Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis

Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

Sarcopenia and cognitive impairment in liver cirrhosis: A viewpoint on the clinical impact of minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) represents the mildest type of hepatic encephalopathy (HE). MHE is considered as a preclinical stage of HE and is part of a wide spectrum of typical neurocognitive alterations characteristic of patients with liver cirrhosis, particularly involving the areas of attention, alertness, response inhibition, and executive functions. MHE can be detected by testing the patients’ psychometric performance, attention, working memory, psychomotor speed, and visuospatial ability, as well as by means of electrophysiological and other functional brain measures. MHE is very frequent, affecting from 20% up to 80% of patients tested, depending of the diagnostic tools used. Although subclinical, MHE is considered to be clinically relevant. In fact, MHE has been related to the patients’ falls, fitness to drive, and working ability. As a consequence, MHE affects the patients and caregivers lives by altering their quality of life and even their socioeconomic status. Recently sarcopenia, a very common condition in patients with advanced liver disease, has been shown to be strictly related to both minimal and overt HE. Aim of this review is to summarize the most recently published evidences about the emerging relationship between sarcopenia and cognitive impairment in cirrhotic patients and provide suggestions for future research.

Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin.Consequently,preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular,histological and pathophysiological features.Intraepithelial neoplasms are reported in biliary tract,as biliary intraepithelial neoplasm(BilIN),and in pancreas,as pancreatic intraepithelial neoplasm(PanIN).Both can evolve to invasive carcinomas,respectively cholangiocarcinoma(CCA)and pancreatic ductal adenocarcinoma(PDAC).Intraductal papillary neoplasms arise in biliary tract and pancreas.Intraductal papillary neoplasm of the biliary tract(IPNB)share common histologic and phenotypic features such as pancreatobiliary,gastric,intestinal and oncocytic types,and biological behavior with the pancreatic counterpart,the intraductal papillary mucinous neoplasm of the pancreas(IPMN).All these neoplastic lesions exhibit similar immunohistochemical phenotypes,suggesting a common carcinogenic process.Indeed,CCA and PDAC display similar clinic-pathological features as growth pattern,poor response to conventional chemotherapy and radiotherapy and,as a consequence,an unfavorable prognosis.The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.

Neurological and psychiatric effects of hepatitis C virus infection

Hepatitis C virus(HCV)infection is widespread and affects 71 million people worldwide.Although hepatic manifestations are the most frequent,ranging from chronic hepatitis to cirrhosis and hepatocellular carcinoma,it is also associated with several extrahepatic manifestations.Infected patients may present nonspecific neurological symptoms,regardless of the presence of liver cirrhosis.Several pathogenetic mechanisms underlying neurological symptoms have been hypothesized:neuroinvasion,immune-mediated damage,neurotransmitter alterations and cryoglobulinemia.Alterations of the central nervous system include cerebral vasculopathy,acute or subacute encephalopathy and inflammatory disorders.HCV infection may be responsible for neuropathies,of which the most frequent form is symmetrical axonal sensory or sensory-motor polyneuropathy which causes loss of leg sensitivity and weakness.Up to 50%of patients with HCV infection may experience cognitive decline and psychological disorders,such as depression and fatigue.HCV associated neurocognitive disorder is independent of the presence of liver cirrhosis and affects different domains than in patients with hepatic encephalopathy.It can be studied using specific tests that mainly explore executive functions,verbal learning and verbal recall.These disorders significantly reduce the quality of life.The new antiviral therapies improve the extrahepatic symptoms of HCV infection and their success depends on the achievement of sustained virological response.However,the effect of therapy may differ depending on the type of organ involved;neurological symptoms can be irreversible if there is organic liver damage.The aim of this review is to provide a critical overview of physiopathological mechanisms,diagnostic and therapeutic strategies of the neurological and psychiatric effects of HCV infection.

Hepatitis C virus eradication with directly acting antivirals improves health-related quality of life and psychological symptoms

BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL after HCV eradication,no data exists on the modifications of neuropsychological symptoms.AIM To investigate the effect of directly acting antivirals(DAAs)treatment on HRQoL and neuropsychological symptoms.METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment,including Zung-Self Depression-Rating-Scale,Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment.HRQoL was detected by Short-Form-36(SF-36).RESULTS All HRQoL domains,but role limitation physical and bodily pain,significantly improved after treatment.Interestingly,after DAAs treatment,all domains of HRQoL returned similar to those of controls.Each neuropsychological test significantly improved after HCV eradication.A significant correlation was observed among each psychological test and the summary components of SF-36.At multiple linear regression analysis including each psychological test as possible covariates,Zung-Self Depression Rating Scale(Zung-SDS)score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment.CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.

Spontaneous porto-systemic shunts in liver cirrhosis:Clinical and therapeutical aspects

Spontaneous porto-systemic shunts(SPSS)are frequent in liver cirrhosis and their prevalence increases as liver function deteriorates,probably as a consequence of worsening portal hypertension,but without achieving an effective protection against cirrhosis'complications.Several types of SPSS have been described in the literature,each one associated with different clinical manifestations.In particular,recurrent or persistent hepatic encephalopathy is more frequent in patients with splenorenal shunt,while the presence of gastric varices and consequently the incidence of variceal bleeding is more common in gastrorenal shunt.In the advanced stage,the presence of large SPSS can lead to the so called“portosystemic shunt syndrome”,characterized by a progressive deterioration of hepatic function,hepatic encephalopathy and,sometimes,portal vein thrombosis.The detection of SPSS in patients with liver cirrhosis is recommended in order to prevent or treat recurrent hepatic encephalopathy or variceal bleeding.

Artificial intelligence-aided colonoscopy:Recent developments and future perspectives

Artificial intelligence(AI)systems,especially after the successful application of Convolutional Neural Networks,are revolutionizing modern medicine.Gastrointestinal Endoscopy has shown to be a fertile terrain for the development of AI systems aiming to aid endoscopists in various aspects of their daily activity.Lesion detection can be one of the two main aspects in which AI can increase diagnostic yield and abilities of endoscopists.In colonoscopy,it is well known that a substantial rate of missed neoplasia is still present,representing the major cause of interval cancer.In addition,an extremely high variability in adenoma detection rate,the main key quality indicator in colonoscopy,has been extensively reported.The other domain in which AI is believed to have a considerable impact on everyday clinical practice is lesion characterization and aid in“optical diagnosis”.By predicting in vivo histology,such pathology costs may be averted by the implementation of two separate but synergistic strategies,namely the“leave-in-situ”strategy for<5 mm hyperplastic lesions in the rectosigmoid tract,and“resect and discard”for the other diminutive lesions.In this opinion review we present current available evidence regarding the role of AI in improving lesions’detection and characterization during colonoscopy.

Safety and efficacy of DEM-TACE performed with drug-eluting microspheres smaller than 300μm in patients with HCC and TIPS

Aim:Safety and efficacy evidence of drug-eluting-microspheres trans-arterial chemoembolization(DEM-TACE)in patients with hepatocellular carcinoma(HCC)and trans-jugular intrahepatic portosystemic shunt(TIPS)is lacking.The aim of this retrospective study was to report the safety and efficacy of DEM-TACE procedures performed with microspheres smaller than 300μm in patients with HCC and TIPS in a high-volume transplant center.Methods:Embolization was standardized by initiating DEM-TACE with microspheres smaller than 100μm,and if stasis was not achieved,adjunctive embolization with 100-300 or 200μm microspheres was administered.With regards to efficacy,the oncological response was evaluated and categorized according to mRECIST criteria at 1,3-6,9-12,and 15-18 months.Reporting the safety profile,detailed laboratory analysis was performed before,at 36-48 h,and 30-60 days after the procedure.Adverse events(AEs)were recorded;post-embolic syndrome was defined as the onset of fever/nausea/pain after the procedure.Late onset hepatobiliary complications were evaluated by follow-up imaging with computed tomography or magnetic resonance(CT/MR).Results:From December 2007 to November 2020,17 HCC patients(25 HCC nodules)with patent TIPS underwent 20 DEM-TACE.Embolization was performed only with microspheres smaller than 100μm in 3/20 DEM-TACE(15%);adjunctive embolization with 100-300 or 200μm microspheres was required in 17/20 DEMTACE(85%).Reported early AEs were post-embolic syndrome(9/20;45%)all of grade 1-2,late AEs were asymptomatic acute liver bile duct injury(2/20;10%),and in one case we observed hepatic abscess(1/20;5%)resulting in death due to sepsis.With regards to efficacy,the oncological response was evaluated and categorized according to mRECIST criteria.Complete response(CR)at 1,3-6,9-12,and 15-18 months was 52%,50%,50%,and 50%,respectively.Objective response(CR+partial response)at 1,3-6,9-12,and 15-18 months was 95%,71%,70%,and 50%,respectively.Conclusion:DEM-TACE with drug-eluting-microspheres smaller than 300μm can be performed in appropriately selected patients with TIPS.

Sarcopenic obesity:recent consensus and clinical implications in patients with chronic liver disease

Sarcopenia and obesity are two major public health concerns,particularly in the elderly population.These conditions have a significant impact on both the individual’s health and quality of life.Sarcopenia is defined as a loss of muscle mass,strength,and function physiologically present with aging,while obesity is an excessive accumulation of body fat.While these conditions are often considered separately,there is growing recognition that they frequently coexist,may synergistically enhance one another,leading to an increased risk of various chronic diseases and mortality.Sarcopenic obesity(SO)is the term utilized to define the simultaneous occurrence of sarcopenia and obesity(1).Since recently,the lack of common diagnostic criteria for SO has made it difficult to diagnose and manage this condition effectively.

Determinants of prognosis in cirrhosis:a new outlook

The metanalysis by Tantai and collaborators highlights the role of sarcopenia in cirrhosis by demonstrating that the presence of muscular alterations is independently related with a mortality(HR 2.61)(1).Sarcopenia is confirmed as a condition with high prevalence in patients with cirrhosis(37.5%),being more representative in males than females(41.9%vs.37.8%)and in subjects with alcoholic etiology(49.6%)or with more advanced degree of liver disease(Child Pugh C 46.7%).Interestingly,authors demonstrate that sarcopenia was associated with mortality in subjects with MELD<15 or>15(HR 2.34)as well evaluating only on studies that excluded patients with hepatocellular carcinoma(HCC),risk of mortality was similar to that of the main analysis(2.35)(1).

The unclear role of VEGF in POEMS syndrome: therapeutic implications of neoangiogenesis in a rare plasma cell disorder

POEMS syndrome is a rare paraneoplastic disorder due to an underlying clone of aberrant plasma cells.The name POEMS is an acronym for some of the major disease manifestations,namely polyneuropathy,organomegaly,endocrinopathy,presence of monoclonal component,and skin changes.The clinical presentation can be various and could lead to delayed diagnosis and treatment.Little is known about the pathogenic mechanism,although the neoangiogenesis due to overproduction of vascular endothelial growth factor(VEGF)by plasma cells seems to play a key role.The latest evidence suggests that the blood concentration of this cytokine correlates with the activity of the syndrome:VEGF could then be used as a therapeutic target and a marker to monitor response.Several case reports have shown the efficacy of this approach,but extended studies are required to better define the use of anti VEGF in patients affected by POEMS syndrome.

How acute myeloid leukemia(AML)escapes from FMS-related tyrosine kinase 3(FLT3)inhibitors?Still an overrated complication?

FMS-related tyrosine kinase 3(FLT3)mutations,present in about 25%-30%of acute myeloid leukemia(AML)patients,constitute one of the most frequently detected mutations in these patients.The binding of FLT3L to FLT3 activates the phosphatidylinositol 3-kinase(PI3K)and RAS pathways,producing increased cell proliferation and the inhibition of apoptosis.Two types of FLT3 mutations exist:FLT3-ITD and FLT3-TKD(point mutations in D835 and I836 or deletion of codon I836).A class of drugs,tyrosine-kinase inhibitors(TKI),targeting mutated FLT3,is already available with 1st and 2nd generation molecules,but only midostaurin and gilteritinib are currently approved.However,the emergence of resistance or the selection of clones not responding to FLT3 inhibitors has become an important clinical dilemma,as the duration of clinical responses is generally limited to a few months.This review analyzes the insights into mechanisms of resistance to TKI and poses a particular view on the clinical relevance of this phenomenon.Has resistance been overlooked?Indeed,FLT3 inhibitors have significantly contributed to reducing the negative impact of FLT3 mutations on the prognosis of AML patients who are no longer considered at high risk by the European LeukemiaNet(ELN)2022.Finally,several ongoing efforts to overcome resistance to FLT3-inhibitors will be presented:new generation FLT3 inhibitors in monotherapy or combined with standard chemotherapy,hypomethylating drugs,or IDH1/2 inhibitors,Bcl2 inhibitors;novel anti-human FLT3 monoclonal antibodies(e.g.,FLT3/CD3 bispecific antibodies);FLT3-CAR T-cells;CDK4/6 kinase inhibitor(e.g.,palbociclib).

Non-invasive tests for fibrosis detection: still in search for the best way

Eilenberg and colleagues’paper highlights the importance of non-invasive detection by using vibration controlled transient elastography(VCTE)and controlled attenuation parameter(CAPTM)for the assessment of fibrosis,steatosis,and non-alcoholic steatohepatitis(NASH).In a real-world cohort of patients with severe obesity(1).

Diagnostic imaging for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)occurs mostly in individuals with cirrhosis,which is why the guidelines of the most important scientific societies indicate that these patients are included in surveillance programs through the repetition of an ultrasound examination every 6 months.The aim is to achieve early identification of the neoplasia in order to increase the possibility of curative therapies(liver transplantation,surgery or local ablative therapies)and to increase patient survival.HCC nodules arising in cirrhotic livers show characteristic angiographic behavior that can be evaluated with dynamic multidetector computed tomography and dynamic magnetic resonance imaging(MRI).However,the use of these techniques in real life is often hindered by the lack of uniform terminology in reporting and in the interpretation of the exams reflected in the impossibility of comparing examinations performed in different centers and/or at different times.Liver Imaging Reporting and Data System?was created to standardize reporting and data collection of computed tomography and MRI for HCC.In some cases HCC arises in patients with healthy livers and,although there is evidence that angiographic behavior is not different from cirrhotic patients in this clinical situation,the guidelines still indicate the execution of a biopsy.Frequent use of palliative therapeutic techniques such as transarterial chemoembolization,transarterial radioembolization or administration of antiangiogenic drugs(sorafenib)poses problems of interpretation of the therapeutic response with repercussions on the subsequent choices that have been attempted to resolve with the use of stringent criteria such as Modified Response Evaluation Criteria In Solid Tumors.