Objective: The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD. Design: The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI) </≥25 kg/m ² ). Liver/non-liver-related events and survival free of transplantation were recorded during the follow-up, compared by log-rank testing and reported by adjusted HR. Results: Lean patients represented 14.4% of the cohort and were predominantly of Italian origin (89%). They had less severe histological disease (lean vs non-lean: non-alcoholic steatohepatitis 54.1% vs 71.2% p<0.001; advanced fibrosis 10.1% vs 25.2% p<0.001), lower prevalence of diabetes (9.2% vs 31.4%, p10 483 person-years), 4.7% of lean vs 7.7% of non-lean patients reported liver-related events (p=0.37). No difference in survival was observed compared with non-lean NAFLD (p=0.069). Conclusions: Caucasian lean subjects with NAFLD may progress to advanced liver disease, develop metabolic comorbidities and experience cardiovascular disease (CVD) as well as liver-related mortality, independent of longitudinal progression to obesity and PNPLA3 genotype. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD where the disease manifests at lower overall BMI thresholds. Lay summary: NAFLD may affect and progress in both obese and lean individuals. Lean subjects are predominantly males, have a younger age at diagnosis and are more prevalent in some geographic areas. During the follow-up, lean subjects can develop hepatic and extrahepatic disease, including metabolic comorbidities, in the absence of weight gain. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD.

To investigate the impact of HDV infection on morbidity and mortality of patients. This was a retrospective study on 188 patients that underwent a program of periodic surveillance until 2008. The demographic data, stage of liver disease, treatment efficacy, development of liver complications (ascites, oesophageal bleeding, encephalopathy), and survival were registered. A Cox regression analysis was carried out to determine the impact of viral and patient features on survival. At baseline, 126 patients (67%) tested positive for serum IgM anti-HDV antibodies, 171 (91%) for anti-HBe, 175 (93%) for serum HDV-RNA, and 61 (33%) for serum HBV-DNA. Eighty-two patients (43%) had chronic hepatitis at histology; the remaining 106 individuals had a clinical/histological diagnosis of cirrhosis. Ninety-six patients received interferon (n = 90) or lamivudine (n = 6) therapy, and 27 of them (30%) attained a sustained response. During follow up, 21 patients with chronic hepatitis progressed to cirrhosis. Of the 127 cirrhotic patients, hepatic decompensation occurred in 42 patients (33%) and hepatocellular carcinoma in 17 (13%). The 5- and 10-year survival free of events were 96.8% and 81.9%, respectively, for patients with chronic hepatitis, and 83.9% and 59.4% for cirrhotics (p<0.01). At multivariate analysis, lack of antiviral therapy (p = 0.01), cirrhosis at presentation (p<0.01), and male sex (p = 0.03) independently predicted a worse outcome. HDV liver disease lasts several decades. Half of all patients who develop cirrhosis later will advance to liver failure. At present, interferon therapy is recommended as soon as possible to slow or alter the natural course of liver disease.

In recent years it has been supposed that impaired intestinal permeability represents an early event preceding the onset of inflammatory bowel disease (IBD). Since zonulin has been proposed as a biomarker of intestinal permeability, we investigated its role in patients with IBD and the correlation between serum and fecal zonulin. A total of 118 IBD patients (86 Crohn's disease [CD] and 32 ulcerative colitis [UC]) and 23 healthy controls (HC) were prospectively enrolled. A serum sample was collected for all the subjects included in the study. A stool specimen collected in the same day of blood drawing was available for a subgroup of 33 IBD patients. Serum and fecal zonulin were tested by ELISA. Non-parametric statistical tests were used for data analysis. Serum zonulin concentration was higher in IBD patients compared to HC (34.5 [26.5-43.9] ng/mL vs. 8.6 [6.5-12.0] ng/mL, P<0.001) showing an area under the curve of 0.98 for their discrimination. No difference in serum zonulin concentration was observed between patients with CD and those with UC (P=0.074). An inverse correlation was observed between serum zonulin concentration and disease duration (rs=-0.30, P=0.001); no correlation was observed between serum and fecal zonulin (rs=0.15, P=0.394). Serum zonulin is highly sensitive for the evaluation of intestinal permeability in IBD patients. There is no correlation between zonulin values in serum and feces.