MORBIDLY OBESE PATIENTS WITH ALANINE AMINOTRANSFERASE (ALT) LEVEL BELOW THE THRESHOLD 0.5 TIMES THE UPPER LIMIT OF NORMAL HAVE NO NASH

Background: The natural course of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic steatohepatitis (NASH) towards cirrhosis or/and liver-cancer is unclear. Aims and Methods: To identify predictor factors for progressive outcome we retrospectively revised our liver biopsy reports done from 2000–2011 in Liver Unit, Holy Family Hospital, Nazareth. We included tested cases with histological documented NAFLD at age over 18 years. Cases with metabolic syndrome or other etiologies for liver diseases were excluded. Clinical characterizations (age, gender, BMI), Histology severity (steatosis in percentage, necroinflammatory activity and fibrosis scoring) and serum levels of vitamin D, liver enzymes (ALT, AST), insulin resistance (serum fasting-insulin levels, HbA1c and HOMA-IR score), lipid profile (TG, HDL and LDL) and CRP were evaluated. For in-vitro settings, lymphocytes were obtained from donors of low and normal levels of vitamin D. These lymphocytes were analyzed for their NK activity (CD107a) and phagocytosis with human hepatic stellate cell line (LX2) by the flow-cytometry. Results: 72 cases fulfill inclusion/exclusion criteria, 44 males, mean age at biopsy timing was 39.4±10.6 years and mean BMI 29±2.8. None of the patients had cirrhosis as Fibrosis scores were up to F3 and activity up to A3. Normal serum vitamin-D levels were found in 15 (21%, 9 men), insufficient levels found in 21 (29.1%, 14 men) and deficient levels in 36 cases (49.9%, 21 men). Lower serum vitamin-D levels significantly correlated with decreased hepatic fat-content but increased liver-injury (CRP, fibrosis-scoring and necro-inflammatory-activity), insulin-resistance (serum insulin levels, HbA1c and HOMA-IR score) and CRP. CRP levels had a significant positive correlation with LDL, CRP, HBA1C, Insulin and HOMA-score. BMI had a significant positive correlation with AST, Insulin and liver fat content. Compared to normal vitamin-D levels with mild liver injury (A1/F1), peripheral blood lymphocytes from low vitamin-D donors increased the in-vitro activation of hepaticstellate cells. In additions, NK cells from low vitamin-D donors showed low count with increased in their activity accompanied with decreased phagocytosis suggesting impairment of their killing effects. In conclusion: Low vitamin-D serum levels predict severe insulin-resistant and liver-injury but decreased hepatic content. Immunological explanations are suggested as a mechanism via immune mechanism of NK-impairment.