Faculty Bibliography

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.

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.

Approximately 30 % of HIV-infected patients are co-infected with hepatitis C virus (HCV). After the release of highly active antiretroviral therapy, liver disease has become the leading cause of morbidity and mortality in HIV patients. Prior to 2011, HCV treatment with pegylated-interferon and ribavirin in HCV/HIV co-infected patients only allowed 14-38 % of patients with HCV genotype 1 to achieve a sustained virologic response (SVR). Additionally, treatment was commonly discontinued as a result of adverse events. Recently, simeprevir and sofosbuvir have been approved by the US Food and Drug Administration (FDA) for HCV mono-infection. Sofosbuvir has been given FDA approval in co-infected patients offering unprecedented SVR rates and the potential for interferon-free therapy. HCV therapies that are in the pipeline offer improved treatment times, safety profiles, and rates of SVR. Despite these improvements, several new issues including adherence, drug-drug interactions with antiretroviral therapies, adverse events, resistance, and patient selection may complicate therapy. This article reviews the current status of direct-acting antivirals (DAA)-containing regimens for HIV/HCV co-infected patients in the USA. New results investigating telaprevir and boceprevir are also discussed as they are relevant for locations where new DAAs are not available. The impact future interferon-free therapies may have on co-infected patients is also discussed.

Hepatitis C virus (HCV)-related liver disease is a major source of mortality in HIV-infected patients. Approximately one third of all patients with HIV are co-infected with HCV. Patients co-infected with HIV/HCV have shown lower rates of sustained virologic response with pegylated-interferon and weight-based ribavirin as well as more rapid progression of fibrosis than those with HCV mono-infection. Several direct-acting antiviral agents (DAAs), developed originally for HCV mono-infection, are being reevaluated for HIV/HCV co-infection. In addition, entirely new DAAs are being developed, including, interferon-free regimens with fewer side effects, allowing novel treatment opportunities for difficult-to-treat patients. In order for HCV DAAs to be successfully used in the HIV/HCV co-infected population several hurdles must be overcome, including adverse event management and drug-drug interactions. The aim of this review is to discuss the results of trials for new HCV therapies being developed for HIV/HCV co-infected patients and the impact of interferon-free regimens on treatment in the future.

Liver disease, specifically cirrhosis, is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The diagnosis of early cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients may be challenging. The development of noninvasive methods for fibrosis assessment empowers the infectious disease specialist to diagnose advanced fibrosis or cirrhosis. Early diagnosis is essential to enroll patients in screening programs for esophageal varices and hepatocellular carcinoma. Cirrhosis may also modify decisions about treatment of both HIV and HCV, including vaccination, medications chosen, and referral for liver transplant.

Since the approval of the first direct-acting antiviral agents (DAAs), treatment for hepatitis C virus (HCV) has undergone significant transformation. A new milestone in the treatment of HCV, the approval of the first interferon-free regimens, could be achieved by the end of 2013. For patients with HCV who have absolute or relative contraindications to pegylated-interferon or have failed the currently available treatments, the arrival of new regimens will have a major impact on long-term outcomes. The combinations of DAAs in trials are numerous, and many have demonstrated sustained virologic response rates higher than 90 %. These improvements have also been observed in previous null responders and patients who failed telaprevir- or boceprevir-based regimens. Some specific subpopulations may not be perfectly served by interferon-free regimens, such as patients with genotypes 1a or 3 or cirrhosis, whereas others, such as HIV-infected patients or transplant patients, will definitively benefit from regimens with a lower burden of side effects. This paper reviews the interferon-free regimens currently in phase II or III for which sustained virologic response data are available and discusses the successes and potential pitfalls of these regimens.

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.

Noncirrhotic portal hypertension (NCPH) is a rare but important clinical entity in human immunodeficiency virus (HIV) populations. The purpose of this study was to describe the clinical factors associated with the condition in an effort to formulate a diagnostic algorithm for easy and early diagnosis. We performed a multicenter, retrospective case-control study of 34 patients with NCPH and 68 control HIV patients. The study found that thrombocytopenia, splenomegaly, didanosine use, elevated aminotransferases, and an elevated alkaline phosphatase level were all significantly more prevalent in the NCPH cohort. Using these easily available clinical parameters, we developed an algorithm for early diagnosis of NCPH in HIV.

BACKGROUND & AIMS: Many Egyptian-born persons in the U.S. are at high risk of chronic hepatitis C virus (HCV) infection, yet are not aware of their infection and lack healthcare coverage or linkage to care. In this study, we target Egyptian-born persons living in the New York City area for screening and link to care. METHODS: A unique partnership, the Hepatitis Outreach Network (HONE), combines the expertise and resources of the Mount Sinai School of Medicine, the NYC Department of Health and Mental Hygiene and community-based organizations, to provide education, screening and link to care in communities with high prevalence of chronic viral hepatitis. RESULTS: Through four community-based screening events, 192 Egyptian-born persons were screened for HCV. Thirty (15.6%) persons were HCV positive. HCV antibody prevalence in those, whose national origin was Egypt, increased strongly with age and was associated with increasing number of years resident in Egypt and rural residents. Of the 30 Egyptian persons with HCV infection, 18 (60%) received a medical evaluation (2 with local providers and 16 at Mount Sinai). Of the HCV-infected persons evaluated, treatment was recommended in four and begun in three (75%). CONCLUSION: Egyptian-born persons living in the New York City area have a high burden of HCV disease. HONE has successfully established targeted HCV screening in Egyptian-born persons through use of several unique elements that effectively link them to care.