Acute steatohepatitis, due to extreme metabolic dysregulation, as the first presentation of non-alcoholic fatty liver disease
A 50-year old man was admitted to our hospital because of a 1-week history of jaundice, fatigue and malaise. On physical examination, the patient was obese, with a body mass index of 37 kg/m, and a waist circumference of 136 cm. His temperature was 36.6°C, blood pressure 160/90 mmHg, and heart rate 107 bpm. Hepatomegaly was detected. The liver was soft, and nontender, with a smooth edge palpable 5 cm below the right costal margin. No xanthomas were found.\nThe patient’s medical history included type II diabetes mellitus, diagnosed 7 years ago, dyslipidemia (elevated triglycerides, mildly increased cholesterol, and reduced high density lipoprotein - cholesterol), two-vessel coronary artery disease, treated with percutaneous transluminal coronary angioplasty plus stenting 7 months before this admission, and an episode of acute pancreatitis 4 years ago. His family history was notable for gastric cancer in his father.\nThe patient was an unmarried chandler, who lived with his parents and brother in a working-class suburb of Athens. He had been a heavy smoker (approximately 115 pack-years), but consumed only small quantities of alcohol during social events (<100 g per week). He reported no use of illicit drugs or anabolic steroids, no ingestion of mushrooms, herbal preparations or nutritional supplements, and no exposure to environmental toxins. He was following an extremely unhealthy dietary pattern, characterized by exorbitant calorie intake (estimated amount of 8000 kcal per day), and excessive consumption of saturated animal fats and simple carbohydrates, combined with a sedentary lifestyle and lack of physical activity. His daily medication regimen included aspirin, nebivolol, enalapril, metformin, vildagliptin, and omega-3 fatty acids [eicosapentaenoic (EPA), and docosahexaenoic acid (DHA)].\nThe most prominent laboratory abnormalities were conjugated hyperbilirubinemia (total bilirubin 10 mg/dL, direct bilirubin 6.6 mg/dL), elevation of liver enzymes, with a disproportionate rise of aminotransferases in comparison to alkaline phosphatase (aspartate transaminase 474 U/L, alanine transaminase 647 U/L, gamma-glutamyltransferase >1453 U/L, alkaline phosphatase 409 U/L), and striking hypertriglyceridemia (triglycerides >1420 mg/dL). The glycosylated hemoglobin value of 11.1% indicated poor diabetic control. Additional abnormal test results were as follows: hematocrit 39%, hemoglobin 13g/dL, mean corpuscular volume 84 fl, lactate dehydrogenase 512 U/L, serum sodium 112 meq/L, glucose 431 mg/dL, total cholesterol >705 mg/dL, high density lipoprotein - cholesterol (HDL-C) 26 mg/dL, erythrocyte sedimentation rate 103 mm/h, C-reactive protein 43 mg/L. The patient’s plasma had a turbid appearance. Urinalysis showed marked glycosuria and bilirubinuria.\nHepatitis A immunoglobulin M (IgM) antibody, hepatitis B surface antigen and core IgM antibody, a polymerase chain reaction assay for hepatitis C viral RNA, and serologic tests for Epstein-Barr virus, human immunodeficiency virus, and cytomegalovirus were negative. Tests for anti-nuclear, anti-smooth-muscle, anti-liver-kidney microsomal type 1, antimitochondrial, and anti-neutrophil cytoplasmic antibodies were also negative. Levels of α1-antitrypsine and ceruloplasmin were normal, and transferrin saturation was less than 40%.\nAbdominal ultrasound examination revealed hepatic enlargement and a diffuse increase in echogenicity of the liver as compared with that of the kidneys (bright liver). No other organ abnormality was observed. An abdominal computed tomography scan (), obtained after oral and intravenous administration of contrast material, demonstrated a low-density hepatic parenchyma, which appeared darker than the spleen. Both imaging studies were consistent with fatty infiltration of the liver.\nGiven the patient’s history, physical examination, laboratory results and imaging findings, we concluded the following clinical diagnoses: first, type IV hyperlipoproteinemia, according to Fredrickson’s classification (familial hypertriglyceridemia), exacerbated by excessive intake of simple carbohydrates, obesity, and insulin resistance, all of which increase very-low-density lipoprotein synthesis; second, acute form of NASH. Moreover, the patient met Adult Treatment Panel III criteria for metabolic syndrome.\nThe patient was then started on a low calorie diet, with complete exclusion of carbohydrates and fats, and pure intake of high quality protein (chicken breast). He was also treated with isophane insulin (40-30 IU), and omega-3 fatty acids (EPA/DHA 920/760 mg bid). During the next 10 days, the patient showed dramatic improvement of his clinical and laboratory status (), and was discharged from the hospital. He was advised to keep on the medication received during his hospitalization, reduce calorie intake, eat plenty of vegetables and fruits, rich in fiber and complex carbohydrates with a low glycemic index, avoid saturated fats and simple carbohydrates, walk 30 min every day, quit smoking, and abstain completely from alcohol.\nEight weeks later, the patient was invited for a follow-up appointment. Having strictly implemented medical recommendations, he had lost 20 kg of body weight. His signs and symptoms were entirely resolved. Further, impressive amelioration of laboratory values was noted (). Continuation of lifestyle modification was emphasized, and isophane insulin dose was reduced by 20% (32-24 IU). Aspirin 100 mg qd, metformin 850 mg bid, pioglitazone 30 mg qd, atorvastatin 20 mg qd, and EPA/DHA 920/760 mg bid were prescribed.