Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential impacts of the Affordable Care Act on the clinical practice of hepatology

The Patient Protection and Affordable Care Act (ACA), along with the Health Care and Education Reconciliation Act, was signed into law and upheld by the Supreme Court earlier this year. The ACA contains a variety of reforms that, if implemented, will significantly affect current models of healthcare delivery for patients with acute and chronic hepatobiliary diseases. One of the Act's central reforms is the creation of accountable care organizations (ACOs) whose mission will be to integrate different levels of care to improve the quality of services delivered and outcomes among populations while maintaining, or preferably reducing, the overall costs of care. Currently, there are clinical practice areas within hepatology, such as liver transplantation, that already have many of the desired features attributed to ACOs. The ACA is sure to affect all fields of medicine, including the practice of clinical hepatology. This article describes the components of the ACA that have the greatest potential to influence the clinical practice of hepatology. Conclusion: Ultimately, it will be the responsibility of our profession to identify optimal healthcare delivery models for providing high‐value, patient‐centered care. (Hepatology 2014;59:1681–1687)
Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis

Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10‐15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health‐related quality of life (HRQoL) were assessed with a 10‐point numeric rating scale, the Medical Outcomes Study Short Form‐36 (SF‐36), and PBC‐40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P < 0.0001; gamma‐glutamyl transpeptidase of 117.9%, P < 0.0001; bilirubin of 50.0%, P < 0.001; alanine aminotransferase of 63.9%, P < 0.005; and aspartate aminotransferase of 45.0%, P < 0.005) and increase of Mayo Risk Score for PSC (change from baseline of +0.5 point; P < 0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. Conclusion: At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short‐term markers of quality of life are unaffected. (Hepatology 2014;60:931–940)
Occupational Exposure to Crystalline Silica at Alberta Work Sites

Although crystalline silica has been recognized as a health hazard for many years, it is still encountered in many work environments. Numerous studies have revealed an association between exposure to respirable crystalline silica and the development of silicosis and other lung diseases including lung cancer. Alberta Jobs, Skills, Training and Labour conducted a project to evaluate exposure to crystalline silica at a total of 40 work sites across 13 industries. Total airborne respirable dust and respirable crystalline silica concentrations were quite variable, but there was a potential to exceed the Alberta Occupational Exposure Limit (OEL) of 0.025 mg/m3 for respirable crystalline silica at many of the work sites evaluated. The industries with the highest potentials for overexposure occurred in sand and mineral processing (GM 0.090 mg/m3), followed by new commercial building construction (GM 0.055 mg/m3), aggregate mining and crushing (GM 0.048 mg/m3), abrasive blasting (GM 0.027 mg/m3), and demolition (GM 0.027 mg/m3). For worker occupations, geometric mean exposure ranged from 0.105 mg/m3 (brick layer/mason/concrete cutting) to 0.008 mg/m3 (dispatcher/shipping, administration). Potential for GM exposure exceeding the OEL was identified in a number of occupations where it was not expected, such as electricians, carpenters and painters. These exposures were generally related to the specific task the worker was doing, or arose from incidental exposure from other activities at the work site. The results indicate that where there is a potential for activities producing airborne respirable crystalline silica, it is critical that the employer include all worker occupations at the work site in their hazard assessment. There appears to be a relationship between airborne total respirable dust concentration and total respirable dust concentrations, but further study is require to fully characterize this relationship. If this relationship holds true, it may provide a useful hazard assessment tool for employers by which the potential for exposure to airborne respirable silica at the work site can be more easily estimated.
Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury

Proliferating ducts, termed “oval cells,” have long been thought to be bipotential, that is, produce both biliary ducts and hepatocytes during chronic liver injury. The precursor to oval cells is considered to be a facultative liver stem cell (LSC). Recent lineage tracing experiments indicated that the LSC is SRY‐related HMG box transcription factor 9 postive (Sox9+) and can replace the bulk of hepatocyte mass in several settings. However, no clonal relationship between Sox9+ cells and the two epithelial liver lineages was established. We labeled Sox9+ mouse liver cells at low density with a multicolor fluorescent confetti reporter. Organoid formation validated the progenitor activity of the labeled population. Sox9+ cells were traced in multiple oval cell injury models using both histology and fluorescence‐activated cell sorting. Surprisingly, only rare clones containing both hepatocytes and oval cells were found in any experiment. Quantitative analysis showed that Sox9+ cells contributed only minimally (<1%) to the hepatocyte pool, even in classic oval cell injury models. In contrast, clonally marked mature hepatocytes demonstrated the ability to self‐renew in all classic mouse oval cell activation injuries. A hepatocyte chimera model to trace hepatocytes and nonparenchymal cells also demonstrated the prevalence of hepatocyte‐driven regeneration in mouse oval cell injury models. Conclusion: Sox9+ ductal progenitor cells give rise to clonal oval cell proliferation and bipotential organoids, but rarely produce hepatocytes in vivo. Hepatocytes themselves are the predominant source of new parenchyma cells in prototypical mouse models of oval cell activation. (Hepatology 2014;60:278–289)
Gd‐EOB‐DTPA‐enhanced magnetic resonance imaging and alpha‐fetoprotein predict prognosis of early‐stage hepatocellular carcinoma

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early‐stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd‐EOB‐DTPA‐enhanced MRI (EOB‐MRI) in combination with serum alpha‐fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd‐EOB‐DTPA uptake in the hepatobiliary phase was observed in ∼15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up‐regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd‐EOB‐DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd‐EOB‐DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd‐EOB‐DTPA uptake in vivo. HCC classification based on EOB‐MRI and serum AFP levels predicted overall survival in a single‐institution cohort (n = 70), and its prognostic utility was validated independently in a multi‐institution cohort of early‐stage HCCs (n = 109). Conclusion: This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease. (Hepatology 2014;60:1674–1685)
Rebleeding prophylaxis improved outcomes in patients with hepatocellular carcinoma: Is it feasible in all patients?

We read with great interest the recent article by Ripoll et al. In this multicenter case-control study, the authors emphasize the survival benefit of second prophylaxis in patients with hepatocellular carcinoma (HCC) and variceal bleeding (VB) regardless of Barcelona Clinic Liver Cancer (BCLC) stage. However, these results should be interpreted with caution. In this study the median survival was only 0.9 months and 0.7 months in patients without second prophylaxis stratified by BCLC A/B and C/D, respectively. Because of the retrospective nature, it is highly probable that patients who were too ill to start or died before the second prophylaxis were inevitably stratified to the group without second prophylaxis; therefore, selection bias of poor survivor in the nonprophylaxis group should be a concern. These phenomena were shown in Supporting Table 1, in which patients without prophylaxis in BCLC C/D had a higher Model for Endstage Liver Disease (MELD) score and poor liver reserve. Moreover, we don’t think the patients in BCLC D should be analyzed together with BCLC C because the patients in BCLC D usually had the poorest hepatic reserve and survival, and also were very unlikely to tolerate second prophylaxis. Actually, our previous randomized controlled trial (RCT) showed that 44.4% (24/54) of patients with unresectable HCC and VB cannot receive a second scheduled ligation after endoscopic hemostasis of acute bleeding; more than 90%(22/24) of these patients were Child-Pugh C. We are very interested to see if the patients in BCLC D can receive second prophylaxis and their outcomes in the current study because the proof of no harm to introduce invasive treatment to terminal and fragile patients is very important. In an earlier study in Japan, neither prophylactic nor emergency endoscopic injection sclerotherapy prolonged the survival of patients with HCC and Child-Pugh C. In another recent retrospective study, Dr. Han found that hepatic reserve instead of endoscopic therapy is associated with in-hospital mortality in patients with HCC and ChildPugh C. On the other hand, the use of a beta-blocker in patients with poor hepatic reserve should be done very cautiously because a study showed that beta-blocker is associated with poor survival in patients with refractory ascites. In conclusion, the benefit of second prophylaxis of VB in patients with HCC and poor hepatic reserve is still unclear and further prospective study is needed.
Comparison of a Wipe Method With and Without a Rinse to Recover Wall Losses in Closed Face 37-mm Cassettes used for Sampling Lead Dust Particulates

Closed-face 37-mm polystyrene cassettes are often used for exposure monitoring of metal particulates. Several methods have been proposed to account for the wall loss in air sampling cassettes, including rinsing, wiping, within-cassette dissolution, and an internal capsule fused to the filter that could be digested with the filter. Until internal capsules replace filters, other methods for assessing wall losses may be considered. To determine if rinsing and wiping or wiping alone is adequate to determine wall losses on cassettes, we collected 54 full-shift area air samples at a battery recycling facility. We collected six replicate samples at three locations within the facility for three consecutive days. The wall losses of three replicate cassettes from each day-location were analyzed following a rinse and two consecutive wipes. The wall losses of the other three replicates from each day-location were analyzed following two consecutive wipes only. Mixed-cellulose ester membrane filter, rinse, and wipes were analyzed separately following NIOSH Method 7303. We found an average of 29% (range: 8–54%) recovered lead from the cassette walls for all samples. We also found that rinsing prior to wiping the interior cassette walls did not substantially improve recovery of wall losses compared to wiping alone. A rinse plus one wipe recovered on average 23% (range: 13–33%) of the lead, while one wipe alone recovered on average 21% (range: 16–22%). Similarly, we determined that a second wipe did not provide substantial additional recovery of lead (average: 4%, range: 0.4–19%) compared to the first wipe disregarding the rinse (average: 18%, range: 4–39%). We concluded that when an internal capsule is not used, wall losses of lead dust in air sampling cassettes can be adequately recovered by wiping the internal wall surfaces of the cassette with a single wipe.
Physical Fitness Assessment Across the Disability Spectrum in Persons With Multiple Sclerosis: A Comparison of Testing Modalities

Background and Purpose: Appropriate assessment of physical fitness (ie, aerobic capacity and muscular strength) is necessary for the design and evaluation of exercise training in multiple sclerosis (MS). However, this is challenging in persons with substantial disability, because of physical inaccessibility and insensitivity of certain exercise testing modalities. This study compared different methods of measuring cardiorespiratory (arm ergometer vs recumbent stepper) and muscular (hand-held dynamometry vs computerized dynamometry) fitness across the MS disability spectrum. Associations between physical fitness and other measures that represented all domains of the International Classification of Functioning, Disability and Health (ICF) were also examined. Methods: Sixty-four participants with MS completed 2 symptom-limited cardiorespiratory fitness and muscular strength tests. We also assessed disability, cognition, fatigue, walking speed and endurance, health-related quality of life, and activities of daily living. Results: Across all levels of disability, peak aerobic capacity assessed by recumbent stepping was higher compared with arm ergometry (P < 0.001). Peak torque of the knee extensors and knee flexors was significantly higher assessed by computerized dynamometry compared with hand-held dynamometry (P < 0.001). Aerobic capacity and peak torque decreased as a function of increasing disability (P < 0.001). Significant, moderate to strong correlations were observed between the physical fitness measures and measures representing all domains of the ICF, irrespective of the fitness testing mode. Discussion and Conclusions: Overall, peak physical capacity was higher when assessed by recumbent stepping and computerized dynamometry. The assessment and prescription of exercise in MS should be based on these modalities to provide the most appropriate stimulus for exercise training adaptations. There continues to be an important association between physical fitness and other measures that represent all domains of the ICF, regardless of fitness assessment mode. Video Abstract available for additional insights from the authors (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/JNPT/A109).
Cost analysis of sofosbuvir/ribavirin versus sofosbuvir/simeprevir for genotype 1 hepatitis C virus in interferon‐ineligible/intolerant individuals

Treatment guidance for chronic hepatitis C (CHC) released by the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) offers two options for interferon (IFN)‐ineligible/intolerant individuals with genotype 1 infection: sofosbuvir/ribavirin (SOF/RBV) for 24 weeks or sofosbuvir/simeprevir (SOF/SMV) for 12 weeks. A 24‐week course of SOF/RBV costs approximately US$169,000, with sustained virologic response (SVR) rates ranging from 52% to 84%; 12 weeks of SOF/SMV costs approximately $150,000, with SVR between 89% and 100%. Because SOF/SMV is currently used off‐label, debate exists among physicians and payers about whether it should be prescribed and covered. This article presents a cost‐effectiveness analysis of these two treatment regimens accounting for costs of drugs, treatment‐related medical care, retreatment for individuals who do not achieve SVR, and natural history of continued HCV infection after failed retreatment. Analysis uses a Markov model with a lifetime horizon and a societal perspective. In the base‐case scenario, SOF/SMV dominated SOF/RBV in a modeled 50‐year‐old cohort of treatment‐naïve and ‐experienced subjects, excluding those who failed earlier therapy with telaprevir or boceprevir. SOF/SMV yielded lower costs and more quality‐adjusted life years (QALYs) for the average subject, compared to SOF/RBV ($165,336 and 14.69 QALYs vs. $243,586 and 14.45 QALYs, respectively). In base‐case cost analysis, the SOF/SMV treatment strategy saved $91,590 per SVR, compared to SOF/RBV. Under all one‐way sensitivity scenarios, SOF/SMV remained dominant and resulted in cost savings. Conclusions: These results suggest that a 12‐week course of SOF/SMV is a more cost‐effective treatment for genotype 1 CHC than 24 weeks of SOF/RBV among IFN‐ineligible/intolerant individuals, supporting the AASLD/IDSA guidance and offering implications for both clinical and regulatory decision making as well as pharmaceutical pricing. (Hepatology 2014;60:37–45)
Inhibition of microRNA‐24 expression in liver prevents hepatic lipid accumulation and hyperlipidemia

The incidence of nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia, with their associated risks of endstage liver and cardiovascular diseases, is increasing rapidly due to the prevalence of obesity. Although the mechanisms of NAFLD have been studied extensively, the underlying pathogenesis and the role of microRNAs in this process remain relatively unclear. MicroRNA (miRNA)‐dependent posttranscriptional gene silencing is now recognized as a key element of lipid metabolism. Here we report that the expression of microRNA‐24 (miR‐24) is significantly increased in the livers of high‐fat diet‐treated mice and in isolated human hepatocytes incubated with fatty acid. Knockdown of miR‐24 in those mice caused impaired hepatic lipid accumulation and reduced plasma triglycerides. Bioinformatic and in vitro and in vivo studies led us to identify insulin‐induced gene 1 (Insig1), an inhibitor of lipogenesis, as a novel target of miR‐24. Inhibition of endogenous miR‐24 expression by way of miR‐24 inhibitors led to up‐regulation of Insig1, and subsequently decreased hepatic lipid accumulation. It is well established that liver‐specific deletion of Insig1 leads to higher hepatic and plasma triglyceride levels by inhibiting the processing of sterol regulatory element‐binding proteins (SREBPs), transcription factors that activate lipid synthesis. As expected, miR‐24 knockdown prevented SREBP processing, and subsequent expression of lipogenic genes. In contrast, the opposite result was observed with overexpression of miR‐24, which enhanced SREBP processing. Thus, our study defines a potentially critical role for deregulated expression of miR‐24 in the development of fatty liver by way of targeting of Insig1. Conclusion: Our findings show a novel mechanism by which miR‐24 promotes hepatic lipid accumulation and hyperlipidemia by repressing Insig1, and suggest the use of miR‐24 inhibitor as a potential therapeutic agent for NAFLD and/or atherosclerosis. (Hepatology 2014;60:554–564)
An Industrial Hygienist Looks at Porn

Deborah Gold, MPH, CIH, is the former Deputy Chief for Health of the Division of Occupational Safety and Health (aka Cal/OSHA) within the California Department of Industrial Relations. During her tenure in that position, and in her previous positions with the agency as a Senior Industrial Hygienist and Senior Safety Engineer she was involved with enforcement actions, and regulatory development concerning the California adult film industry. The opinions expressed are not intended to represent the views of the agency.
Prevalence and predictors of sexual problems, relationship stress, and depression in female partners of infertile couples.

INTRODUCTION Infertility has been associated with anxiety, stress, and sexual problems in both men and women. AIM To assess quality of life, sexual health, and depression in the female partner of infertile couples. METHODS Couples presenting for the evaluation of infertility at two tertiary care medical centers were invited to participate in a survey study. MAIN OUTCOME MEASURES Female partners completed the Female Sexual Function Index (FSFI) and a modified Self-Esteem and Relationship (SEAR) Questionnaire. Male partners completed the SEAR and the International Index of Erectile Function (IIEF). Both partners completed the Center for Epidemiological Studies Depression Scale (CES-D) for depression and the Short Form-36 (SF-36) for general quality of life. Demographic, fertility, and comorbidity information was recorded. RESULTS One hundred and twenty-one couples constitute the study population. Mean female and male age was 32 +/- 5 and 35 +/- 7 years, respectively. Most (92%) couples were married. Mean duration of relationship and marriage were 6.4 +/- 3.9 and 3.8 +/- 3.2 years, respectively. Mean duration of attempted conception was 24 +/- 24 months. On CES-D, 19% of women had moderate and 13% had severe depression. Women reported significantly worse SF-36 Mental Health subscale scores (mean = 47.8, P < 0.05) compared with normative values. The mean total FSFI score was 28 +/- 7 (maximum score of 36), with 26% of the women scoring below 26.55, an established cut-off for high risk of female sexual dysfunction. FSFI scores had a modest positive correlation with male IIEF scores (r = 0.37, P < 0.01), and there was a trend toward a negative correlation with female CES-D scores (r = -0.16, P < 0.06). These relationships were maintained on multivariate analysis. CONCLUSIONS Depression and sexual dysfunction are prevalent in female partners of infertile couples. Female sexual function is positively correlated with male partner sexual function in this population.