Training for a Career in Hepatology: Which Path to Take?

Hepatology has matured significantly over the past two decades, and most gastroenterologists now believe that it is a distinct subspecialty. An unmet public health need exists for professional expertise in the care of patients with liver diseases. However, our current training programs are struggling to adequately recruit and train physicians with the appropriate expertise in advanced and transplant hepatology. This review briefly summarizes the recent discoveries and developments in clinical hepatology, describes the past and current training paradigms, and suggests potential pathways to improve the number and quality of physicians trained in advanced and transplant hepatology.     

Assessing the impact of COVID-19 on the management of patients with liver diseases: A national survey by the Italian association for the study of the Liver

BackgroundThe COVID-19 pandemic had a huge impact on national and regional health systems. The impact of SARS-CoV-2 on the quality of care for patients with liver disease is still unknown.AimsThe Italian Association for the Study of the Liver (AISF) conducted a survey to assess the impact of SARS-CoV-2 on hepatology units activities in Italy.MethodsA prospective web-based survey was proposed to all AISF active members. The survey was available online from April 8 2020, to May 3 2020, (lockdown phase in Italy).Results194 AISF members answered the questionnaire, most of whom were specialists in Gastroenterology (41%) or Internal Medicine (28%), and worked in Northern Italy (51%). 26% of hepatology wards had been converted into COVID-19 wards, and 33% had bed reductions. All hepatological activities, including the management of patients with decompensated liver disease, liver transplant and HCC had been significantly reduced/stopped. The number of physicians answering that their practices had not been modified ranged between 0.6% (for chronic hepatitis) to 47% (for the execution of paracentesis). The recorded answers were consistent among different regions, and did not show any north-south gradientConclusionCOVID-19 outbreak significantly impacted on hepatological clinical activity. This survey can serve as a basis to compare the impact of future measures aimed at delivering an acceptable level of liver care during a national pandemic or crisis.     

Aetiological spectrum of hyperferritinemia

Serum ferritin levels may be increased in many conditions: renal diseases, liver diseases, human immunodeficiency virus infection. The purpose of this study was to assess the aetiological spectrum of high serum ferritin levels in a 1200-bed university hospital, to compare our results with the data already published and to assess a potential association between aetiology and ferritin levels. PATIENTS AND METHODS: Patients with a serum ferritin level higher than 600 microg/l were retrospectively included between 15 November 2003 and 15 January 2004, and their medical records were reviewed. RESULTS: Ninety-eight patients (38 women and 60 men; median age: 59,5 years [19-92]) were recruited in departments of hepatology and gastroenterology (22%), haematology (14%) and internal medicine (18%). Diagnosis performed were: non-HIV systemic infections (23,8%), haematological diseases (16,1%), alcoholism (11,2%) and malignancies (9,8%). Dialysed chronic renal failure, liver diseases, haemochromatosis and systemic inflammatory diseases counted for 4.2 to 5.2% of cases. Serum ferritin level lied between 600 and 1000 microg/l for 50 patients, between 1000 and 1500 microg/l for 24, and over 1500 microg/l for 24. There was no significant difference between the three groups as regards the etiological distribution. DISCUSSION: In our study, chronic renal failure was not a major cause of high ferritin level: this is probably due to the current use of erythropoietin, which has decreased the use of blood transfusions. The two major aetiology of hyperferritinemia were non-HIV infections and malignancies.     

Artificial Intelligence in hepatology,liver surgery and transplantation: Emerging applications and frontiers of research

The integration of artificial intelligence (AI) and augmented realities into the medical field is being attempted by various researchers across the globe. As a matter of fact, most of the advanced technologies utilized by medical providers today have been borrowed and extrapolated from other industries. The introduction of AI into the field of hepatology and liver surgery is relatively a recent phenomenon. The purpose of this narrative review is to highlight the different AI concepts which are currently being tried to improve the care of patients with liver diseases. We end with summarizing emerging trends and major challenges in the future development of AI in hepatology and liver surgery.     

Realities and prospects for the use of cell technologies for the treatment of chronic diffuse liver diseases

Chronic liver disease (CLD) leads to disability annually hundreds of thousands of patients worldwide. Originating as a rule, at a young age (20-40 years), they are always significantly degrade the quality of life of patients, making them socially significant. Moreover, the conventional treatment (hepatoprotectors, antiviral drugs, corticosteroids, immunosuppressive medication) not always lead to achieving the desired effect, and therefore is constantly searching for alternative treatments. Cell therapy with embryonic fetal, mononuclear, mesenchymal stromal cells is the most advanced front of modern biotechnology and medicine. Using the SC with the purpose of treatment in chronic liver diseases is the possibility of disturbed regulation of cell-cell interactions in the liver, the impact on the mechanisms of cell death (necrosis - apoptosis) and fibrogenesis, which makes this method the most relevant and promising in hepatology. The article presents an analysis of the results of studies conducted in the field of stem cell technologies by leading domestic and foreign scholars in the treatment of liver diseases. Were studied questions of transdifferentiation, the mechanisms of stem cells in hepatology, as well as the possible risks of this therapy (pro-oncogene action, increased fibrosis). Also was presented our own experience of applying cellular technology in experimental models of acute toxic hepatitis in animals.     

Australian Liver Association (ALA) expert consensus recommendations for the use of transient elastography in chronic viral hepatitis

Since the introduction of Transient Elastography (TE) into Australia in 2008, non‐invasive liver fibrosis assessments have integrated themselves into clinical hepatology. The Australian Liver Association (ALA) recognizes these technologies perform an important role in the assessment of chronic viral hepatitis B and C. However, in the setting of viral hepatitis and many other chronic liver diseases, there remains no consensus or guidelines regarding the performance, utility or reporting of TE. Accordingly, the ALA sought to produce an expert consensus statement for the use of TE in chronic viral hepatitis. The recommendations incorporated in this document are based upon a thorough literature review and draw on extensive clinical experience using TE. The initial draft was presented at Australian Gastroenterology Week (AGW) 2013. Through a collaborative process and expert external review a finalized document was presented at AGW 2014.     

Elastography in hepatology.

A common characteristic of all chronic liver diseases is the occurrence and progression of fibrosis toward cirrhosis. Consequently, liver fibrosis assessment plays an important role in hepatology. Besides its importance for prognosis, determining the level of fibrosis reveals the natural history of the disease and the risk factors associated with its progression, to guide the antifibrotic action of different treatments. Currently, in clinical practice, there are three available methods for the evaluation of liver fibrosis: liver biopsy, which is still considered to be the 'gold standard'; serological markers of fibrosis and their mathematical combination - suggested in recent years to be an alternative to liver biopsy - and, more recently, transient elastography (TE). TE is a new, simple and noninvasive method used to measure liver stiffness. This technique is based on the progressing speed of an elastic shear wave within the liver. Currently, there are only a few studies that have evaluated TE effectiveness in chronic liver diseases, mostly in patients infected with the hepatitis C virus. Further studies are needed in patients with chronic liver disease, to assess the effectiveness of the fibrosis treatment.     

The burden of acute nonfulminant drug-induced hepatitis in a United States tertiary referral center [corrected

BACKGROUND/GOALS: There are limited data regarding the frequency and proportionality of drug-induced hepatotoxicity in the United States. We sought to determine the scope of nonfulminant drug-induced hepatitis as seen in a community-based hepatology referral service. STUDY: From a population of 4,039 outpatients referred for evaluation of acute (n = 96) and chronic (n = 3,943) liver disease over a 10-year period, we reviewed the records of those patients diagnosed with acute bona fide drug-induced hepatitis. RESULTS: Thirty-two patients presented with self-limited acute drug-induced hepatitis, representing 0.8% of all hepatology patients and 33% of those patients presenting with acute liver injury. Antibiotics (amoxicillin/clavulanic acid, minocycline, nitrofurantoin, an investigational ketolide antibiotic, trimethoprim-sulfamethoxazole, and trovafloxacin) were the class of drugs most frequently implicated (14 of 32; 44%), while amiodarone was the single agent most commonly associated with liver injury (7 of 32; 22%). The mean age of affected patients was 52.2 years, and we found a male predominance (18 of 32; 56%). The mean time to biochemical resolution after discontinuation of the offending agent was 14.1 weeks. CONCLUSIONS: Drug-induced hepatitis is an uncommon entity in clinical hepatology but does represent a significant proportion of acute self-limited liver disease in the United States. Antibiotics and amiodarone were the most common drug culprits in our population. Time to resolution following the discontinuation of the offending agent may be protracted. Prospective studies are needed to further assess the burden of drug-induced liver injury.     

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration

Extracellular vesicles are membrane fragments that can be produced by all cell types. Interactions between extracellular vesicles and various liver cells constitute an emerging field in hepatology and recent evidences have established a role for extracellular vesicles in various liver diseases and physiological processes. Extracellular vesicles originating from liver cells are implicated in intercellular communication and fluctuations of specific circulating extracellular vesicles could constitute new diagnostic tools. In contrast, extracellular vesicles derived from progenitor cells interact with hepatocytes or non‐parenchymal cells, thereby protecting the liver from various injuries and promoting liver regeneration. Our review focuses on recent developments investigating the role of various types of extracellular vesicles in acute and chronic liver diseases as well as their potential use as biomarkers and therapeutic tools.     

Bibliometric analysis of the 100 most-cited articles in the field of hepatology

ObjectiveBibliometric search of citation classics can function as a tool to identify extraordinary landmark articles and advanced research studies. We aimed to examine and characterize the 100 most-cited published articles in the field of hepatology.Patients and methodsA comprehensive list of the 100 most-cited articles published from 1950 to 2017 in the field of hepatology was compiled after searching the Web of Science with relevant terms, including “liver,” “hepatitis,” “hepatic,” “hepatocellular,” “hepatology,” “cirrhosis,” and “steatohepatitis.” The articles were ranked according to their citation counts and were evaluated for characteristics including country, institution, authorship, publication year, subspecialty and others.ResultsThe database search returned 323,291 articles associated with liver disease published between 1950 and 2017. The 100 most-cited articles were from 21 major journals, with the highest number of articles being published in Hepatology (n = 20). The average number of citations of the 100 most-cited articles was 1946.8; among these articles, the most frequently cited article received 5515 citations, and the least frequently cited article received 1155 citations. In total, 60 were original articles among the 100 most-cited articles. The most frequently represented specialties were hepatitis, hepatocellular carcinoma, and nonalcoholic fatty liver disease, which accounted for 53.3%, 23.3%, and 11.7% of these articles, respectively.DiscussionOur study identified citation classics and provided a review of the most advanced studies in the field of hepatology. This can help to guide clinical treatment and future academic research resulting in advancements in hepatology.     

2008～2012年上海地区胃肠病学与肝病学SCI论文计量学分析

背景：近年来,上海地区作者参与发表的胃肠病学与肝病学SCI论文数量增长明显。目的：评估上海地区胃肠病学与肝病学领域的发展现状和学术地位。方法：应用Web of Knowledge检索平台获得2008～2012年间上海地区作者参与发表的胃肠病学与肝病学SCI论文,对发文数、发文作者和机构、期刊来源、被引频次等进行统计分析。结果：2008—2012年上海地区作者参与发表的胃肠病学与肝病学SCI论文共计1522篇,其中以第一作者身份发表者1278篇。发文数排名第一的作者是第二军医大学附属长海医院消化科李兆申,发文数排名前3位的机构是上海交通大学、第二军医大学、复旦大学,载文量最多的期刊是WORLD JOURNAL OF GASTROENTEROLOGY,被引频次最高的文献系肝病学研究,共被引用75次。结论：上海地区胃肠病学与肝病学SCI论文数量呈稳定增长趋势,论文质量则有待进一步加强,尤其是应加强胃肠病学领域的研究。     

Kommentar zu den neuen Leitlinien (2010) der Europäischen Gesellschaft für Kardiologie (ESC) zum Management von Erwachsenen mit angeborenen Herzfehlern (EMAH)

The new Guidelines of the European Society of Cardiology for the Management of Grown-up Congenital Heart (GUCH) Disease, published in 2010, have been endorsed by the German Cardiac Society and the pocket version has been translated. The present comments outline the concept of the new document, specific German aspects are highlighted and the most important differences compared to the previous version published in 2003 and to the guidelines published by the German-speaking societies are summarized. Finally, the document is compared to the recent guidelines of the American Heart Association and the American College of Cardiology. The new ESC guidelines should be the new standard for Germany together with the German recommendations for the organization of care for GUCH and the accreditation in the subspecialty GUCH. Compared to previous documents the guidelines provide more comprehensive information with more precise recommendations that should help to improve the quality of care.     

Actualización en COVID-19 y enfermedad hepática

The SARS-CoV-2 pandemic has proven to be a serious challenge for the Spanish healthcare system. The impact of the virus on the liver is not well known, but in patients with chronic liver disease, mostly in advanced stages, it can critically compromise survival and trigger decompensation. Treatment in this subpopulation is complex due to the potential hepatotoxicity of some of the medicinal products used. Moreover, the pandemic has also negatively impacted patients with liver disease who have not contracted COVID-19, since the reallocation of human and material resources to the care of patients with the virus has resulted in a decrease in the treatment, diagnosis and follow-up of patients with liver disease, which will surely have negative consequences in the near future. Efficient reorganization of hepatology units is a priority to minimise the impact of the pandemic on a population as vulnerable as liver disease patients.     

Functional glycomics: Application to medical science and hepatology

Glycomics refers to the comprehensive analysis of glycans. Recent progress in glycotechnology enables the determination of a variety of biological functions of glycans. Among different glycosylation patterns, certain types of aberrant glycosylation are linked to cancer and/or inflammation, and thus have biological importance. Glycotechnology has been applied to many fields of medical science, including hepatology. In particular, dramatic changes in glycosylation are observed in the progression of liver diseases. As the liver produces so many serum glycoproteins, changes in glycosylation of these proteins might provide useful disease biomarkers. Furthermore, many patients with genetic diseases of glycosylation who have liver dysfunction have been found as a result from whole genome sequencing, and various kinds of glycotherapy have been developed, especially in immunotherapy. In this review, we describe our basic knowledge of glycobiology and discuss the application of these data to medical science, especially hepatology.     

Percutaneous liver biopsy in clinical practice.

Percutaneous liver biopsy (PLB) is the standard procedure for obtaining hepatic tissue for histopathological examination, and remains an essential tool in the diagnosis and management of parenchymal liver diseases. The use of liver biopsy (LB) is increasing with the advent of liver transplantation and the progress being made in antiviral therapeutic agents. While blind percutaneous needle biopsy is the traditional technique, the use of ultrasound (US) guidance has increased considerably. Literatures were reviewed to assess the existing clinical practice of PLB with an emphasis on the technique, the operator, types of biopsy needles, quality of LB specimens and the risk of complications. The best available evidence indicates that the use of ultrasound-guided biopsy (UGB) is superior to blind needle biopsy (BNB). The odds ratios of the controlled studies showed that BNB carried a higher risk for major complications, postbiopsy pain and biopsy failure. Therefore, percutaneous LB under US control is superior to BNB and it is recommended that UGB be considered the standard of care for this important and widely used invasive procedure in the field of clinical hepatology.     

肝衰竭和失代偿期肝硬化患者肠外营养新理念

笔者综合欧洲肠外肠内营养学会最新发布的肝病肠外营养指南、ICU肠外营养指南和近期相关文献，着重简述了肝衰竭和失代偿期肝硬化患者肠外营养指证、时机、要点和注意事项等，以临床实际需求和问题为导向，尽量给出明确的意见和条款，为专科医师和ICU医护人员提供决策帮助。     

Is the ‘driving test’ a robust quality indicator of colonoscopy performance?

Colorectal cancer is a major cause of death in the western world and is currently the second commonest cause of death from malignant disease in the UK. Recently a "driving test" for colonoscopists wishing to take part in the National Health Service Bowel Cancer Screening Program has been introduced, with the aim of improving quality in colonoscopy. We describe the accreditation process and have reviewed the published evidence for its use. We compared this method of assessment to what occurs in other developed countries. To the authors' knowledge no other countries have similar methods of assessment of practicing colonoscopists, and instead use critical evaluation of key quality criteria. The UK appears to have one of the most rigorous accreditation processes, although this still has flaws. The published evidence suggests that the written part of the accreditation is not a good discriminating test and it needs to be improved or abandoned. Further work is needed on the best methods of assessing polypectomy skills. Rigorous systems need to be in place for the colonoscopist who fails the assessment.     

COVID-19 pandemic: Its impact on liver disease and liver transplantation

Severe pulmonary disease caused by the novel coronavirus [severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)], has devastated many countries around the world.It has overwhelmed the medical system.The priorities of many institutions have changed to manage critically ill corona virus infectious disease-2019(COVID-19) patients,which affected the working style of many departments.Hepatologists and transplant surgeons look after a very sensitive patient group.Patients with liver disease need special attention and continuous follow-up.Similarly,transplant candidates also need special care.Healthcare professionals in the field of hepatology face the overwhelming task of taking care of COVID-19 patients with hepatic complications,liver disease or transplant patients who are SARS-CoV-2 positive,and the patients on routine surveillance who do not have COVID-19.This review will evaluate COVID-19 from the perspective of its effect on the liver and its possible effects on patients with liver disease.Furthermore,the level of care for liver transplant recipients during the pandemic will be discussed.     

Adherence to Appropriate Nutrition in Acute Alcoholic Hepatitis is Low

Malnutrition is a common cause of impeding recovery in patients with acute alcoholic hepatitis (AAH). Previous reports have shown that appropriate nutritional supplementation reduce short and long-term mortality in patients with AAH. Despite these clear recommendations, the element of nutrition in AAH is often neglected. We designed a quality improvement project to evaluate and improve compliance with appropriate nutrition in patients presenting with AAH at our institution. Patients admitted with AAH between December 2015 to December 2016 were included. Our primary outcome was compliance with appropriate nutrition. Secondary outcomes included nutrition consultation and hepatology consultation. A total of fifty-four patients were included. Nine of the 53 patients (17%) received high calorie and high protein diets. Hepatology was consulted in 72% (38/53) of the patients, and 21% (8/38) of these patients received appropriate nutrition as compared to only 8.3% (1/12) in whom hepatology was not consulted. Nutrition was consulted in 55% (29/53) of these patients and 67% (19/28) of those patients received appropriate nutrition. In conclusion, our compliance of appropriate nutrition in AAH is low. Our initial investigation suggests that hepatology and nutrition consultation improved compliance with appropriate nutrition. The next step will be to implement protocolized care for appropriate nutrition in AAH by incorporating consultation of hepatology and nutrition services, assess the effect on adherence to appropriate nutrition, and determine the impact on patient outcomes.     

Nonalcoholic fatty liver disease in patients investigated for elevated liver enzymes.

Nonalcoholic fatty liver disease (NAFLD) is a common diagnosis among patients referred to gastroenterology and hepatology clinics for the evaluation of elevated liver enzymes. The diagnosis of NAFLD is supported by blood work to exclude other liver diseases, and by ultrasound evidence of fat in the liver in patients without a significant history of alcohol intake. The gold standard, however, is a liver biopsy to show the typical histological features of NAFLD, which are almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. A variety of retrospective series have linked NAFLD to obesity, diabetes, hyperlipidemia, total parenteral nutrition, jejunoileal bypass surgery and certain medications. A subset of patients with NAFLD that had an initial presentation of elevated liver enzymes was studied. Two hundred and two patients were reviewed, of whom 49 met the inclusion criteria including a liver biopsy. Patients were excluded if insufficient data were available, if the patients had a significant history of ethanol intake or if they had other coexisting liver disease. These patients were seen between 1996 and 2000 in gastroenterology and hepatology clinics in two community hospitals and one regional liver transplant centre in Edmonton, Alberta. NAFLD was associated with a spectrum of changes in the liver ranging from mild steatosis to more significant steatosis with inflammation and fibrosis. Cases of NAFLD with steatosis and mixed inflammatory infiltration but lacking ballooning degeneration or fibrosis were prevalent in young (20 to 40 years of age) patients with no other significant medical history except for obesity. NAFLD with biopsies showing significant fibrosis and ballooning cell degeneration was associated with obesity, diabetes and older age. It was concluded that, in this predominantly outpatient setting, age over 40 years and diabetes at any age are risk factors for both nonalcoholic steatohepatitis and nonalcoholic steatohepatitis with cirrhosis. It is therefore recommended that patients with raised liver enzymes and suspected NAFLD be targeted for liver biopsy in their evaluation.