Faculty Bibliography

BACKGROUND: An all-oral, pegylated interferon (pegIFN)-free and ribavirin (RBV)-free single-tablet of ledipasvir (LDV) and sofosbuvir (SOF) is now approved for the treatment of patients infected with hepatitis C virus (HCV) genotype 1. AIM: To estimate the health economic outcomes for LDV/SOF compared with current treatments in US patients infected with HCV genotype 1. METHODS: A hybrid decision-tree and Markov state-transition model was developed. For a cohort of 10,000 patients, the model captured outcomes for several pairings of LDV/SOF with comparators, including long-term health outcomes, number need to treat, life-years gained, quality-adjusted life-years (QALYS) gained, incremental cost-effectiveness ratios and costs per sustained virologic response (SVR). Patients with different levels of treatment experience and different cirrhosis stages were included. RESULTS: LDV/SOF decreased the number of advanced liver disease cases by 0-93% compared with current regimens or no treatment in treatment-naive patients. In treatment-experienced [pegIFN plus ribavirin (PR) or protease inhibitor (PI) + PR] patients, treatment with LDV/SOF decreased the incidence of advanced liver disease complications in most of the cases analysed, except SOF + SMV. For all patient sub-cohorts, LDV/SOF was associated with the lowest 1-year costs per SVR and, with regard to lifetime incremental costs per QALY gained, was either dominant or the most cost-effective treatment. Overall, treatment initiation at earlier stages of liver fibrosis resulted in improved health economic outcomes. CONCLUSION: LDV/SOF is associated with more favourable short- and long-term health economic outcomes compared with current therapies for patients across all levels of treatment experience and cirrhosis stages.

BACKGROUND: Hepatic encephalopathy (HE) represents a significant burden to the healthcare system. The aim of this study was to determine factors influencing the hospital length of stay among patients hospitalized with HE. METHODS: A data warehouse query was performed to identify 316 patients with a first hospitalization during which HE occurred, between April 2010 and February 2012. Baseline and hospitalization characteristics were collected with IRB approval. A negative binomial multivariable model was used to control for potential confounders on the length of hospitalization. RESULTS: Median age was 59 years, and 60.4% of admitted patients were male. The median MELD score was 22 (IQR: 17-28). Median length of stay was 8 days (IQR: 3.25-14.25). After controlling for MELD score, female gender (2.2 days; p = 0.04), being initially admitted for a reason other than HE (liver-related: 7.6 days; p < 0.01 and non liver-related 10.7 days; p < 0.01) and receiving antibiotics other than rifaximin (10.5 days; p < 0.01) were associated with longer length of stay whereas hepatitis C (-3.1 days; p < 0.01) was associated with a shorter length of stay. CONCLUSIONS: MELD score, gender, use of antibiotics other than rifaximin, reason for admission and hepatitis C are predictors readily available in clinic that can help identify patients at risk for longer length of stay.

Introduction: In registration trials, triple therapy with telaprevir (TVR), pegylated-interferon (IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64-75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Methods: Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (5/2011-12/2011) were reviewed. Direct medical costs for pre-treatment, on-treatment, and post-treatment care were calculated using data from Medicare reimbursement databases, RED Book, and Healthcare Cost and Utilization Project database. Costs are presented in 2012 US dollars. SVR (undetectable HCV RNA 24 weeks after the end-of-treatment) was determined on an intention-to-treat basis. Cost-per-SVR was calculated by dividing the median cost by the SVR rate. Results: Median age of the 147 patients was 56 years [interquartile range (IQR) = 51 - 61], 68% were male, 19% were black, 11% had HIV/HCV co-infection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores >/= 3.25), 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR=$66,652- $98,102). The median cost-per-SVR was $189,338 (IQR=$150,735 - $221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%). Conclusions: TVR and IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost-per-SVR. (Hepatology 2014;).

Approximately one-third of patients infected with human immunodeficiency virus (HIV) are concomitantly infected with hepatitis C virus (HCV). As a result, liver disease remains a major source of morbidity and mortality in HIV patients. Prior to 2011, treatments of HCV lacked efficacy in clinical trials in HIV/HCV co-infected patients. Fortunately, several direct-acting antivirals (DAAs) have now entered clinical practice and others have reached advanced stages of clinical development. These therapies offer significant benefits such as improved rates of sustained virologic response (SVR), shortened durations of treatment, and compatibility with HIV antiretroviral therapies. Treatments such as sofosbuvir (SOF) have received approval for HIV/HCV co-infected patients. Moreover, interferon-free options exist for HIV/HCV co-infected patients who may be ineligible or intolerant of interferon. Despite these improvements, physicians must be aware of the differences between these DAAs, the patient characteristics that play a role on the effectiveness of these medications, and the drug-drug interactions these DAAs may have with existing HIV antiretroviral therapies. The aim of this review is to discuss the prevalence and incidence of HIV/HCV co-infection, critical factors related to patient evaluation, current treatment options, and new developments in the management of HIV/HCV co-infected patients.

INTRODUCTION: Liver disease is a major burden in patients co-infected with HIV and hepatitis C virus (HCV). From the time of its approval, pegylated-IFNalpha-2a (pegIFN-alpha2a) has played a major role in treatment of HCV in HIV/HCV co-infection. AREAS COVERED: This article briefly summarizes the epidemiology of HCV/HIV co-infection, the pharmacokinetic, and pharmacodynamic properties of pegIFN-alpha2a. Results from clinical trials investigating therapies containing pegIFN-alpha2a for HIV/HCV co-infected patients will be discussed with a focus on efficacy and safety. EXPERT OPINION: PegIFN-alpha2a has improved rates of sustained virologic response for co-infected patients. In combination with direct-acting antivirals (DAA), the disparity between mono- and co-infected patients is beginning to disappear. For the first time, IFN-free regimens are available in clinical practice. It is unlikely that pegIFN-alpha2a will continue to be a critical component in treatments for HCV in the general co-infected population.

BACKGROUND & AIMS: Adding telaprevir to pegylated-interferon and ribavirin increased both response rates and side effects of hepatitis C virus (HCV) treatment. We identified variables associated with severe anaemia during telaprevir-based triple therapy. METHODS: An observational study was performed on 142 HCV-infected patients between June 2011 and March 2012. All subjects completed 12 weeks of telaprevir-based triple therapy or discontinued early because of anaemia. Severe anaemia was defined by a haemoglobin /=3.25. RESULTS: The 47 (33%) patients who developed severe anaemia were similar to those who did not in sex, race, and prior response to dual therapy, but they were more likely to have diabetes (23.4% vs. 6.3%, P < 0.01), advanced fibrosis (46.8% vs. 29.5%, P = 0.04) and a history of anaemia during previous dual therapy (29.7% vs. 11.4%, P = 0.02). Patients developing severe anaemia were older (59 vs. 56 years, P = 0.02), had lower baseline platelet counts (134 vs. 163 x 109 /L, P = 0.04), haemoglobin (14.0 vs. 15.0 g/dl, P < 0.01), estimated glomerular filtration rate (79 vs. 90 ml/min/1.73 m2 , P = 0.03) and a higher median ribavirin/weight ratio (14.9 vs. 13.2 mg/kg, P < 0.01). In multivariable logistic regression, presence of diabetes (OR = 5.61, 95% CI: 1.59-19.72), Fib-4 >/=3.25 (OR = 3.09, 95% CI: 1.28-7.46), higher ribavirin/weight ratio (OR = 1.31 per mg/kg, 95% CI: 1.13-1.52) and lower baseline haemoglobin (OR = 0.57 per g/dl, 95% CI, 0.41-0.80) were independently associated with developing severe anaemia. CONCLUSIONS: Severe anaemia occurred in one-third of patients receiving telaprevir-based triple therapy. Risk was greater in patients with diabetes, advanced liver fibrosis, higher ribavirin/weight ratio and lower baseline haemoglobin.

PURPOSE: To evaluate the effect of different methods to convert magnetic resonance (MR) signal intensity (SI) to gadolinium concentration ([Gd]) on estimation and reproducibility of model-free and modeled hepatic perfusion parameters measured with dynamic contrast-enhanced (DCE)-MRI. MATERIALS AND METHODS: In this Institutional Review Board (IRB)-approved prospective study, 23 DCE-MRI examinations of the liver were performed on 17 patients. SI was converted to [Gd] using linearity vs. nonlinearity assumptions (using spoiled gradient recalled echo [SPGR] signal equations). The [Gd] vs. time curves were analyzed using model-free parameters and a dual-input single compartment model. Perfusion parameters obtained with the two conversion methods were compared using paired Wilcoxon test. Test-retest and interobserver reproducibility of perfusion parameters were assessed in six patients. RESULTS: There were significant differences between the two conversion methods for the following parameters: AUC60 (area under the curve at 60 s, P < 0.001), peak gadolinium concentration (Cpeak, P < 0.001), upslope (P < 0.001), Fp (portal flow, P = 0.04), total hepatic flow (Ft, P = 0.007), and MTT (mean transit time, P < 0.001). Our preliminary results showed acceptable to good reproducibility for all model-free parameters for both methods (mean coefficient of variation [CV] range, 11.87-23.7%), except for upslope (CV = 37%). Among modeled parameters, DV (distribution volume) had CV <22% with both methods, PV and MTT showed CV <21% and <29% using SPGR equations, respectively. Other modeled parameters had CV >30% with both methods. CONCLUSION: Linearity assumption is acceptable for quantification of model-free hepatic perfusion parameters while the use of SPGR equations and T1 mapping may be recommended for the quantification of modeled hepatic perfusion parameters. J. Magn. Reson. Imaging 2014;40:90-98 (c) 2013 Wiley Periodicals, Inc.