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| 1 | Hepatocellular carcinoma:A comprehensive review显示文摘Hepatocellular carcinoma(HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals withchronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival. | Lisa P Waller Vrushak Deshpande Nikolaos Pyrsopoulos | 2015 | World Journal of Hepatology2015，7，26： | 26 |
| 2 | Efficacy and safety of anti-hepatic fibrosis drugs显示文摘Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease(the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety. | Konstantinos Damiris Zaid H Tafesh Nikolaos Pyrsopoulos | 2020 | World Journal of Gastroenterology2020，26，41： | 8 |
| 3 | Characteristics and Inpatient Outcomes of Primary Biliary Cholangitis and Autoimmune Hepatitis Overlap Syndrome显示文摘Background and Aims:Primary biliary cholangitis(PBC)and autoimmune hepatitis(AIH)are hepatobiliary diseases of presumed immune-mediated origin that have been shown to overlap.The aim of this retrospective trial was to use national data to examine the characteristics and outcomes of patients hospitalized with overlapping PBC and AIH(PBC/AIH).Methods:The National Inpatient Sample was used to identify hospitalized adult patients with PBC,AIH,and PBC/AIH from 2010 to 2014 by International Classification of Diseases-Ninth Edition Revision codes;patients with hepatitis B virus and hepatitis C virus infection were excluded.Primary outcomes measures were in-hospital outcomes that included mortality,respiratory failure,septic shock,length of stay,and total hospital charges.Secondary outcomes were the clinical characteristics of PBC/AIH,including the comorbid extrahepatic autoimmune disease pattern and complications of cirrhosis.Results:A total of 3,478 patients with PBC/AIH were included in the study.PBC/AIH was associated with higher rates of Sjögren’s syndrome(p<0.001;p<0.001),lower rates of Crohn’s disease(p<0.05;p<0.05),and higher rates of cirrhosis-related complications when compared to PBC or AIH alone.There were similar rates of mortality between the PBC/AIH,PBC,and AIH groups.The PBC/AIH group had higher rates of septic shock when compared to the PBC group(p<0.05)and AIH group(p<0.05)after adjusting for possible confounders.Conclusions:PBC/AIH is associated with a lower rate of Crohn’s disease,a higher rate of Sjögren’s syndrome,higher rates of cirrhosis-related complications,and significantly increased risk of septic shock compared to PBC and AIH individually. | Yi Jiang Bing-Hong Xu Brandon Rodgers Nikolaos Pyrsopoulos | 2021 | Journal of Clinical and Translational Hepatology2021，9，3： | 7 |
| 4 | Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection显示文摘 | Arie Regev Mariana Berho Lennox J Jeffers Clara Milikowski Enrique G Molina Nikolaos T Pyrsopoulos Zheng-Zhou Feng K.Rajender Reddy Eugene R Schiff | 2002 | The American Journal of Gastroenterology2002，，10： | 7 |
| 5 | Liver injury induced by paracetamol and challenges associated with intentional and unintentional use显示文摘Drug induced liver injury(DILI)is a common cause of acute liver injury.Paracetamol,also known as acetaminophen,is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels.Hepatotoxicity from paracetamol overdose,whether intentional or nonintentional,is the most common cause of DILI in the United States and remains a global issue.Given the increased prevalence of combination medications in the form of pain relievers and antihistamines,paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity,as evidenced by its contribution to over half of all acute liver failure cases in the United States.This is especially concerning given that,when co-ingested with other medications,the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy.This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options. | Laura Rotundo Nikolaos Pyrsopoulos | 2020 | World Journal of Hepatology2020，12，4： | 4 |
| 6 | Immunobiology of hepatocarcinogenesis: Ways to go or almost there?显示文摘Hepatocellular carcinoma is on the rise and occurs in the setting of chronic liver disease and cirrhosis.Though treatment modalities are available,mortality from this cancer remains high.Medical therapy with the utilization of biologic compounds such as the Food and Drug Administration approved sorafenib might be the only option that can increase survival.Immunotherapy,with modern pharmacologic developments,is a new frontier in cancer therapy and therefore the immunobiology of hepatocarcinogenesis is under investigation.This review will discuss current concepts of immunobiology in hepatocarcinogenesis along with current treatment modalities employing immunotherapy.The tumor microenvironment along with a variety of immune cells coexists and interplays to lead to tumorigenesis.Tumor infiltrating lymphocytes including CD8+ T cells,CD4+ T cells along with regulatory T cells,tumor associated macrophages,tumor associated neutrophils,myeloid derived suppressor cells,and natural killer cells interact to actively provide anti-tumor or pro-tumor effects.Furthermore,oncogenic pathways such as Raf/mitogenactivated protein kinase/extracellular-signal-regulated kinase pathway,phosphatidyl-3-kinase/AKT/mammalian target or rapamycin,Wnt/β-catenin,nuclear factor-κB and signal transducers and activators of transcription 3 may lead to activation and proliferation of tumor cells and are also considered cornerstones in tumorigenesis.Immunotherapy directed at this complex milieu of cells has been showned to be successful in cancer treatment.The use of vaccines,adoptive cell therapy and immune checkpoint inhibitor modulation are current options for therapy.Further translational research will shed light to concepts such as anti-tumor immunity which can add another alternative in the therapeutic armamentarium. | Pavan Patel Steven E Schutzer Nikolaos Pyrsopoulos | 2016 | World Journal of Gastrointestinal Pathophysiology2016，7，3： | 3 |
| 7 | Emerging concepts in alcoholic hepatitis显示文摘Severe alcoholic hepatitis is implicated as a costly,worldwide public health issue with high morbidity and mortality. The one-month survival for severe alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from alcohol is the recommended firstline treatment. Although corticosteroids remain as the current evidence based option for selected patients with discriminant function > 32, improvement of short-term survival rate may be the only benefit. Identification of individuals with risk factors for the development of severe alcoholic hepatitis may provide insight to the diverse clinical spectrum and prognosis of the disease. The understanding of the complex pathophysiologic processes of alcoholic hepatitis is the key to elucidating new therapeutic treatments. Newer research describes the use of gut microbiota modification, immune modulation, stimulation of liver regeneration, caspase inhibitors, farnesoid X receptors, and the extracorporeal liver assist device to aid in hepatocellular recovery. Liver transplantation can be considered as the last medical option for patients failing conventional medical interventions. Although the preliminary data is promising in patients with low risk of recividism, controversy remains due to organ scarcity. This review article comprehensively summarizes the epidemiology, pathophysiology, risk factors, and prognostic indicators of severe alcoholic hepatitis with a focus on the current and emerging therapeutics. | Phoenix Fung Nikolaos Pyrsopoulos | 2017 | World Journal of Hepatology2017，9，12： | 3 |
| 8 | Cellular based treatment modalities for unresectable hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC)is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high mortality.Early and intermediate stages of HCC allow for treatment with surgical resection,ablation and even liver transplantation,however disease progression warrants conventional systemic therapy.For years treatment options were limited to molecular-targeting medications,of which sorafenib remains the standard of care.The recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of HCC,but there is an urgent need for the development of further novel therapeutic treatments that prolong overall survival and minimize recurrence.Current investigation is focused on adoptive cell therapy including chimeric antigen receptor-T cells(CAR-T cells),T cell receptor(TCR)engineered T cells,dendritic cells,natural killer cells,and tumor infiltrating lymphocyte cells,which have shown remarkable success in the treatment of hematological and solid tumor malignancies.In this review we briefly introduce readers to the currently approved systemic treatment options and present clinical and experimental evidence of HCC immunotherapeutic treatments that will hopefully one day allow for revolutionary change in the treatment modalities used for unresectable HCC.We also provide an up-to-date compilation of ongoing clinical trials investigating CAR-T cells,TCR engineered T cells,cancer vaccines and oncolytic viruses,while discussing strategies that can help overcome commonly faced challenges when utilizing cellular based treatments. | Konstantinos Damiris Hamza Abbad Nikolaos Pyrsopoulos | 2021 | World Journal of Clinical Oncology2021，12，5： | 2 |
| 9 | Lipid-lowering agents and hepatotoxicity显示文摘 | Demyen M Alkhalloufi K Pyrsopoulos NT | 2013 | Clin Liver Dis2013，17，4： | 1 |
| 10 | Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation 显示文摘 | Tuteja S Pyrsopoulos NT Wolowich WR | 2008 | Pharmacotherapy2008，28，9： | 1 |
| 11 | Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection显示文摘 | Arie Regev Mariana Berho Lennox J Jeffers Clara Milikowski Enrique G Molina Nikolaos T Pyrsopoulos Zheng-Zhou Feng K.Rajender Reddy Eugene R Schiff | 2002 | The American Journal of Gastroenterology2002，，10： | 1 |
| 12 | Simvastatin-ezetimibe-induced hepatic failure neces sitating liver transplantation显示文摘 | Tuteja S Pyrsopoulos NT Wolowich WR | 2008 | Pharmacotherapy2008，28，9： | 1 |
| 13 | Hepatitis E in immunocompromised individuals显示文摘Hepatitis E virus(HEV)originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States.While there are eight identified genotypes to date,genotype 1(HEV1),HEV2,HEV3,HEV4 are the most common to infect humans.HEV1 and HEV2 are most common in developing countries including Latina America,Africa and Asia,and are commonly transmitted through contaminated water supplies leading to regional outbreaks.In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat.The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing.In majority of cases,HEV infection is a selflimiting hepatitis requiring only symptomatic treatment.However,this is not the case in immunocompromised individuals,including those that have undergone solid organ or stem cell transplantation.In this subset of patients,chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death.The need for re-transplantation as a result of post-transplant hepatitis is of great concern.In addition,there have been many reported incidents of extrahepatic manifestations,for which the exact mechanisms remain to be elucidated.The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies,while attempting to minimize the risk of organ rejection.Subsequent treatment options include ribavirin,and pegylated interferon alpha in those who have demonstrated ribavirin resistance.Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden.Given this concern,vaccination has been approved in China with other investigations underway throughout the world.In this review we introduce the epidemiology,diagnosis,clinical manifestations,and treatment of HEV,with emphasis on immunocompromised individuals in the United States. | Konstantinos Damiris Mohamad Aghaie Meybodi Mumtaz Niazi Nikolaos Pyrsopoulos | 2022 | World Journal of Hepatology2022，14，3： | 1 |
| 14 | Cannabis use history is associated with increased prevalence of ascites among patients with nonalcoholic fatty liver disease:A nationwide analysis显示文摘BACKGROUND Recent studies have revealed the endocannabinoid system as a potential therapeutic target in the management of nonalcoholic fatty liver disease(NAFLD).Cannabis use is associated with reduced risk for NAFLD,we hypothesized that cannabis use would be associated with less liver-related clinical complications in patients with NAFLD.AIM To assess the effects of cannabis use on liver-related clinical outcomes in hospitalized patients with NAFLD.METHODS We performed a retrospective matched cohort study based on querying the 2014 National Inpatient Sample(NIS)for hospitalizations of adults with a diagnosis of NAFLD.The NIS database is publicly available and the largest all-payer inpatient database in the United States.The patients with cannabis use were selected as cases and those without cannabis were selected as controls.Case-control matching at a ratio of one case to two controls was performed based on sex,age,race,and comorbidities.The liver-related outcomes such as portal hypertension,ascites,varices and variceal bleeding,and cirrhosis were compared between the groups.RESULTS A total of 49911 weighed hospitalizations with a diagnosis of NAFLD were identified.Of these,3820 cases were selected as the cannabis group,and 7625 noncannabis cases were matched as controls.Patients with cannabis use had a higher prevalence of ascites(4.5%vs 3.6%),with and without cannabis use,P=0.03.The prevalence of portal hypertension(2.1%vs 2.2%),varices and variceal bleeding(1.3%vs 1.7%),and cirrhosis(3.7%vs 3.6%)was not different between the groups,with and without cannabis use,all P>0.05.Hyperlipidemia,race/ethnicity other than White,Black,Asian,Pacific Islander or Native American,and higher comorbidity score were independent risk factors for ascites in the cannabis group.Among non-cannabis users,obesity and hyperlipidemia were independent protective factors against ascites while older age,Native American and higher comorbidity index were independent risk factors for ascites.CONCLUSION Cannabis was associated with higher rates of ascites,but there was no statistical difference in the prevalence of portal hypertension,varices and variceal bleeding,and cirrhosis. | Catherine J Choi Stanley H Weiss Umair M Nasir Nikolaos T Pyrsopoulos | 2020 | World Journal of Hepatology2020，12，11： | 1 |
| 15 | Anesthetic and perioperative management of intestinal and multivisceral allograf/ recipient in nontransplant surgery显示文摘 | Kostopanagiotou G Sidiropoulou T Pyrsopoulos N | 2008 | Transpl 1nt2008，21，5： | 1 |
| 16 | Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection显示文摘 | Arie Regev Mariana Berho Lennox J Jeffers Clara Milikowski Enrique G Molina Nikolaos T Pyrsopoulos Zheng-Zhou Feng K.Rajender Reddy Eugene R Schiff | 2002 | The American Journal of Gastroenterology2002，，10： | 1 |
| 17 | ExWahepatic manifestations of chronicviral hepatitis 显示文摘 | Pyrsopoulos NT Reddy KR | 2001 | Curr Gastroenterol Rep2001，3，1： | 1 |
| 18 | Randomized Trial of Steroid-Free Induction Versus Corticosteroid Maintenance Among Orthotopic Liver Transplant Recipients With Hepatitis C Virus: Impact on Hepatic Fibrosis Progression at One Year显示文摘 | Tomoaki Kato Jeffrey J. Gaynor Hideo Yoshida Marzia Montalvano Hidenori Takahashi Nikolaos Pyrsopoulos Seigo Nishida Jang Moon Gennaro Selvaggi David Levi Phillip Ruiz Eugene Schiff Andreas Tzakis | 2007 | Transplantation2007，，7： | 1 |
| 19 | Lipid-lowering agents and hepatotoxicity显示文摘 | Demyen M Alkhalloufi K Pyrsopoulos NT | 2013 | Clin Liver Dis2013，17，4： | 1 |
| 20 | Hepatobiliary Scintigraphy in Liver Transplant Patients: The “Blind End Sign” and Its Differentiation from Bile Leak显示文摘 | Steven A. Young George N. Sfakianakis Nikolaos Pyrsopoulos Seigo Nishida | 2003 | Clinical Nuclear Medicine2003，，8： | 1 |
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