More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune live...More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune liver diseases.Advances in understanding tumor immunity have led to a major shift in the treatment of HCC,with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells.Regulatory T cells(Tregs)are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression,invasiveness,as well as metastasis.Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function.Notably,Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor(ICI)immunotherapy.Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity,it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events(irAEs).Since the use of ICI becomes common in oncology,with an increasing number of new ICI currently under clinical trials for cancer treatment,the occurrence of irAEs is expected to dramatically rise.Herein,we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease,and we discuss their involvement in irAEs due to the new immunotherapies.展开更多
BACKGROUND Wheat and other gluten-containing grains are widely consumed,providing approximately 50%of the caloric intake in both industrialised and developing countries.The widespread diffusion of gluten-containing di...BACKGROUND Wheat and other gluten-containing grains are widely consumed,providing approximately 50%of the caloric intake in both industrialised and developing countries.The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence.This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media.However,in recent years,the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease(CD)from obscurity to global prominence.These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD.Different scientific societies,mainly from Europe and America,have proposed guidelines based on CD's most recent evidence.AIM To identify the most recent scientific guidelines on CD,aiming to find and critically analyse the main differences.METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language.PubMed was lastly accessed on 1 March 2021.RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions.Differences were noted in the possibility of a no-biopsy diagnosis,HLA testing,follow-up protocols,and procedures.CONCLUSION We found a relatively high concordance between the guidelines for CD.Important modifications have occurred in the last years,especially about the possibility of a no-biopsy diagnosis in children.Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.展开更多
AIM: Our goals were to analyze the known genetic predispositions for autoimmune hepatitis (AIH) in AIH Italian population and to compare them with North American counterparts. METHODS: Human leukocyte antigens (HLA) B...AIM: Our goals were to analyze the known genetic predispositions for autoimmune hepatitis (AIH) in AIH Italian population and to compare them with North American counterparts. METHODS: Human leukocyte antigens (HLA) B8, C7, DR3, DR4, DR7, DR11, DR13, DQ2 and the B8-DR3-DQ2 phenotype were determined by microlymphocytotoxicity and polymerase chain reaction in 74 Italian patients (57 with type 1 and 17 with type 2 AIH) and 149 North American patients with type 1 AIH, and in adequate controls. RESULTS: B8-DR3-DQ2 occurred more frequently in Italian patients with type 1 AIH than in Italian controls (30% vs 7%, P<0.0001), but less frequently than in North American counterparts (30% vs 48%, P= 0.02). DR4 occurred less frequently in Italian patients with type 1 AIH (23% vs 43%, P= 0.01) and in controls (16% vs 34%, P= 0.0003) than in North American counterparts. No differences were found in alleles' frequency between type 1 and type 2 Italian AIH patients. DR11 had a frequency lower in type 1 Italian AIH patients than controls (17% vs 35%, P= 0.01). CONCLUSION: HLA DR4 is not associated with AIH in Italy. The known HLA risk factors for AIH occur similarly in Italian patients with type 1 and type 2 AIH, and they are less frequent than in North American patients. B8-DR3-DQ2 is the predominant phenotype of type 1 AIH also in Italy, and HLA DR11 may be a regionally distinctive protective factor against type 1 AIH.展开更多
BACKGROUND Dermatologic adverse events(DAEs)are associated with a better outcome in patients with hepatocellular carcinoma(HCC)irrespective of the therapeutic agent received.The exact mechanisms associated with the de...BACKGROUND Dermatologic adverse events(DAEs)are associated with a better outcome in patients with hepatocellular carcinoma(HCC)irrespective of the therapeutic agent received.The exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors(TKIs)to the skin or an immune-mediated reaction triggered by the oncologic treatment.As is the case in other conditions,individual genetic variants may partially explain a higher risk of DAEs.AIM To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with TKIs.METHODS We first analyzed 27 single-nucleotide polymorphisms(SNPs)from 12 genes selected as potential predictors of adverse event(AE)development in HCC patients treated with sorafenib[Barcelona Clinic Liver Cancer 1(BCLC1)cohort].Three additional cohorts were analyzed for AGT1(rs699)and AGT2(rs4762)polymorphisms-initially identified as predictors of DAEs:BCLC2(n=79),Northern Italy(n=221)and Naples(n=69)cohorts,respectively.The relation between SNPs and DAEs and death were assessed by univariate and multivariate Cox regression models,and presented with hazard ratios and their 95%confidence intervals(95%CI).RESULTS The BCLC1 cohort showed that patients with arterial hypertension(AHT)(HR=1.61;P value=0.007)and/or AGT SNPs had an increased risk of DAEs.Thereafter,AGT2(rs4762)AA genotype was found to be linked to a statistically significant increased probability of DAEs(HR=5.97;P value=0.0201,AA vs GG)in the Northern Italy cohort by multivariate analysis adjusted for BCLC stage,ECOG-PS,diabetes and AHT.The value of this genetic marker was externally validated in the cohort combining the BCLC1,BCLC2 and Naples cohorts[HR=3.12(95%CI:1.2-8.14),P value=0.0199,AGT2(rs4762)AA vs AG genotype and HR=2.73(95%CI:1.18-6.32)P value=0.0188,AGT2(rs4762)AA vs GG genotype].None of the other gene variants tested were found to be associated with the risk of DAE development.CONCLUSION DAE development in HCC patients receiving TKIs could be explained by the AGT2(rs4762)gene variant.If validated in other anti-oncogenic treatments,it might be considered a good prognosis marker.展开更多
Hepatocellular carcinoma(HCC)is rarely associated with autoimmune paraneoplastic syndromes.We report a case of anti-transcriptional intermediary factor-1 gamma(TIF1-γ)-positive dermatomyositis(DM)as clinical presenta...Hepatocellular carcinoma(HCC)is rarely associated with autoimmune paraneoplastic syndromes.We report a case of anti-transcriptional intermediary factor-1 gamma(TIF1-γ)-positive dermatomyositis(DM)as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue,myalgia,and typical skin rash.His medical history was notable for hepatitis C-related cirrhosis,successful treatment with direct-acting antiviral agents,and previously efficacious treatment of HCC.Laboratory testing showed significant rhabdomyolysis with antiTIF1-γantibodies at high titer,and DM was diagnosed.After a careful diagnostic workup,HCC recurrence was diagnosed.After first-line corticosteroid treatment,azathioprine and intravenous immunoglobulin treatments were administered;unfortunately,he mounted only partial response.Owing to the compromised performance status,no HCC treatment was feasible,and,according to international guidelines,he received only best supportive care.Here,we discuss the diagnostic,prognostic,and pathogenic roles of anti-TIF1-γantibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients.Considering the TIF1 gene family’s established role in oncogenesis,we also review the role of TIF1-γas a tumor-related neoantigen,leading to the development of clinically overt antiTIF1-γantibodies-positive DM.展开更多
Aim:The present study evaluated the duration of chemoembolization in patients with hepatocellular carcinoma,analyzing possible factors affecting the procedural time.Methods:In total,175 patients who underwent chemoemb...Aim:The present study evaluated the duration of chemoembolization in patients with hepatocellular carcinoma,analyzing possible factors affecting the procedural time.Methods:In total,175 patients who underwent chemoembolization have been prospectively enrolled.The procedural length was considered the time between the insertion and the removal of the angiographic sheath.The features related to the tumor burden and angiographic procedures,which could be related to the procedural time,were recorded.Results:The chemoembolization time resulted in a mean of 58.1 min.The longer procedural time was associated with a number of nodules treated per patient≥2(P<0.001),a number of segments with nodules≥2(P<0.001),the presence of more than 1 nodule in the same segment(P<0.001),the location of the tumor in the left lobe(P=0.001),the exclusion from the Milan criteria(P<0.001),and a number of segments treated≥2(P<0.001).Only the number of nodules treated per patient resulted significantly in multivariate analysis(OR 2.927,95%CI:2.015-4.251,P<0.001).Conclusion:The factors related to longer procedural time are the number of nodules treated≥2,the number of segments with nodules≥2,the involvement of the left lobe,the tumor burden outside the Milan criteria,and the number of segments treated≥2.All these characteristics,known in the pre-procedural phase,represent useful tools for a correct planning of the angiographic room’s workflow during the pandemic era as well as in the future to reduce downtime and increase productivity.展开更多
文摘More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune liver diseases.Advances in understanding tumor immunity have led to a major shift in the treatment of HCC,with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells.Regulatory T cells(Tregs)are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression,invasiveness,as well as metastasis.Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function.Notably,Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor(ICI)immunotherapy.Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity,it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events(irAEs).Since the use of ICI becomes common in oncology,with an increasing number of new ICI currently under clinical trials for cancer treatment,the occurrence of irAEs is expected to dramatically rise.Herein,we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease,and we discuss their involvement in irAEs due to the new immunotherapies.
文摘BACKGROUND Wheat and other gluten-containing grains are widely consumed,providing approximately 50%of the caloric intake in both industrialised and developing countries.The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence.This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media.However,in recent years,the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease(CD)from obscurity to global prominence.These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD.Different scientific societies,mainly from Europe and America,have proposed guidelines based on CD's most recent evidence.AIM To identify the most recent scientific guidelines on CD,aiming to find and critically analyse the main differences.METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language.PubMed was lastly accessed on 1 March 2021.RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions.Differences were noted in the possibility of a no-biopsy diagnosis,HLA testing,follow-up protocols,and procedures.CONCLUSION We found a relatively high concordance between the guidelines for CD.Important modifications have occurred in the last years,especially about the possibility of a no-biopsy diagnosis in children.Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.
文摘AIM: Our goals were to analyze the known genetic predispositions for autoimmune hepatitis (AIH) in AIH Italian population and to compare them with North American counterparts. METHODS: Human leukocyte antigens (HLA) B8, C7, DR3, DR4, DR7, DR11, DR13, DQ2 and the B8-DR3-DQ2 phenotype were determined by microlymphocytotoxicity and polymerase chain reaction in 74 Italian patients (57 with type 1 and 17 with type 2 AIH) and 149 North American patients with type 1 AIH, and in adequate controls. RESULTS: B8-DR3-DQ2 occurred more frequently in Italian patients with type 1 AIH than in Italian controls (30% vs 7%, P<0.0001), but less frequently than in North American counterparts (30% vs 48%, P= 0.02). DR4 occurred less frequently in Italian patients with type 1 AIH (23% vs 43%, P= 0.01) and in controls (16% vs 34%, P= 0.0003) than in North American counterparts. No differences were found in alleles' frequency between type 1 and type 2 Italian AIH patients. DR11 had a frequency lower in type 1 Italian AIH patients than controls (17% vs 35%, P= 0.01). CONCLUSION: HLA DR4 is not associated with AIH in Italy. The known HLA risk factors for AIH occur similarly in Italian patients with type 1 and type 2 AIH, and they are less frequent than in North American patients. B8-DR3-DQ2 is the predominant phenotype of type 1 AIH also in Italy, and HLA DR11 may be a regionally distinctive protective factor against type 1 AIH.
基金the Bayer Grant,No.JBT-SOR 2013-01the Instituto de Salud Carlos III,No.PI18/00768,PI15/00145 and PI18/0358+2 种基金Fondo Europeo de Desarrollo Regional(FEDER)from the European Commission“Una manera de hacer Europa”Pla estratègic de recerca i innovacióen salut(PERIS)Grant,No.PERIS_IPIF19-SLT008/18/00182-RH0Contratos Predoctorales de Formación en Investigación en Salud(PFIS),No.FI19/00222.
文摘BACKGROUND Dermatologic adverse events(DAEs)are associated with a better outcome in patients with hepatocellular carcinoma(HCC)irrespective of the therapeutic agent received.The exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors(TKIs)to the skin or an immune-mediated reaction triggered by the oncologic treatment.As is the case in other conditions,individual genetic variants may partially explain a higher risk of DAEs.AIM To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with TKIs.METHODS We first analyzed 27 single-nucleotide polymorphisms(SNPs)from 12 genes selected as potential predictors of adverse event(AE)development in HCC patients treated with sorafenib[Barcelona Clinic Liver Cancer 1(BCLC1)cohort].Three additional cohorts were analyzed for AGT1(rs699)and AGT2(rs4762)polymorphisms-initially identified as predictors of DAEs:BCLC2(n=79),Northern Italy(n=221)and Naples(n=69)cohorts,respectively.The relation between SNPs and DAEs and death were assessed by univariate and multivariate Cox regression models,and presented with hazard ratios and their 95%confidence intervals(95%CI).RESULTS The BCLC1 cohort showed that patients with arterial hypertension(AHT)(HR=1.61;P value=0.007)and/or AGT SNPs had an increased risk of DAEs.Thereafter,AGT2(rs4762)AA genotype was found to be linked to a statistically significant increased probability of DAEs(HR=5.97;P value=0.0201,AA vs GG)in the Northern Italy cohort by multivariate analysis adjusted for BCLC stage,ECOG-PS,diabetes and AHT.The value of this genetic marker was externally validated in the cohort combining the BCLC1,BCLC2 and Naples cohorts[HR=3.12(95%CI:1.2-8.14),P value=0.0199,AGT2(rs4762)AA vs AG genotype and HR=2.73(95%CI:1.18-6.32)P value=0.0188,AGT2(rs4762)AA vs GG genotype].None of the other gene variants tested were found to be associated with the risk of DAE development.CONCLUSION DAE development in HCC patients receiving TKIs could be explained by the AGT2(rs4762)gene variant.If validated in other anti-oncogenic treatments,it might be considered a good prognosis marker.
文摘Hepatocellular carcinoma(HCC)is rarely associated with autoimmune paraneoplastic syndromes.We report a case of anti-transcriptional intermediary factor-1 gamma(TIF1-γ)-positive dermatomyositis(DM)as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue,myalgia,and typical skin rash.His medical history was notable for hepatitis C-related cirrhosis,successful treatment with direct-acting antiviral agents,and previously efficacious treatment of HCC.Laboratory testing showed significant rhabdomyolysis with antiTIF1-γantibodies at high titer,and DM was diagnosed.After a careful diagnostic workup,HCC recurrence was diagnosed.After first-line corticosteroid treatment,azathioprine and intravenous immunoglobulin treatments were administered;unfortunately,he mounted only partial response.Owing to the compromised performance status,no HCC treatment was feasible,and,according to international guidelines,he received only best supportive care.Here,we discuss the diagnostic,prognostic,and pathogenic roles of anti-TIF1-γantibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients.Considering the TIF1 gene family’s established role in oncogenesis,we also review the role of TIF1-γas a tumor-related neoantigen,leading to the development of clinically overt antiTIF1-γantibodies-positive DM.
文摘Aim:The present study evaluated the duration of chemoembolization in patients with hepatocellular carcinoma,analyzing possible factors affecting the procedural time.Methods:In total,175 patients who underwent chemoembolization have been prospectively enrolled.The procedural length was considered the time between the insertion and the removal of the angiographic sheath.The features related to the tumor burden and angiographic procedures,which could be related to the procedural time,were recorded.Results:The chemoembolization time resulted in a mean of 58.1 min.The longer procedural time was associated with a number of nodules treated per patient≥2(P<0.001),a number of segments with nodules≥2(P<0.001),the presence of more than 1 nodule in the same segment(P<0.001),the location of the tumor in the left lobe(P=0.001),the exclusion from the Milan criteria(P<0.001),and a number of segments treated≥2(P<0.001).Only the number of nodules treated per patient resulted significantly in multivariate analysis(OR 2.927,95%CI:2.015-4.251,P<0.001).Conclusion:The factors related to longer procedural time are the number of nodules treated≥2,the number of segments with nodules≥2,the involvement of the left lobe,the tumor burden outside the Milan criteria,and the number of segments treated≥2.All these characteristics,known in the pre-procedural phase,represent useful tools for a correct planning of the angiographic room’s workflow during the pandemic era as well as in the future to reduce downtime and increase productivity.
