Charissa Y Chang

Mount Sinai Medical Center, New York City, New York, United States

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Publications (14)55.46 Total impact

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    ABSTRACT: In patients with hepatocellular carcinoma (HCC), liver transplantation (LT) is an excellent therapy if tumor characteristics are within the Milan criteria. We aimed to define genomic features enabling to identify HCC patients beyond Milan criteria who have acceptable transplant outcomes. Among 770 consecutive HCC patients transplanted between 1990 and 2013, 132 had tumors exceeding Milan criteria on pathology and were enrolled in the study; 44% of the patients satisfied the 'up-to-7 rule' [7=sum of the size of the largest tumor and the number of tumors]. Explant tumors were assessed for genomic signatures and immunohistochemical markers associated with poor outcome. At a median follow-up of 88 months, 64 patients had died and 45 recurred; the 5-year overall survival (OS) and recurrence rates were 57% and 35%, respectively. Cytokeratin 19 (CK19) gene signature was independently associated with recurrence [Hazard ratio (HR)=2.95, p<0.001], along with tumor size (HR=3.37, p=0.023) and presence of satellites (HR=2.98, p=0.001). S2 subclass signature was independently associated with poor OS (HR=3.18, p=0.001), along with tumor size (HR=5.06, p<0.001) and up-to-7 rule (HR=2.50, p=0.002). Using the presence of progenitor cells markers (either CK19 or S2 signatures) patients were classified into poor-prognosis (n=58; 5-year recurrence 53%, survival 45%) and good-prognosis (n=74; 5-year recurrence 19%, survival 67%) (HR=3.16, p<0.001 for recurrence, and HR=1.72, p=0.04 for OS). HCC patients transplanted beyond Milan criteria without gene signatures of progenitor markers (CK19 and S2) achieved survival rates similar as those within Milan criteria. Once prospectively validated, these markers may support a limited expansion of LT indications. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 07/2015; DOI:10.1016/j.jhep.2015.07.025 · 11.34 Impact Factor
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    ABSTRACT: Hepatocellular adenoma (HCA) is a benign neoplasm arising from hepatocytes. There is evidence that the inflammatory subtype may be associated with obesity and alcohol use and that men with metabolic syndrome may be at risk for malignant transformation of HCA. We sought to explore the combined experience of US centers as reported in the literature to document the epidemiologic shift in risk factors for HCA formation in the United States, namely, a shift from oral contraceptive pills (OCPs) to an emerging role of obesity as a contributing factor. Methods. Publications reporting HCA in the United States were identified through a PubMed search and a review of the literature. We excluded publications prior to 1970, single case reports, and publications for which there was no data available regarding patient characteristics including OCP use and the number of adenomas. Conclusion. Whereas earlier reports of HCA in the United States described cases exclusively in women exposed to OCPs, there is a trend towards an increase in HCAs reported in men, HCAs in the absence of OCP use, and increased reporting of multiple HCAs. This may be a result of newer OCP formulations and increasing prevalence of obesity.
    02/2013; 2013:604860. DOI:10.1155/2013/604860
  • Devina Bhasin · Xuchen Zhang · Stephen C Ward · Charissa Y Chang ·
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    ABSTRACT: A 40-year-old man with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection was referred for evaluation of abnormal liver enzyme activities. The patient was maintained on antiretroviral therapy for HIV as well as medication to suppress HBV and had previously undergone treatment for HCV with durable sustained virologic response. The patient was clinically well without any symptoms or evidence of liver decompensation. Laboratory findings were notable for aminotransferase activities in the 200 to 225 U/L range that had been persistent for several months. An extensive workup for the etiology of the aminotransferase elevation ensued. Imaging studies showed no evidence of biliary obstruction. Serology revealed negative autoantibodies, negative serum HCV-RNA, and low level HBV-DNA by polymerase chain reaction. Further testing revealed positive hepatitis delta virus (HDV) antibody and positive HDV RNA in the serum. A percutaneous liver biopsy was performed to further elucidate the cause of the elevated aminotransferase activities. Based on histology, serology, and clinical presentation, a diagnosis of chronic HDV infection was made. HDV infection should be considered in patients with known chronic viral hepatitis B with low viral load, who present with worsening liver function or elevation in aminotransferase activities.
    Seminars in Liver Disease 08/2012; 32(3):262-6. DOI:10.1055/s-0032-1323632 · 4.95 Impact Factor
  • Ana C Tuyama · Charissa Y Chang ·
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It is closely associated with metabolic syndrome. The alarming epidemics of diabetes and obesity have fueled an increasing prevalence of NAFLD, particularly among these high-risk groups. Histologically, NAFLD encompasses a disease spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury, inflammation, and variable degrees of fibrosis on liver biopsy. Non-alcoholic steatohepatitis can progress to cirrhosis in a fraction of patients. There is currently little understanding of risk factors for disease progression and the disease pathogenesis has not been fully defined. Liver biopsy remains the gold standard for diagnosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. There are no well-established pharmacological agents for treatment of NASH, although this is a subject of ongoing research.
    Journal of Diabetes 05/2012; 4(3):266-80. DOI:10.1111/j.1753-0407.2012.00204.x · 1.93 Impact Factor
  • Charissa Y Chang ·

    Liver international: official journal of the International Association for the Study of the Liver 10/2011; 31(9):1246-9. DOI:10.1111/j.1478-3231.2011.02612.x · 4.85 Impact Factor
  • Charissa Y Chang · Paul Martin · Anastasia Fotiadu · Prodromos Hytiroglou ·
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    ABSTRACT: We present a patient with HBeAg-negative chronic hepatitis B, in whom significant regression of hepatic fibrosis was achieved after a lengthy antiviral treatment. A liver biopsy specimen obtained at initiation of treatment showed chronic hepatitis B with mild activity (histologic activity index: 7) and marked fibrosis (stage 4, in a scale of 0 to 6). A second biopsy specimen, obtained 10 years later, demonstrated almost complete resolution of necroinflammatory activity and fibrosis. One year after the second biopsy, seroconversion from HBsAg positive to anti-HBs positive status was achieved, and antiviral treatment was discontinued. This case is illustrative of the significant histologic improvement that can be accomplished in chronic hepatitis B when viral activity is suppressed long term. Lengthy antiviral treatment can achieve resorption of excess fibrous tissue, even in patients with marked fibrosis.
    Seminars in Liver Disease 08/2010; 30(3):296-301. DOI:10.1055/s-0030-1262515 · 4.95 Impact Factor
  • Anja Lachenmayer · Clara Alsinet · Charissa Y Chang · Josep M Llovet ·
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    ABSTRACT: Hepatocellular carcinoma (HCC) remains a highly complex disease resistant to commonly used chemotherapy and radiotherapy. As the sixth most common cancer worldwide with the third highest mortality rate and very poorly understood molecular pathways driving hepatocarcinogenesis, new treatment strategies are urgently needed for this devastating disease. The multikinase inhibitor sorafenib was the first molecular targeted drug in HCC that led to significant survival benefit in patients with advanced tumors. It is the first drug to be considered standard of care for advanced HCC and supports the importance of molecular therapies in the treatment of this cancer. Analyses of genetic and epigenetic alterations as well as different molecular pathways involved in the development of HCC help to identify potential new druggable targets. A variety of novel compounds are already under preclinical or clinical investigation, and accumulating evidence suggests that combination therapy targeting different pathways will potentiate anti-tumoral effects and will become the future therapeutic approach. In addition the establishment of a robust molecular classification will pave the way for a more personalized treatment scheme in HCC. In this article we review the current knowledge of the molecular pathogenesis of HCC and provide an overview of molecular targeted therapies in the management of HCC.
    Digestive and Liver Disease 07/2010; 42 Suppl 3(Suppl 3):S264-72. DOI:10.1016/S1590-8658(10)60515-4 · 2.96 Impact Factor
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    ABSTRACT: While obesity is associated with liver cancer in studies from western societies, the paucity of data from Asia limits insights into its aetiological role in this population. We examined the relationship between body mass index (BMI) and liver cancer mortality using data from the Asia Pacific Cohort Studies Collaboration. In 309,203 Asian study members, 4 years of follow-up gave rise to 11,135 deaths from all causes, 420 of which were ascribed to liver cancer. BMI, whether categorised according to current guidelines for Asian groups or World Health Organisation recommendations, was not associated with liver cancer in any of our analyses.
    11/2009; 33(6):469-72. DOI:10.1016/j.canep.2009.09.010
  • Stephen C Ward · Charissa Y Chang · Lan Peng · Lawrence U Liu ·
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    ABSTRACT: We present the case of a patient with hepatitis B virus infection and alcohol use (30 g/day by self-report) who developed cirrhosis and proceeded to liver transplantation at age 49. The explanted liver showed cirrhosis with evidence of burnt-out steatohepatitis and hepatitis B virus and a 0.7-cm focus of well-differentiated hepatocellular carcinoma. He was managed following transplant with tacrolimus, prednisone, lamivudine, adefovir, and hepatitis B immune globulin infusions. His post-transplant course was complicated by several episodes of elevated liver enzymes. Liver biopsy 3 months after liver transplantation showed acute rejection and mild steatohepatitis. Liver biopsy 6 months after liver transplantation showed marked steatosis (approximately 95%) with moderate steatohepatitis and evidence of treated rejection. Subsequent biopsies (15 and 21 months post liver transplantation) showed resolution of the steatohepatitis, but development of chronic rejection. We discuss the interaction of alcoholic liver disease and hepatitis B virus in the development of cirrhosis and hepatocellular carcinoma, as well as the role of liver transplantation in these patients.
    Seminars in Liver Disease 06/2009; 29(2):233-7. DOI:10.1055/s-0029-1216299 · 4.95 Impact Factor
  • Hui-Hui Tan · Charissa Y Chang · Paul Martin ·
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    ABSTRACT: APAP overdose is a major cause of acute liver failure. Although early administration of the specific antidote NAC can prevent severe hepatotoxicity, there are still patients who may progress to acute liver failure, requiring a liver transplant.
    Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine 02/2009; 76(1):75-83. DOI:10.1002/msj.20065 · 1.62 Impact Factor
  • Charissa Y. Chang · Kerry Whitt · Zhenqi Liu · Stephen H. Caldwell ·
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    ABSTRACT: Recognition of a link between insulin resistance (IR) and liver disease dates back at least 100 years to the term “hepatogenous diabetes”, which describes the association between cirrhosis and development of diabetes (1) and more recently to the term “diabetic fatty liver” which antedated the now more common terms “nonalcoholic steatohepatitis” (NASH) and “nonalcoholic fatty liver disease” (NAFLD). These terms were introduced in the 1980s and 1990s, respectively. Since their introduction, the ever-rising prevalence of obesity has brought increased attention to these disorders as the hepatic manifestation of “metabolic” or “insulin resistance” syndrome. Indeed, IR appears to be the common link among metabolic syndrome, obesity, and nonalcoholic fatty liver. Metabolic alterations and hepatic steatosis can develop in the insulin-resistant state in the absence of and prior to diabetes mellitus. Moreover, it is now known that IR correlates with increasing fibrosis in other liver diseases including hepatitis C.
    12/2008: pages 229-244;
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    ABSTRACT: The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print., *2007 Journal Citation Report (Thomson Reuters, 2008)
    The American Journal of Gastroenterology 08/2006; 101(7):1677-8. DOI:10.1111/j.1572-0241.2006.00627_8.x · 10.76 Impact Factor
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    ABSTRACT: Lipid peroxidation and secondary cellular injury are the dominant mechanism in the transition from relatively stable hepatic steatosis to potentially progressive steatohepatitis in nonalcoholic fatty liver disease (NAFLD). Oxidation of excessive fatty acids generates free radicals (reactive oxygen species) that damage organelles and stimulate signaling pathways leading to fibrosis and cellular injury. Both antioxidant agents (by breaking the chain reaction of lipid peroxidation) and cytoprotective agents (by stabilizing cellular and organelle phospholipid membranes) may be effective agents in treating an active steatohepatitis through amelioration of the driving force and attenuation of the secondary effects. Here we have reviewed the existing studies on such therapies, including vitamin E, S-adenosylmethionine (SAMe), betaine, and ursodeoxycholic acid. Small trials suggest possible improvement in liver enzymes with the use of these agents in NAFLD. However, controlled studies have not uniformly demonstrated benefit from these agents when compared with control groups treated with diet and weight loss alone, and measurement of reliable histologic endpoints is limited. These agents may show benefit in NAFLD through future larger controlled studies. Particular promise may exist in the use of these agents in combination therapy with ones that target other aspects in the pathogenesis of NAFLD, such as insulin-sensitizing agents.
    Journal of Clinical Gastroenterology 04/2006; 40 Suppl 1(supplement 1):S51-60. DOI:10.1097/01.mcg.0000168648.79034.67 · 3.50 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver (NAFL) is associated with fundamental issues of fat metabolism and insulin resistance. These abnormalities have been linked to impairment of ATP homeostasis, and a growing body of literature has reported mitochondrial abnormalities in various forms of hepatic steatosis. The changes are evident as structural abnormalities, including greatly increased size and the development of crystalline inclusions, and are usually regarded as pathologic, reflecting either a protective or degenerative response to injury. Although the relationships between structural changes,decreased mitochondrial function, and disease states are becoming clearer, the molecular basis for the perturbations is not well understood. Oxidative damage is the most likely causative process and may result in alterations of mitochondrial DNA (mtDNA), stimulated apoptotic pathways, and increased propensity for necrosis.Overall mitochondrial health likely depends on multiple factors including the integrity of the mtDNA, the composition of cellular lipids, lipoprotein trafficking, the balance of pro- and antioxidant factors, and the metabolic demands placed on the liver. Mitochondrial dysfunction may play a role in numerous clinical conditions associated with NAFL, such as hepatocellular carcinoma, lipodystrophy,age-related insulin resistance, gut dysmotility, cryptogenic cirrhosis, a mild form of gaze palsy, and possibly other more severe neurodegenerative diseases. The prominent role of mitochondrial dysfunction in NAFL provides a new and exciting paradigm in which to view this disorder, its complications, and potential dietary and pharmacologic intervention.
    Clinics in Liver Disease 09/2004; 8(3):595-617, x. DOI:10.1016/j.cld.2004.04.009 · 3.66 Impact Factor