The practical utility of non-invasive indices in metabolic hepatic steatosis.

BACKGROUND: Metabolic hepatic steatosis (metHS) is the most frequent cause of chronic liver disease in our environment. The "gold standard" for its diagnosis continues to be liver biopsy, but this is an invasive technique, is not risk-free, and has great interobserver variability, so noninvasive diagnostic methods are necessary. OBJECTIVE: To determine the diagnostic accuracy of non-invasive methods based on clinical and analytical data compared to liver biopsy, and to analyse their concordance with each other in the overall cohort and in subpopulations at risk of metHS. METHODS: Prospective observational study of 245 patients aged 19-80 years diagnosed with metHS by liver biopsy. Steatosis indices were calculated: FLI (Fatty Liver Index), LAP (Liver Accumulation Product), HSI-(Hepatitis Score Index) and fibrosis indices: Non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) and Hepamet Fibrosis Score (HFS). RESULTS: The non-invasive steatosis indices showed high sensitivity, and those of fibrosis, high specificity. To assess steatosis, FLI was the most sensitive index in all subpopulations (89-97%), except in women. To assess fibrosis, HFS offers maximum sensitivity in diabetics (86.7%) and is the index with the highest negative predictive value overall. The COR curves for non-invasive indices in steatosis and fibrosis compared to liver biopsy showed greater areas under the curve for the fibrosis indices, with NFS and HFS offering greater diagnostic accuracy (area > 0.8, p < 0.05). HFS also offers high diagnostic sensitivity in the diabetic population. CONCLUSIONS: Non-invasive indices of steatosis are more sensitive and those of fibrosis more specific than liver biopsy. NFS and HFS offer the highest diagnostic accuracy, with HFS having the highest negative predictive value.

Pathogenesis of occult chronic hepatitis B virus infection.

Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this "occult" HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

Leptin receptor Lys656Asn polymorphism is associated with decreased leptin response and weight loss secondary to a lifestyle modification in obese patients.

BACKGROUND: Human obesity is characterized by high levels of leptin, and it has been suggested that obese patients may be leptin resistant. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on leptin response and weight loss secondary to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients. METHODS: A population of 67 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of lifestyle modification program, bipolar electrical bioimpedance, blood pressure, and a serial assessment of nutritional intake with 3 days written food records and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% carbohydrates, 25% lipids and 23% proteins). The exercise program consisted of aerobic exercise for at least three times per week (60 min each). Statistical analysis was performed for the combined Lys656/Asn656 and Asn656/Asn656 as mutant group and type Lys656/Lys 656 as wild-type second group. RESULTS: Sixty seven patients gave informed consent and were enrolled in the study. The mean age was 45.7 +/- 16.6 years and the mean BMI 34.1 +/- 5.1, with 18 males (26.9%) and 49 females (73.1%). Thirty six patients (10 males/26 females) (46.8%) had the genotype Lys656/Lys 656 (wild-type group) and 31 patients (8 males/23 females) (46.3%) Lys656/Asn656 (n = 28, 41.8%) or Asn656/Asn656 (n = 3, 4.5%) (mutant group). The percentage of responders (weight loss) was similar in both groups (91.7 vs. 87.1%). In wild-type group (responders and nonresponders), BMI, weight, fat mass, systolic blood pressure and waist circumference decreased. In mutant group, BMI, weight and waist circumference decreased. No differences were detected between basal values in both groups. Only leptin levels decreased significantly in wild-type group (11.5%; p <0.05) (57.3 +/- 31.5 ng/mL vs. 45.8 +/- 29.3 ng/mL; p <0.05). In mutant group, leptin increased without statistical differences (0.44%; ns). CONCLUSIONS: Patients with Asn656 allele of LEPR gene have a different response than wild-type patients, and Lys656Lys patients have a significant decrease in weight, BMI, fat mass, waist circumference, systolic blood pressure and leptin levels.