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BACKGROUND: Medicare has proposed quality-of-care indicators for chronic hepatitis C virus (HCV) infection. The extent to which these standards are met in practice is largely unknown. OBJECTIVE: To evaluate the quality of health care that patients with HCV receive and the factors associated with receipt of quality care. DESIGN: Retrospective cohort study. SETTING: Nationwide U.S. health insurance company research database. PARTICIPANTS: 10 385 patients with HCV enrolled in the database between 2003 and 2006. Patients were included if they were eligible for at least 1 quality indicator. MEASUREMENTS: Quality of HCV care received by patients, as measured by 7 explicit quality indicators included in Medicare's 2009 Physician Quality Reporting Initiative. RESULTS: Proportions of patients meeting quality indicators varied, ranging from 21.5% for vaccination to 79% for the HCV genotype testing indicator. Overall, 18.5% of patients (95% CI, 18% to 19%) received all recommended care. Older age and presence of comorbid conditions were associated with lower quality, whereas elevated liver enzyme levels, cirrhosis, and HIV infection were associated with higher quality. Patients who saw both generalists and specialists received the best care (odds ratio of receiving care for which a patient is eligible: specialists alone, 0.79 [CI, 0.66 to 0.95]; primary care physician alone, 0.44 [CI, 0.40 to 0.48]). LIMITATIONS: The study had an observational retrospective design, used a convenience sample, and had no information on patient ethnicity. It may be that the indicators or the reporting of the indicators of HCV care--and not the care itself--is suboptimum. CONCLUSION: Health care quality, based on Medicare criteria, is suboptimum for HCV. Care that included both specialists and generalists is associated with the best quality. Our results support the development of specialist and primary care collaboration to improve the quality of HCV care. PRIMARY FUNDING SOURCE: Saint Louis University Liver Center. [ABSTRACT FROM AUTHOR]

Carefully eliciting risk factors and screening accordingly are optimal methods of detecting hepatitis C in primary care patients before server hepatic dysfunction develops. [ABSTRACT FROM AUTHOR]

Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP), HFE, neogenin (NEO1), transferrin receptor 1 (TFRC), transferrin receptor 2 (TFR2), and hemojuvelin (HFE2) in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

Abstract Background Hereditary hemochromatosis (HH) encompasses genetic disorders of iron overload characterized by deficient expression or function of the iron-regulatory hormone hepcidin. Mutations in 5 genes have been linked to this disease: HFE, TFR2 (encoding transferrin receptor 2), HAMP (encoding hepcidin), SLC40A1 (encoding ferroportin) and HJV (encoding hemojuvelin). Hepcidin inhibits iron export from cells into plasma. Hemojuvelin, an upstream regulator of hepcidin expression, is expressed in mice mainly in the heart and skeletal muscle. It has been suggested that soluble hemojuvelin shed by the muscle might reach the liver to influence hepcidin expression. Heart muscle is one of the target tissues affected by iron overload, with resultant cardiomyopathy in some HH patients. Therefore, we investigated the effect of iron overload on gene expression in skeletal muscle and heart using Illumina™ arrays containing over 47,000 probes. The most apparent changes in gene expression were confirmed using real-time RT-PCR. Results Genes with up-regulated expression after iron overload in both skeletal and heart muscle included angiopoietin-like 4, pyruvate dehydrogenase kinase 4 and calgranulin A and B. The expression of transferrin receptor, heat shock protein 1B and DnaJ homolog B1 were down-regulated by iron in both muscle types. Two potential hepcidin regulatory genes, hemojuvelin and neogenin, showed no clear change in expression after iron overload. Conclusion Microarray analysis revealed iron-induced changes in the expression of several genes involved in the regulation of glucose and lipid metabolism, transcription and cellular stress responses. These may represent novel connections between iron overload and pathological manifestations of HH such as cardiomyopathy and diabetes.

Background: Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin.Methods: We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV RNA level (<50 IU per milliliter) 24 weeks after the end of treatment.Results: The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen. The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks (62% vs. 70%; odds ratio for 16 weeks vs. 24 weeks, 0.67; 95% confidence interval, 0.54 to 0.84; P<0.001). In addition, the rate of relapse (a detectable HCV RNA level during follow-up in patients who had undetectable HCV RNA at the end of treatment) was significantly greater in the 16-week group (31%, vs. 18% in the 24-week group; P<0.001). The sustained virologic response rates in patients with a pretreatment serum HCV RNA level of 400,000 IU per milliliter or less was 82% with the 16-week regimen and 81% with the 24-week regimen. Among patients with a rapid virologic response (an undetectable HCV RNA level by week 4), sustained virologic response rates were 79% in the 16-week group and 85% in the 24-week group (P=0.02).Conclusions: Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen. (ClinicalTrials.gov number, NCT00077636 [ClinicalTrials.gov].). [ABSTRACT FROM AUTHOR]

Objective: Our objective was to describe non-concussion head and neck ice hockey injuries in children in the US., Methods: This is a retrospective cohort study using data from the NEISS database. The NEISS database was reviewed from 2010 to 2021 for injuries in the head, neck, mouth, eye, and ear related to ice hockey in children 1-18 years old. Records where the only injury was a concussion or internal head injury were removed. Frequencies were calculated and chi-squared tests were performed., Results: 475 children were included, with mean age of 13.1 years old (95 % CI 12.7-13.4), and 426 (89.7 %) were male. Females were significantly younger with mean age 11.8 years versus 13.2 years for males (t = -2.4, df = 473, p = .018). 110 (23.2 %) injuries were related to hockey sticks, 92 (19.4 %) involved a fall, and 32 (6.7 %) were subsequent to body checking. 301 of the injuries (63.4 %) were lacerations, 71 (14.9 %) contusions or abrasions, and 26 (5.5 %) strains and sprains. The type of injury varied according to head and neck region (p < .001). 231 (82.8 %) of facial injuries, 16 (76.2 %) of ear injuries, and 33 (62.3 %) of oral injuries were lacerations. Eight (1.7 %) patients were admitted or observed overnight, while the rest were discharged home., Conclusion: Female ice hockey players sustain injuries at younger ages than males, which may reflect the loss of older girls from the sport. In older boys, injury rates may reflect the loss of mandated full face protective shields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Since December 2021, the number of children with COVID-19 infections has increased. Sequelae in children have not been well-described. Our goal was to determine if children with a history of COVID-19 infection (C19 group) were more likely to present with recurrent acute otitis media (rAOM) or post-ventilation tube otorrhea (VTO) than children who had no history of COVID-19 infection (NoC19 group)., Methods: Charts of consecutive children presenting at a pediatric otolaryngology clinic from March-May 2022 were reviewed. Demographics, COVID-19 test history, comorbidities, ultimate diagnosis, physical exam findings, and management plan were included. No children had a known COVID-19 infection at the time of visit., Results: 524 children were included, 228 (43.5 %) girls and 296 (56.5 %) boys. Mean age was 5 years (95 % CI 4.6-5.4). 115 (21.9 %) had a history of COVID-19 infection. 104 (19.8 %) had a diagnosis of rAOM or VTO, 26.1 % (30/115) children in C19 and 18.1 % (74/409) children in NoC19 (Fisher's Exact p = .04, OR = 1.6). For children without ventilation tubes in place, 23.5 % (27/115) in C19 had rAOM versus 15.2 % (62/409) in NoC19 (p = .03, OR = 1.7). 18.3 % (21/115) of the C19 group had nasal congestion compared to 6.6 % (27/409) of the NoC19 group (p < .001, OR = 3.2). There was no difference in incidence of otitis media with effusion, tonsil/adenoid hypertrophy, sleep-disordered breathing, or epistaxis between the groups., Conclusion: Infection with COVID-19 may be associated with an increased risk of rAOM and VTO in children. This may affect healthcare utilization by increasing the need for pediatric and otolaryngologic care., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Our goal is to determine if there is a correlation between Modified Epworth Sleepiness Scale (M-ESS) scores, obstructive sleep apnea (OSA)-18 scores, and polysomnography (PSG) outcomes in children., Study Design: Retrospective chart review., Setting: Pediatric otolaryngology clinic., Methods: Charts of consecutive children presenting from July 2021 to July 2023 were reviewed. Demographics, body mass index (BMI), BMI Z score, M-ESS score, OSA-18 score, PSG results, and sleep apnea severity were included. One-way analysis of variance and Pearson/Spearman correlation coefficients were calculated., Results: Three hundred sixty-seven children were included, 162 (44.1%) girls and 205 (55.9%) boys. Mean patient age was 7.8 (95% confidence interval [CI]: 7.3-8.3) years. M-ESS score was 6.3 (n = 348, 95% CI: 5.8-6.8), mean OSA-18 score was 56.2 (n = 129, 95% CI: 53.0-59.4). Mean apnea-hypopnea index (AHI) was 10.1 (95% CI: 8.7-11.4) events/h, obstructive AHI 9.3 (95% CI: 8.0-12.7) events/h, respiratory distress index 14.6 (95% CI: 8.4-20.8) events/h, and oxygen saturation nadir 89.8% (95% CI: 89.1-90.4). Sixty-two children (17.2%) had mild, 192 (53.5%) moderate, and 105 (29.2%) severe sleep apnea. M-ESS score correlated weakly to AHI (r = .19, P = <.001), and OSA-18 score to oxygen saturation nadir (r = -.16, P = .002). After logistic regression adjusted for age and BMI, neither clinical scores were independently associated with AHI., Conclusion: M-ESS and OSA-18 scores have a weak correlation with OSA severity in children. More reliable, age-appropriate screening tools are needed in pediatric sleep apnea., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: Our goal was to see if children with a history of COVID infection had subclinical hyposmia., Methods: Consecutive patients at a pediatric otolaryngology clinic aged 5-17 years were recruited. Demographics including gender, race, use of nasal topical medications (NTM), previous nasal surgery including adenoidectomy (NSA), and previous COVID-19 infection were collected. Each child performed a test of their sense of smell using the Pediatric Smell Wheel (PSW, Sensonics Intl, USA) under the direct supervision and scores were compared., Results: 260 children were included; mean age 10.1 years (95% CI 9.7-10.5), 128 (49.2%) female and 132 (50.8%) male. 65 (25%) used steroid nasal sprays, 100 (38.5%) had undergone adenoidectomy, and 36 (13.8%) had other nasal surgery. 120 (46.2%) had a previous COVID-19 infection. The COVID+ and COVID- groups were the same for age, gender, race, use of NTMs, and previous NSA (p > 0.05). Mean PSW score was 7.8 (95% CI 7.6-8.0), median of 8, ranging from 2 to 11. The mean PSW score was 8.0 for the COVID- group and 7.6 for the COVID+ group (p = 0.005). There was no significant difference in total PSW scores based on gender, race, use of NTMs, previous NSA. Linear regression showed previous COVID infection was significantly negatively associated with total PSW score (Beta -0.636, p = 0.006) with age significantly positively associated (Beta 0.122, p < 0.001)., Conclusion: Children with a history of COVID infection performed slightly worse when identifying odors than children without a COVID history. More study into the rates of pediatric anosmia related to COVID infection is needed., Level of Evidence: 3 Laryngoscope, 134:901-906, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To determine the proportion of parents that have some knowledge of abnormal maxillary frenulum, or "lip tie," and their sources of this information., Study Design: Cross-sectional study., Setting: Otolaryngology clinic., Methods: Consecutive parents of children ≤12 years of age presenting at a pediatric otolaryngology clinic were surveyed to discover their understanding of "lip tie" in children. The survey included questions on the effects of "lip tie," where they learned about "lip tie," whether they thought their child had "lip tie," whether they had a child undergo "lip tie" division, and how concerned they would be if they thought their child had "lip tie." Information on participant demographics and social media was collected., Results: Overall, 59.8% (193) of the 323 parents surveyed had heard of "lip tie"; of those, 17.1% (33) had a child that had undergone "lip tie" surgery. Most parents (91.2%, 176) thought "lip tie" caused breastfeeding problems. Roughly one-quarter of parents (51 of 197 responses) rated their concern about "lip tie" as >8 of 10 on a Likert scale (mean, 5.7). The reported sources of "lip tie" information included lactation consultants (36.8%, 71), nurses (22.8%, 44), and pediatricians (31.6%, 61) as well as nonmedical sources, such as social media, family, and friends (68.4%, 132). Overall, 87% (282) of the 323 participants reported daily use of social media., Conclusion: Although many parents are concerned about "lip tie," much of their information on this condition comes from nonmedical sources. Social media would be a valuable platform to provide accurate information on "lip tie.", Competing Interests: The authors have no conflicts of interest to disclose., (© 2023 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

In this article, we describe three life-changing patient cases demonstrating high-quality and timely care they received in their communities, thanks to the Show-Me ECHO project. Early autism diagnosis, a potentially deadly tumor manifesting as a benign-looking rash, a recalcitrant case of hepatitis C: rural and underserved Missourians now have access to state-of-the-art care through their local providers receiving interdisciplinary telementoring on evidence based practices., (Copyright 2020 by the Missouri State Medical Association.)

Background & Aims: Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents., Methods: We analyzed data from 2369 patients infected with HCV genotypes 1-6 and compensated liver disease treated with an all-oral regimen of glecaprevir/pibrentasvir for 8-16 weeks. We compared efficacy and pharmacokinetics among patients receiving at least 1 dose of an acid-reducing agent (a PPI, an H2 blocker, or antacid). High-dose PPI was defined as daily dose greater than 20 mg omeprazole dose equivalent. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and to assess steady-state glecaprevir and pibrentasvir exposures in patients on acid-reducing agents., Results: Of the 401 patients (17%) who reported use of acid-reducing agents, 263 took PPIs (11%; 109 patients took a high-dose PPI and 154 patients took a low-dose PPI). Rates of SVR12 were 97.0% among patients who used acid-reducing agents and 97.5% among those not using acid-reducing agents (P = .6). An SVR12 was achieved in 96.3% taking a high-dose PPI and 97.4% taking a low-dose PPI, with no virologic failures in those receiving a high-dose PPI (P = .7). Glecaprevir, but not pibrentasvir, bioavailability was affected; its exposure decreased by 41% in patients taking a high-dose PPI., Conclusions: In an analysis of data from 9 clinical trials, we observed a high rate of SVR12 (approximately 97%) among patients treated with glecaprevir/pibrentasvir for HCV infection-even among patients taking concomitant ARA or high-dose PPI. This was despite decreased glecaprevir exposures in patients when on high-dose PPIs. ClinicalTrials.gov numbers, NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02640482 (ENDURANCE-2), NCT02640157 (ENDURANCE-3), NCT02636595 (ENDURANCE-4), NCT02642432 (EXPEDITION-1), NCT02651194 (EXPEDITION-4), NCT02446717 (MAGELLAN-I)., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are two major immune-mediated chronic liver diseases. Overlap syndrome (OS) is diagnosed if patients have features of both AIH and PBC; however, there is no consensus on the definition or diagnostic criteria for OS. Here, we report a new scoring classification for OS and evaluate its usefulness. This new scoring classification was developed by modifying the International Autoimmune Hepatitis Group classification by selecting histologic features of AIH and PBC along with modifications of biochemical and immunologic characteristics. We evaluated 272 patients with chronic liver disease, including 105 with AIH, 102 with PBC, and 65 with OS. The best performance for the diagnosis of OS was noted among patients with an overlap score of ≥21 who had a sensitivity of 98.5%, a specificity of 92.8%, a positive predictive value of 81.0%, and a negative predictive value of 99.5%. By using a cut-off score of 21, 64 (98.5%) patients were diagnosed with OS as opposed to 9 (8.8%) and 6 (5.7%) with PBC and AIH, respectively. All patients with OS had an aggregate score of >19, whereas most patients with PBC or AIH scored <19, making this a safe discriminatory cut-off point against OS. Conclusion : The new scoring system for the diagnosis of OS has a high sensitivity and specificity for scores ≥21, while a score <19 suggests a diagnosis other than OS. This classification can identify patients and diagnose OS with a reasonable amount of accuracy and may be superior to current OS scoring systems in detecting mild forms of OS. ( Hepatology Communications 2018;2:245-253).

Background: Regulation of body iron occurs at cellular, tissue, and systemic levels. In healthy individuals, iron absorption and losses are minimal, creating a virtually closed system. In the setting of chronic kidney disease and hemodialysis (HD), increased iron losses, reduced iron absorption, and limited iron availability lead to iron deficiency. Intravenous (IV) iron therapy is frequently prescribed to replace lost iron, but determining an individual's iron balance and stores can be challenging and imprecise, contributing to uncertainty about the long-term safety of IV iron therapy., Summary: Patients on HD receiving judicious doses of IV iron are likely to be in a state of positive iron balance, yet this does not appear to confer an overt risk for clinically relevant iron toxicity. The concomitant use of iron with erythropoiesis-stimulating agents, the use of maintenance iron dosing regimens, and the reticuloendothelial distribution of hepatic iron deposition likely minimize the potential for iron toxicity in patients on HD. Key Messages: Because no single diagnostic test can, at present, accurately assess iron status and risk for toxicity, clinicians need to take an integrative approach to avoid iron doses that impose excessive exposure while ensuring sufficient replenishment of iron stores capable of overcoming hepcidin blockade and allowing for effective erythropoiesis., (© 2018 S. Karger AG, Basel.)

Background: Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid., Methods: The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid. Patients, recruited at 29 sites in North America and Europe, were randomly assigned to placebo, seladelpar 50 mg/day, or seladelpar 200 mg/day while ursodeoxycholic acid was continued. Randomisation was done centrally (1:1:1) by a computerised system using an interactive voice-web response system with a block size of three. Randomisation was stratified by region (North America and Europe). The primary outcome was the percentage change from baseline in alkaline phosphatase over 12 weeks, analysed in the modified intention-to-treat (ITT) population (any randomised patient who received at least one dose of medication and had at least one post-baseline alkaline phosphatase evaluation). This study is registered with ClinicalTrials.gov (NCT02609048) and the EU Clinical Trials Registry (EudraCT2015-002698-39)., Findings: Between Nov 4, 2015, and May 26, 2016, 70 patients were screened at 29 sites in North America and Europe. During recruitment, three patients treated with seladelpar developed fully reversible, asymptomatic grade 3 alanine aminotransferase increases (one on 50 mg, two on 200 mg), ranging from just over five to 20 times the ULN; as a result, the study was terminated after 41 patients were randomly assigned. The modified ITT population consisted of 12 patients in the placebo group, 13 in the seladelpar 50 mg group, and 10 in the seladelpar 200 mg group. Mean changes from baseline in alkaline phosphatase were -2% (SD 16) in the placebo group, -53% (14) in the seladelpar 50 mg group, and -63% (8) in the seladelpar 200 mg group. Changes in both seladelpar groups versus placebo were significant (p<0·0001 for both groups vs placebo), with no significant difference between the two seladelpar groups (p=0·1729). All five patients who received seladelpar for 12 weeks had normal alkaline phosphatase values at the end of treatment, based on a central laboratory ULN for alkaline phosphatase of 116 U/L. The most frequently reported adverse events were pruritus (16%; one patient on placebo, four on seladelpar 50 mg, and one on seladelpar 200 mg), nausea (13%; one patient on placebo, three on seladelpar 50 mg, and one on seladelpar 200 mg), diarrhoea (10%; two patients on placebo, one on seladelpar 50 mg, and one on seladelpar 200 mg), dyspepsia (8%; two patients on seladelpar 50 mg and one on seladelpar 200 mg), muscle spasms (8%; three patients on seladelpar 200 mg), myalgia (8%; one patient on placebo and two on seladelpar 200 mg), and dizziness (8%; one patient on placebo and two on seladelpar 50 mg)., Interpretation: Seladelpar normalised alkaline phosphatase levels in patients who completed 12 weeks of treatment. However, treatment was associated with grade 3 increases in aminotransferases and the study was stopped early. The effects of seladelpar should be explored at lower doses., Funding: CymaBay Therapeutics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background and Aims: Hyperinsulinemia and insulin resistance are hallmark features of nonalcoholic fatty liver disease and steatohepatitis (NASH). It remains unclear whether and how insulin contributes to the development of fibrosis in NASH. In this study, we explored insulin signaling in the regulation of hepatic stellate cell (HSC) activation and the progression of NASH-fibrosis., Methods: Phosphorylation of Akt and p70S6K were examined in primary HSC and in a rat model of NASH-fibrosis induced by high-fat and high-cholesterol diet for 24 weeks. HSC activation was analyzed for the changes in cell morphology, intracellular lipid droplets, expression of α-SMA and cell proliferation. The serum markers and histology for NASH-fibrosis were also characterized in animals., Results: Insulin enhanced the expression of smooth muscle actin-α in quiescent but not in activated HSC in culture. Insulin-mediated activation of the PI3K/Akt-p70S6K pathway was involved in the regulation of profibrogenic effects of insulin. Although insulin did not stimulate HSC proliferation directly, the insulin-PI3K/Akt-p70S6K pathway was necessary for serum-enhanced cell proliferation during initial HSC activation. In a rat model of NASH-fibrosis induced by high-fat and high-cholesterol diet, hyperinsulinemia is associated with the activation of p70S6K and enhanced fibrosis., Conclusion: The insulin-PI3K/Akt-p70S6K pathway plays an important role in the early activation of HSC. The profibrogenic effect of insulin is dependent on the activation stage of HSC. Dysregulation of the insulin pathway likely correlates with the development of fibrosis in NASH, suggesting a potentially novel antifibrotic target of inhibiting insulin signaling in HSC.

Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted., (© 2016 John Wiley & Sons Ltd.)

Many patients with chronic hepatitis C virus (HCV) are on prolonged proton-pump inhibitor (PPI) therapy and wish to remain on PPI therapy once treatment for HCV starts. A preliminary report recently suggested decrease rates of sustained virological response (SVR) for patients taking concomitant PPI and ledipasvir/sofosbuvir (LDV/SOF). We sought to determine the effect of PPI use on the rate of SVR in a real-world cohort of 1,979 patients with chronic HCV treated with LDV/SOF. We collected clinical data and pharmacy dispensing records on patients taking 8, 12, or 24 weeks of LDV/SOF ± ribavirin (RBV). The primary outcome was sustained virological response at 12 weeks after treatment completion (SVR12) in a per-protocol analysis in order to determine the effect of PPI use adjusted for confounders. Statistical adjustment was performed in propensity-matched analysis. Among treatment completers, SVR12 was achieved in 441 (97.1%) of PPI recipients compared with 1,497 (98.2%) in PPI nonrecipients (P = 0.19). Neither low- nor high-dose PPI was associated with decreased SVR, although patients taking twice-daily PPI achieved a lower SVR12 rate (91.2%; 95% confidence interval [CI], 77.0-97.0; P = 0.046). After propensity matching for PPI use, there were no significant associations between SVR12 and any dose or frequency of PPI use. However, in a sensitivity analysis focusing on patients with cirrhosis, twice-daily PPI use was associated with lower odds ratio for SVR12 (0.11; 95% CI, 0.02-0.59)., Conclusion: These data from a cohort of real-world patients receiving hepatitis C antibody therapy with LDF/SOF ± RBV support the prescription labeling suggesting that patients take no more than low-dose (20-mg omeprazole equivalents) PPI daily. (Hepatology 2016;64:1893-1899)., (© 2016 by the American Association for the Study of Liver Diseases.)

Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid-covered group, must be resolved., (© 2016 John Wiley & Sons Ltd.)

Background & Aims: Liver biopsy is invasive and associated with complications, sampling errors, and observer variability. Vibration-controlled transient elastography (VCTE) with FibroScan can be used to immediately assess liver stiffness. We aimed to define optimal levels of liver stiffness to identify patients with chronic viral hepatitis and significant fibrosis, advanced fibrosis, or cirrhosis., Methods: In a prospective, 2-phase study, patients with chronic hepatitis C or B underwent VCTE followed by liver biopsy analysis from January 2005 through May 2008 at 6 centers in the United States. In phase 1 we identified optimal levels of liver stiffness for identification of patients with stage F2-F4 or F4 fibrosis (the development phase, n = 188). In phase 2 we tested these cutoff values in a separate cohort of patients (the validation phase, n = 560). All biopsies were assessed for METAVIR stage by a single pathologist in the phase 1 analysis and by a different pathologist in the phase 2 analysis. Diagnostic performances of VCTE were assessed by area under the receiver operating characteristic curve (AUROC) analyses., Results: In phase 1 of the study, liver stiffness measurements identified patients with ≥ F2 fibrosis with AUROC value of 0.89 (95% confidence interval, 0.83-0.92) and identified patients with F4 fibrosis with AUROC value of 0.92 (95% confidence interval, 0.87-0.95). Liver stiffness cutoff values (kPa) in phase 1 were 8.4 for ≥ F2 (82% sensitivity, 79% specificity) and 12.8 for F4 (84% sensitivity, 86% specificity). In the phase 2 analysis, the liver stiffness cutoff values identified patients with ≥ F2 fibrosis with 58% sensitivity (P < .0001 vs phase 1) and 75% specificity (nonsignificant difference vs phase 1); they identified patients with F4 fibrosis with 76% sensitivity (P < .0001 vs phase 1) and 85% specificity (nonsignificant differences vs phase 1). VCTE had an interobserver agreement correlation coefficient of 0.98 (n = 26) and an intraobserver agreement correlation coefficient of 0.95 (n = 34)., Conclusions: In a large U.S. multicenter study, we confirmed that VCTE provides an accurate assessment of liver fibrosis in patients with chronic viral hepatitis. Our findings are similar to those from European and Asian cohorts., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: HCV-infected cirrhotics may urgently need therapy but are often under-represented in clinical trials resulting in limited data to guide their management. We performed a meta-analysis of well-compensated cirrhotic patients from five Phase 3 trials., Methods: Patients received P/R (peginterferon/ribavirin; 4 weeks) followed by BOC (boceprevir)/P/R or P/R for 24, 32, or 44 weeks. Sustained virologic response (SVR) rates were calculated by Metavir score. Multivariate logistic regression (MLR) models identified baseline and on-treatment predictors of SVR. Safety was evaluated by adverse-event (AE) reporting and laboratory monitoring., Results: Pooled meta-estimates for SVR rates (95% confidence interval) in 212 F4 (cirrhotic) patients were 55% (43, 66) with BOC/P/R vs.17% (0, 41) with P/R. MLR identified 4 predictors of SVR in F3/F4 patients: undetectable HCV-RNA at treatment week (TW) 8; ⩾ 1 log10 decline in HCV-RNA from baseline at TW4; male; and baseline HCV-RNA ⩽ 800,000 IU/ml. SVR rate was 89% (65/73) in F4 patients who were HCV-RNA undetectable at TW8. No F3 (0/5) or F4 (0/17) patients with <3 log10 decline and detectable HCV-RNA at TW8 achieved SVR. Anemia and diarrhea occurred more frequently in cirrhotic than non-cirrhotic patients. Serious AEs, discontinuations due to an AE, interventions to manage anemia, infections, and thrombocytopenia occurred more frequently in cirrhotics with BOC/P/R than P/R. Potential hepatic decompensation and/or sepsis were identified in 2 P/R and 3 BOC/P/R recipients., Conclusions: BOC/P/R appears to have a generally favorable benefit-risk profile in compensated cirrhotic patients. SVR rates were particularly high in cirrhotic patients with undetectable HCV-RNA at TW8., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: MK-5172 is an inhibitor of the hepatitis C virus (HCV) nonstructural protein 3/4A protease; MK-5172 is taken once daily and has a higher potency and barrier to resistance than licensed protease inhibitors. We investigated the efficacy and tolerability of MK-5172 with peginterferon and ribavirin (PR) in treatment-naive patients with chronic HCV genotype 1 infection without cirrhosis., Methods: We performed a multicenter, double-blind, randomized, active-controlled, dose-ranging, response-guided therapy study. A total of 332 patients received MK-5172 (100, 200, 400, or 800 mg) once daily for 12 weeks in combination with PR. Patients in the MK-5172 groups received PR for an additional 12 or 36 weeks, based on response at week 4. Patients in the control group (n = 66) received a combination of boceprevir and PR, dosed in accordance with boceprevir's US product circular., Results: At 24 weeks after the end of therapy, sustained virologic responses were achieved in 89%, 93%, 91%, and 86% of the patients in the groups given the combination of PR and MK-5172 (100, 200, 400, or 800 mg), respectively, vs 61% of controls. In the MK-5172 group receiving 100 mg, 91% of patients had undetectable levels of HCV RNA at week 4 and qualified for the short duration of therapy. The combination of MK-5172 and PR generally was well tolerated. Transient increases in transaminase levels were noted in the MK-5172 groups given 400 and 800 mg, at higher frequencies than in the MK-5172 groups given 100 or 200 mg, or control groups., Conclusions: Once-daily MK-5172 (100 mg) with PR for 24 or 48 weeks was highly effective and well tolerated among treatment-naive patients with HCV genotype 1 infection without cirrhosis. Studies are underway to evaluate interferon-free MK-5172-based regimens. ClinicalTrials.gov number: NCT01353911., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Practice guidelines define the criteria and standards of care in patients with cirrhosis and varices. However, the extent to which the patients receive recommended care is largely unknown. We evaluated the quality of varices related care and factors associated with receipt of such care., Methods: We conducted a retrospective cohort study of 550 patients with cirrhosis who sought care at three VA facilities between 2000 and 2007. Using administrative and clinical data, we assessed quality of varices care as measured by eight explicit Delphi panel-derived quality indicators. We also conducted a structured implicit review of patients' medical records to explore the role of patients' refusal, receipt of care outside the VA, or justifiable exclusions to certain care processes as explanations for non-adherence to the quality indicators., Results: Quality scores (max. 100%) varied across individual indicators, ranging from 24.3% for upper endoscopy for varices screening to 72.4% for secondary prophylaxis for variceal bleeding. Justifiable exclusions to indicated care documented in charts were common for primary prophylaxis in patients with varices; receipt of endoscopy; and endoscopic treatment in patients with active bleeding. In contrast, significant shortfalls remained in the receipt of screening endoscopy, use of beta-blockers (in the absence of varices), and use of somatostatin analogs, antibiotics, and secondary prophylaxis in patients with variceal bleeding. Younger patients (<60 vs. >60 year, odds ratio (OR)=1.29, 95% confidence interval (CI) 1.01-1.68), those who saw a gastroenterologist (OR=1.55, 95% CI=1.09-2.21), or those who were seen in the facility with academic affiliation (OR=1.26, 95% CI=1.01-1.58) received higher quality care., Conclusions: Health-care quality, measured according to whether patients received recommended varices-related care, was suboptimal in this health-care setting. Care that included gastroenterologists was associated with high quality.

Background & Aims: Treatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety., Methods: Patients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavirin dosage reduction (n = 249) or erythropoietin therapy (n = 251)., Results: Rates of SVR were comparable between patients whose anemia was managed by ribavirin dosage reduction (71.5%) vs erythropoietin therapy (70.9%), regardless of the timing of the first intervention to manage anemia or the magnitude of ribavirin dosage reduction. There was a threshold for the effect on rate of SVR: patients who received <50% of the total milligrams of ribavirin assigned by the protocol had a significantly lower rate of SVR (P < .0001) than those who received ≥50%. Among patients who did not develop anemia, the rate of SVR was 40.1%. Eleven thromboembolic adverse events were reported in 9 of 295 patients who received erythropoietin, compared with 1 of 392 patients who did not receive erythropoietin., Conclusions: Reduction of ribavirin dosage can be the primary approach for management of anemia in patients receiving peginterferon, ribavirin, and boceprevir for HCV infection. Reduction in ribavirin dosage throughout the course of triple therapy does not affect rates of SVR. However, it is important that the patient receives at least 50% of the total amount (milligrams) of ribavirin assigned by response-guided therapy. ClinicalTrials.gov number, NCT01023035., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Adherence to therapeutic regimens affects the efficacy of peginterferon alfa (P) and ribavirin (R) therapy in patients with chronic hepatitis C virus genotype 1., Aim: To determine if medication adherence impacts efficacy [sustained virological response (SVR)] with triple therapy that includes boceprevir (BOC) plus P/R., Methods: Adherence was determined in two Phase 3 clinical studies with BOC: SPRINT-2 (previously untreated patients) and RESPOND-2 (patients who failed previous therapy with P/R). Adherence to the assigned duration of the dosing regimen and adherence to the three times a day (t.d.s.) dosing interval of 7-9 h for BOC were assessed by the recording of data from patients' dosing diaries and by the amount of study drug dispensed and returned., Results: Most patients (63-71%) adhered to ≥80% of their assigned treatment duration and achieved SVR rates of 86-90%. In contrast, patients who adhered to <80% of their assigned treatment duration achieved SVR rates of 8-32% (P < 0.0001), particularly low in patients who failed previous therapy (SVR = 8-15%). Different rates of adherence (<60% to >80%) to the t.d.s. dosing interval (7-9 h) with BOC did not influence the SVR rates (SVR = 60-83%) with the exception of patients who failed previous treatment and adhered to <60% of the t.d.s. dosing interval with BOC (SVR = 48-50%; P = 0.005)., Conclusions: The achievement of an SVR is more dependent on adherence to the assigned duration of treatment than adherence to the t.d.s. dosing interval with boceprevir. Adherence to >60% of t.d.s. dosing with boceprevir is important in patients who failed previous therapy., (© 2013 John Wiley & Sons Ltd.)

Unlabelled: Chronic infection with the hepatitis C virus (HCV) is a leading cause of global morbidity and mortality. Although recent advances in antiviral therapy have led to significant improvements in treatment response rates, only a minority of infected patients are treated. Multiple barriers may impede the delivery of HCV therapy. The aim of this study was to identify perceived barriers to care, knowledge, and opinions among a global sample of HCV treatment providers. An international, multidisciplinary survey of HCV treatment providers was conducted. Each physician responded to a series of 214 questions concerning his or her practice characteristics, opinions regarding the state of HCV care, knowledge regarding HCV treatment, and perception of treatment barriers. A total of 697 physicians from 29 countries completed the survey. Overall, physicians viewed patient-level barriers as most significant, including fear of side effects and concerns regarding treatment duration and cost. There were distinct regional variations, with Central and Eastern European physicians citing government barriers as most important. In Latin America, the Middle East, and Africa, payer-level barriers, including lack of treatment coverage, were prominent. Overall, the perception of barriers was strongly associated with physician knowledge, experience, and region of origin, with the fewest barriers reported by Nordic physicians and the most reported by Middle Eastern and African physicians. Globally, physicians demonstrated deficits in basic treatment principles, including the role of viral kinetics and the management of treatment nonresponders. Two thirds of surveyed physicians believed that patients do not have adequate access to providers in their community., Conclusion: Barriers to HCV treatment vary globally, though patient-level factors are viewed as most significant by treating physicians. Efforts to improve awareness, education, and specialist availability are needed., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Background & Aims: The addition of boceprevir to therapy with peginterferon alfa-2b and ribavirin results in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection, compared with peginterferon alfa-2b and ribavirin alone. We assessed SVR with boceprevir plus peginterferon alfa-2a-ribavirin (PEG2a/R) in patients with identical study entry criteria., Methods: In a double-blind, placebo-controlled trial, 201 patients with HCV genotype-1 who had relapsed or not responded to previous therapy were assigned to groups (1:2) and given a 4-week lead-in phase of PEG2a/R, followed by placebo plus PEG2a/R for 44 weeks (PEG2a/R) or boceprevir plus PEG2a/R for 44 weeks (BOC/PEG2a/R). The primary end point was SVR 24 weeks after therapy ended., Results: The addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R significantly increased the rate of SVR from 21% in the PEG2a/R group to 64% in the BOC/PEG2a/R group (P < .0001). Among patients with poor response to interferon therapy (<1-log(10) decline in HCV RNA at week 4), 39% in the BOC/PEG2a/R group had SVRs, compared with none of the patients in the PEG2a/R group. Among patients with good response to interferon (≥1-log(10) decline), 71% in the BOC/PEG2a/R group had SVRs, compared with 25% in the PEG2a/R group. A ≥1-log(10) decline in HCV RNA at treatment week 4 was the strongest independent predictor of SVR, exceeding that of IL-28B genotype. Among 8 patients who began the study with HCV amino acid variants associated with boceprevir resistance, 3 (38%) achieved SVRs. Fifty percent of patients in the BOC/PEG2a/R group developed anemia (hemoglobin <10.0 g/dL), compared with 27% in the PEG2a/R group; 43% vs 21%, respectively, developed neutropenia (neutrophil count <750/mm(3))., Conclusions: The addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R caused significantly higher rates of SVR in previously treated patients with chronic HCV genotype-1 infection, compared with patients given only PEG2a/R. ClinicalTrials.gov Identifier: NCT00845065., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Portopulmonary hypertension (POPH) is a not infrequent but serious complication of liver cirrhosis. Continuous intravenous epoprostenol infusion is a treatment option for this condition. Progressive splenomegaly with pancytopenia (hypersplenism) is associated with epoprostenol use in POPH. After recognizing a case of epoprostenol-induced hypersplenism that resolved upon stopping the drug, the authors retrospectively reviewed all patients treated with epoprostenol at the center for both POPH and pulmonary hypertension due to other causes. Five of 11 patients with POPH developed hypersplenism secondary to epoprostenol. In 1 patient, and possibly in a second, the hypersplenism resolved upon discontinuation of epoprostenol. None of 9 patients with pulmonary hypertension due to other causes developed splenomegaly. This report confirms hypersplenism as a complication of epoprostenol therapy for POPH. Furthermore, the authors demonstrate for the first time that hypersplenism may be reversed by stopping the medication and propose a mechanism for this phenomenon.

Background & Aims: Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors., Methods: Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 28-48 wk). A good response to interferon was defined as a ≥ 1 log(10) decrease in HCV RNA at week 4; a poor response was defined as a <1 log(10) decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism interleukin [IL]-28B rs12979860) associated with response. The polymorphism IL-28B rs8099917 also was assessed., Results: In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR], 11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs, 2.6 and 2.1, respectively), absence of cirrhosis (OR, 4.3), HCV subtype 1b (OR, 2.0), and non-black race (OR, 2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous nonresponse (OR, 2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%-89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was associated more strongly with a good response to interferon than other baseline factors; however, a ≥ 1 log(10) decrease in HCV-RNA level at week 4 was associated more strongly with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR., Conclusions: The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥ 1 log(10) decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Ascites are the most common complication of cirrhosis. Evidence-based guidelines define the criteria and standards of care for patients with cirrhosis and ascites. However, little is known about the extent to which patients with ascites meet these standards., Methods: We evaluated the quality of ascites care, measured by 8 explicit Delphi panel-derived quality indicators, in 774 patients with cirrhosis and ascites, seen at 3 Veterans Affairs Medical Centers between 2000 and 2007. We also conducted a structured implicit review of patients' medical charts to determine whether patient refusal, outside care, or other justifiable exceptions to care processes account for nonadherence to the quality indicators., Results: Quality scores (maximum 100%) varied among individual indicators, ranging from 30% for secondary prophylaxis of spontaneous bacterial peritonitis, to 90% for assays for cell number and type in the paracentesis fluid. In general, care targeted at treatment was more likely to meet standards than preventive care. Only 33.2% (95% confidence interval [CI]: 29.9%-32.9%) of patients received all recommended care. Patients with no comorbidity (Deyo index 0 vs >3; odds ratio = 2.21; 95% CI: 1.43-3.43), who saw a gastroenterologist (odds ratio = 1.33; 95% CI, 1.01-1.74), or were seen in a facility with academic affiliation (odds ratio = 1.73; 95% CI: 1.29-2.35) received higher-quality care. Justifiable exceptions to indicated care, documented in charts, were common for patients with paracentesis after diagnosis with ascites, patients that received antibiotics for gastrointestinal bleeding, and patients that required diuretics. However, most patients did not have an explanation documented for nonadherence to recommended care., Conclusions: Health care quality, measured by whether patients received recommended services, was suboptimal for patients with cirrhosis-related ascites. Care that included gastroenterologists was associated with high quality. However, for some of the quality indicators, too many denominator exceptions existed to allow for accurate automated measurement., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism affecting about 1 in 250 individuals. HH results in an increased absorption of iron at the baso-lateral surface of the enterocyte with aberrant regulation of ferroportin-mediated transfer of iron in turn brought on by a decrease in circulating hepcidin. The medical literature describes a colorful history of HH with important contributions from faculty at Saint Louis University.

This is an excellent time for patients with hepatitis C virus infection who have failed past treatment with standard of care (SOC) peginterferon (PEG-IFN) and ribavirin (RBV). New treatments have been shown to increase sustained virological response (SVR) rates. Previous relapsers and those with some responsiveness to interferon will clearly benefit from protease inhibitor-based therapy. Patients with little interferon response may not be suited for these regimens, but can be treated by careful selection on a case-by-case basis. Resistance needs to be carefully monitored as these newer and more potent drugs are added to IFN and RBV backbone drugs. Adverse events will be more frequent and will require special attention., (© 2012 John Wiley & Sons A/S.)

Individuals infected with hepatitis C virus (HCV) are at risk for cirrhosis and/or hepatocellular carcinoma. Treatment of HCV infection has undergone several revisions over the past 15 years and continues to evolve. The current major advance is with the protease inhibitors in addition to pegylated interferon and ribavirin. The emergence of resistance needs to be monitored carefully as newer and more potent drugs are added to the interferon and ribavirin backbone drugs. In addition, adverse events will be more frequent and some novel ones will require special attention., (Copyright © 2011 Elsevier Inc. All rights reserved.)

An estimated 170 million people in the world are infected with hepatitis C virus (HCV). These individuals are at risk for developing complications like cirrhosis and/or hepatocellular carcinoma. Occurrence of HCV has been recorded to be high in certain parts of the world like Africa and Southeast Asia. The prevalence is considerably lower in the United States, with an estimated number of people with positive HCV antibodies around 1.8% of the population and an estimated 3.1 million individuals having active HCV infection. Treatment of hepatitis C has undergone a complete overhaul several times over the past decade and continues to evolve striving for constant improvement. We now are at the cusp of yet another such overhaul with the protease inhibitors about to be introduced into the market.