Direct-acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (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 to 2015. A total of 47,591 adults wait-listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic 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 < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (-17%; P = 0.002) and DAA eras (-24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all).

Conclusion

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. (Hepatology 2017;65:804-812).

1. We examined responses of aquatic macroinvertebrates to pulsed acidification experiments in twelve streamside channels located in the Sierra Nevada, California. Experiment 1 consisted of a single 8 h acid addition, and Experiment 2 consisted of two 8 h acid additions administered 2 weeks apart. Replicated treatments (four reps/ treatment) consisted of a control (pH 6.5–6.7) and pH levels of 5.1–5.2 and 4.4–4.6. Invertebrate drift was monitored continuously and benthic densities were determined before and after acid addition. 2. Drift responses to pH reduction were: (i) increased drift during acidification in pH 5.2 and pH 4.6 treatment channels, often with depressed post‐acidification drift in treatment channels relative to controls (exhibited by Baetis only). Depressed post‐acidification drift in treatment channels appeared to be due to low benthic densities because a positive relationship between benthic and drift densities was noted for most common taxa; (ii) increased drift rates during acidification only at pH 4.6 (Epeorus, Drunella, Paraleptophlebia, Zapada, and Simulium); (iii) decreased drift at pH 5.2 and/or pH 4.6 relative to control channels (Rhyacaphila and chironomid larvae); (iv) no significant response to acidification (Ameletus, Amiocentrus, Dixa and Hydroporus). 3. A high proportion (45–100%) of acid‐induced drift in Baetis, Epeorus, and chironomid larvae could be attributed to dead, drifting individuals. 4. Except for chironomids, most common invertebrates (i.e. Baetis and Paraleptophlebia) showed reduced benthic densities in treatment relative to control channels after acidification. 5. For sensitive taxa, drift was enhanced and benthic densities reduced by single (Experiment 1) and initial [Experiment 2(a)] acid pulses. Drift responses to a second acid pulse [Experiment 2(b)] were not as pronounced as those to the single or initial acid pulses [Experiments 1 and 2(a)], and the second acid pulse had no additional effect on benthic density. Copyright © 1994, Wiley Blackwell. All rights reserved

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.

In this review article, we discuss the model for end-stage liver disease (MELD) score and its dual purpose in general and transplant hepatology. As the landscape of liver disease and transplantation has evolved considerably since the advent of the MELD score, we summarise emerging concepts, methodologies, and technologies that may improve mortality prognostication in the future. Finally, we explore how these novel concepts and technologies may be incorporated into clinical practice.

SUMMARY. 1. During the summer of 1987 we conducted an acidification experiment using large enclosure at Emerald Lake, a dilute, high‐elevation lake in the Sierra Nevada, California, U.S.A. The experiment was designed to examine the effects of acidification on the zooplankton and zoobenthos assemblages of Sierran lakes. 2. Treatments consisted of a control (pH 6.3) and pH levels of 5.8, 5.4, 5.3, 5.0 and 4.7; each treatment was run in triplicate. The experiment lasted 35 days. 3. The zooplankton assemblage was sensitive to acidification. Daphnia rosea Sars emend. Richard and Diaptomns signicauda Lilljeborg decreased in abundance below pH 5.5–5.8, and virtually disappeared below pH 5.0. Bosmina longirostris (Müller) and Keratella taurocephala Ahlstrom became more abundant with decreasing pH. although B. longirostris was rare in the pH 4.7 treatment. These species might serve as reliable indicators of early acidification in lakes such as Emerald Lake. 4. The elimination of D. rosea in acidified treatments probably allowed the more acid‐tolerant taxa to increase in abundance because interspecific competition was reduced. Even slight acidification can therefore alter the structure of the zooplankton assemblage. 5. In contrast to the zooplankton, there was no evidence that the zoobenthos in the enclosures was affected by acidification. Copyright © 1990, Wiley Blackwell. All rights reserved

Purpose

The mechanisms of brain metastasis are incompletely understood. Circulating tumor cells travel to the right heart and through the pulmonary circulation, where they may become lung metastases, and can circulate further to the left heart and brain. In patients who develop brain metastases without lung involvement, we hypothesized that cancer cells may travel directly from the right atrium to left atrium via a patent foramen ovale (PFO), akin to paradoxical embolism. If the prevalence of PFO is greater in these individuals compared to the general population (20-30%), PFO may play a role in brain metastasis, and prophylactic closure may provide benefit. Accordingly, we investigated the prevalence of PFO in patients with brain metastases without prior lung involvement.

Methods

We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding or concurrent lung involvement. Nine eligible participants underwent a transcranial Doppler study with intravenous agitated saline to assess for PFO.

Results

Among nine participants, primary cancers were breast (n = 6), upper gastrointestinal (n = 2), and thyroid (n = 1). A positive bubble study was identified in 2/9 (22.2%) participants: one female with breast cancer and one male with duodenal adenocarcinoma. No participants developed lung metastases on subsequent chest imaging.

Conclusion

In this prospective pilot study, we found a similar prevalence of PFO in patients who developed brain metastases without preceding lung involvement compared to estimates for the general population. Through a larger study is needed, the development of brain metastases in these individuals may primarily reflect tumor-specific biological factors diecting metastasis organotropism.

There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide (T_LCO); however, it is not always clear which reference set should be used in clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for T_LCOData from 19 centres in 14 countries were collected to define T_LCO reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R.12 660 T_LCO measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5-85 years were derived for T_LCO, transfer coefficient of the lung for carbon monoxide and alveolar volume.This is the largest collection of normative T_LCO data, and the first global reference values available for T_LCO.