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HEV and HBV Dual Infection:A Review

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Journal of Clinical and Translational Hepatology 2020年第3期8卷 313-321页

作者： My.a Nasir george y.wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Hepatitis E virus(HEV)is a global health problem,affecting about 20 million people *** is significant overlap of hepatitis B virus(HBV)and HEV endemicity.in many.Asian countries where dual infections with HEV and HBV can *** the clinical course of HEV is largely.self-limited,HEV superinfection in patients with chronic hepatitis B(CHB)can result in acute exacerbation of underly.ng *** superinfection in patients with CHB-related cirrhosis has been identified as a risk factor for decompensated cirrhosis and an independent predictor of *** acute HEV infection in pregnancy.can cause fulminant liver failure,the few studies on pregnant patients with dual HBV and HEV infection have shown a subclinical *** is a risk factor for the development of chronic HEV infection,which can be managed by.decreasing the dose of immune-suppressants and administering *** for HEV has been developed and is in use in China but its efficacy.in patients with CHB has y.t to be established in the *** this review,we appraise studies on dual infection with HEV and HBV,including the effect of HEV superinfection and coinfection in CHB,management strategies used and the role of active vaccination in the prevention of HEV.

关键词： Hepatitis B Hepatitis E Coinfection Superinfection Chronic hepatitis B

Primary.Sclerosing Cholangitis and Primary.Biliary.Cirrhosis Overlap Sy.drome:A Review

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Journal of Clinical and Translational Hepatology 2020年第3期8卷 336-346页

作者： Sheena Mago george y.wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Primary.sclerosing cholangitis(PSC)and primary.biliary.cirrhosis(PBC)are slow progressive diseases which have been increasing in *** pathogeneses of PBC and PSC are incompletely.understood but the underly.ng mechanisms appear to be fundamentally.autoimmune in *** PBC and PSC appear to be separate entities,overlap has been *** depends on a combination of serological markers,imaging,and pathological *** mainstay.of treatment has been ursodeoxy.holic acid and in some cases of extrahepatic biliary.obstruction and overlap disorder,endoscopic retrograde cholangiopancreatography.has been useful.

关键词： Primary.sclerosing cholangitis Primary.biliary.cirrhosis Overlap sy.drome

A DNA delivery.sy.tem containing listerioly. in Oresults in enhanced hepatocy.edirected gene expression

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World Journal of Gastroenterology 1999年第6期5卷 465-469页

作者： Cherie M. Walton, Catherine H. wu and george y. wu Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT United States Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT 06030 United States

AIM To determine whether incorporation of the pH dependent bacterial toxin listerioly.in O (LLO) into the DNA carrier sy.tem could increase the endosomal escape of internalized DNA and result gene expression. METHODS A multi component delivery.sy.tem was prepared consisting of asialogly.oprotein (ASG), poly.L ly.ine (PL), and LLO. Two marker genes, luciferase and β galactosidase in plasmids were complexed and administered in vitro to Huh7[ASG receptor (+) ] and SK Hep1[ASG receptor (-) ] cells. Purity. hemoly.ic activity. gene expression, specificity. and toxicity.were evaluated. RESULTS An LLO containing conjugate retained cell targeting specificity.and membranoly.ic activity. In ASG receptor (+) cells, luciferase gene expression was enhanced by.more than 7 fold over that of conjugates without the incorporation of listerioly.in O. No significant expression occurred in ASG receptor (-) cells. Enhancement of β galactosidase gene expression was less, but still significantly.increased over controls. There was no detectable toxicity.at concentrations shown to be effective in transfection studies. CONCLUSIONS ASOR PL can be coupled to LLO using disulfide bonds, and successfully.target and increase the gene expression of foreign DNA.

关键词： DNA gene expression listerioly.in O hepatocy.es

Cy.omegalovirus Hepatitis in Immunocompetent and Immunocompromised Hosts

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 106-115页

作者： Teresa Da Cunha george y.wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA Department of Medicine University of Connecticut Health CenterFarmingtonCTUSA

Human cy.omegalovirus (HCMV) infection is common and affects between 40–100% of the worldwide population. However, the majority.of cases are asy.ptomatic and when severe disease occurs, it is usually.restricted to immunocompromised patients. Liver involvement by.HCMV differs significantly. accordingly.to the immune status of the host. In immunocompromised patients, particularly.liver transplant patients, it often causes clinically.significant hepatitis. On the other hand, in immunocompetent patients, HCMV hepatitis requiring hospitalization is extremely.rare. This review aims to appraise studies regarding the pathophy.iology.of HCMV hepatitis, including mechanisms of latency.and reactivation and its contribution to disease development, clinical presentation, diagnostic modalities and treatment, with a focus on comparing different aspects between immunocompromised and immunocompetent hosts.

关键词： CMV hepatitis Cy.omegalovirus hepatitis Cy.omegalovirus hepatitis immunocompetent Cy.omegalovirus hepatitis immunocompromised

Celiac Disease and Elevated Liver Enzy.es: A Review

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 116-124页

作者： Jaimy.Villavicencio Kim george y.wu Department of Medicine University of Connecticut Health CenterFarmingtonCTUSA Division of Gastroenterology.epatology University of Connecticut Health CenterFarmingtonCTUSA

Aminotransferases are commonly.found to be elevated in patients with celiac disease in association with two different ty.es of liver dy.function:cry.togenic liver disorders and autoimmune *** purpose of this review is to discuss the mechanisms by.which aminotransferases become elevated in celiac disease,clinical manifestations,and response to gluten-free *** studies have shown that celiac patients with cry.togenic liver disease have normalization in aminotransferases,intestinal histologic improvement and serologic resolution after 6–12 months of strict gluten-free *** patients with an underly.ng autoimmune liver disease,simultaneous treatment for both conditions resulted in normalized elevated *** literature suggests that intestinal permeability.may.be at least one of the mechanisms by.which liver damage *** with celiac disease should have liver enzy.es routinely.checked and treated with a strict gluten-free diet if found to be *** of improvement in patients who have strictly.adhered to gluten-free diet should prompt further workup for other causes of liver disease.

关键词： Celiac disease Gluten free diet Celiac hepatitis Autoimmune liver disease

Hepatitis B virus infection of transplanted human hepatocy.es causes a biochemical and histological hepatitis in immunocompetent rats

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World Journal of Gastroenterology 2003年第5期9卷 978-983页

作者： Catherine H.wu Edwin C.Ouy.ng Cherie Walton Kittichai Promrat Faripour Forouhar george y. wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA Department of Pathology University of Connecticut Health CenterFarmingtonCTUSA

AIM: To characterize the host response to hepatitis B virus (HBV) infection in human hepatocy.es transplanted into immunocompetent rodent rats tolerized by. and transplanted with primary.human ***: One week after the transplantation, rats were inoculated with HBV, and viral gene expression, replication,and host response was ***: HBV DNA was detectable in serum for at least 60 day.. HBsAg levels rose steadily.for 3 weeks postinoculation and then plateaued at a level of about 0.6 pg/mi. HBV RNA was also found in liver at levels that remained constant through the time course. Immunofluorescence revealed clusters of hepatocy.es that stained positive for HBcAg. The presence of HBV covalently.closed circular DNA (cccDNA) in liver was demonstrated using nuclease digestion of single-stranded DNA followed by.PCR. Serum ALT levels rose and reached a peak level of 180 IU/L on day.18, but remained elevated for 60 day.. Histology.revealed a progressive predominantly.mononuclear lobular ***: These data indicate that human hepatocy.estransplanted into rats rendered tolerant to these cells, when infected by.HBV, results in biochemical as well as histological evidence of hepatitis that accompanies viral gene expression,and DNA replication.

关键词：肝实质细胞种植乙型肝炎病毒生物化学病理组织学免疫原性动物实验

Chy.ous Ascites:A Review of Pathogenesis,Diagnosis and Treatment

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Journal of Clinical and Translational Hepatology 2018年第1期6卷 105-113页

作者： Richa Bhardwaj Haleh Vaziri Arun Gautam Enrique Ballesteros David Karimeddini george y. wu Department of Medicine Division of Gastroenterology-HepatologyUCONN HealthFarmingtonCTUSA Department of Pathology.and Lab Medicine UCONN HealthFarmingtonCTUSA Department of Diagnostic Imaging and Therapeutics UCONN HealthFarmingtonCTUSA Department of Medicine Division of Gastroenterology-HepatologyUCONN HealthFarmingtonCT 06030USA

Chy.ous ascites(CA)is a rare form of ascites that results from the leakage of lipid-rich ly.ph into the peritoneal *** usually.occurs due to trauma and rupture of the ly.phatics or increased peritoneal ly.phatic pressure secondary.to *** underly.ng etiologies for CA have been classified as traumatic,congenital,infectious,neoplastic,postoperative,cirrhotic or *** malignancy.and cirrhosis account for about two-thirds of all the cases of CA in Western countries,in this article we have attempted to reclassify.CA based on portal and non-portal *** diagnosis of CA is based on the distinct characteristic of the ascitic fluid which includes a milky.appearance and a trigly.eride level of>200 mg/*** management consists of identify.ng and treating the underly.ng disease process,dietary.modification,and *** studies have also supported the use of agents such as orlistat,somatostatin,octreotide and *** and surgical interventions in the form of transjugular intrahepatic portosy.temic shunt(commonly.known as TIPS),peritoneal shunt,angiography.with embolization of a leaking vessel,and laparotomy.remain as treatment options for cases refractory.to medical management.

关键词： Chy.ous ascites Portal hy.ertension Cirrhosis Ascitic fluid Ly.phatic sy.tem

Update on the Development of Anti-Viral Agents Against Hepatitis C

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Journal of Clinical and Translational Hepatology 2013年第1期1卷 9-21页

作者： Kristin L. MacArthur Robert Smolic Martina V. Smolic Catherine H. wu george y. wu Department of Medicine Beth Israel Deaconess Medical Center Boston MA02215 Faculty.of Medicine Osijek Croatia University of Connecticut Health Center Farmington CT USA Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT USA

Hepatitis C virus (HCV) infects nearly.170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy.and minimizes side effects is quickly.evolving. This review will discuss a wide range of drug targets currently.in all phases of development for the treatment of HCV. Direct data from agents in phase Ⅲ/Ⅳ clinical trials will be presented, along with reported side-effect profiles. The mechanism of action of all treatments and resistance issues are highlighted. Special attention is given to available trial data supporting interferon-free treatment regimens. HCV has become an increasingly.important public health concern, and it is important for phy.icians to stay.up to date on the rapidly.growing novel therapeutic options.

关键词： HCV Protease Poly.erase Triple therapy Drug.

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Found in Translation

Journal of Clinical and Translational Hepatology 2013年第1期1卷 1-1页

作者： george y. wu Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT USA

Since the identification of the hepatitis C virus (HCV) and subsequent cloning of its genome in 1989, only.relatively.modest progress had been made in the treatment of its chronic infection until recently. Interferon-alfa was approved in 1991 for the treatment of HCV infection, and provided a sustained virological response (SVR) of 9% for genoty.e 1, and 20–30% for genoty.es 2 and 3. With the addition of ribavirin in 1998, the SVR of interferon-ribavirin combination therapy.increased to 29% for genoty.e 1, and 62% for genoty.es 2 and 3. The development of long-acting pegy.lated (PEG)-interferons plus ribavirin in 2001–2002 increased SVR incrementally.to 41% for genoty.e 1, and 82% for genoty.es 2 and 3. After this advance, the situation remained static for almost 10 y.ars without significant breakthroughs, until the advent of the protease inhibitors telaprevir and boceprevir in 2011. These agents represent the vanguard of a new class of HCV drugs, the direct-acting antiviral agents, and a new era in the treatment of HCV. With the triple therapy.regimen of PEG-interferon, ribavirin, and either telaprevir or boceprevir, the SVR for genoty.e 1 HCV ranges from 70 to 80%. Now, for the first time, persons infected with genoty.e 1 HCV can expect a higher than 50%chance of achieving an SVR to antiviral therapy.

关键词： interferon sustained drugs