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Graphical distributions of CD3+ and CD8+ T lymphocyte densities in the TI and IM.

ImageJ plug-in code for image analysis.

Bivariate analysis of TIL pattern and tumor stage, cellular differentiation, and vascular invasion.

Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3+) and cytotoxic (CD8+) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3+ and CD8+ cells and clinical outcome. High densities of both CD3+ and CD8+ T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3+ and CD8+ cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6–21.8] for CD3+ and 3.9 (95% CI, 1.1–14.1) for CD8+. Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419–30. ©2016 AACR.

Kaplan-Meier analysis of RFS stratified by pattern of CD3+ and CD8+ T lymphocytes.

Example of computer-assisted evaluation of infiltrate densities.

Bivariate analysis of CD3+ and CD8+ cell density and beta-catenin expression.

Flowchart of image analysis process.

Bivariate analysis of tumor stage with vascular invasion and cellular differentiation.

Known risk factors for hepatocellular adenoma (HCA) bleeding are size5 cm, growth rate, visible vascularity, exophytic lesions, β-catenin and Sonic Hedgehog activated HCAs. Most studies are based on European cohorts. The objective of this study is to identify additional risk factors for HCA bleeding in a US cohort.Retrospective chart review was performed on patients diagnosed with HCA on magnetic resonance imaging (n = 184) at an academic tertiary institution. Clinical, pathological, and imaging data were collected. Primary outcomes measured were HCA bleeding and malignancy. Statistical analysis was performed with SAS 9.4 using Chi-Square, Fisher's exact test, sample t test, non-parametric Wilcoxon test, and logistic regression.After excluding patients whose pathology showed focal nodular hyperplasia and non-adenoma lesions, follow-up data were available for 167 patients. 16% experienced microscopic or macroscopic bleeding and 1.2% had malignancy. HCA size predicted bleeding (P .0001) and no patients with lesion size1.8 cm bled. In unadjusted analysis, hepatic adenomatosis (≥10 lesions) trended towards 2.8-fold increased risk of bleeding. Of patients with a single lesion that bled, 77% bled from a lesion5 cm. In patients with multiple HCAs that bled, 50% bled from lesions5 cm. In patients with multiple adenomas, size (P = .001) independently predicted bleeding and hepatic steatosis trended towards increased risk of bleeding (P = .05).In a large US cohort, size predicted increased risk of HCA bleeding while hepatic adenomatosis trended towards increased risk of bleeding. In patients with multiple HCAs, size predicted bleeding and hepatic steatosis trended toward increased risk of bleeding.

End-stage liver disease (ESLD) is increasingly prevalent and shares many risk factors with coronary artery disease (CAD). No specific guidelines exist for pre-liver transplant evaluation of CAD, and pretransplant cardiovascular testing varies widely. The aim of this study is to characterize pre-transplant cardiac testing practices with post-transplant clinical outcomes. We retrospectively reviewed patients undergoing initial liver transplantation at our transplant center between January 2015 and March 2019. Patients with previous liver transplantation or multi-organ transplantation were excluded. Electronic medical records were reviewed for relevant demographic and clinical data. We included 285 patients with a mean follow-up of 2.4 years. Of 274 patients (96.1%) with pre-transplant transthoracic echocardiogram (TTE), 18 (6.6%) were abnormal. Non-invasive ischemic testing was performed in 193 (68%) patients: 165 (58%) underwent stress TTE, 24 (8%) underwent myocardial perfusion imaging, 3 underwent coronary computed tomography, and 1 underwent exercise electrocardiogram. Sixteen patients (6%) had left heart catheterization of which 10 (63%) were abnormal and 5 proceeded to revascularization before transplant. There were 4 (1.4%) deaths within 30 days of transplant and 23 deaths (8.1%) in total. ST-elevation myocardial infarction was seen in 1 patient within 30 days and 1 patient after 30 days (0.7% total). No cardiovascular deaths were observed. Among patients undergoing liver transplantation, pre-transplantation cardiovascular testing is exceedingly common and post-transplant cardiovascular complications are rare. Additional research is needed to determine the optimal testing and surveillance in this patient population.

This article reviews the historical evolution of the current deceased donor liver allocation and distribution policy in the USA and describes the continued efforts to address limitations within our current allocation system. Due to the finding that hyponatremia is an independent predictor of mortality, since January 2016, the Model for End-stage Liver Disease (MELD)-Na score incorporating serum sodium is now used for patients with MELD score

Despite an unmet need for hepatologists in the United States, every year transplant hepatology (TH) fellowship positions remain unfilled. To address this, we investigated factors that influence trainee decisions about pursuing a career in hepatology. We invited current gastroenterology (GI) and TH fellows from all Accreditation Council for Graduate Medical Education-accredited programs for the academic year 2014-2015 to participate in an online survey about factors influencing decisions to train in hepatology. The same paper-based survey was distributed at a nationally recognized GI board review course. The survey was completed by 180 participants of which 91% were current GI or TH fellows and 24% were not aware of the pilot 3-year combined GI and TH training program. A majority of respondents (57%) reported that a shorter time (3 versus 4 years) to become board certification eligible would influence their decisions to pursue TH. The most common reasons for not pursuing hepatology were less endoscopy time (67%), additional length of training (64%), and lack of financial compensation (44%). Personal satisfaction (66%), management of complex multisystem disease (60%), and long-term relationships with patients (57%) were the most attractive factors. Sixty-one percent of participants reported having a mentor, and 94% of those with mentors reported that their mentors influenced their career decisions. Conclusion: We have identified several factors that affect fellows' decision to pursue TH. Shorter training, increased financial compensation, and increased endoscopy time are potentially modifiable factors that may increase the number of trainees seeking careers in hepatology and help alleviate the deficit of hepatologists. (Hepatology Communications 2017;1:347-353).

Hepatitis C virus (HCV) recurrence after liver transplant (LT) is associated with worse outcomes. Ledipasvir and sofosbuvir (LDV/SOF) has been approved for HCV treatment after LT, but there is limited data on the effectiveness and safety of LDV/SOF in the “real world” setting. This multi-center study is the largest report to date, on the effectiveness and safety of LDV/SOF in the post-LT setting. Two hundred and four patients (72% male, 68% Caucasian, 66% genotype 1a, 21% METAVIR F3-F4, 49% treatment-experienced) were treated with LDV/SOF. The mean duration from LT to treatment initiation was 4.8 years. The overall sustained virologic response rate 12 weeks after completion of therapy (SVR12) was 96%. Patients treated with 8 or 12 weeks of LDV/SOF without RBV experienced an SVR12 rate of 100% and 96%, respectively. Calcineurin inhibitors were used in 89% of patients and 32% of patients underwent adjustment in immunosuppression during treatment. One episode of mild rejection, responsive to an increase in immunosuppression dosage, was observed. There was no graft loss attributed to HCV treatment. Four deaths occurred unrelated to HCV treatment, and no significant serious adverse events were documented. Conclusion: Sofosbuvir and ledipasvir with or without RBV for 8, 12, or 24 weeks in post LT patients was effective and safe with a high SVR12 rate across a spectrum of genotypes and stages of fibrosis. This article is protected by copyright. All rights reserved.

Hepatopulmonary syndrome (HPS) is a complication of cirrhosis and is associated with increased pre-orthotopic liver transplant (OLT) mortality. Diagnosis requires intrapulmonary vascular dilatation (IPVD) and hypoxemia. The clinical significance of IPVD severity on post-OLT mortality is unknown.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD.

Our institution shifted the care of patients with chronic liver disease (CLD) from Internal Medicine faculty, house staff, and consulting hepatology service to a co-managed unit staffed by academic hospitalists and hepatologists. The effect of co-management between hospitalists and hepatologists on the care of patients hospitalized with complications of CLD such as spontaneous bacterial peritonitis (SBP) is unknown.A retrospective chart review of 56 adult patients admitted with CLD and SBP from July 1, 2004 to June 30, 2010 was performed. Adherence rates to current management guidelines were measured along with costs and outcomes of care.Patients admitted under the 2 models of care were similar; however, they consistently underwent paracentesis within 24 hours (100% vs. 79%, P=0.013), had appropriate avoidance of fresh-frozen plasma use (75% vs. 43%, P=0.05), received albumin (97% vs. 65%, P=0.002), and were discharged on SBP prophylaxis (91% vs. 37%, P0.001) under the co-managed model compared with the conventional model. Costs of care were similar between the 2 groups. We note a trend toward improved outcomes of care under the co-management model as measured by transfer rates to the intensive care unit, inpatient mortality, 30-day readmission, and mortality rates.These results support co-management between hospitalists and hepatologists as a superior model of care for hospitalized patients with SBP. Furthermore, this study adds to the growing literature indicating that efforts are needed to improve the quality of care delivered to CLD patients.

In 2002, the use of the MELD scoring system was adopted as the primary means of determining the priority of patients listed for liver transplantation. Implementation of the MELD system has changed the face of organ allocation for livers and as a result, overall waitlist times along with pre- and post-transplant mortality for patients with significant liver disease have declined. Although the MELD accurately predicts mortality in most patients with end stage liver disease, it may not adequately risk stratify some patients who have a high risk of morbidity and mortality not reflected in the score. Automatic exception points are granted for a subset of conditions if candidates meet agreed upon criteria. However, even within this framework, there are some at risk patients who will be missed. Herein we review conditions associated with increased mortality and morbidity that are not reflected in the MELD score and reflect on the issues which arise when considering allocation of organs to these patients.

Organ transplantation carries a risk of disease transmission from donor to recipient, primarily infection or malignancy. Although donors are thoroughly screened, donor-related malignancies are reported to occur in 0.01% of solid organ transplants. Plasma cell neoplasm, to the best of our knowledge, has not been reported as a donor-transmitted malignancy in liver transplantation. We describe a liver transplant from a donor with unrecognized plasmacytoma requiring retransplantation. Three years after the first transplant a single peritoneal mass was detected on surveillance imaging and radically excised; HLA phenotyping confirmed the mass to be an isolated extra-medullary plasmacytoma of chimeric donor and recipient origin.

Pre-transplant evaluation for orthotopic liver transplantation (OLT) commonly includes a cardiac evaluation using dobutamine stress echocardiography (DSE). We performed a quantitative systematic review assessing DSE's use in detecting coronary artery disease (CAD) and predicting perioperative and long term cardiac events in patients undergoing OLT. Published studies in pubmed were accessed using keyword searches and bibliographic review. Included studies evaluated the use of DSE in patients undergoing OLT, including its accuracy for detection of CAD, and in predicting perioperative and long term cardiac prognosis for both hard (myocardial infarction, cardiac death, cardiac arrest, and asystole) and soft cardiac events (all other events that were cardiovascular in nature). We calculated DSE's sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) in the above areas. We identified 7 studies, including a total of 580 patients, which included 4 accuracy studies (n = 110 patients), 4 perioperative studies, and 3 long term studies. Accuracy for CAD included a sensitivity of 0.32, specificity of 0.78, PPV of 0.37, and NPV of 0.75. Accuracy for prediction of perioperative hard and soft cardiac events was a sensitivity of 0.20 and 0, specificity of 0.99 and 0.99, PPV of 0.33 and 0, and NPV of 0.98 and 0.89, respectively. For long term hard and soft cardiac events, sensitivity was 0.5 and 0, specificity 0.99 and 0.98, PPV 0.33 and 0, and NPV 0.99 and 0.96, respectively. DSE has a limited accuracy for the detection of CAD in candidates for OLT. However, among those patients selected for OLT, the negative predictive value of DSE for both perioperative and long term cardiac events is high.

The protease inhibitors (PIs) boceprevir and telaprevir are currently standard treatment as part of triple therapy regimens (TTx) for chronic HCV genotype 1 (GT1) patients. In this preliminary analysis, we have compared demographic variables, polypharmacy, and Charlson’s comorbid index (CCI) with Rapid Virological Response (RVR) and extended RVR (eRVR) rates in HCV GT1 patients receiving PI containing TTx. Retrospective descriptive cohort study. Among 74 HCV patients (46 M, 28 F; age: 54.43 ± 9.52 years; African Americans: 59.5 %) in this initial analysis, 44 % achieved RVR. All these RVR patients also achieved eRVR. Patients achieving RVR and eRVR were 50 ± 11.7 (mean ± SD) years old, compared to 58 ± 5.2 years without an RVR (p

Healthcare guidelines and recommendations have broad-reaching impact. They serve as the evidence to enforce medical testing by establishing a bar for standard of care through their intrinsic credibility but also by affecting reimbursement. In this article, we discuss the various organizations in the United States that develop healthcare policy and guidelines. We focus on the recent recommendations for hepatitis C virus (HCV) screening put forward by these agencies and the potential effect of these documents. Additional discussion is provided on the recent draft HCV screening recommendations provided by the United States Preventive Services Task Force (USPSTF), comparison of these to the Centers for Disease Control and Prevention (CDC) guidelines, and professional societies' response to these. Conclusion: As written, the USPSTF recommendations may reduce physician adoption of HCV screening in the 1945-1965 birth cohort as advocated by the CDC. Conflicting guidelines may further confuse providers and the public. This will ultimately hinder recognition of chronic HCV in an otherwise easily identifiable, high prevalence group, allowing progression of disease at a time when therapeutic advances make cure a realistic opportunity for many. (HEPATOLOGY 2013 )

The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise and liver transplantation (LT) represents an established curative treatment for early stage disease. As a result of organ shortage, guidelines have restricted transplantation to HCC patients with an expected 5-year post transplantation survival greater than 70 %. The Milan criteria (MC) remain a reliable and noninvasive instrument for selecting patients with 5-year survival meeting this criteria. Since the adoption of the MC by United Network for Organ Sharing (UNOS), attempts have been made to expand MC to account for the projected increase in the incidence of HCC over the next 20 years. An area of active debate focuses on identifying a subgroup of patients outside of MC with similar or better outcomes through either new expanded criteria or identifying other prognostic factors to enhance MC.

Immune function test (Immuknow TM ) is a measure of cell- mediated immunity based on peripheral CD4 + T cell adenosine triphosphate activity (desired range, 225-525 ng/mL). We evaluated the role of immune function test (IFT) in monitoring and adjustment of immunosuppression in orthotopic liver transplant (OLT) recipients. A total of 289 IFTs were obtained from 171 patients from March 2007 to June 2008. Graft/patient status was classified as stable, serious infection, or malignancy. IFT levels were analyzed with duration of follow-up after OLT, graft/patient status, and the presence of hepatitis C (HCV) infection. The mean age was 54 ± 14 yr, with 62% men. The median follow-up was 65 (2-249) months. Mean IFT levels were significantly lower in patients who were

Objectives: Spontaneous bacterial peritonitis (SBP) is associated with a high mortality rate. After antibiotic therapy, improvement in fluid polymorphonuclear (PMN) cell count is expected within 2 days. However, our institution recognized cases unresponsive to standard treatment. Methods: To study these recalcitrant cases, we completed a retrospective chart review of patients admitted for SBP to the University of Chicago from 2002 to 2007. SBP was defined by an ascitic PMN cell count ≥250/ ml. Results: Of 55 patients with SBP, 15 did not show improvement in fluid PMN cell count to below 250/ ml with standard treatment, leading to a prevalence of 27%. The patients with persistent SBP were younger than those with nonpersistent SBP [mean (SD) 51.80 (9.84) compared with 58.13 (8.79); p = 0.0253]. Persistent SBP had a higher serum ascites albumin gradient (SAAG) [median (Q1, Q3) 1.85 (1.50, 2.41) compared with 1.10 (0.60, 1.60)] and a higher score in the model for end-stage liver disease (MELD) [mean (SD) 27.98 (8.09) compared with 22.22 (8.10)] than nonpersistent SBP patients; p = 0.027 and p = 0.023, respectively. In addition, persistent SBP patients were more likely to have a positive ascitic fluid culture than nonpersistent SBP patients [odds ratio (OR) (95% CI) 4.33 (1.21, 15.47); p = 0.024]. Importantly, in-hospital mortality in the persistent SBP group was 40%, compared with 22.5% in the nonpersistent SBP group [OR = 2.30 (0.64, 8.19); p = 0.20]. Conclusions: The risk of persistent SBP is nearly 40% in patients with MELD score >25, SAAG >1.5 or positive ascitic fluid culture. Furthermore, patients who develop persistent SBP tend to experience a higher mortality rate. This study underscores the importance of further examination of this vulnerable population.

Patients with end-stage renal diseases on hemodialysis have a high prevalence of hepatitis C infection (HCV). In most patients, treatment for HCV is delayed until postrenal transplant. We assessed the effectiveness and tolerance of ledipasvir/sofosbuvir (LDV/SOF) in 32 postkidney transplant patients infected with HCV. The group was composed predominantly of treatment-naïve (75%) African American (68.75%) males (75%) infected with genotype 1a (62.5%). Most patients received a deceased donor kidney graft (78.1%). A 96% sustained viral response (SVR) was reported (27/28 patients). One patient relapsed. One patient with baseline graft dysfunction developed borderline rejection. No graft loss was reported. Six HIV-coinfected patients were included in our analysis. Five of these patients achieved SVR 12. There were four deaths, and one of the deaths was in the HIV group. None of the deaths were attributed to therapy. Coinfected patients tolerated therapy well with no serious adverse events. Serum creatinine remained stable at baseline, end of therapy, and last follow-up, (1.351±.50 mg/dL; 1.406±.63 mg/dL; 1.290±.39 mg/dL, respectively). In postkidney transplant patients with HCV infection with or without coinfection with HIV, a combination of LDV/SOF was well tolerated and effective.

Aspirin is thought to be a relatively safe drug in adults. The association of aspirin and Reye syndrome in children is well documented. We report a 41-year-old female with pericarditis who was treated with high-dose aspirin and developed subsequent acute liver injury. After discontinuation of aspirin, liver enzyme elevation and right upper quadrant pain both resolved. We conclude that high-dose aspirin should be considered as a potentially hepatotoxic agent.

Background: Complications from chronic hepatitis C virus (HCV) infection are a major cause of morbidity and mortality among individuals with inherited blood disorders (IBLD). Inability to tolerate ribavirin and frequent comorbidities have limited HCV treatment options in these patients. The aim of the C-EDGE IBLD study was to evaluate the efficacy and safety of a once-daily, fixed-dose combination of elbasvir 50 mg (EBR, an NS5A inhibitor) and grazoprevir 100 mg (GZR, an NS3/4A protease inhibitor) in patients with HCV infection and IBLD, including those with hemoglobinopathies. Methods: C-EDGE-IBLD was a randomized, double-blind, placebo-controlled study of treatment-naïve and treatment-experienced patients with HCV genotype (GT)1, 4, or 6 infection and IBLD (hemophilia A/B, von Willebrand disease, β-thalassemia, or sickle cell anemia). Patients were randomized in a 2:1 ratio to an immediate-treatment group (ITG; 12 weeks of EBR/GZR) or deferred-treatment group (DTG; 12 weeks of placebo, followed by EBR/GZR for 12 weeks). Randomization was stratified according to the presence of cirrhosis and IBLD diagnosis. The primary endpoints were the proportion of patients in the ITG who achieved sustained virologic response (SVR12, HCV RNA Results: One hundred fifty-nine patients were randomized (ITG, n = 107; DTG, n = 52). Three patients in the DTG did not commence deferred active treatment; therefore, 156 patients received ≥1 dose of EBR/GZR. Mean age was 44 years. Other baseline patient demographics were as follows: 75% male; 18% black; 41% GT1a-infected; 46% GT1b-infected; 11% GT4-infected; 24% cirrhotic; 6% HIV/HCV co-infected; 43% with hemophilia A/B or von Willebrand disease; 38% with β-thalassemia; 18% with sickle cell anemia. SVR12 was achieved by 92.9% (145/156) of patients receiving EBR/GZR (ITG 93.5% [100/107]; DTG 91.8% [45/49]). Of the 11 patients who did not achieve SVR12, 2 discontinued treatment for reasons unrelated to study medication and 9 relapsed, including 7 who had NS5A resistance-associated variants present at baseline. One patient achieved SVR12 but relapsed between follow-up weeks 12 and 24. SVR12 was achieved by 90.8% (59/65), 95.7% (67/70), and 94.4% (17/18) of patients with HCV GT1a, GT1b, and GT4 infection, respectively (2 patients with GT1 non-a,b achieved SVR and the 1 patient with GT6 infection relapsed). SVR 12 was achieved by 96.3% (26/27) of patients with sickle cell anemia, 95% (57/60) with β-thalassemia, and 89.9% (62/69) with hemophilia A/B or von Willebrand disease. During the initial treatment period (EBR/GZR vs placebo), serious adverse events were reported in 3 (2.9%) patients in the ITG (1 drug-related, 2 related to IBLD) and 6 (11.5%) patients receiving placebo in the DTG (1 drug-related, 3 related to IBLD). In the DTG placebo phase, 1 patient discontinued treatment due to an adverse event and 1 patient withdrew consent. No patient in either arm discontinued treatment due to worsening of underlying IBLD. There was 1 hepatic event of clinical interest in each arm (ALT >3× baseline and >100 U/L). In the EBR/GZR treatment phase of the DTG (n = 49), 3 patients reported serious adverse events; none were drug-related and 2 were related to IBLD. Conclusions: Final data from the C-EDGE IBLD study indicate that EBR/GZR is well tolerated and effective in patients with HCV GT1 or 4 infection with IBLD. Disclosures Hézode: BMS: Consultancy; Janssen: Consultancy; MSD: Consultancy; AbbVie: Consultancy; Gilead: Consultancy. Fried:NIH: Research Funding; Gilead: Consultancy, Research Funding; TARGET PharmaSolutions: Equity Ownership; Merck: Consultancy, Research Funding; BMS: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding. Colombo:Merck: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Tibotec: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Vertex: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lundbeck: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GenSpera: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AlfaWasserman: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jennerex: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Intercept: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bourlière:MSD: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; Janssen: Consultancy; GSK: Consultancy; BMS: Consultancy. Ben-Ari:Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Strasser:MSD/Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Norgine: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Honoraria. Perumalswami:Merck: Research Funding; Gilead: Research Funding. Zamor:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lee:Eli Lilly: Consultancy; BMS: Research Funding; Gilead: Research Funding; Sanofi: Consultancy; Merck: Research Funding; Novartis: Consultancy. Satoskar:Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Research Funding. Sherman:AbbVie: Research Funding; Gilead: Research Funding; BMS: Research Funding; Merck: Consultancy, Research Funding. Morgan:Merck & Co., Inc.: Employment, Equity Ownership. Qiu:Merck: Employment. Hwang:Merck: Employment, Equity Ownership. Robertson:Merck: Employment, Equity Ownership. Nguyen:Merck: Employment. Barr:Merck: Employment, Equity Ownership. Wahl:Merck: Employment. Haber:Merck: Employment. Chase:Merck: Employment. Talwani:Merck & Co., Inc: Employment. Di Marco:Gilead: Research Funding.