lonardo E. Pellegrini M. Bertolotti P. Loria (&) Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics, University of Modena and Reggio Emilia, Nuovo Ospedale Civile Sant’Agostino Estense di Baggiovara, Via Giardini 1355, 41100 Modena, Italy e-mail: loria.paola@unimore.it
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