Quantitative assessment of self-management in patients with nonalcoholic fatty liver disease: An unmet clinical need

In this editorial we comment on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al published in a recent issue of the World Journal of Gastroenterology.Non-alcoholic fatty liver disease(NAFLD)represents one of the current challenges in hepatology and public health,due to its continuous growing prevalence and the rising incidence of NAFLD-related fibrosis,non-alcoholic steatohepatitis and cirrhosis.The only effective therapeutic strategy for this dis-ease is represented by encouraging patients to improve their lifestyle through the modification of dietary intake and increased physical exercise,but the effective application of such modifications is often limited by various factors such as lack of information,psychological barriers or poor social support.While poor adherence to a healthy lifestyle can be decisive in determining the clinical outcome,in daily practice there is a lack of quantitative instruments aimed at identifying patients with the lowest adherence to lifestyle changes and higher risk of disease progre-ssion in the course of follow-up.In this article,Zeng et al propose a quantitative scale to assess the grade of adherence of patients with NAFLD to hea-lthy lifestyle intervention,called the Exercise and Diet Adherence Scale(EDAS).This scale,consisting of 33 items divided into 6 dimensions which relates to six subjective aspects in the self-management of NAFLD,has shown a good correlation with the identification of the sub-cohort of patients with the highest reduction in caloric intake,increase in physical exercise,probability of a reduction in liver stiffness measurement and alanine aminotransferase levels.The cor-relation among clinical outcomes and specific dimensions of this scale also highlights the pivotal role of a good and confidential doctor-patient relationship and of an effective communication.There is an urgent need for practical and effective instruments to assess the grade of self-management of NAFLD patients,together with the development of multidisciplinary teams with the aim of applying structured behavioral interventions.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication:A systematic review and meta-analysis

BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Non-invasive differential diagnosis between hepatocellular carcinoma(HCC)and other liver cancer(i.e.cholangiocarcinoma or metastasis)is highly challenging and definitive diagnosis still relies on histological exam.The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features.Dynamic contrast-enhanced ultrasound(DCEUS)with standardized software could help to overcome these obstacles,providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.AIM To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.METHODS A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS Rise time was significantly higher in HCC patients with a standardized mean difference(SMD)of 0.83(95%CI:0.48-1.18).Similarly,other statistically significant parameters were mean transit time local with a SMD of 0.73(95%CI:0.20-1.27),peak enhancement with a SMD of 0.37(95%CI:0.03-0.70),area wash-in area under the curve with a SMD of 0.47(95%CI:0.13-0.81),wash-out area under the curve with a SMD of 0.55(95%CI:0.21-0.89)and wash-in and wash-out area under the curve with SMD of 0.51(95%CI:0.17-0.85).SMD resulted not significant in fall time and wash-in rate,but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.CONCLUSION DCEUS could improve non-invasive diagnosis of HCC,leading to less liver biopsy and early treatment.This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

This pain drives me crazy:Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome

BACKGROUND Interstitial cystitis/bladder pain syndrome(IC/BPS)is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic,abdominal,and/or pelvic pain.Although the term cystitis suggests an inflammatory or infectious origin,no definite cause has been identified.It occurs in both sexes,but women are twice as much affected.AIM To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS.METHODS Hypothesizing that particular psychological characteristics could underpin IC/BPS,we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy:("interstitial cystitis"OR"bladder pain syndrome")AND("mood disorder"OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk).RESULTS On September 27,2023,the PubMed search produced 223 articles,CINAHL 62,and the combined PsycLIT/PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36.Search on ClinicalTrials.gov produced 14 studies,of which none had available data.Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS,i.e.63 articles spanning from 2000 to October 2023.These studies identified depression and anxiety problems in the IC/BPS population,along with sleep problems and the tendency to catastrophizing.CONCLUSION Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS.Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

Frequency of and reasons behind non-listing in adult patients referred for liver transplantation: Results from a retrospective study

BACKGROUND Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation candidates.AIM To assess the ineligibility rate for liver transplantation and its motivations.METHODS A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation eligibility.The predictors for listing were evaluated using multivariable logistic regression.RESULTS In our center,314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year period.The most frequent reasons for transplant evaluation were decompensated cirrhosis(51.6%)and hepatocellular carcinoma(35.7%).The non-listing rate was 53.8%and the transplant rate was 34.4%for the whole cohort.Two hundred and five motivations for ineligibility were collected.The most common contraindications were psychological(9.3%),cardiovascular(6.8%),and surgical(5.9%).Inappropriate or premature referral accounted for 76(37.1%)cases.On multivariable analysis,a referral from another hospital(OR:2.113;95%CI:1.259–3.548)served as an independent predictor of non-listing.CONCLUSION A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of three.The referral from another hospital was taken as a strong predictor of non-listing.

Gut microbiota in women:The secret of psychological and physical well-being

The gut microbiota works in unison with the host,promoting its health.In particular,it has been shown to exert protective,metabolic and structural functions.Recent evidence has revealed the influence of the gut microbiota on other organs such as the central nervous system,cardiovascular and the endocrine-metabolic systems and the digestive system.The study of the gut microbiota is outlining new and broader frontiers every day and holds enormous innovation potential for the medical and pharmaceutical fields.Prevention and treatment of specific women’s diseases involves the need to deepen the function of the gut as a junction organ where certain positive bacteria can be very beneficial to health.The gut microbiota is unique and dynamic at the same time,subject to external factors that can change it,and is capable of modulating itself at different stages of a woman’s life,playing an important role that arises from the intertwining of biological mechanisms between the microbiota and the female genital system.The gut microbiota could play a key role in personalized medicine.

Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis:Evidence and uncertainties

Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated with a worse prognosis and increased risk of complication.Serum levels of branched-chain amino acids(BCAAs)are decreased in patients with liver cirrhosis.The imbalance of amino acids levels has been suggested to be associated with the development of complications,such as hepatic encephalopathy and sarcopenia,and to affect the clinical presentation and prognosis of these patients.Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis,but uncertainties remain about the real efficacy,the best route of administration,and dosage.

Minimum platelet count threshold before invasive procedures in cirrhosis:Evolution of the guidelines

Cirrhotic patients with severe thrombocytopenia are at increased risk of bleeding during invasive procedures.The need for preprocedural prophylaxis aimed at reducing the risk of bleeding in cirrhotic patients with thrombocytopenia who undergo scheduled procedures is assessed via the platelet count;however,establishing a minimum threshold considered safe is challenging.A platelet count≥50000/μL is a frequent target,but levels vary by provider,procedure,and specific patient.Over the years,this value has changed several times according to the different guidelines proposed in the literature.According to the latest guidelines,many procedures can be performed at any level of platelet count,which should not necessarily be checked before the procedure.In this review,we aim to investigate and describe how the guidelines have evolved in recent years in the evaluation of the minimum platelet count threshold required to perform different invasive procedures,according to their bleeding risk.

Dynamic contrast enhanced ultrasound in gastrointestinal diseases:A current trend or an indispensable tool?

Contrast enhanced ultrasound(CEUS)has been widely implemented in clinical practice because of the enormous quantity of information it provides,along with its low cost,reproducibility,minimal invasiveness,and safety of the secondgeneration ultrasound contrast agents.To overcome the limitation of CEUS given by the subjective evaluation of the contrast enhancement behaviour,quantitative analysis of contrast kinetics with generation of time-intensity curves has been introduced in recent years.The quantification of perfusion parameters[named as dynamic-CEUS(D-CEUS)]has several applications in gastrointestinal neoplastic and inflammatory disorders.However,the limited availability of large studies and the heterogeneity of the technologies employed have precluded the standardisation of D-CEUS,which potentially represents a valuable tool for clinical practice in management of gastrointestinal diseases.In this article,we reviewed the evidence exploring the application of D-CEUS in gastrointestinal diseases,with a special focus on liver,pancreas,and inflammatory bowel diseases.

Impact of COVID-19 in individuals with and without pre-existent digestive disorders with a particular focus on elderly patients

Coronavirus disease 2019(COVID-19)has several extrapulmonary symptoms.Gastrointestinal(GI)symptoms are among the most frequent clinical manifestations of COVID-19,with severe consequences reported in elderly patients.Furthermore,the impact of COVID-19 on patients with pre-existing digestive diseases still needs to be fully elucidated,particularly in the older population.This review aimed to investigate the impact of COVID-19 on the GI tract,liver,and pancreas in individuals with and without previous digestive diseases,with a particular focus on the elderly,highlighting the distinctive characteristics observed in this population.Finally,the effectiveness and adverse events of the anti-COVID-19 vaccination in patients with digestive disorders and the peculiarities found in the elderly are discussed.

Portal vein thrombosis:Insight into physiopathology,diagnosis,and treatment

Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an important role in PVT pathogenesis. Frequently, more than one risk factor could be identified; however, occasionally no single factor is discernable. Clinical examination, laboratory investigations, and imaging are helpful to provide a quick diagnosis, as prompt treatment might greatly affect a patient's outcome. In this review, we analyze the physiopathological mechanisms of PVT development, together with the hemodynamic and functional alterations related to this condition. Moreover, we describe the principal factors most frequently involved in PVT development and the recent knowledge concerning diagnostic and therapeutic procedures. Finally, we analyze the implications of PVT in the setting of liver transplantation and its possible influence on patients' future prognoses.

Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers

Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.

Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation

The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis.In this mutual relationship,the liver acts as a second firewall towards potentially harmful substances translocated from the gut,and is,in turn,is implicated in the regulation of the barrier.Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage.In particular,in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment,diet and gut dysbiosis as the primary pathogenic trigger.In advanced liver disease,intestinal permeability is enhanced by portal hypertension.The clinical consequence is an increased bacterial translocation that further worsens liver damage.Furthermore,this pathogenic mechanism is implicated in most of liver cirrhosis complications,such as spontaneous bacterial peritonitis,hepatorenal syndrome,portal vein thrombosis,hepatic encephalopathy,and hepatocellular carcinoma.After liver transplantation,the decrease in portal pressure should determine beneficial effects on the gut-liver axis,although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking.How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area,which deserves further attention.

Portal vein thrombosis in cirrhosis: Why a well-known complication is still matter of debate

Portal vein thrombosis(PVT)represents a well-known complication during the natural course of liver cirrhosis(LC),ranging from asymptomatic cases to lifethreating conditions related to portal hypertension and hepatic decompensation.Portal flow stasis,complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development.However,PVT occurrence remains unpredictable and many issues regarding its natural history,prognostic significance and treatment are still elusive.In particular although spontaneous resolution or disease stability occur in most cases of PVT,factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet.Moreover,PVT impact on LC outcome is still debated,as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression.Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases,even if the safer therapeutic option and the optimal therapy duration are still unknown.Nevertheless,their impact on mortality rates should be addressed more extensively.In this review we present the most debated questions regarding PVT,whose answers should come from prospective cohort studies and large sample-size randomized trials.

Gut microbiota in autism and mood disorders

The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal(GI)system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases.In the last few years,the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism,dementia and mood disorder,has been raised.The evidence of the inflammatory state alteration,highlighted in disorders such as schizophrenia,major depressive disorder and bipolar disorder,strongly recalls the microbiota alteration,highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders.Up to now,available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders.The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date,with few but promising results.A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder(ASD),as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.

What we should know about portal vein thrombosis in cirrhotic patients:A changing perspective

Portal vein thrombosis(PVT) is one of the most common complications occurring during the natural course of liver cirrhosis.Even though PVT is often asymptomatic,the worsening of liver function,an unexpected episode of gastrointestinal bleeding or ascitic decompensation may be landmarks of PVT development.Beyond these clinical manifestations,it is debated whether PVT really has an impact on liver cirrhosis natural history or rather represents only one of its consequences.Probably PVT development should not only be considered as a matter of impaired blood flow or pro-coagulation tendency.On one hand,PVT seems a consequence of the worsening in portal vein outflow due to the increased hepatic resistance in cirrhotic livers.On the other hand,vascular microthrombosis secondary to necroinflammation may cause liver ischemia and infarction,with loss of hepatic tissue(parenchymal extinction) which is replaced by fibrotic tissue.Therefore,PVT might also be considered as the overt manifestation of the liver fibrosing process evolution and anticoagulant therapy may thus have microscopic indirect effects also on the progression of liver disease.At present,a connection between PVT development and the progression of liver fibrosis/cirrhosis has not yet been demonstrated.Nevertheless,it is not clear if PVT development may worsen cirrhotic patients' outcome by itself.Some authors tried to assess liver transplant benefit in PVT cirrhotic patients but data are contrasting.In this review,we will try to answer these questions,providing a critical analysis of data reported in literature.

Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation

Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.

Role and mechanisms of action of escherichia coli nissle 1917 in the maintenance of remission in ulcerative colitis patients: an update

Ulcerative colitis (UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the “forgotten organ”, Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle (EcN) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor® (Ardeypharm GmbH, Herdecke, Germany and EcN, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of EcN 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of EcN.

Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate

Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation(FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, Pub Med was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.

Combined locoregional treatment of patients withhepatocellular carcinoma： state of the art

In recent years, a combination of intervention therapies has been widely applied in the treatment of hepatocellular carcinoma(HCC). One such combined strategy is based on the combination of the percutaneous approach, such as radiofrequency ablation(RFA), and the intra-arterial locoregional approach, such as trans-arterial chemoembolization(TACE). Several types of evidence have supported the feasibility and benefit of combined therapy, despite some studies reporting conflicting results and outcomes. The aim of this review was to explain the technical aspects of different combined treatments and to comprehensively analyze and compare the clinical efficacy and safety of this combined treatment option and monotherapy, either as TACE or RFA alone, in order to provide clinicians with an unbiased opinion and valuable information. Based on a literature review and our experience, combined treatment seems to be a safe and effective option in the treatment of patients with early/intermediate HCC when surgical resection is not feasible; furthermore, this approach provides better results than RFA and TACE alone for the treatment of large HCC, defined as those exceeding 3 cm in size. It can also expand the indication for RFA to previously contraindicated "complex cases", with increased risk of thermal ablation related complications due to tumor location, or to "complex patients" with high bleeding risk.