BACKGROUND & AIMS: Q9Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although biannual ultrasound surveillance with or without a-fetoprotein (AFP) testing is recommended for at-risk patients, sensitivity for early stage HCC, for which potentially curative treatments exist, is suboptimal. We conducted studies to establish the multitarget HCC blood test (mt-HBT) algorithm and cut-off values and to validate test performance in patients with chronic liver disease.

Ultrasound-based surveillance has suboptimal sensitivity for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis. There are several emerging alternatives, including a novel multitarget HCC blood test (Mt-HBT).We compared performance of mt-HBT against ultrasound with or without alpha-fetoprotein (AFP) for early HCC detection in patients with cirrhosis. Per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, two reviewers searched PubMed, Cochrane, Embase, and clini caltr ials.gov databases from January 1990 through December 2020 to identify studies reporting sensitivity and/or specificity of ultrasound and AFP for overall and early stage HCC detection in patients with cirrhosis. Mt-HBT diagnostic performance was derived from a clinical validation study. A network meta-analysis model was built for comparative assessment, and pooled estimates of sensitivity at a fixed specificity were estimated based on Bayesian binormal receiver operating characteristic models for each modality. Forty-one studies (comprising 62,517 patients with cirrhosis) met inclusion criteria. Ultrasound-alone sensitivity was 51.6% (95% credible interval [CrI], 43.3%-60.5%) for early stage HCC detection, which increased with the addition of AFP to 74.1% (95% CrI, 62.6%-82.4%); however, this was offset by decreased specificity (87.9% vs. 83.9%, respectively). With specificity fixed at 90%, mt-HBT sensitivity for early stage HCC detection was higher than ultrasound alone (18.2%; 95% CrI, 0.2%-37.7%) and similar to ultrasound with AFP (−3.3%; 95% CrI, −22.3%-17.4%). Pairwise posterior probabilities suggested a preference for mt-HBT over ultrasound alone in 97.4% of cases but only 36.3% of cases versus ultrasound with AFP. Conclusion: A blood-based mt-HBT has higher sensitivity than ultrasound alone for early stage HCC detection but similar sensitivity compared to ultrasound and AFP.

Objective: The objective of this study was to identify factors involved in the success of 2 well-established population-based carrier screening programs – Tay-Sachs disease (TSD) in Ashkenazi Jews and β-thalassemia in Sardinia and Cyprus – and to assess the potential for success of a population-based cystic fibrosis (CF) carrier screening strategy using these factors. Methods: We performed a literature review and key informant interviews. Results: Factors involved in the success of TSD and β-thalassemia carrier screening programs include disease characteristics (well-defined population at risk, severe disease with predictable course, availability of effective treatment), test characteristics (high sensitivity, straightforward interpretation of results), and community characteristics (involvement of community, support of families and advocacy groups, consensus in favor of avoiding affected births). Current CF screening strategies include few of the factors listed above. Unlike TSD and β-thalassemia, the purpose of current CF carrier screening strategies is informed reproductive decision-making, without an explicit goal of reducing disease incidence. Conclusion: When compared to TSD and β-thalassemia, CF is a less favorable candidate for population-based carrier screening. Because of its different purpose, CF carrier screening will require different measures of success than those used for TSD and β-thalassemia carrier screening, and a consensus on the value or success of CF carrier screening may be difficult to achieve.

BACKGROUND Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol. AIM To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF. METHODS A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups. RESULTS A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients ( P = 0.05), patients on Ursodiol ( P < 0.001), and patients on dual therapy ( P = 0.003). The highest incidence of cirrhosis was found among patients treated with Ursodiol alone, compared to untreated patients ( P < 0.001) or patients on Ursodiol and CFTR modulators ( P = 0.01). CONCLUSION CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

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Clopidogrel exposure within 5 days of CABG is associated with an increased risk of major bleeding.

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A single-institution study demonstrated that PIW was more strongly correlated than RW with actual medication expenditure. PIS may be a more accurate acuity metric than CMI for predicting changes in drug expense over time.