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Hemochromatosis: pathophysiology, evaluation, and management of hepatic iron overload with a focus on MRI

Golfeyz, Shmuel; Lewis, Sara; Weisberg, Ilan S
INTRODUCTION/BACKGROUND:Hereditary hemochromatosis (HH) is an autosomal recessive disorder that occurs in approximately 1 in 200-250 individuals. Mutations in the HFE gene lead to excess iron absorption. Excess iron in the form of non-transferrin-bound iron (NTBI) causes injury and is readily uptaken by cardiomyocytes, pancreatic islet cells, and hepatocytes. Symptoms greatly vary among patients and include fatigue, abdominal pain, arthralgias, impotence, decreased libido, diabetes, and heart failure. Untreated hemochromatosis can lead to chronic liver disease, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Many invasive and noninvasive diagnostic tests are available to aid in diagnosis and treatment. MRI has emerged as the reference standard imaging modality for the detection and quantification of hepatic iron deposition, as ultrasound (US) is unable to detect iron overload and computed tomography (CT) findings are nonspecific and influenced by multiple confounding variables. If caught and treated early, HH disease progression can significantly be altered. Area covered: The data on Hemochromatosis, iron overload, and MRI were gathered by searching PubMed. Expert commentary: MRI is a great tool for diagnosis and management of iron overload. It is safe, effective, and a standard protocol should be included in diagnostic algorithms of future treatment guidelines.
PMID: 29966105
ISSN: 1747-4132
CID: 4309812

Primer on Hepatitis C Virus Resistance to Direct-Acting Antiviral Treatment: A Practical Approach for the Treating Physician

Weisberg, Ilan S; Jacobson, Ira M
Treatment of hepatitis C virus has been vastly transformed by the arrival of all-oral, interferon-free, direct-acting antiviral regimens. Despite the high rate of success with these agents, a small portion of treated patients fail therapy and the emergence of viral resistance is the most common cause of treatment failure. Given the error-prone hepatitis C virus polymerase, baseline resistance-associated substitutions (RASs) may be present before direct-acting antiviral exposure. Clinicians need to understand the role of baseline RAS testing and the settings and manner in which the treatment regimens need to be customized based on the presence of RASs.
PMID: 28987254
ISSN: 1557-8224
CID: 2758642

Viral hepatitis screening in transgender patients undergoing gender identity hormonal therapy

Mangla, Neeraj; Mamun, Rifat; Weisberg, Ilan S
BACKGROUND AND AIM/OBJECTIVE:Viral hepatitis is a global health issue and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Guidelines for viral hepatitis screening in the transgender population do not exist. Transgender patients may be at higher risk for contracting viral hepatitis due to socioeconomic and behavioral factors. The aim of this study was to measure the quality of screening, prevalence, and susceptibility of viral hepatitis, and to identify barriers to screening in transgender patients undergoing gender identity hormonal therapy. METHODS:LGBTQ-friendly clinic visits from transgender patients older than 18 years in New York City from 2012 to 2015 were reviewed. RESULTS:Approximately 13% of patients were screened for any viral hepatitis on initial consultation. Screening rates for hepatitis C virus (HCV), hepatitis B virus (HBV), and hepatitis A virus (HAV) at any point were 27, 22, and 20%. HAV screening was performed in 28% of the female to male (FtM) patients and 16% of male to female (MtF) (P<0.05) patients. HBV screening was performed in 30% of FtM patients and 18% of MtF patients (P<0.05). Thirty-one percent of FtM, 24% of MtF, and 17% of genderqueer patients were tested for HCV (P>0.05). Prevalence of HCV, HBV, and HIV in FtM was 0, 0, and 0.44% and that in MtF was 1.78, 0.89, and 1.78%, respectively. Percentage of patients immune to hepatitis A in FtM and MtF subgroups were 55 and 47% (P>0.05). Percentage of patients immune to HBV in FtM and MtF subgroups were 54 and 48% (P>0.05). CONCLUSION/CONCLUSIONS:This study indicates a significant lack of hepatitis screening in the transgender population and a concerning proportion of patients susceptible to disease.
PMID: 28857896
ISSN: 1473-5687
CID: 4309242

A pangenotypic, single tablet regimen of sofosbuvir/velpatasvir for the treatment of chronic hepatitis C infection

Weisberg, Ilan S; Jacobson, Ira M
INTRODUCTION: Hepatitis C virus (HCV) infects nearly 170 million people worldwide and is a leading cause of progressive liver damage, cirrhosis, and hepatocellular carcinoma. Curative therapies have historically relied on interferon-based treatments and were limited by significant toxicity and poor response rates, particularly among patients with prior treatment failure and advanced hepatic fibrosis. The recent advent of direct acting antiviral (DAA) agents which target key steps in the HCV viral life cycle has transformed the landscape of HCV treatment by offering highly effective and well tolerated interferon-free treatments. However, current therapies are genotype-specific and have variable efficacy amongst less prevalent HCV variants. Areas covered: This review covers the preclinical and clinical development of sofosbuvir/velpatasvir (SOF/VEL), an interferon-free, once daily, pangenotypic treatment for the treatment of chronic hepatitis C virus (HCV) infection. All relevant literature from 2014 through September of 2016 is included. Expert opinion: SOF/VEL offers the promise of a single tablet, interferon- and ribavirin-free treatment that has extremely high efficacy in persons with chronic HCV infection regardless of genotype, subtype, treatment history or fibrosis status. It is expected to play a major role on a global scale in the therapeutic armamentarium against this ubiquitous threat to human health.
PMID: 28092171
ISSN: 1744-7666
CID: 2568052

IMPACT OF DEPRESSION AND HEPATIC ENCEPHALOPATHY ON HEALTH-RELATED QUALITY OF LIFE IN CIRRHOTIC HEPATITIS C PATIENTS [Meeting Abstract]

Barboza, K; Salinas, L; Sahebjam, F; Jesudian, A; Weisberg, I; Sigal, S
ISI:000398711700304
ISSN: 1600-0641
CID: 2545202

Fatal hepatitis B reactivation due to everolimus in metastatic breast cancer: case report and review of literature

Teplinsky, Eleonora; Cheung, Derrick; Weisberg, Ilan; Jacobs, Ramon E A; Wolff, Martin; Park, James; Friedman, Kent; Muggia, Franco; Jhaveri, Komal
Hepatitis B reactivation can occur with cytotoxic chemotherapy in patients with hepatitis B and cancer. Reactivation can occur in a patient with chronic hepatitis, an inactive carrier, or one with resolved hepatitis. Clinical presentation may range from subclinical elevation of liver enzymes to fatal fulminant hepatic failure. Mammalian target of rapamycin inhibitors, which include everolimus, are a new generation of targeted agents that are currently approved for many cancers (since March 2009) including advanced hormone receptor positive, human epidermal growth factor receptor 2-negative breast cancer, in conjunction with exemestane (as of July 2012). We are therefore still learning the various adverse events that occur with this new class of agents. Here, we present an unfortunate case of fatal hepatitis B reactivation in a woman with metastatic breast cancer treated with everolimus and exemestane. We have detailed the controversies around hepatitis B screening prior to immunosuppressive therapy. Clinicians and patients should be aware of this rare but fatal complication prior to everolimus use, and a detailed history, screening for hepatitis B and prophylactic antiviral treatment should be considered.
PMID: 24002736
ISSN: 0167-6806
CID: 551472

Cardiovascular diseases and the liver

Weisberg, Ilan S; Jacobson, Ira M
The dual blood supply of the liver, originating from the portal vein and the hepatic artery, makes it relatively resistant to minor circulatory disturbances. However, hepatic manifestations of common cardiovascular disorders are frequently encountered in both the inpatient and outpatient setting. Beginning with the macro- and microcirculation of the liver, this article reviews the pathophysiology of hepatic blood flow and gives a detailed appraisal of ischemic hepatitis, congestive hepatopathy, and other less common hepatic conditions that arise when cardiovascular function is impaired.
PMID: 21111990
ISSN: 1089-3261
CID: 551512

Transvenous Liver Biopsy

Chapter by: Weisberg, Ilan S; Sigal, Samuel H; Brown, Robert S Jr
in: Clinical hepatology by Dancygier, Henryk [Eds]
Berlin ; London : Springer, 2010
pp. 473-484
ISBN: 364204509x
CID: 1509252

A Case of Acquired Hemorrhagic Telangiectasia (AHT) [Meeting Abstract]

Nabi, Eiman; Mallik, Alka; Bosworth, Brian; Weisberg, Ilan
ISI:000282917701027
ISSN: 0002-9270
CID: 1861412

Telaprevir: hope on the horizon, getting closer

Weisberg, Ilan S; Jacobson, Ira M
Standard therapy with pegylated interferon and ribavirin for chronic hepatitis C is effective in 40% to 50% of individuals with genotype 1 hepatitis C virus (HCV) infection and is associated with significant treatment-related toxicities. Newly developed small molecules that target key enzymes essential for HCV replication are in development. Telaprevir, a peptidomimetic inhibitor of the HCV NS3/4A protease, has shown great promise in early trials and is currently in advanced stages of clinical development. In treatment-naive patients and those with previous treatment failure, the addition of telaprevir to standard interferon and ribavirin therapy is well tolerated and enhances rates of sustained virologic response while shortening the treatment duration. In this report, the current experience using telaprevir to treat chronic HCV infection as monotherapy and in combination with other agents is reviewed.
PMID: 19628160
ISSN: 1089-3261
CID: 551522