SCCA-IgM as a Potential Biomarker of Non-Alcoholic Fatty Liver Disease in Patients with Obesity, Prediabetes and Diabetes Undergoing Sleeve Gastrectomy

Background: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. Objective: The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. Method: Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. Results: At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. Conclusions: Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD

Metabolic flexibility after bariatric surgery-induced weight loss: does diabetes impair a proper substrates utilization?

The onset of type 2 diabetes is a critical step for the prognosis of obese patients, being crucial for disease evolution and complications development. Obese diabetic subjects generally obtain poorer outcomes in terms of weight loss as compared to non-diabetic ones after treatment. Our aim was to assess if the metabolic flexibility in substrates utilization following bariatric surgery was different in diabetic, pre-diabetic and normoglycemic obese subjects.We examined 95 consecutive morbid obese females (mean-age 44.1\ub111.1, BMI 44.7\ub17.5), undergoing laparoscopic sleeve gastrectomy (LSG), before (T0) and 12 months after (T1) bariatric surgery. Among them 61 were normoglycemic, 17 pre- diabetic and 17 diabetic. Evaluation included anthropometric parameters, blood samples collection, resting energy expenditure (REE) and body composition assessment.At T0, diabetic patients were older than normoglycemic and pre-diabetic subjects and had higher basal glucose levels (6.8\ub11.8 mmol/L vs 5.6\ub10.6 mmol/L in pre-diabetic and 5.2\ub10.5 mmol/L in normoglycemic respectively). The three subgroups did not differ significantly in BMI, waist circumference, REE and body composition. Percent weight loss was 30.5\ub110.2% in normoglycemic, 27.6\ub18.9% in pre-diabetic and 25.9\ub1 6.7% in diabetic patients (p<0,05 vs normoglycemic). After weight loss, all patients showed a statistically significative decrease in REE (1760\ub1358 kcal/die vs 1285\ub1236 kcal/die) and no differences were found among subgroups. Respiratory quotient (RQ) tends to decrease after surgery (0.816 T0 vs 0.779 T1; p=0.22). Analyzing separately the three subgroups, a reduction in RQ was observed in normoglycemic (0.820 vs 0.781; p=0.52) and in prediabetic patients (0.821 vs 0,748; p=0,03), but not in diabetic patients (0.806 vs 0.806; p=1.00).Weight loss was associated to a metabolic shift toward an increased fat oxidation (RQ reduction) in normoglycemic and pre-diabetic patients, whereas RQ in diabetic females did not show any change. This impaired metabolic flexibility could partly explain the lower weight loss observed in diabetic patients after LSG

Effect of Bariatric Surgery on Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) risk should be screened in patients with metabolic risk factors, the most important being obesity. The effects of laparoscopic sleeve gastrectomy (LSG) in patients with NAFLD are not well established. Liver biopsy is essential for the diagnosis of nonalcoholic steatohepatitis (NASH) and is the only procedure that differentiates NAFLD from NASH. Non invasive assessment is needed to identify the risk of NAFLD among patients with increased metabolic risk and patients with worse prognosis. SCCA-IgM is a known biomarker of progression to hepatocellular carcinoma from viral hepatitis but its role in diagnosis of fatty liver disease is under investigation. The aim of this prospective study was to evaluate if bariatric surgery can affect the biochemical features of NAFLD and to assess the prognostic value of squamous cell carcinoma antigen-IgM (SCCA-IgM) among non-invasive markers of liver injure.Fifty six (40 females and 16 males) treated with LSG were studied before (time 0) and twelve months after surgery. Anthropometric measurements, resting energy expenditure (REE) (by indirect calorimetry) and body composition data (fat-free mass or FFM, fat mass or FM, extrapolated by the means of bioelectrical impedance analysis), biochemical data (full blood count, glucometabolic profile, lipid profile, kidney and liver function tests, inflammatory markers) and clinical data (patient history, smoking and drinking habits, medication history, diet and lifestyle, anthopometric measures) were collected at baseline and one year later. An ultrasound scan was obtained for each patient at time 0 in order to ascertain the presence of hepatic steatosis, which was graded using a semiquantitative scale ranging from 0 (no steatosis) to 2 (severe steatosis). SCCA-IgM was measured by commercial ELISA kit (Xeptagen S.p.A., Venice, Italy). The data were analyzed by the software Statistical Package for the Social Sciences (SPSS v.20.0). Weight loss was 20,4\ub19,5%. We observed that the grading of steatosis was associated with glycemic profile (euglycemic vs prediadiabetic vs diabetic, squared-chi test p = 0,03) at baseline. ALT/AST ratio decreased after surgery (ALT/AST before LSG: median 1,06 IQR 0,92-1,39; ALT/AST after LSG: median 0,90 IQR 0,72-1,16 p <0,001) and its change was correlated with weight loss (r = 0,273; p= 0,046), BMI reduction (r = 0,388; p = 0,004) and decrease of HOMA index (r = 0,303; p = 0,037). No statistical difference was noted between the distributions of SCCA-IgM before and after surgery, nor there was any association between the decrease of SCCA-IgM titer and variations of body weight, HOMA index, platelets, ALT, AST, GGT, glucose titers. Only three patients had a value of SCCA-IgM above upper normal limit (cut-off value 200 AU/ml) and the decrease in their SCCA-IgM was not significant after a year. A correlation between SCCA-IgM titer and basal insulin levels was present titer before LSG (r = 0,335 p = 0,009) but not after bariatric surgery. Post LSG SCCA-IgM titer was found to be correlated to the titers of highsensitivity C-reactive protein (r = 0,288, p = 0,032) and IL6 (r = 0,355; p = 0,007), but no correlation was found between the variation of SCCA-IgM titer and the variations of the aforesaid inflammatory markers. Bariatric surgery resulted in a significant reduction of ALT, AST, GGT and ALT/AST ratio related to the degree of weight loss. NAFLD determined by the association of ultrasound scan and steatosis biomarkers confirm the tight link with insulin resistance. The role of SCCA-IgM in the development of fatty liver disease is still unclear. We can hypothesise the absence of a difference in SCCA IgM levels before and after LSG was related to the shortness of our follow-up, assuming that the healing processes in liver may require a longer period of time