Treatment of Coronary Heart Disease from the Perspective of Liver Controlling Dispersion

The liver is in charge of distributing and regulating the movement of qi throughout the whole body,coordinating the transportation and transformation of the internal organs in the middle part of the body,promoting the biochemical circulation of qi,blood,and body fluids,and regulating emotions.Liver dysfunction can disrupt the transportation and transformation of qi,blood,and body fluids,causing phlegm turbidity,blood stasis,and other unwanted symptoms.Poor regulation of emotion further aggravates the accumulation of pathological substances,resulting in the obstruction of heart vessels,and ultimately coronary heart disease(CHD).Through regulating lipid metabolism,inflammatory reaction,vasoactive substances,platelet function,neuroendocrine,and other factors,liver controlling dispersing qi plays a comprehensive role in the prognosis of atherosclerosis,the primary cause of CHD.Therefore,it is recommended to treat CHD from the perspective of liver-controlling dispersion.

Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions

Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Function of macrophage-derived exosomes in chronic liver disease:From pathogenesis to treatment

Chronic liver disease(CLD)imposes a heavy burden on millions of people worldwide.Despite substantial research on the pathogenesis of CLD disorders,no optimal treatment is currently available for some diseases,such as liver cancer.Exosomes,which are extracellular vesicles,are composed of various cellular components.Exosomes have unique functions in maintaining cellular homeostasis and regulating cell communication,which are associated with the occurrence of disease.Furthermore,they have application potential in diagnosis and treatment by carrying diverse curative payloads.Hepatic macrophages,which are key innate immune cells,show extraordinary heterogeneity and polarization.Hence,macrophage-derived exosomes may play a pivotal role in the initiation and progression of various liver diseases.This review focuses on the effects of macrophage-derived exosomes on liver disease etiology and their therapeutic potential,which will provide new insights into alleviating the global pressure of CLD.

Epidemiology,therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont,Italy

BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide.It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate.HCC patients have increasingly complex and constantly changing characteristics,thus up-to-date and comprehensive data are fundamental.AIM To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019.METHODS In this retrospective study,we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at"Santa Croce e Carle"Hospital in Cuneo(Italy)between 1 January 2010 and 31 December 2019.To highlight possible changes in HCC patterns over the 10-year period,we split the population into two 5-year groups,according to the diagnosis period(2010-2014 and 2015-2019).RESULTS Of the 328 HCC patients who were included(M/F 255/73;mean age 68.9±11.3 years),154 in the first period,and 174 in the second.Hepatitis C virus infection was the most common HCC risk factor(41%,135 patients).The alcoholic etiology rate was 18%,the hepatitis B virus infection etiology was 5%,and the non-viral/non-alcoholic etiology rate was 22%.The Child-Pugh score distribution of the patients was:class A 75%,class B 21%and class C 4%.The average Mayo end-stage liver disease score was 10.6±3.7.A total of 55 patients(17%)were affected by portal vein thrombosis and 158(48%)by portal hypertension.The average nodule size of the HCC was 4.6±3.1 cm.A total of 204 patients(63%)had more than one nodule<3,and 92%(305 patients)had a non-metastatic stage of the disease.The Barcelona Clinic Liver Cancer(BCLC)staging distribution of all patients was:4%very early,32%early,23%intermediate,34%advanced,and 7%terminal.Average survival rate was 1.6±0.3 years.Only 20%of the patients underwent treatment.Age,presence of ascites,BCLC stage and therapy were predictors of a better prognosis(P<0.01).A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology(P<0.05)and alpha-fetoprotein(AFP)levels(P<0.01).CONCLUSION In this study analyzing patients with a new diagnosis of HCC between 2010-2019,hepatitis C virus infection was the most common etiology.Most patients presented with an advanced stage disease and a poor prognosis.When comparing the two 5-year groups,we observed a statistically significant difference only in global etiology(P<0.05)and AFP levels(P<0.01).

Interleukins in liver disease treatment

Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.

Stem cell transplantation for the treatment of end-stage liver disease

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer,liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety,mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.

Global trends and hotspots of treatment for nonalcoholic fatty liver disease:A bibliometric and visualization analysis(2010-2023)

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD.An up-to-date overview on the knowledge structure of NAFLD through bibliometrics,focusing on research hotspots,is necessary to reveal the rational and timely directions of development in this field.AIM To research the latest literature and determine the current trends in treatment for NAFLD.METHODS Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database,from 2010 to 2023.VOSviewers,CiteSpace,and R package“bibliometrix”were used to conduct this bibliometric analysis.The key information was extracted,and the results of the cluster analysis were based on network data for generating and investigating maps for country,institution,journal,and author.Historiography analysis,bursts and cluster analysis,cooccurrence analysis,and trend topic revealed the knowledge structure and research hotspots in this field.GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization.RESULTS In total,10829 articles from 120 countries(led by China and the United States)and 8785 institutions were included.The number of publications related to treatment for NAFLD increased annually.While China produced the most publications,the United States was the most cited country,and the United Kingdom collaborated the most from an international standpoint.The University of California-San Diego,Shanghai Jiao Tong University,and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions.The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals,and Hepatology was the most cited and co-cited journal.Sanyal AJ was the most cited author,the most co-cited author was Younossi ZM,and the most influential author was Loomba R.The most studied topics included the epidemiology and mechanism of NAFLD,the development of accurate diagnosis,the precise management of patients with NAFLD,and the associated metabolic comorbidities.The major cluster topics were“emerging drug,”“glucagon-like peptide-1 receptor agonist,”“metabolic dysfunction-associated fatty liver disease,”“gut microbiota,”and“glucose metabolism.”CONCLUSION The bibliometric study identified recent research frontiers and hot directions,which can provide a valuable reference for scholars researching treatments for NAFLD.

Antioxidant and anti-inflammatory agents in chronic liver diseases:Molecular mechanisms and therapy

Chronic liver disease(CLD)is a continuous process that causes a reduction of liver function lasting more than six months.CLD includes alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD),chronic viral infection,and autoimmune hepatitis,which can lead to liver fibrosis,cirrhosis,and cancer.Liver inflammation and oxidative stress are commonly associated with the development and progression of CLD.Molecular signaling pathways such as AMPactivated protein kinase(AMPK),C-Jun N-terminal kinase,and peroxisome proliferator-activated receptors(PPARs)are implicated in the pathogenesis of CLD.Therefore,antioxidant and anti-inflammatory agents from natural products are new potent therapies for ALD,NAFLD,and hepatocellular carcinoma(HCC).In this review,we summarize some powerful products that can be potential applied in all the stages of CLD,from ALD/NAFLD to HCC.The selected agents such asβ-sitosterol,curcumin,genistein,and silymarin can regulate the activation of several important molecules,including AMPK,Farnesoid X receptor,nuclear factor erythroid 2-related factor-2,PPARs,phosphatidylinositol-3-kinase,and lysyl oxidase-like proteins.In addition,clinical trials are undergoing to evaluate their efficacy and safety.

Management of restless legs syndrome in chronic liver disease:A challenge for the correct diagnosis and therapy

AIM To investigate the association between restless legs syndrome(RLS) and well-defined chronic liver disease, and the possible therapeutic options. METHODS Two hundred and eleven patients with chronic liver disease, complaining of sleep disturbances, painful leg sensation and daily sleepiness, were included. Patients with persistent alcohol intake, recent worsening of clinical conditions, or hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns Hopkins questionnaire and verified by fulfilling the diagnostic criteria by Allen. All patients were tested, both at baseline and during follow-up, with the Hamilton rating scale for depression, sleep quality assessment(PSQI), Epworth sleepiness scale(ESS), International Restless Legs Syndrome Study Group evaluation, and international RLS severity(IRLS) scoring system. Ironfree level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological examinations and blood testoccurred at the beginning of the therapy, after 2 wk, and at the 28^(th), 75 th, 105 th, 135 th, 165 th and 205 th day. Regarding therapy, pramipexole or gabapentin were used.RESULTS Patients were moderately depressed, with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep problems and involuntary leg movements had been underestimated, and RLS s yndrome had not be e n c ons ide re d be fore t he neurological visit. All(211/211) patients fulfilled the RLS diagnostic criteria. Twenty-two patients considered their symptoms as mild, according to IRSL, but 189 found them moderate to very severe. No correlation was found between ammonium level and ESS or PSQI. Augmentation was rather precocious in our patients(135 th day), and more frequent(35%) than previous data(8.3%-9.1%). The dosage of dopamine agonists was found to be associated with augmentation and appears in range with the literature. Previous intake of alcohol and lower levels of vitamins have been related to the phenomenon in our study.CONCLUSION RLS is a common disorder, requiring rapid diagnosis and treatment. Further research is therefore fundamental.

Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer

This review describes woodchucks chronically infected with the woodchuck hepatitis virus(WHV)as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma(HCC)induced by the hepatitis B virus(HBV).Since laboratory animal models susceptible to HBV infection are limited,woodchucks experimentally infected with WHV,a hepatitis virus closely related to HBV,are increasingly used to enhance our understanding of virus-host interactions,immune response,and liver disease progression.A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established,which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans.HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size,morphology,and molecular gene signature to those of HBV-infected patients.Accordingly,woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC.In addition,drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs,alone or in combination with other compounds,minimizes the risk of liver disease progression to HCC.More recently,woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute,self-limited and chronic infections.Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae,including the onset of HCC.Therefore,woodchucks with chronic WHV infection constitute a well-characterized,fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities,which are based on chemo,gene,and immune therapy,for the prevention and treatment of HCC in patients for which current treatment options are dismal.

Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments

BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

The Therapeutic Ways for Chronic Liver Diseases Accompanied by Diseases of the Endocrine and Mammary Glands

It is discovered by the authors of this article thatchronic hepatitis and hepatocirrhosis (hereinafterchronic hepatopathy for short) are often accompaniedby some diseases of endocrine and mammary glands.The authors have studied the pathogenesis andtreatment of the complications as presented in thefollowing.

Application of artificial intelligence in liver diseases: From diagnosis to treatment

Infectious or noninfectious liver disease has inexorably risen as one of the leading causes of global death and disease burden.There were an estimated 2.14 million liver-related deaths in 2017,representing an 11.4%increase since 2012.Traditional diagnosis and treatment methods have various dilemmas in different causes of liver disease.As a hot research topic in recent years,the application of artificial intelligence(AI)in different fields has attracted extensive attention,and new technologies have brought more ideas for the diagnosis and treatment of some liver diseases.Machine learning(ML)is the core of AI and the basic way to make a computer intelligent.ML technology has many potential uses in hepatology,ranging from exploring new noninvasive means to predict or diagnose different liver diseases to automated image analysis.The application of ML in liver diseases can help clinical staff to diagnose and treat different liver diseases quickly,accurately and scientifically,which is of importance for reducing the incidence and mortality of liver diseases,reducing medical errors,and promoting the development of medicine.This paper reviews the application and prospects of AI in liver diseases,and aims to improve clinicians’awareness of the importance of AI in the diagnosis and treatment of liver diseases.

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.

Unsuccessful treatment of four patients with acute graft-vs-host disease after liver transplantation

AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.

Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma:Current knowledge and potential for therapeutics

Metabolic diseases such as nonalcoholic fatty liver disease(NAFLD)are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma(HCC).The gut microbiome is closely connected to the liver via the portal vein,and has recently been identified as a predictor of liver disease state.Studies in NAFLD,cirrhosis and HCC have identified certain microbial signatures associated with these diseases,with the disease-associated microbiome changes collectively referred to as dysbiosis.The pathophysiologic underpinnings of these observations are an area of ongoing investigation,with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability(leaky gut)and activation of the innate immune system.In the innate immune system,pathogen recognition receptors(Toll like receptors)on resident liver cells and macrophages cause liver inflammation,fibrosis,hepatocyte proliferation and reduced antitumor immunity,leading to chronic liver disease and carcinogenesis.Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR(nuclear receptor),which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease.Longitudinal experimental and clinical studies are needed in different populations to examine these questions further.The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet,probiotics,fecal microbiota transplantation and prebiotics in improving liver disease in experimental models.Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis.The microbial profile is different in responders to cancer immunotherapy including liver cancer,but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.

Treatment of nonalcoholic fatty liver disease

不含酒精的脂肝疾病(NAFLD ) 是为在发达国家的提高的肝酶的最普通的原因。在因为超重孩子的增加的数字，具有特别兴趣的预防节目以外，处理应该集中于最重要的风险因素，肥胖和抗胰岛素性。作为阐明的后果 NAFLD 的 pathomechanisms，潜在的治疗学的选择的数字增加了。然而，调查治疗学的效果的许多研究在至少一个下列点显示出缺点：连续的肝活体检视，治疗的短术语和包括的病人的有限数字的缺乏。第二产生胰岛素抗体 pioglitazone 和 rosiglitazone 为注意在 NAFLD，而是重量获得和潜在的 hepatotoxicity 电话显示出最有希望的改进。在结论，为特定的药的应用程序的一个一般建议不能被给。在肥胖的病人改进胰岛素敏感度的而且控制的临床的试用，体重减轻和物理活动应该是优先级目的。

Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the progressive forms of NAFLD,non-alcoholic steatohepatitis and associated advanced liver fibrosis.Moreover,diabetes is an independent risk factor for NAFLD progression,and for hepatocellular carcinoma development and liver-related mortality in prospective studies.Notwithstanding,patients with NAFLD have an elevated prevalence of prediabetes.Recent studies have shown that NAFLD presence predicts the development of type2 diabetes.Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients.The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods,although histopathological evaluation is still considered the gold standard diagnostic method.An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking.We sought to outline the published data including epidemiology,pathogenesis,diagnosis and treatment of NAFLD in diabetic patients,in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases

The outbreak of coronavirus disease 2019(COVID-19)is a global pandemic.Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality.The drugs of higher interest include umifenovir,bromhexine,remdesivir,lopinavir/ritonavir,steroid,tocilizumab,interferon alpha or beta,ribavirin,fivapiravir,nitazoxanide,ivermectin,molnupiravir,hydroxychloroquine/chloroquine alone or in combination with azithromycin,and baricitinib.Gastrointestinal(GI)symptoms and liver dysfunction are frequently seen in patients with COVID-19,which can make it difficult to differentiate disease manifestations from treatment adverse effects.GI symptoms of COVID-19 include anorexia,dyspepsia,nausea,vomiting,diarrhea and abdominal pain.Liver injury can be a result of systemic inflammation or cytokine storm,or due to the adverse drug effects in patients who have been receiving different treatments.Regular monitoring of liver function should be performed.COVID-19 vaccines have been rapidly developed with different technologies including mRNA,viral vectors,inactivated viruses,recombinant DNA,protein subunits and live attenuated viruses.Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks.Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.