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.

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.

Polycystic liver disease: Classification, diagnosis, treatment process, and clinical management

Polycystic liver disease(PLD)is a rare hereditary disease that independently exists in isolated PLD,or as an accompanying symptom of autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease with complicated mechanisms.PLD currently lacks a unified diagnostic standard.The diagnosis of PLD is usually made when the number of hepatic cysts is more than 20.Gigot classification and Schnelldorfer classification are now commonly used to define severity in PLD.Most PLD patients have no clinical symptoms,and minority with severe complications need treatments.Somatostatin analogues,mammalian target of rapamycin inhibitor,ursodeoxycholic acid and vasopressin-2 receptor antagonist are the potentially effective medical therapies,while cyst aspiration and sclerosis,transcatheter arterial embolization,fenestration,hepatic resection and liver transplantation are the options of invasion therapies.However,the effectiveness of these therapies except liver transplantation are still uncertain.Furthermore,there is no unified strategy to treat PLD between medical centers at present.In order to better understand recent study progresses on PLD for clinical practice and obtain potential directions for future researches,this review mainly focuses on the recent progress in PLD classification,clinical manifestation,diagnosis and treatment.For information,we also provided medical treatment processes of PLD in our medical center.

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.

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).

Hepatorenal syndrome: Update on diagnosis and treatment

Acute kidney injury(AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome(HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.

Pyogenic liver abscess in children: Diagnosis and treatment at the teaching hospital Gabriel Touré, Bamako, Mali

Purpose: To determine diagnostic and therapeutic problems of pyogenic liver abscess in our hospital. Method and material: We conducted a retrospective study from January 2006 to December 2010 of all children aged from 0 - 15 years admitted and treated for pyogenic liver abscesses. Amoebic liver abscesses and other hepatobiliary disorders were not considered. Results: Pyogenic abscesses accounted for 50 cases. The mean age of patients at presentation was 2.4 ± 0.78 years (range from 6 months to 15 years). Sex ratio was 2.8 for boys. Abdominal pain was the primary reason for consultation in 27 cases (54%). Fever has been noted in 42 patients (84%) and the patient general state was altered in 13 patients (26%). Escherishia coli was the most frequent bacteria found at pus. The pus was sterile in 25 cases (50%). The ultrasonographic percutaneous drainage was performed in 33 patients (66%), open surgery in 6 (12%) and antibiotics alone in 11 others (22%). The short outcomes were simple in 36 patients (72%) while pain and fever persisted in 12 others (24%). Two patients (4%) died from sepsis soon after the operating room. Improving the frequency of early diagnosis will depend on education of clinicians about the need for clinical suspicion aided by ultrasound.

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.

Role of noncoding RNAs in liver fibrosis

Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection,obesity,or excessive alcohol.It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix.Advanced fibrosis could lead to cirrhosis and even liver cancer,which has become a significant health burden worldwide.Many studies have revealed that noncoding RNAs(ncRNAs),including microRNAs,long noncoding RNAs and circular RNAs,are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-βpathway,phosphatidylinositol 3-kinase/protein kinase B pathway,and Wnt/β-catenin pathway.NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis.NcRNAs mimics,ncRNAs in mesenchymal stem cell-derived exosomes,and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis.In this review,we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis,and discuss the potentials and challenges to use these ncRNAs for diagnosis,staging and treatment of liver fibrosis.All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.

Epidemic of non-alcoholic fatty liver disease and hepatocellular carcinoma

Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.

Clinical assessment and management of liver fibrosis in nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is among the most frequent etiologies of cirrhosis worldwide,and it is associated with features of metabolic syndrome;the key factor influencing its prognosis is the progression of liver fibrosis.This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD,analyzing the currently available literature.In the assessment of NAFLD patients,it is important to identify clinical,genetic,and environmental determinants of fibrosis development and its progression.To properly detect fibrosis,it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores,followed by a complementary imaging study(transient elastography,magnetic resonance elastography or acoustic radiation force impulse)and finally a liver biopsy,when needed.To help with the selection of the most appropriate method a Fagan′s nomogram analysis is provided in this review,describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis.Finally,treatment should always include diet and exercise,as well as controlling the components of the metabolic syndrome,+/-vitamin E,considering the presence of sleep apnea,and when available,allocate those patients with advanced fibrosis or high risk of progression into clinical trials.The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD,aiming to decrease/stop its progression and improve their prognosis.

Graft-verse-host disease after liver transplantation:A report of two cases and review of literature

Graft-verse-host disease (GVHD) is an uncommon fatal complication following liver transplantation (LTx). In China's Mainland, only six cases have been reported with a morbidity rate up to 1%-2%. Definitive diagnosis was achieved by molecular techniques (HLA typing or PCR-STR) in only two cases and the remaining cases were diagnosed based on typical clinical features with exclusion of other possible causes. All patients died of septic shock or multiple organ failure even after administration of increased corticosteroids and supportive therapy, and reduced immunosuppressive agents. In our center, two cases of GVHD were found among 128 (1.56%) patients. One case was diagnosed by detecting lymphocyte macrochimerism through DNA-STR. Both of them died even after aggressive treatment. In China, the incidence of GVHD is similar to that reported by foreign centers except for an extremely bad prognosis. Rapid diagnosis is crucial for a better prognosis. In China, only 37.5% of cases are diagnosed by molecular methods. We recommend detecting lymphocyte macrochimerism through DNA-STR to get a rapid diagnosis, and interleukin 2-receptor antibody (basiliximab or daclizumab) therapy seems to be a good choice for the disease.

Undifferentiated embryonal sarcoma of the liver:Clinical characteristics and outcomes

BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare liver malignancy originating from primary mesenchymal tissue.The clinical manifestations,laboratory tests,and imaging examinations of the disease lack specificity and the preoperative misdiagnosis rate is high.The overall prognosis is poor and survival rate is low.AIM To investigate the diagnosis,treatment,and prognosis of UESL.METHODS We performed a retrospective,single-center cohort study in Shengjing Hospital of China Medical University,which is a central hospital in northeast China.From 2005 to 2017,we recruited 14 patients with pathologically confirmed UESL.We analyzed the clinical manifestations,laboratory tests,imaging examinations,pathological examinations,therapy,and prognosis of these patients.RESULTS There were nine males and five females aged 2-60 years old included in the study.The major initial symptoms were abdominal pain(71.43%)and fever(57.14%).Preoperative laboratory tests revealed that seven patients had increased leukocyte levels,four showed a decrease in hemoglobin levels,seven patients had increased glutamyl transpeptidase levels,nine had increased lactate dehydrogenase levels,and three showed an increase in carbohydrate antigen 199.There was no difference in the rate of misdiagnosis in preoperative imaging examinations of UESL between adults and children(6/6 vs 5/8,P=0.091).The survival rate after complete resection was 6/10,while that after incomplete resection was 0/4(P=0.040),suggesting that complete resection is important to improve survival rate.In total,five out of the eight children achieved survival.During the follow-up,the maximum survival time was shown to be 11 years and minimum survival time was 6 mo.Six adult patients relapsed late after surgery and all of them died.CONCLUSION Preoperative imaging examination for UESL has a high misdiagnosis rate.Multidisciplinary collaboration can improve the diagnostic accuracy of UESL.Complete surgical resection is the first choice for treatment of UESL.

Hepatitis C cirrhosis: New perspectives for diagnosis and treatment

Chronic hepatitis C infection is the leading cause of chronic liver disease, cirrhosis, hepatocellular carcinoma as well as the primary indication for liver transplantation in the United States. Despite recent advances in drugs for the treatment of hepatitis C, predictive models estimate the incidence of cirrhosis due to hepatitis C infection will to continue to rise for the next two decades. There is currently an immense interest in the treatment of patients with fibrosis and early-stage cirrhosis as treatment can lead to decrease in the rates of decompensated cirrhosis, hepatocellular carcinoma and need for liver transplantation in these patients. The goal of this paper is to provide clinicians and health care professionals further information about the treatment of patients with hepatitis C infection and cirrhosis. Additionally, the paper focuses on the disease burden, epidemiology, diagnosis and the disease course from infection to treatment. We provide an overview of multiple studies for the treatment of chronic hepatitis C infection that have included patients with cirrhosis. We also discuss the advantages and disadvantages of treatment in cirrhotic patients and focus on the most up to date guidelines available for treatment.

Clinical analysis of Wernicke encephalopathy after liver transplantation

Background:Wernicke encephalopathy(WE)is an acute neurological disease resulting from vitamin B1 deficiency,and there are only very few case reports of WE after liver transplantation.The present study aimed to investigate the clinical characteristics,etiology,magnetic resonance imaging(MRI)features,treatment and prognosis of patients with WE after liver transplantation.Methods:Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital,Zhejiang University School of Medicine and Jiangxi Provincial People’s Hospital between January 2011 and December 2021 were retrospectively analyzed.Results:Among the 23 patients diagnosed with WE after liver transplantation,6(26%)had a classic triad of impaired consciousness,oculomotor palsy and ataxia,and 17(74%)had two features.The misdiagno-sis rate was 65%.After treatment with high-dose vitamin B1,19(83%)patients showed improvement,whereas 4(17%)showed no improvement,including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia.Conclusions:The misdiagnosis rate is high in the early stage of WE,and the prognosis is closely asso-ciated with whether WE is diagnosed early and treated timely.High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment.Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation.

Hydatid Cyst of the Liver: About a Case at the Digestive and General Surgery Department of the University Hospital of Bouaké(Côte d’Ivoire)

Hydatid cyst of the liver (KHF) is a parasitic condition caused by the development of the larval form of the dog tapenia Echinococcus granulosus. In sub-Saharan Africa, few writings are interested in this pathology, which remains common and constitutes a public health problem in highly endemic countries [1] [2]. We report the observation of a 61-year-old hypertensive patient owner of a dog admitted for abdominal pain without abdominal mass. In whom ultrasound and computed tomography have made it possible to make the diagnosis of hydatid cyst of the liver (KHF). The patient underwent surgery. We performed an associated conservative treatment post-operative albendazole. The post-operative follow-up was simple. In our patient the evolution was good after a setback of more than 2 months. Through this observation and a review of the literature, we insist on the contribution of imaging in diagnosis and treatment, which is essentially surgical.

Parasites of the liver:A global problem?

Parasitic liver diseases can be caused by trematodes,cestodes,nematodes,and protozoa.This pathology is significant because millions of people in different parts of the world have liver parasites,which can manifest themselves in the development of inflammation,liver cysts,cholecystitis,cholelithiasis,pancreatitis and liver cirrhosis that are often threatening their lives.The International Agency for Research on Cancer considers three species of trematodes,Schistosoma haematobium,Opisthorchis viverrini and Clonorchis sinensis,to be carcinogens.Complex modern examination methods,in some cases including extensive screening of large populations,are required for diagnosing liver parasites.Treatment of parasitic liver diseases is differentiated and can involve a combination of surgical and therapeutic measures.There is no doubt that the clinical and epidemiological scale allows one to regard parasitic liver diseases as a global healthcare problem.

An expert consensus on the evaluation and treatment of acute thoracolumbar spine and spinal cord injury in China

This is an expert consensus on the evaluation and treatment of thoracolumbar spinal injury, estab- lished from February 2009 to July 2010. The expert consensus consists mainly of six parts with a total of 54 recommendations including the overview （one item）; pre-hospital care （one item）; evaluation and diagnosis （13 items）; treatment （23 items）; prevention and treatment of major com- plications （12 items）; and rehabilitation （four items）. This is the first time that Chinese experts have published a consensus on spine and spinal cord injury. The expert consensus was established based on Delphi methods, literature analysis, and clinical experiences. Each recommendation is supported by and was interpreted using multi-level evidences. The level of agreement with the rec- ommendation among the panel members was assessed as either low, moderate, or strong. Each panel member was asked to indicate his or her level of agreement on a 5-point scale, with ＂1＂ cor- respondJng to neutrality and ＂5＂ representJng maxJmum agreement. Scores were aggregated across the panel members and an arithmetic mean was calculated. This mean score was then translated into low, moderate, or strong. After all of the votes were collected and calculated, the results showed no low-level recommendations, 10 moderate-level recommendations, and 44 strong-level recom- mendations. An expert consensus was reached and was recognized by Chinese spine surgeons. Wide-scale adoption of these recommendations is urgent in the management of acute thora- columbar spine and spinal cord injury in a broader attempt to create a standard evaluation and treatment strategy for acute thoracolumbar spine and spinal cord injury in China.

Focus on alcoholic liver disease:From nosography to treatment

Abusive alcohol intake currently ranks as a major cause of liver disease, and is associated with significant mortality worldwide. Alcoholic liver disease(ALD) generically defines liver abnormalities ranging from liver steatosis to the end-stages of disease such as liver cirrhosis. Information regarding the precise incidence and prevalence of ALD is still limited by a lack of large population-based studies and by the absence of large systematic reviews of all epidemiological data available. However, existing collected data show an overall increase in the number of alcohol abusers and alcoholrelated liver disease. The burden exerted on medical systems worldwide is significant, with hospitalization and management costs rising constantly over the years. A great number of all cirrhosis-related deaths in Europe and a significant percentage worldwide areassociated with alcohol consumption. The main possible risk factors for ALD are the amount and duration of alcohol abuse, patterns of drinking and the type of alcoholic beverage consumed. However, ALD does not progress to cirrhosis in all patients, therefore a series of additional factors are implicated. Even though insufficiently studied, genetic factors are generally regarded as highly important, and the presence of comorbidities and dietary habits seem to play a role in disease onset and progression. This lack of clear pathophysiological data further translates in the absence of definite treatment for ALD and shall prove challenging in the coming years. In this article, we aimed to briefly review epidemiologic data on the burden of ALD, risk factors, clinical and nosographic as well as therapeutic aspects of this disease. Without attempting to be exhaustive, this short topic highlight emphasizes each point and may serve as a general guidance tool in the complicated literature related to ALD.

Chinese expert consensus on multidisciplinary diagnosis and treatment of pancreatic neuroendocrine liver metastases

Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases.However,a lack of biological,molecular,and genomic information and an absence of data from rigorous trials limit the validity of these strategies.This review presents the viewpoints from an international conference consisting of several expert working groups.The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature,evaluating the evidence on which management decisions were based,developing internationally acceptable recommendations for clinical practice,and making recommendations for clinical and research endeavors.The review for each question will be followed by recommendations from the panel.