UNASSIGNED: Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease.
UNASSIGNED: In this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained.
UNASSIGNED: Participants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial β-cell secretory response (AUC C-peptide 3h) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1).
UNASSIGNED: In this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.

In chronic hepatitis B (CHB), hepatitis D virus (HDV) superinfection can lead to acute liver failure. The incidence of HDV superinfection is unknown, but is often detected in immigrants from HDV endemic countries. In this report, we characterize long-term clinical and virological outcomes in a hepatitis B virus (HBV) infected carrier before and after HDV superinfection, acquired from their spouse having HBV/HDV co-infection. A 38 year-old Mongolian male with CHB on anti-HBV therapy developed acute liver failure following HDV superinfection. Although he recovered, avoiding the need for liver transplant, HDV serological and molecular markers of infection persisted for the subsequent 16-month follow-up period, suggesting the development of CHB/HDV co-infection. The source of his HDV was from his wife of 10 years, a 34-year old Mongolian female known to have inactive CHB/HDV co-infection but who was not on anti-HBV therapy. Phylogenetic analysis of the complete HDV genome from the couple showed >99% similarity, with post-transmission longitudinal sequence revealing specific nucleotide substitutions between both spouse\'s HDV genome sequences. This study highlights the ongoing risk of HDV superinfection due to long-term co-habitation or sexual transmission in CHB patients. The fact that transmission occurred after almost a decade of marriage may be due to host immune or environmental factors that created a more favorable condition for transmission.

BACKGROUND: Liver fibrosis and its sequel cirrhosis represent a major health care burden, and assessment of fibrosis by biopsy is gradually being replaced by noninvasive methods. In clinical practice, the determination of fibrosis stage is important, since patients with advanced fibrosis have faster progression to cirrhosis and antiviral therapy is indicated in these patients.
OBJECTIVE: To assess the role of transient elastography (TE) and compare it with APRI and FIB4 for predicting liver fibrosis and assessing the effect of host and viral factors on fibrosis and treatment outcome in CHC patients.
METHODS: In a retrospective analysis, 330 CHC patients underwent liver stiffness measurement (LSM) by TE and tests needed for calculating APRI and FIB4 scores at baseline. 228 patients received a combination of Pegylated IFN-based antiviral therapy and were analyzed for therapeutic response.
RESULTS: The study included 330 patients (median age 39 years [range 18-67]), predominantly males (n = 227, 68.8%) with baseline LSMs. The median liver stiffness was 7.8 kPa (range 3.2-69.1 kPa). LSMs and its thresholds for severe fibrosis progression (≥9.5 kPa) and cirrhosis (≥12.5 kPa) were significantly higher in patients with age ≥40 years, diabetes mellitus, and patients with significant alcohol intake (P = 0.003 to P < 0.001). By taking TE as a reference, the diagnostic accuracy of FIB4 scores for predicting cirrhosis (AUROC 0.896) was good (+LR 13.4) compared to APRI (AUROC 0.823) with moderate likelihood ratio (+LR 6.9). Among 228 treated patients the SVR rate in genotype 3 was 70% versus 57.8% in genotype 1. Fibrosis score F4 (P = 0.023) and HCV genotype (P = 0.008) were independent predictors of SVR.
CONCLUSIONS: The study shows that LSM by TE and fibrosis assessment by FIB4/APRI scores can be used with fair reliability to predict fibrosis and treatment response in patients with CHC infection.