We report long-term intention-to-treat outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing down-staging to within Milan/UNOS T2 criteria before liver transplantation (LT) since 2002, and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The down-staging subgroups include 1 lesion >5 cm and ≤8 cm (n=43), 2 or 3 lesions at least one >3 cm and ≤5 cm with total tumor diameter ≤8 cm (n=61), or 4 to 5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n=14). In the down-staging group, 64 patients (54.2%) had received LT, and 5 (7.5%) developed HCC recurrence. Two of the 5 patients with HCC recurrence had 4–5 tumors at presentation. The 1- and 2-year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the down-staging group, versus 20.3% and 25.6% in the T2 group (p=0.04). The Kaplan-Meier 5-year post-transplant survival and recurrence-free probabilities were 77.8% and 90.8%, respectively, in the down-staging group, versus 81% and 88%, respectively, in the T2 group (p=0.69 and p=0.66, respectively). The 5-year intention-to-treat survival was 56.1% in the down-staging group, versus 63.3% in the T2 group (p=0.29). Factors predicting dropout in the down-staging group included pre-treatment alpha-fetoprotein ≥1000 ng/mL (multivariate HR 2.42, p=0.02) and Child’s B versus Child’s A cirrhosis (multivariate HR 2.19, p=0.04). Conclusion: Successful down-staging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post-transplant survival, comparable to those meeting T2 criteria without down-staging. Due to the small number of patients with 4–5 tumors, further investigations are needed to confirm the efficacy of down-staging in this subgroup.

Recent approval of direct-acting antiviral (DAA) therapy for patients with decompensated cirrhosis (DC) secondary to hepatitis C (HCV) is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait-listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003-2015. 47,591 adults wait-listed for LT from HCV, hepatitis B (HBV) and non-alcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the model for end-stage liver disease (MELD) at WL was ≥ 15 or hepatocellular carcinoma (HCC). Era of listing was divided into “interferon” ([IFN] 2003-2010), “protease inhibitor” ([PI] 2011-2013), and “direct-acting antiviral” ([DAA] 2014-2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P <.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (−17%, P = 0.002) and DAA eras (−24%, P <.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P <.001) and 81% in the DAA era (P <.001). WL for HCC in both the HCV and NASH populations increased in both PI and DAA eras (P <.001 for all) while HCC WL in HBV remained stable (P > 0.05 for all). Conclusions: The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy.

BACKGROUND All patients with cirrhosis are at risk of developing hepatocellular carcinoma (HCC). This risk is not uniform because other patient-related factors influence the risk of HCC. The objective of the current study was to develop an HCC risk prediction model to estimate the 1-year probability of HCC to assist with patient counseling. METHODS Between 2002 and 2011, a cohort of 34,932 patients with cirrhosis was identified from a national liver transplantation waitlist database from the United States. Cox proportional hazards regression methods were used to develop and validate a risk prediction model for incident HCC. In the validation cohort, discrimination and calibration of the model was examined. External validation was conducted using patients with cirrhosis who were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) study. RESULTS HCC developed in 1960 patients (5.6%) during a median follow-up of 1.3 years (interquartile range, 0.47 years-2.83 years). Six baseline clinical variables, including age, diabetes, race, etiology of cirrhosis, sex, and severity (ADRESS) of liver dysfunction were independently associated with HCC and were used to develop the ADRESS-HCC risk model. C-indices in the derivation and internal validation cohorts were 0.704 and 0.691, respectively. In the validation cohort, the predicted cumulative incidence of HCC by the ADRESS-HCC model closely matched the observed data. In patients with cirrhosis in the HALT-C cohort, the model stratified patients correctly according to the risk of developing HCC within 5 years. CONCLUSIONS The ADRESS-HCC risk model is a useful tool for predicting the 1-year risk of HCC among patients with cirrhosis.

BackgroundTo evaluate screening and treatment strategies, large-scale real-world data on liver disease-related outcomes are needed. We sought to validate health administrative data for identification of cirrhosis, decompensated cirrhosis and hepatocellular carcinoma among patients with known liver disease.MethodsPrimary patient data were abstracted from patients of the Toronto Center for Liver Disease with viral hepatitis (2006–2014), and all patients with liver disease from the Kingston Health Sciences Centre Hepatology Clinic (2013). We linked clinical information to health administrative data and tested a range of coding algorithms against the clinical reference standard.ResultsA total of 6,714 patients had primary chart data abstracted. A single physician visit code for cirrhosis was sensitive (98–99%), and a single hospital diagnostic code for cirrhosis was specific (91–96%). The most sensitive algorithm for decompensated cirrhosis was one cirrhosis code with any of: a hospital diagnostic code, death code, or procedure code for decompensation (range 88–99% across groups). The most specific was one cirrhosis code and one hospital diagnostic code (range 89–98% across groups). Two physician visit codes or a single hospital diagnostic code, death code, or procedure code combined with a code for cirrhosis were sensitive and specific for hepatocellular carcinoma (sensitivity 94–96%, specificity 93–98%).ConclusionThese sensitive and specific algorithms can be used to define patient cohorts or detect clinical outcomes using health administrative data. Our results will facilitate research into the adequacy of screening and treatment for patients with chronic viral hepatitis or other liver diseases.

No abstract

No abstract

The present series of experiments assessed how information from the whiskers controls and modulates infant rat behavior during early learning and attachment. Passive vibrissal stimulation can elicit behavioral activity in pups throughout the first two postnatal weeks, although orienting to the source of stimulation is evident only after ontogenetic emergence of whisking. In addition, while pups were capable of demonstrating learning in a classical conditioning paradigm pairing vibrissa stimulation with electric shock, no corresponding changes were detected in the anatomy of the barrel cortex as determined by cytochrome oxidase (CO) staining. Finally, the role of whiskers in a more naturalistic setting was determined in postnatal day (PN)3-5 and PN11-12 pups. Our results showed that both nipple attachment and huddling were disrupted in whisker-clipped PN3-5 pups but only marginally altered in PN11-12 pups. Together, these results suggest that the neonatal whisker system is behaviorally functional and relevant for normal mother-infant interactions, though it lacks the sophistication of a mature whisker system that evokes very specific and directed responses.

A low-residue breakfast on the day before elective colonoscopy does not compromise the overall quality of bowel preparation as compared with a standard clear-fluid diet and is likely to be preferred by patients.