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The impact of chronic liver disease on critically ill patients

Soulsby, Charlotte Rebecca (2019) The impact of chronic liver disease on critically ill patients. MD thesis, University of Glasgow.

In the UK, mortality from liver disease has increased by 400% between 1970 and 2010 with death rates for those under 65 having risen by almost 500% (1). Up to 75% of deaths related to chronic liver disease have an underlying aetiology of alcohol and are preventable (1, 2). Advanced chronic liver disease leads to multi-system clinical manifestations, many of which will require critical care. Evidence supporting this claim is seen in the increase in admissions to critical care for those patients with cirrhosis (3). These patients have higher rates of readmission to ICU (Intensive Care Unit), longer length of ICU stay and have an increased requirement for organ support (4). Despite this, both ICU and hospital mortality in those with cirrhosis have improved since the 1980s where mortality was reported to be up to 100% (5-7).

With fewer beds compared to the USA or other European countries the existing demand on critical care capacity in the UK is increasing. There remains a need for a greater number of centres offering both critical care and hepatology input, with a significant number of hospitals nationwide lacking any hepatology input (8). Assessment of critically ill patients with cirrhosis is challenging, with many prognostic scoring systems in use. To date, no scoring system has been demonstrated to be superior in stratifying which patients would benefit from ICU admission. With the existing pressure on limited critical care beds within the UK and the increased demand to support critically ill patients, identifying those patients who merit admission to critical care will become an increasingly important challenge.

This thesis focuses on the factors used in the decision to admit a patient with advanced chronic liver disease or cirrhosis to critical care, their long-term survival and quality of life. Attention is given to the utility of the Child-Pugh score and when it should be assessed. As the majority of deaths due to chronic liver disease have an underlying aetiology of alcohol, this thesis will also address how an alcohol use disorder can be assessed in the critically ill.

The first investigation of this thesis explores the criteria used in the decision to escalate a patient to intensive care. This is explored through 2 Scottish surveys of consultant gastroenterologists and intensivists. Results highlighted agreement by both specialities on the importance of Child-Pugh score measured when a patient was clinically stable. Inconsistencies were evident in the escalation of therapy with intensivists more likely to offer intensive care and multi-organ support as compared to gastroenterologists.

In response to these findings, the timing and utility of Child-Pugh score was investigated. This observational cohort study compared Child-Pugh score measured on ICU admission with the score when a patient was clinically stable and short-term mortality. Only Child-Pugh score measured at time of ICU admission was associated with hospital mortality, which contradicted the findings of the previous chapter. The degree of change in Child-Pugh score between these time points was associated with mortality.

Given that the majority of deaths due to chronic liver disease in the UK are primarily caused by alcohol, challenges exist in identifying alcohol use disorders in the critically ill. A prospective study examined the use of a proxy to report an alcohol use disorder in critically ill patients and suggested that a proxy could be used as a reliable historian.

Whilst short-term survival of critically ill cirrhotics has improved, there is a paucity of studies reporting long-term outcomes. An observational cohort study investigated survival at 12 months for cirrhotic patients admitted to a general ICU in the UK. Long-term survival following an ICU stay has improved, in keeping with other studies. When measured on admission to ICU, Child-Pugh class was demonstrated to stratify patients into 3 distinct groups for long-term survival.

With the improvement in survival, the sequelae of an ICU stay were investigated. A prospective observational cohort study explored the long-term quality of life and prevalence of sleep disturbance. A number of survivors reported that their quality of life was worse than, or equal to death. Quality of life and sleep disturbance were influenced by pre-existing comorbidity and events during their ICU. In this study, there was no association found between QOL and insomnia in those with liver cirrhosis.

This thesis addresses the decision to admit a patient with advanced chronic liver disease or cirrhosis to critical care, reports their long-term survival and quality of life and explores how one preventable cause of chronic liver disease can be assessed in the critically ill by use of a proxy.

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The University of Glasgow is a registered Scottish charity: Registration Number SC004401

• © 2019

Clinical Epidemiology of Chronic Liver Diseases

• Robert J. Wong 0 ,
• Robert G. Gish 1

Division of Gastroenterology and Hepatology, Alameda Health System Highland Hospital, Oakland, USA

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Robert G. Gish Consultants LLC, Hepatitis B Foundation, Stanford Health Care, San Diego, USA

Summary table with each chapter to highlight key articles and key outcomes from included studies

Emphasis on understanding clinical epidemiology, including recent incidence, prevalence, and improved survival trends. Focus will not be on diagnostic approach or treatment approaches

Emphasis on the methodology of clinical research studies included with chapters specifically devoted to clinical epidemiology

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• Table of contents

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Table of contents (18 chapters)

Front matter, principles of clinical epidemiology.

• Rita Popat, Julia Simard

Understanding Study Design for Clinical Epidemiology Studies

• Jenny Krause Cohen, Irene H. Yen

Understanding the Interpretation of Disease Incidence and Prevalence

• Ehsan Chitsaz, Sheila Kumar

Understanding Survival Analyses

• Somasundaram Subramaniam

Global Epidemiology of Chronic Liver Disease

• Nimzing Gwamzhi Ladep, Sheikh Mohammad Fazle Akbar, Mamun Al Mahtab

Epidemiology of Chronic Liver Disease in the United States

• Yihan Yang, Jeffrey Luk, Andre N. Sofair

Epidemiology of Alcoholic Liver Disease

• C. Taylor Richardson, Ashwani K. Singal

Hepatitis B Virus: Asian Perspective

• Wai-Kay Seto, Man-Fung Yuen

Viral Hepatitis: The African Experience

Hepatitis b: the western perspective.

• Elana Rosenthal, Rachel Baden

Hepatitis D Virus

• Mario Rizzetto

Clinical Epidemiology of Hepatitis C Virus

• Aparna Goel, Aijaz Ahmed, Imam Waked

Enteric Hepatitis Viruses: Hepatitis A Virus and Hepatitis E Virus

• Mohammad Sultan Khuroo, Mehnaaz S. Khuroo, Naira S. Khuroo

Clinical Epidemiology of NAFLD

• Donghee Kim, Osama Siddique, Brandon J. Perumpail, Aijaz Ahmed

Clinical Epidemiology of Chronic Liver Disease: Hepatocellular Carcinoma

• Duminda Suraweera, Peter Konyn, Thomas Vu, Sammy Saab

Autoimmune Hepatitis and Immune-Mediated Cholestatic Liver Diseases

• Albert J. Czaja

The Epidemiology of Rare Hereditary Metabolic Liver Diseases

• Marinos Pericleous, Claire Kelly, Aftab Ala, Michael L. Schilsky

Cryptogenic Cirrhosis

• Zachary Henry, Curtis K. Argo, Stephen H. Caldwell

This book emphasizes the clinical epidemiology of chronic liver diseases with a specific focus on the methodology of the discussed studies. The whole spectrum of liver diseases is covered, from chronic hepatitis B and C, to hepatocellular carcinoma, alcoholic and non-alcoholic fatty liver diseases and autoimmune and cholestatic liver diseases.

Readers will find the most up-to-date information on clinical epidemiology of hepatology, and will also be able to learn about important methodology and biostatistics information. Each chapter contains a summary table at the end of each chapter that highlights the most relevant landmark studies, their main outcomes and the unique features of the methodology.  

• Hepatitis B Virus
• Hepatitis C Virus
• Non-alcoholic Fatty Liver Disease
• Alcoholic Fatty Liver Disease
• Hepatocellular Carcinoma
• case-control study
• cohort study
• survival analysis
• Alcoholic cirrhosis
• liver cancer
• biliary cholangitis
• sclerosing cholangitis
• pharmacoeconomics

Robert J. Wong

Robert G. Gish

Robert Wong is a graduate of the University of California San Francisco School of Medicine. He completed his internship and residency in internal medicine at California Pacific Medical Center. Following residency, he completed his gastroenterology and hepatology fellowship at Stanford University Hospitals and Clinics during which time he also completed his Masters in Clinical Epidemiology. After completing fellowship, he joined the gastroenterology faculty at Alameda Health System - Highland Hospital, where he also holds an appointment as Assistant Clinical Professor of Medicine at University of California San Francisco School of Medicine. His clinical interests include viral hepatitis and chronic liver diseases. His research interests include clinical epidemiology and outcomes research with a focus on chronic liver diseases and gastrointestinal malignancies.

Dr Gish has made key contributions to hepatitis research and treatment; he was a major early contributor to the decipherment of methods for the detection of hepatitis B and C virus and characterizing its epidemiology and clinical presentation in humans. He was involved in studies that led to the genotypic classification strategies and methods now in use worldwide. As of Sept 26th, Dr Gish has joined, part-time, Dr Richard Manch in Phoenix Arizona at St Joseph’s Hospital and Medical Center to help start a liver transplant program at that facility and to help expand their Liver Disease Center to enhance research and education. In April 2014, Dr Gish joined Stanford to assist with the liver program development as a Professor Consultant.

Book Title : Clinical Epidemiology of Chronic Liver Diseases

Editors : Robert J. Wong, Robert G. Gish

DOI : https://doi.org/10.1007/978-3-319-94355-8

Publisher : Springer Cham

eBook Packages : Medicine , Medicine (R0)

Copyright Information : Springer International Publishing AG, part of Springer Nature 2019

Hardcover ISBN : 978-3-319-94354-1 Published: 08 November 2018

Softcover ISBN : 978-3-030-06838-7 Published: 31 January 2019

eBook ISBN : 978-3-319-94355-8 Published: 24 October 2018

Edition Number : 1

Number of Pages : VIII, 349

Number of Illustrations : 7 b/w illustrations, 30 illustrations in colour

Topics : Hepatology , Gastroenterology , Epidemiology , Pharmacoeconomics and Health Outcomes

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Showing result 1 - 5 of 110 swedish dissertations containing the words thesis on chronic liver disease .

1. Susceptibility to chronic liver disease

Author : Maria Antonella Burza ; Göteborgs universitet ; [] Keywords : MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; chronic liver disease ; susceptibility ; human genetics ; NAFLD ; ALD ; PNPLA3 ;

Abstract : The onset and the progression of chronic liver disease involve environmental and genetic factors. Hepatic stellate cells (HSCs) are important players in these processes and are the main storage site for retinol. READ MORE

2. Studies on alcoholic liver disease

Author : Knut Stokkeland ; Karolinska Institutet ; Karolinska Institutet ; [] Keywords : alcohol cirrhosis ; cytochromes ; autoantibodies ; mortality ; morbidity ; prognosis ; epidemiology ; esophageal varices ; lifetime drinking ; lifetime alcohol intake ;

Abstract : The overall aim of this thesis was to explore the impact of alcoholic cirrhosis in Sweden, and the relation between drinking patterns and beverage types and alcoholic cirrhosis, and to evaluate the possible role of autoantibodies in the pathogenesis of alcohol related liver disease. We found that rats had appearance of IgG against rat CYP3A 1 and CYP2E 1 during chronic ethanol feeding We found that patients had reactivity against CYP3A4 and CYP2E I in about 20 to 30% and 10 to 20% of the alcoholic sera. READ MORE

3. Non-Alcoholic Fatty Liver Disease : Aspects on Diagnosis and Long-term Prognosis

Author : Patrik Nasr ; Stergios Kechagias ; Mattias Ekstedt ; Peter Lundberg ; Einar Stefán Björnsson ; Linköpings universitet ; [] Keywords : MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ;

Abstract : Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease affecting approximately 25% of the global population and is commonly recognized as the hepatic manifestation of the metabolic syndrome. The histological spectrum of NAFLD ranges from isolated steatosis to non-alcoholic steatohepatitis (NASH), with risk of developing fibrosis and subsequent cirrhosis and hepatocellular carcinoma. READ MORE

4. Serologic Markers in Screening for Coeliac Disease, Clinical significance and immunogenetic basis

Author : Klas Sjöberg ; Gastroenterologi ; [] Keywords : MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; Gastro-enterology ; transglutaminase ; specificity ; sensitivity ; prevalence ; HLA ; liver disease ; endomysial antibodies ; gliadin antibodies ; diabetes ; Autoimmune disease ; coeliac disease ; Gastroenterologi ;

Abstract : The prevalence of coeliac disease (CD) was initially estimated to 1/1537. Based on serial analysis [GA and endomysial antibodies (EMA)], the prevalence was 6/1970 (0.30%). In autoimmune chronic hepatitis 5. READ MORE

5. Liver-related complications and metabolic comorbidities during long-term follow-up of patients with Non-Alcoholic Fatty Liver Disease

Author : Kristina Önnerhag ; Gastroenterologi ; [] Keywords : MEDICIN OCH HÄLSOVETENSKAP ; MEDICAL AND HEALTH SCIENCES ; Chronic kidney disease CKD ; Epidemiology ; Fibrosis ; Hepatocellular cancer ; Insulin resistance ; Liver cirrhosis ; Metabolic syndrome ; NAFLD ; NASH ; Non-alcoholic fatty liver disease ; non-alcoholic steatohepatitis ;

Abstract : Background: Non-alcoholic fatty liver disease (NAFLD) is highly associated with the metabolic syndrome, and due to increasing prevalence of for example obesity it is now the most common liver disease in the world. A minority progress to advanced fibrosis/cirrhosis, which is associated with increased mortality, but it is not entirely clear which patients who have an increased risk of fibrosis. READ MORE

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• Review Article
• Published: 29 August 2018

The changing epidemiology of liver diseases in the Asia–Pacific region

• Martin C. S. Wong 1 , 2 , 3 , 4 ,
• Jason L. W. Huang 3 ,
• Jacob George 5 ,
• Junjie Huang 3 ,
• Colette Leung 3 ,
• Mohammed Eslam 5 ,
• Henry L. Y. Chan 1 , 2 , 4 &
• Siew C. Ng 1 , 2 , 4  

Nature Reviews Gastroenterology & Hepatology volume  16 ,  pages 57–73 ( 2019 ) Cite this article

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• Epidemiology
• Liver diseases
• Risk factors

This Review presents current epidemiological trends of the most common liver diseases in Asia–Pacific countries. Hepatitis B virus (HBV) remains the primary cause of cirrhosis; despite declining prevalence in most Asian nations, this virus still poses a severe threat in some territories and regions. Mortality resulting from HBV infection is declining as a result of preventive measures and antiviral treatments. The epidemiological transition of hepatitis C virus (HCV) infection has varied in the region in the past few decades, but the medical burden of infection and the prevalence of its related cancers are increasing. The lack of licensed HCV vaccines highlights the need for novel treatment strategies. The prevalence of nonalcoholic fatty liver disease (NAFLD) has risen in the past decade, mostly owing to increasingly urbanized lifestyles and dietary changes. Alternative herbal medicine and dietary supplements are major causes of drug-induced liver injury (DILI) in some countries. Complications arising from these chronic liver diseases, including cirrhosis and liver cancer, are therefore emerging threats in the Asia–Pacific region. Key strategies to control these liver diseases include monitoring of at-risk populations, implementation of national guidelines and increasing public and physician awareness, in concert with improving access to health care.

In the Asia–Pacific region, HBV, HCV, excessive alcohol consumption, the metabolic syndrome and concomitant liver diseases are the major factors resulting in chronic liver injury and end-stage liver pathology.

The expanding implementation of HBV vaccination has been effective in reducing the incidence of liver cancer, especially in countries like China.

Further effort is required to tackle the rising prevalence of HCV infection, for which a vaccine is not available.

Nonalcoholic fatty liver disease (NAFLD) prevalence is increasing owing to increasingly urbanized lifestyles and dietary changes; as a result, the rising trend of NAFLD is becoming comparable to that of Western countries.

As NAFLD is associated with the development of cardiovascular and kidney diseases, patients with this disease should receive tailor-made advice and continuous support for lifestyle modification.

Liver cancer is prevalent, particularly in China, Vietnam, North Korea and Thailand.

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Acknowledgements

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Government statistics and literature published since 2000 were searched. Data regarding these diseases were comprehensively reviewed. The authors also retrieved data from international studies such as Global Burden of Disease 2015 and GLOBOCAN 2012 . This Review does not cover the Asia–Pacific or Western–Pacific regions as defined by the WHO or by any other body. It covers only those countries specifically mentioned in the text and the tables.

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Wong, M.C.S., Huang, J.L.W., George, J. et al. The changing epidemiology of liver diseases in the Asia–Pacific region. Nat Rev Gastroenterol Hepatol 16 , 57–73 (2019). https://doi.org/10.1038/s41575-018-0055-0

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Global research trends in the field of liver cirrhosis from 2011 to 2020: A visualised and bibliometric study

Pei-ling gan.

Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China

Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China

Department of Gastroenterology, The People’s Hospital of Lianshui, Huaian 223400, Jiangsu Province, China

Hui-Fang Xia

Xin-yi zeng, wen-sen ren, xiao-wei tang.

Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China. moc.liamtoh@4385edutilos

Corresponding author: Xiao-Wei Tang, MD, PhD, Doctor, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang Region, Luzhou 646099, China. moc.liamtoh@4385edutilos

Liver cirrhosis is the leading cause of liver-related mortality worldwide. It is currently a global health challenge.

This research intended to explore and analyse research trends and frontiers in this field during the last 10 years, providing new inspiration for clinical decision-making and scientific research.

Publications on hepatic cirrhosis research were retrieved from the Web of Science Core Collection on April 4, 2021. Bibliometric visualisation was conducted through VOSviewer and CiteSpace.

The analytic research was based on original articles and reviews. A total of 7775 records of hepatic cirrhosis published from 2011 to 2020 were retrieved. In the past ten years, the number of related annual publications has increased significantly, especially in the United States and China. All publications were distributed among 109 countries. The United States contributed the most (21.95%) and was consistently the leading driving force, with a solid academic reputation in this area. The University of Barcelona distributed the most related articles (177 articles) and was cited the most frequently. The Journal of Hepatology ranked third in the top 10 journals, which has the highest impact factor (impact factor 2019 = 20.582). Jasmohan S. Bajaj was the most productive author (72 articles). Burst keywords ( e.g. , sofosbuvir, burden, care, sarcopenia, chronic liver failure, human gut microbiome, and nonalcoholic fatty liver disease) and a succession of reference citation bursts have provided clues about research frontiers in recent years.

This study identified developing trends in the evolution of liver cirrhosis to provide new inspiration for researchers.

Core Tip: This research explored and analyzed research trends and frontiers in this field during the last 10 years, further providing new inspiration for scientific research. We found sarcopenia, human gut microbiome, and nonalcoholic fatty liver disease are of particular interest in studies of cirrhosis. Treatment of diseases that cause cirrhosis, such as hepatitis C, is also a hot topic.

INTRODUCTION

Liver cirrhosis is a common clinical chronic progressive disease with high mortality caused by one or more factors. It is the fifth leading cause of adult deaths, the top cause of liver-related death worldwide[ 1 ], and the eighth of the primary diseases in economic cost[ 2 ]. Cirrhosis is a heterogeneous disease classified into two prognosis stages: compensated cirrhosis and decompensated cirrhosis[ 3 ]. In the early stage, due to the essential liver compensatory function, there are no visible symptoms. Later, the primary symptoms are liver function impairment and portal hypertension, and multiple systems are affected. Ascites, upper gastrointestinal haemorrhage, secondary infection, hepatic encephalopathy, canceration, and other complications are common in the late stage. Thus, cirrhosis is a high-burden treatment option for patients, health care systems, and the government.

Bibliometric research is a quantitative analytic method that employs mathematics and statistics to determine scientific activity[ 4 ]. It can help researchers identify the research focus and trends of a particular subject. In addition, the research results may be beneficial to future research.

Professor Chen (Drexel University) created CiteSpace V, a Java-based information visualisation program for bibliometric analysis. Researchers may assess a discipline's evolution and identify frontier trends intuitively by providing numerous data in the form of knowledge maps[ 5 ]. CiteSpace has recently been used for bibliometric analysis in various fields; however, there is yet to be a bibliometric analysis of cirrhosis. In this study, we first used CiteSpace V to analyse articles on liver cirrhosis from 2011 to 2020 utilizing the Web of Science Core Collection (WoSCC) database, providing new inspiration for clinical decision-making and scientific research.

MATERIALS AND METHODS

Data collection and search strategy.

Data were retrieved from the WoSCC on a single day, April 4, 2021. WoSCC offers extensive citation index information for over 8000 influential and famous journals globally. It is a comprehensive database, notably in natural science and medicine. The following were included in the search strategy: title = “cirrhosis,” database selected = Web of Science Core Collection, time span = 2011–2020. Only original articles and reviews were included. We obtained 7775 records for this study. A flowchart representing the retrieval strategies is shown in Supplementary Figure 1 . In addition, high-quality references were retrieved and cited by the Reference Citation Analysis ( https://www.referencecitationanalysis.com/ ) database.

Analysis tool

For bibliometric analysis, Microsoft Excel 2016, VOSviewer, and CiteSpace were chosen. Information on authors, journals, institutions, and countries may be integrated with these computer systems. Parameters such as article count, impact factor (IF), centrality, and occurrence/citation burst were utilized in this article. Productivity was measured by the number of articles published and was used to identify productive individuals or groups. The IF was obtained using Journal Citation Reports (JCR). The IF is a recognized metric for assessing a journal's impact worldwide. The IF in this study was based on JCR (2019). The network visualisation maps were constructed using VOSviewer to examine the cooperative relationships between countries and institutions with highly cocited references. Coauthorship analysis identifies research output. We selected “countries” and “organizations” as the unit of analysis. CiteSpace V adopts a time slicing technique to create a timeline of network models and integrates these individual networks to produce an overview network for the systematic analysis of the relevant publications. In this study, we utilized CiteSpace V to conduct a cocitation analysis of the references and clusters. After that, a timeline view of cocited references was built. As a result, we were able to clarify the origin and period of certain clustering fields[ 6 ]. These parameters help identify potential collaborative relationships in the field of liver cirrhosis. Furthermore, an occurrence burst denotes a word that appears often over a specific period, whereas a citation burst denotes a reference that is referenced frequently during a specific period[ 7 ]. Keywords and references with the highest citation bursts were selected to demonstrate research hot spots and frontiers because they can identify whether relevant scholars have paid extensive attention to these areas in a specific period[ 5 ].

Publication output and temporal trend

A total of 7775 publications satisfied the search criteria. Table ​ Table1 1 lists the top-10 cited articles in descending order based on the number of citations. Figure ​ Figure1A 1A depicts the global distribution of yearly publications on cirrhosis research from 2011 to 2020. The overall worldwide publishing trend rose from 520 to 955 between 2011 and 2020. However, during the periods of 2015-2017 and 2019-2020, the number of publications showed a modest decrease. The annual publication trends of the top 10 academic output countries are presented in Figure ​ Figure1B. 1B . The number of publications on cirrhosis published by the United States and China has increased remarkably within the last decade.

Trends in the number of publications and analysis of countries in the field of cirrhosis. A: The annual worldwide publication output; B: The annual publication output for the top 10 countries.

The top 10 cited articles of Web of Science Core Collection bibliometrics in cirrhosis research field

WoSCC: Web of Science Core Collection.

Distribution by country and institution

All of the publications come from 109 countries and 6902 institutions. The distribution of countries/regions that published no fewer than 100 papers is shown in Supplementary Figure 2 . Table ​ Table2 2 contains detailed information on the top 10 countries. The United States had the most publications (1707 publications), followed by China (1672 publications) and Japan (711 publications). Among the top 10 countries, France exhibits high academic quality, and its citation/article ratio (46.67) was far greater than that of other listed countries.

The top 10 countries that published articles on cirrhosis research

Using VOSviewer, we constructed a network visualisation map for liver cirrhosis research publications to assess international collaborations. Collaborations between countries and institutions are depicted in Supplementary Figure 3 . Nodes with higher co-occurrence were classified as the same colour. Nodes with similar colours formed one cluster, indicating that they had closer cooperative relationships. The width of the lines describes the magnitude of the collaboration. As shown, the United States had the highest total link strength, suggesting that it cooperated most with other countries worldwide. The country that collaborated the most with the United States was China. The most productive institutions are listed in Table ​ Table3. 3 . The University of Barcelona (177 publications) ranked first, followed by Virginia Commonwealth University (120 publications) and University College London (119 publications). The cluster coloured in green was led by the University of Barcelona, collaborating most with Virginia Commonwealth University. Furthermore, three of the top 10 institutions are in the United States, two are in China, and two are in Italy, suggesting that these three countries have many outstanding research groups in this field.

The top 10 institutions that published articles on cirrhosis research

Distribution by journals and authors

Liver cirrhosis research articles were published in 1511 journals. The number of articles in the top 10 journals ranged from 119 to 259, accounting for 22.73% of the total (1767) ( Supplementary Table 1 ). Among these journals, Liver International contributed the highest number of publications on cirrhosis research (259 publications, IF 2019 = 5.175), followed by Hepatology (242 publications, IF 2019 = 14.679) and Journal of Hepatology (212 publications, IF 2019 = 20.582). Journal of Hepatology had the highest IF, and its citation/article ratio (68.30) was far more than that of other listed journals. The most frequently cited journal was Hepatology (14922 citations). The following most frequently cited journals were Journal of Hepatology (14479 citations) and Liver International (5721 citations).

A total of 35653 authors contributed to the overall output. The most productive authors are listed in Supplementary Table 2 . Jasmohan S. Bajaj published 72 articles, ranking first in the number of publications, followed by M. Eric Gershwin (70 articles) and Qi Xingshun (61 articles). Pere Gines had the highest citation/article ratio (89.27), followed by Paolo Angeli (74.07) and Guadalupe Garcia-Tsao (69.13).

Analysis of keywords

Figure ​ Figure2 2 shows the top 25 keywords with the strongest occurrence burst. The occurrence burst, which demonstrated a sharp rise over a certain period, referred to frontier disciplines and dynamic changes in a particular field. Hot topics were represented by keywords whose occurrence burst lasted until 2020. The most recent burst keywords were “sofosbuvir” (2016–2020), “burden” (2017–2020), “care” (2017–2020), “sarcopenia” (2018–2020), “chronic liver failure” (2018–2019), “human gut microbiome” (2018–2020), “nonalcoholic fatty liver disease (NAFLD)” (2018–2020), “American association” (2018–2020), and “ma” (2018–2020).

Keywords with the strongest occurrence burst on cirrhosis research.

Analysis of references

In bibliometric research, reference analysis is an important indication. The pieces of literature with the strongest citation burst are considered to be the knowledge fundamentals of the research frontiers. Clusters along horizontal timelines are depicted in Figure ​ Figure3, 3 , which is a timeline visualisation in CiteSpace. From left to right, each cluster is presented. The publication time legend is displayed at the top. The clusters were arranged vertically and in declining order of size. The largest cluster is presented at the top. Cocitation linkages are shown by the stained curves. Large-sized nodes were especially concerning since they were highly cited. The most cited references in a given year are displayed under each timeline. Clusters were numbered from 0. Cluster #0 was the largest cluster. As shown in the timeline overview, the largest cluster in this study was #0 acute kidney injury, indicating a significant research interest and direction in recent years. This was followed by #1 hepatitis C, #2 clonal selection theory, #3 hepatic encephalopathy, #4 Liver cirrhosis, and #5 variceal bleeding. Some clusters remained active until 2020. Figure ​ Figure4 4 depicts cirrhosis-related references with the strongest citation burst during the last 10 years. Citation bursts until the end of 2020 were led by de Franchis et al (2015), who had the strongest burst (40.22), followed by Garcia-Tsao et al (2017), Tsochatzis et al (2014), Vilstrup et al (2014), Mokdad et al (2014), Albillos et al (2014), Jalan et al (2014), and Heimbach et al (2018).

A timeline visualization of the largest clusters.

References with the strongest citation burst on cirrhosis research.

Liver cirrhosis is a chronic disease with high mortality and is a serious public health problem, afflicting more than 160 million people globally in 2017[ 8 ]. The most common cause is chronic viral hepatitis, specifically hepatitis B virus (HBV) and hepatitis C virus (HCV)[ 3 , 9 ]. Previous studies have shown that the prevalence of liver cirrhosis varies by region. East Asia has the most significant prevalence of liver cirrhosis. In contrast, Southern Latin America has the lowest incidence of 12.1%[ 9 ]. Furthermore, the worldwide incidence of liver cirrhosis is increasing continuously, and it ranks eighth in terms of economic cost among significant diseases[ 2 ], even though various public health measures have been implemented. As a result, to better comprehend the advanced research hotspots in the field of cirrhosis, a study is necessary.

From the retrieved data, we can easily conclude that the general research trend of liver cirrhosis has been growing, especially in China and the United States. Eight of the top 10 countries that most produce related research were developed countries, while 2 were developing countries. The United States had the most publications, followed by China and Japan, and India ranked last. In 2017, among individuals with prevalent liver cirrhosis worldwide, HBV infection accounted for approximately 28.72%. East Asia has the highest prevalence of liver cirrhosis. China had the world's greatest number of patients. Therefore, China and India rank among the top 10 countries in terms of the occurrence of liver cirrhosis and may be relevant for these potential causes. However, in terms of citations per article, although China temporarily ranked in the top position in number of articles, it still has a long way to go to improve the overall quality of articles. China must continue to increase research in this area and strengthen collaborations with other countries. In contrast, although only a few French articles were published, they were of high academic quality.

Nine of the top 10 institutions were universities, suggesting that universities are the most common research groups. Three of the top 10 institutions were from the United States (Virginia Commonwealth University, Mayo Clinic, and University of California, Davis); thus, the United States is the main domain in the field. Two of the top 10 institutions were from China (Capital Medical University and Zhejiang University), and two institutions were from Italy (the University of Padua and University of Milan). According to the findings of this analysis, the three countries have numerous great research groups in this area.

In this study, we found some great research works from some excellent authors. They made significant contributions to this discipline. For example, Guadalupe Garcia-Tsao ranked 7 th among the top 10 authors, and her practice guideline of portal hypertensive bleeding in cirrhosis also ranked among the top 10[ 10 ]. Her study effort provides academic researchers and clinical professionals with a better and deeper understanding of risk stratification, diagnosis, and management of portal hypertensive bleeding in liver cirrhosis. Moreau et al [ 11 ] analysed data from patients with cirrhosis and acute decompensation (AD) to establish diagnostic criteria for acute-on-chronic liver failure (ACLF), which he discovered was distinct from AD. In addition, his research demonstrated that ACLF mortality is linked to loss of organ function and high leukocyte counts and that ACLF is particularly severe in individuals with no prior history of AD.

CiteSpace V was used to detect keyword bursts in this study. These statistics are potentially valuable in forecasting research frontiers. The keywords “sofosbuvir,” “burden,” “care,” “sarcopenia,” “chronic liver failure,” “human gut microbiome,” and the “NAFLD” are expected to appear often in the following years, indicating emerging trends. The top five cirrhosis frontiers are as follows: (1) Sarcopenia: The skeletal muscle is the body's largest organ, and atrophy comes from a change in the balance of protein production and degradation towards protein breakdown. Primary sarcopenia is a loss of skeletal muscle strength, mass, or physical function owing to ageing, whereas secondary sarcopenia is recognized as a loss of skeletal muscle strength, mass, or physical function due to underlying disorders. Liver cirrhosis is one of the representational disorders that might be complicated with secondary sarcopenia. In patients with cirrhosis, muscle mass loss worsens as their liver reserve deteriorates. Sarcopenia and frailty have a negative impact on clinical outcomes and prognosis. It has been convincingly demonstrated that patients with cirrhosis, sarcopenia, and frailty have a lower quality of life and survival, more cirrhotic complications and infections, and poorer outcomes following liver transplant surgery[ 12 - 14 ]. As a result, emphasis must be placed on early detection, active diagnosis, and treatment. Consequently, further investigations in the context of assessment criteria for sarcopenia and frailty are warranted to deepen our current knowledge of sarcopenia and frailty in patients with cirrhosis; (2) Chronic liver failure: ACLF, a clinical syndrome in patients with chronic liver disease, is more often discussed clinically. It is associated with multiple organ failure and increased short-term mortality. It is a significant cause of mortality in people with cirrhosis. Although the precise causative mechanism is unknown, systemic inflammation plays a critical role in its pathogenesis, and the strength of this inflammatory response paralleled the severity of ACLF. Aside from organ failure and a very high risk of short-term death, patients with ACLF exhibited other characteristics that separated them from non-ACLF patients. They were, for example, younger, had more alcoholic cirrhosis and less HCV-related cirrhosis, and mainly had a higher frequency of active alcoholism and severe bacterial infections[ 11 ]. More research for new findings into the mechanisms underlying ACLF, risk prediction models, therapeutic targets, and liver transplantation for ACLF is needed; (3) Sofosbuvir: An oral nucleotide analogue inhibitor of the HCV-specific NS5B polymerase has been approved to treat chronic HCV infection. A study showed that ledipasvir-sofosbuvir for eight weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis[ 15 ]. A recent article published in The Lancet Gastroenterology & Hepatology stated that ravidasvir plus sofosbuvir was effective in patients with chronic HCV infection. Furthermore, by offering a new affordable, simple, and efficacious public health tool for large-scale implementation, this treatment has the potential to eradicate HCV-related morbidity and mortality[ 16 ]; (4) Human gut microbiome: The function of gut microbiota in human health and disease has recently received much attention. Several chronic illnesses have been linked to the gut microbiota, such as obesity[ 17 - 19 ], inflammatory bowel disease[ 20 ], diabetes mellitus[ 21 ], and NAFLD[ 22 ]. Through the hepatic portal and bile secretion systems, the liver interacts directly with the gut. Enteric dysbiosis, namely, the translocation of bacteria and their products over the gut epithelial barrier, is involved in the development of liver cirrhosis. However, the phylogenetic and functional composition alterations in the human gut microbiota associated with this progression remain obscure[ 23 ]. Furthermore, research suggests that microbiome manipulation to eliminate manganese and reduce GABA levels in the gut might provide a novel therapeutic approach for treating hepatic encephalopathy[ 24 ]. In addition, novel probiotics may be helpful in the prevention of the aggravation of liver cirrhosis. More broadly, microbiome manipulation may offer up new pathways for the treatment of liver cirrhosis. A combination of microbial genes distinguishes patients with liver cirrhosis from healthy individuals with high specificity. This might pave the way for a novel method of monitoring and preventing liver cirrhosis; and (5) NAFLD: NAFLD is a progressive liver disease spectrum encompassing simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and, eventually, cirrhosis. NAFLD is closely associated with characteristics of metabolic syndrome such as abdominal obesity, insulin resistance, glucose intolerance or type 2 diabetes (T2DM), and atherogenic dyslipidaemia[ 25 ]. Over the last few decades, people's lifestyles have become more sedentary, and dietary habits have changed, leading to an increase in the prevalence of obesity and insulin resistance[ 26 , 27 ]. In light of this, NAFLD quickly became the most common cause of abnormal liver biochemistry in both developed and developing countries. Several prior epidemiological studies have identified a strong association between NAFLD and an elevated risk of developing T2DM. In addition, patients with NAFLD, whether adults or adolescents, have several risk factors for cardiovascular disease. A notable minority proportion of NAFLD patients proceed to a more severe disease characterized by NASH and fibrosis and cirrhosis or, in some circumstances, progress to hepatocellular carcinoma[ 28 ]. The mechanisms linking NAFLD to the diseases mentioned above and the current pharmacological treatments for NAFLD need to be further explored.

The articles with the strongest citation burst are potentially valuable for exploring research frontiers. In this study, #0 acute kidney injury was the largest cluster, and #3 hepatic encephalopathy remained active until the most recent publication year for a cited reference. References with the top three citation bursts were as follows: (1) de Franchis et al [ 29 ] contributed to the writing of expanding consensus in portal hypertension, further elaborating the stratifying risk and individualizing care for portal hypertension; (2) Garcia-Tsao et al [ 10 ] coauthored a practice guideline and elaborated the risk stratification, diagnosis, and management of portal hypertensive bleeding in cirrhosis; and (3) Tsochatzis et al [ 30 ] reviewed the current understanding of cirrhosis as a dynamic process and outlined therapeutic options for preventing and treating complications of cirrhosis based on the subclassification in clinical stages. Meanwhile, we proposed a new concept for managing patients with cirrhosis and the challenge in the 21 st century.

Limitations

To the best of our knowledge, this study was the first bibliometric analysis of cirrhosis in the past ten years. This study, however, has certain limitations. First, we considered the WoSCC database a reputable and reliable service for publications and citations; hence, we extracted data only from it. This may restrict the coverage of all available articles and result in a reduced number of documents included in the analysis. Second, the search method may also have been insufficient because we only searched for publications with the phrase "cirrhosis," which may have resulted in a paucity of papers due to other terminology. Finally, we analysed the data selectively. We mainly utilized a quantitative analysis approach, while little emphasis has been paid to the qualitative aspects of this study. As a result, certain critical points and details may have been missed. All of the considerations mentioned above may lead to bias in the results. Hence, the results should be interpreted with caution.

This study might aid researchers in identifying new trends in cirrhosis from 2011 to 2020, thus, providing new inspiration for scientific research.

ARTICLE HIGHLIGHTS

Research background.

Liver cirrhosis is a common clinical chronic progressive disease with high mortality caused by one or more factors.

Research motivation

Identifying new trends in cirrhosis from 2011 to 2020, thus, providing new inspiration for scientific research.

Research objectives

This research intended to explore and analyse research trends and frontiers in this field of cirrhosis during the last 10 years.

Research methods

Using VOSviewer and CiteSpace, assess a discipline's evolution and identify frontier trends intuitively by knowledge maps.

Research results

The general research trend of liver cirrhosis has been growing, especially in China and the United States. The keywords “sofosbuvir,” “burden,” “care,” “sarcopenia,” “chronic liver failure,” “human gut microbiome,” and the “NAFLD” are expected to appear often in the following years, indicating emerging trends. The top five cirrhosis frontiers are Sarcopenia, Chronic liver failure, Sofosbuvir, Human gut microbiome and Nonalcoholic fatty liver disease.

Research conclusions

Research perspectives.

The top five cirrhosis frontiers are sarcopenia, chronic liver failure, sofosbuvir, human gut microbiome and nonalcoholic fatty liver disease.

Conflict-of-interest statement: We declared that no conflicts of interest or financial ties to disclose.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Peer-review started: April 14, 2022

First decision: June 10, 2022

Article in press: August 6, 2022

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: China

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B, B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: El-Shabrawi MH, Egypt; Fernandes SA, Brazil; Silva LD, Brazil S-Editor: Zhang H L-Editor: A P-Editor: Yuan YY

Contributor Information

Pei-Ling Gan, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China. Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China.

Shu Huang, Department of Gastroenterology, The People’s Hospital of Lianshui, Huaian 223400, Jiangsu Province, China.

Xiao Pan, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China. Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China.

Hui-Fang Xia, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China. Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China.

Xin-Yi Zeng, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China. Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China.

Wen-Sen Ren, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China. Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China.

Xian Zhou, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China. Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China.

Mu-Han Lv, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China. Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China.

Xiao-Wei Tang, Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China. Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China. moc.liamtoh@4385edutilos .

• Frontiers in Nutrition
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Nutritional Approaches in Chronic Liver Diseases

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There is exponential growth of new cases of chronic liver disease worldwide. Even with the advances related to the treatment of viral hepatitis, this epidemiological scenario can be explained with a significant increase in obesity, alcoholism and physical inactivity. Nutrition plays a fundamental role as a ...

Keywords : liver disease, cirrhosis, nutritional assessment, microbiota, sarcopenia, chronic liver disease, clinical nutrition, body composition, fatty liver disease, fatty liver, hepatocellular carcinoma, liver cirrhosis

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Dissertations / Theses on the topic 'Alcohol related liver disease'

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Campbell, Stewart. "Metabolic interactions between alcohol, the liver and the gastrointestinal tract." Thesis, University of Glasgow, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248184.

Niemelä, Onni. "Aminoterminal propeptide of type III procollagen and basement related antigens in alcoholic liver disease." Oulu : University of Oulu, 1985. http://catalog.hathitrust.org/api/volumes/oclc/14472875.html.

Krasnoff, Joanne B. "Health-related fitness, physical activity, and non-alcoholic fatty liver disease." [Bloomington, Ind.] : Indiana University, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3274261.

Bolden, Lois Vennesta. "Depression, anxiety, hazardous drinking, subjective burden, and rewards in family caregivers of patients with chronic liver disease." View the abstract Download the full-text PDF version (on campus access only), 2006. http://etd.utmem.edu/ABSTRACTS/2006_009_bolden_index.html.

Fleming, Christina Katelyn, and Jonathan M. Peterson. "Ethanol Feeding Reduces Circulating CTRP3 Levels." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/128.

Pathak, Preeti. "Retinoic acid related orphan nuclear receptor a (RORa) regulates diurnal rhythm and fasting induction of sterol 12a-hydroxylase (CYP8B1) in bile acid synthesis." Kent State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1375097774.

Blaszczak, Alecia Marie. "Defining the Inflammatory Microenvironment of Human Adipose Tissue in Obesity and How It Contributes to the Development of Obesity-Related Comorbidities." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1553601004244596.

Dinsmore, W. W. "Studies on alcohol and liver disease." Thesis, University of Aberdeen, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356812.

Sliz, E. (Eeva). "Genetics and molecular epidemiology of metabolic syndrome-related traits:focus on metabolic profiling of lipid-lowering therapies and fatty liver, and the role of genetic factors in inflammatory load." Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526222554.

Stokkeland, Knut. "Studies on alcoholic liver disease /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-853-3/.

Fang, Che. "Cytokines, alcohol metabolizing enzymes and stress-inducible ER proteins in alcoholic liver disease /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4160-2/.

Nguyen, Van Thi Thuy Public Health &amp Community Medicine Faculty of Medicine UNSW. "Hepatitis B-related liver disease burden in Vietnam and Australia." Publisher:University of New South Wales. Public Health & Community Medicine, 2008. http://handle.unsw.edu.au/1959.4/42118.

Barnes, Mark Aaron Jr. "MACROPHAGE MIGRATION INHIBITORY FACTOR AND LIVER DISEASE: THE ROLE OF MIF IN ALCOHOL-INDUCED LIVER INJURY AND CARBON TETRACHLORIDE (CCI4)-INDUCED LIVER FIBROSIS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1396429556.

Ghazali, Reem. "Mechanisms into the development of fatty liver disease : role of free fatty acids and alcohol." Thesis, University of Westminster, 2017. https://westminsterresearch.westminster.ac.uk/item/q5vv0/mechanisms-into-the-development-of-fatty-liver-disease-role-of-free-fatty-acids-and-alcohol.

Viitala, K. (Katja). "Carbohydrate-deficient transferrin (CDT) and serum antibodies against acetaldehyde adducts as markers of alcohol abuse." Doctoral thesis, University of Oulu, 1998. http://urn.fi/urn:isbn:9514251075.

Frith, James. "Falls and fall related injury in older people with chronic liver disease." Thesis, University of Newcastle Upon Tyne, 2011. http://hdl.handle.net/10443/1157.

DeGroat, Ashley. "The Effect of Alcohol Consumption on Adipokine Secretion." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etd/3425.

Lee, Matthew L., and Jonathan M. Peterson. "CTRP3 Protects Liver Cells From Alcohol-Induced Damage, But Not Through Enhanced Akt Signaling Type." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/70.

Öström, Mats. "Vehicle-related injuries : with emphasis on fatality prevention." Doctoral thesis, Umeå universitet, Rättsmedicin, 1993. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-101291.

Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 7 uppsatser.

Lee, Matthew L., and Jonathan M. Peterson. "Ethanol Disrupts Metabolic Signaling in Liver Cells." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/69.

Bartling, Brandon Alan. "Development of a Thick-Film Printed Ir/C Biosensor for the Detection of Liver Disease Related Biomarkers." Cleveland, Ohio : Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1258751380.

Tyas, Suzanne Leigh. "Are tobacco and alcohol use related to Alzheimer's disease?, results from three Canadian data sets." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0027/NQ31091.pdf.

Ryan, Jennifer Marie. "Neutrophil dysfunction in alcoholic hepatitis and alcohol-related cirrhosis : a contributor to immunoparesis and disease state." Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/neutrophil-dysfunction-in-alcoholic-hepatitis-and-alcoholrelated-cirrhosis(a7577731-209d-44f9-a48e-c30ce8172af9).html.

Marshall, Jonathan Charles Walter. "The interdisciplinary relationship between alcohol consumption and liver disease on the prevalence and disease manifestations of Helicobacter pylori : a clinical, histological and in vitro study." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402117.

Kriss, Crystina Leah. "Investigation of Alcohol-Induced Changes in Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics." Scholar Commons, 2018. http://scholarcommons.usf.edu/etd/7185.

Delacôte, Claire. "Vers une meilleure compréhension de la maladie du foie liée à l'alcool et des facteurs influençant sa progression : approche de modélisation." Thesis, Lille 2, 2020. http://www.theses.fr/2020LIL2S029.

Lanquetin, Anastasia. "Étude translationnelle des interactions cerveau-foie dans les troubles de l'usage de l'alcool Role of inflammation in alcohol-related brain abnormalities: a translational study." Thesis, Normandie, 2020. http://www.theses.fr/2020NORMC407.

Spree, Eckhard. "Lebertransplantation bei äthyltoxischer Lebererkrankung." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2000. http://dx.doi.org/10.18452/14544.

Williams, Simon Graham John. "Cystic fibrosis related chronic liver disease : a study of its influence upon prognosis and possible mechanisms for this; with specific reference to pulmonary and systemic haemodynamics." Thesis, Queen Mary, University of London, 1995. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1796.

Mucci, Samantha [UNIFESP]. "Questionário para Avaliação de Qualidade de Vida em Portadores de Doença Hepática Crônica: Tradução e Validação do CLDQ – Chronic Liver Disease Questionnaire." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/10002.

Youssef, Naglaa F. A. "Health-related quality of life, symptoms experience and perceived social support among patients with liver cirrhosis : a cross-sectional study in Egypt." Thesis, University of Stirling, 2013. http://hdl.handle.net/1893/15990.

Ciocan, Dragoş Marius. "Le microbiote intestinal comme cible thérapeutique dans la maladie alcoolique du foie : implication des acides biliaires et de la pectine." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS553.

Li, Ying, Tammy Ozment, Gary L. Wright, and Jonathan M. Peterson. "Identification of Putative Receptors for the Novel Adipokine CTRP3 Using Ligand-Receptor Capture Technology." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/67.

Herman, Grace E. "A comparison of post-transplantation mortality of liver recipients with and without alcohol use disorder." Thesis, 2019. https://hdl.handle.net/2144/38670.

Teng-Chi, Yang, and 楊登琦. "A Study on Alcohol Drinking Related Liver Diseases and Gout in HuaLien Aborigines." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/66423805009012794834.

Lin, Wei-Hsiang, and 林煒翔. "To establish the animal models for alcohol liver disease and nanoparticles-induced lung injuries in rat/mice and related researches." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/48796166470854999412.

Gonçalves, Inês. "The role of exercise on non-alcoholic fatty liver disease (NAFLD) systemic and mitochondrial-related mechanisms." Tese, 2013. http://hdl.handle.net/10216/76792.

Gonçalves, Inês Oliveira. "The role of exercise on non-alcoholic fatty liver disease (NAFLD) systemic and mitochondrial-related mechanisms." Tese, 2013. https://repositorio-aberto.up.pt/handle/10216/91531.

Gonçalves, Inês Oliveira. "The role of exercise on non-alcoholic fatty liver disease (NAFLD) systemic and mitochondrial-related mechanisms." Doctoral thesis, 2014. https://repositorio-aberto.up.pt/handle/10216/91531.

Pan, Hsiang-Ju, and 潘湘如. "Tamoxifen Related Non-alcoholic Fatty Liver disease: How Much the Impact and Has any Risk Factors Exist?" Thesis, 2014. http://ndltd.ncl.edu.tw/handle/31980651294680806391.

Long, Michelle. "Association between alcohol use behavior and liver fat in the Framingham Heart Study." Thesis, 2019. https://hdl.handle.net/2144/36033.

Hsu, Chi-Jen, and 許智仁. "Prospective Analysis of Small Metabolites and Obesity-Related Liver Disease in Hepatitis B." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/36625923099514155516.

Wu, Ting Jung, and 吳庭榕. "Liver Transplantation in Patients with Hepatitis B Related End-Stage Liver Disease: the Influence of Viral Characteristics on Clinical Outcome." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/17099353820709983334.

Chen, Chien-Hung, and 陳建宏. "Pre-S Deletion and Complex Mutations of Hepatitis B Virus Related to Advanced Liver Disease." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/22xu2u.

Menezes, Colin Nigel. "The role of increased gastrointestinal alcohol production in patients with the metabolic syndrome: Implications for the pathogenesis of non-alcoholic fatty liver disease." Thesis, 2007. http://hdl.handle.net/10539/2048.

Canha, Maria Inês Silvestre Rêgo. "The lifestyle influence on alcoholic pancreatitis versus alcoholic liver disease: a case-control study." Master's thesis, 2017. http://hdl.handle.net/10316/82091.

Cheng, Yu-Han, and 鄭羽涵. "Machine Learning Application: Classification of Non-Alcohol Fatty Liver Disease and its Risk Factors in Taiwanese High-Tech Industry Workers." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/368467.

Huang, Chung-Feng, and 黃釧峰. "Association of host genetic variants with HCV related natural course, liver disease severity, hepatocarcinogenesis and antiviral treatment efficacy." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/77507791723119983753.

Shen, Yi-Ching, and 沈宜靜. "Incidence and factors related to end stage renal disease on dialysis in Taiwanese type 2 diabetes with liver cirrhosis." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/64030248895781405963.

Chang, Yen-Hsin, and 張言信. "Experimental and Computational Analysis of Disease-related Primate Promoters: Novel Regulatory Motifs in RNase2 and Their Functions in Liver Cells." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/09392821642922150392.