Background & Aims Cystic fibrosis liver disease (CFLD), a leading cause of death in cystic fibrosis (CF), is mostly described in pediatric populations. Adult-onset CFLD lacks sufficient characterization and diagnostic tools. Methods A cohort of CF patients without CFLD during childhood were followed for up to 38 years with serologic testing, imaging, and noninvasive fibrosis markers. Historical CFLD diagnostic criteria were compared with a newly proposed CFLD criteria. Results 36 CF patients were followed for a median of 24.5 years(IQR=15.6, 32.9). By the last follow-up, 11(31%) had died. With conventional criteria, 8(22%) patients had CFLD, and by new criterion, 17 (47%) had CFLD at a median age of 36.6 years(IQR=26.5, 43.2). By new criterion, those with CFLD had higher median ALT(42 vs 27, p=0.005), AST(26 vs 21, p=0.01), direct bilirubin(0.13 vs 0.1, p=0.01), PT(14.4 vs 12.4, p=0.002), and APRI(0.31 vs 0.23, p=0.003) over the last two years of follow-up. Subjects with a Fibroscan® >6.8kPa had higher ALT(42 vs 28U/L, p=0.02), AST(35 vs 25U/L, p=0.02), APRI(0.77 vs 0.25, p=0.0004), FIB-4(2.14 vs 0.74, p=0.0003) and lower platelet counts(205 vs 293, p=0.02). One CFLD patient had nodular regenerative hyperplasia. Longitudinally, mean platelet counts significantly declined in the CFLD group(310 to 230U/L, p=0.0005). Deceased CFLD patients had lower platelet counts than those alive with CFLD(143 vs 258 U/L, p=0.004) or those deceased with no CFLD(143 vs 327U/L, p=0.006). Conclusion Adult-onset CFLD may be more prevalent than previously described which suggests a later wave of CFLD that impacts morbidity. Routine liver tests, radiologic imaging, noninvasive fibrosis markers and fibroscan® can be utilized algorithmically to identify adult CFLD. Further evaluation in other CF cohorts should be performed for validation.

Objective Despite evidence for the validity of premenstrual dysphoric disorder (PMDD) and its recent inclusion in DSM-5, variable diagnostic practices compromise the construct validity of the diagnosis and threaten the clarity of efforts to understand and treat its underlying pathophysiology. In an effort to hasten and streamline the translation of the new DSM-5 criteria for PMDD into terms compatible with existing research practices, we present the development and initial validation of the Carolina Premenstrual Assessment Scoring System (C-PASS). The C-PASS is a standardized scoring system for making DSM-5 PMDD diagnoses using 2 or more menstrual cycles of daily symptom ratings using the Daily Record of Severity of Problems (DRSP). Method Two hundred women recruited for retrospectively-reported premenstrual emotional symptoms provided 2–4 menstrual cycles of daily symptom ratings on the DRSP. Diagnoses were made by expert clinician and the C-PASS. Results Agreement of C-PASS diagnosis with expert clinical diagnosis was excellent; overall correct classification by the C-PASS was estimated at 98%. Consistent with previous evidence, retrospective reports of premenstrual symptom increases were a poor predictor of prospective C-PASS diagnosis. Conclusions The C-PASS (available as a worksheet, Excel macro, and SAS macro) is a reliable and valid companion protocol to the DRSP that standardizes and streamlines the complex, multilevel diagnosis of DSM-5 PMDD. Consistent use of this robust diagnostic method would result in more clearly-defined, homogeneous samples of women with PMDD, thereby improving the clarity of studies seeking to characterize or treat the underlying pathophysiology of the disorder.

Background Serum fibrosis markers are useful in staging chronic hepatitis B (HBV) and C (HCV) but have not been evaluated in chronic hepatitis D (HDV). Aims We evaluated the utility of serum fibrosis markers (fibrosis-4 score [FIB-4], AST to ALT ratio [AAR], age-platelet index [API], AST-to-platelet-ratio-index [APRI] and Hui score) in HDV infection. Methods Clinical and histologic laboratory data from HBV, HCV and HDV patients were evaluated and serum fibrosis markers were calculated. The ability of fibrosis markers to detect advanced fibrosis (Ishak ≥4) and cirrhosis (Ishak =6) were evaluated and compared between viral infections. Results 1003 subjects (HCV=701, HBV=240 and HDV=62) with mean age of 46 ±11 and 66% male were evaluated. HDV subjects had higher ALT and AST than HCV and lower platelets than both HBV and HCV. Histologically, HDV had the greatest percentage of Ishak≥4 and necroinflammation. FIB-4 performed best in detecting advanced fibrosis and cirrhosis in all viral cohorts. In HDV, area under the receiver operator curve (AUROC) 95% confidence intervals for detecting advanced fibrosis were: FIB-4=0.70 (0.55–0.84), API=0.69 (0.55–0.82), APRI=0.68 (0.54–0.82), Hui score=0.63 (0.49–0.78), AAR=0.63 (0.48–0.77). The AUROC for detecting cirrhosis in HDV were: FIB-4=0.83(0.69–0.97), API=0.80(0.66–0.95), APRI=0.75(0.61–0.89), Hui score=0.70(0.49–0.91) and AAR=0.70(0.48–0.93). Adjustment of published cut-offs led to marginal improvements in FIB4 for advanced fibrosis and of APRI for cirrhosis in HDV. Conclusions Serum fibrosis markers have lower performance accuracy in chronic HDV infected patients compared to HBV and HCV patients. Other noninvasive fibrosis markers should be explored to assist in the management of these patients.

Hepatocellular carcinoma (HCC) is an aggressive malignancy with its global incidence and mortality rate continuing to rise, although early detection and surveillance are suboptimal. We performed serological profiling of the viral infection history in 899 individuals from an NCI-UMD case-control study using a synthetic human virome, VirScan. We developed a viral exposure signature and validated the results in a longitudinal cohort with 173 at-risk patients who had long-term follow-up for HCC development. Our viral exposure signature significantly associated with HCC status among at-risk individuals in the validation cohort (area under the curve: 0.91 [95% CI 0.87-0.96] at baseline and 0.98 [95% CI 0.97-1] at diagnosis). The signature identified cancer patients prior to a clinical diagnosis and was superior to alpha-fetoprotein. In summary, we established a viral exposure signature that can predict HCC among at-risk patients prior to a clinical diagnosis, which may be useful in HCC surveillance.