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Role of inflammation and infection in the pathogenesis of human acute liver failure: clinical implications for monitoring and therapy

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World Journal of Gastroenterology 2016年第26期22卷 5958-5970页

作者： Mhairi C Donnelly Peter C Hayes Kenneth J Simpson Department of hepatology and Scottish Liver Transplant unit Royal Infirmary of Edinburgh

Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multiorgan failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research.

关键词： Inflammation Neuroinflammation Acute liver failure Biomarker Infection

Cystic tumors of the liver:A practical approach

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World Journal of Gastroenterology 2008年第23期14卷 3616-3620页

作者： Paolo Del Poggio Marco Buonocore hepatology unit Treviglio HospitalTreviglio(Bg) 24047Italy

Biliary cyst tumors(cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver,but differential diagnosis with multiloculated or complicated biliary cysts,atypical hemangiomas,hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography(CT) and magnetic resonance imaging(MRI) are often not diagnostic and in these cases fine needle aspiration(FNA) is used to confirm the presence of atypical biliary cells. FNA,however,lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma,it is important to exclude liver metastasis,of which colonic cancer is the most common primary site. Multiple biliary hamartomas(von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic,but occasionally a percutaneous biopsy may be required.

关键词： Biliary cyst tumor Liver cystic neoplasia Cystadenoma Cystadenocarcinoma Atypical hepatic cysts

Adherence to surveillance endoscopy following hospitalization for index esophageal variceal hemorrhage

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World Journal of Gastrointestinal Surgery 2018年第4期10卷 40-48页

作者： Brendan T Everett Steven D Lidofsky Gastroenterology and hepatology unit University of Vermont Medical Center

AIM To investigate patient adherence to surveillance endoscopy after index esophageal variceal hemorrhage and the extent to which adherence influences *** We reviewed the records of patients with cirrhosis admitted to the medical intensive care unit between 2000 and 2014 for first time esophageal variceal hemorrhage treated with endoscopic variceal ligation who were subsequently discharged and scheduled for surveillance endoscopy at our medical center. Demographic and clinical data were obtained through the medical records, including etiology of cirrhosis, completion of variceal obliteration, attendance at surveillance endoscopy, zip code of primary residence, distance from home to hospital, insurance status, rehospitalization for variceal hemorrhage, beta-blocker at discharge, pharmacologically treated psychiatric disorder, and transplant free survival. RESULTS Of 99 consecutive survivors of esophageal variceal bleeding, the minority(33) completed variceal obliteration and fewer(12) adhered to annual surveillance. Completion of variceal obliteration was associated with fewer rehospitalizations for variceal rebleeding(27% vs 56%, P = 0.0099) and when rehospitalizations occurred, they occurred later in those who had completed obliteration(median 259 d vs 207 d, P = 0.0083). Incomplete adherence to endoscopic surveillance was associated with more rehospitalizations for variceal rebleeding compared to those fully adherent to annual endoscopic surveillance(51% vs 17%, P = 0.0328). Those adherent to annual surveillance were more likely to be insured privately or through Medicare compared to those who did not attend post-hospital discharge endoscopy(100% vs 63%, P = 0.0119).CONCLUSION Most patients do not complete variceal obliteration after index esophageal variceal hemorrhage and fewer adhere to endoscopic surveillance, particularly the uninsured and those insured with Medicaid.

关键词： Liver cirrhosis Endoscopy Esophageal varices Secondary prevention Patient adherence

Hyperferritinemia is a risk factor for steatosis in chronic liver disease

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World Journal of Gastroenterology 2009年第17期15卷 2132-2138页

作者： Anna Licata Maria Elena Nebbia Giuseppe Cabibbo Giovanna Lo Iacono Francesco Barbaria Virna Brucato Nicola Alessi Salvatore Porrovecchio Vito Di Marco Antonio Craxì Calogero Cammà Gastroenterology and hepatology unit Department of Internal Medicine University of Palermo 90127 Palermo Italy

AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and γ-glutamyltransferase were independent predictors of steatosis. Ferritin levels were signifi cantly related to low platelet count, steatosis and hepatitis C virus infection. CONCLUSION: In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.

关键词： Steatosis Serum ferritin Chronic liverdisease Hepatitis C γ-glutamyltransferase

Promoting genetics in non-alcoholic fatty liver disease: Combined risk score through polymorphisms and clinical variables

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World Journal of Gastroenterology 2018年第43期24卷 4835-4845页

作者： Umberto Vespasiani-Gentilucci Paolo Gallo Chiara Dell' Unto Mara Volpentesta Raffaele Antonelli-Incalzi Antonio Picardi unit of Internal Medicine and hepatology Department of Medicine University Campus Bio-Medico

Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention

关键词： Non-alcoholic fatty liver disease Single nucleotide polymorphism Patatin-like phospholipase domain-containing protein 3 Transmembrane 6 superfamily member 2 Membrane bound O-acyltransferasedomain containing 7 Glucokinase regulatory gene Risk score Non-alcoholic steatohepatitis Non-alcoholic steatohepatitis cirrhosis Hepatocellular carcinoma

Hepatitis C treatment in the elderly:New possibilities and controversies towards interferon-free regimens

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World Journal of Gastroenterology 2015年第24期21卷 7412-7426页

作者： Umberto Vespasiani-Gentilucci Giovanni Galati Paolo Gallo Antonio De Vincentis Elisabetta Riva Antonio Picardi Internal Medicine and hepatology unit University Campus Bio-Medico Virology unit University Campus Bio-Medico

Due to the progressive aging of the hepatitis C virus(HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extrahepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the wellknown contraindications and side effects of interferon(IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn't mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the "old" IFN-based regimens and with the newer drugs. We will conclude that the availability of IFNfree regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key issues g

关键词： Hepatitis C virus Elderly Interferon Ribavirin Telaprevir Boceprevir Sofosbuvir Simeprevir Daclatasvir Side effects Drug-drug interactions

COVID-19 in normal,diseased and transplanted liver

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World Journal of Gastroenterology 2021年第20期27卷 2576-2585页

作者： Alessandro Signorello Ilaria Lenci Martina Milana Giuseppe Grassi Leonardo Baiocchi hepatology unit Department of MedicineUniversity of Tor VergataRome 00133Italy

Starting from December 2019 the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has extended in the entire world giving origin to a *** the respiratory system is the main apparatus involved by the infection,several other organs may suffer coronavirus disease 2019(COVID-19)-related *** human tissues expressing angiotensin-converting enzyme 2(ACE2)are all possible targets of viral *** fact myocarditis,meningo-encephalitis,acute kidney injury and other complications have been described with regard to SARS-CoV-2 *** liver has a central role in the body homeostasis contributing to detoxification,catabolism and also synthesis of important factor such as plasma ***2 is significantly expressed just by cholangiocytes within the liver,however transaminases are increased in more than one third of COVID-19 patients,at hospital *** reasons for liver impairment in the course of this infection are not completely clear at present and multiple factors such as:Direct viral effect,release of cytokines,ischemic damage,use of hepatotoxic drugs,sepsis,and others,may contribute to *** COVID-19 seems to elicit just a transient alteration of liver function tests in subjects with normal hepatic function,of concern,more severe sequelae are frequently observed in patients with a reduced hepatic *** this review we report data regarding SARS-CoV-2 infection in subjects with normal or diseased *** addition the risks of COVID-19 in immunosuppressed patients(either transplanted or suffering for autoimmune liver diseases)are also described.

关键词： COVID-19 Liver Non-alcoholic fatty-liver-disease Cirrhosis Liver transplant Angiotensin-converting enzyme 2

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World Journal of Gastroenterology 2011年第45期17卷 4945-4951页

作者： Amedeo Carraro Dania El Mazloum Florian Bihl Department of Surgery Veneto Oncological Institute IRCCS School of Medicine University of Padova Gastroenterology and hepatology unit San Giovanni Hospital Gastroenterology and hepatology Service University Hospital of Geneva

Gallbladder diseases are very common in developed countries. Complicated gallstone disease represents the most frequent of biliary disorders for which surgery is regularly advocated. As regards, cholecystectomy represents a common abdominal surgical intervention; it can be performed as either an elective intervention or emergency surgery, in the case of gangrene, perforation, peritonitis or sepsis. Nowadays, the laparoscopic approach is preferred over open laparotomy. Globally, numerous cholecystectomies are performed daily; however, little evidence exists regarding assessment of post-surgical quality of life (QOL) following these interventions. To assess post-cholecystectomy QOL, in fact, documentation of high quality care has been subject to extended discussions, and the use of patientreported outcome satisfaction for quality improvement has been advocated for several years. However, there has been little research published regarding QOL out-comes following cholecystectomy; in addition, much of the current literature lacks systematic data on patientcentered outcomes. Then, although several tools have been used to measure QOL after cholecystectomy, diffi culty remains in selecting meaningful parameters in order to obtain reproducible data to reflect postoperative QOL. The aim of this study was to review the impact of surgery for gallbladder diseases on QOL. This review includes Medline searches of current literature on QOL following cholecystectomy. Most studies demonstrated that symptomatic patients profi ted more from surgery than patients receiving an elective intervention. Thus, the gain in QOL depends on the general conditions before surgery, and patients without symptoms profi t less or may even have a reduction in QOL.

关键词： Gallbladder disease Gallstones Quality of life Laparoscopy

Genotype 3 is the predominant hepatitis C genotype in a multi-ethnic Asian population in Malaysia

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Hepatobiliary & Pancreatic Diseases International 2015年第3期14卷 281-286页

作者： Shiaw-Hooi Ho Kee-Peng Ng Harvinder Kaur Khean-Lee Goh Gastroenterology and hepatology unit Department of Internal MedicineUniversity of Malaya Department of Medical Microbiology University of Malaya

BACKGROUND： Genotypes of hepatitis C virus （HCV） are distributed differently across the world. There is a paucity of such data in a multi-ethnic Asian population like Malaysia. The objectives of this study were to determine the distribution of HCV genotypes between major ethnic groups and to ascer- tain their association with basic demographic variables like age and gender.

关键词： Asian genotype hepatitis C Malaysia multi-ethnic