BACKGROUND Wilson disease(WD)is a progressive,potentially fatal degenerative disease affecting the liver and central nervous system.Given its low prevalence,collecting data on large cohorts of patients with WD is chal...BACKGROUND Wilson disease(WD)is a progressive,potentially fatal degenerative disease affecting the liver and central nervous system.Given its low prevalence,collecting data on large cohorts of patients with WD is challenging.Comprehensive insur-ance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare diseases.AIM To describe patients with WD in the United States,their treatment and clinical outcome,using a large insurance claims database.METHODS This retrospective,longitudinal study was performed in the Clarivate Real-World Data Product database.All patients with≥2 claims associated with an Interna-tional Classification of Diseases 10(ICD-10)diagnostic code for WD(E83.01)between 2016 and 2021 were included and followed until death or study end.Patients were divided into two groups by whether or not they were documented to have received a specific treatment for WD.Clinical manifestations,hospital-isations,liver transplantation and death were documented.RESULTS Overall,5376 patients with an ICD-10 diagnostic code for WD were identified.The mean age at inclusion was 41.2 years and 52.0%were men.A specific WD treatment was documented for 885 patients(15.1%),although the number of patients taking zinc salts may be underestimated due to over the counter purchase.At inclusion,the mean age of patients with a documented treatment was 36.6±17.8 years vs 42.2±19.6 years in those without a documented treatment.During follow-up,273 patients(5.1%)died.Compared with the American general population,the standardised mortality ratio was 2.19.The proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0%and the mean age at death 52.7 years.CONCLUSION Patients treated for WD in the United States had an excess early mortality compared with the American population.These findings indicate that there is a significant unmet need for effective treatment for WD in the United States.展开更多
目的探讨Wilson病(Wilson disease,WD)患者冲动性对数字成瘾倾向的影响及其相关因素。方法纳入66例WD患者为研究对象,根据临床表现分为脑型组42例、肝型组24例。采用网络成瘾量表(internet addiction test,IAT)评估患者网络成瘾倾向,总...目的探讨Wilson病(Wilson disease,WD)患者冲动性对数字成瘾倾向的影响及其相关因素。方法纳入66例WD患者为研究对象,根据临床表现分为脑型组42例、肝型组24例。采用网络成瘾量表(internet addiction test,IAT)评估患者网络成瘾倾向,总分>50分界定为具有网络成瘾倾向;使用Barratt冲动量表中文版(the Chinese version of the Barratt impulsiveness scale,11version,BIS-11-C)评估患者冲动性;手机依赖量表(mobile phone addiction index,MPAI)评估对手机使用的依赖程度;通过颅脑MRI检查患者病变脑区的部位和累计频次。结果66例WD患者中有数字成瘾倾向者45例(68.2%),其中脑型组中35例(53.0%)、肝型组中10例(15.2%),两组成瘾倾向者比例差异有统计学意义(P=0.001)。脑型组患者在BIS-11-C、MPAI量表多项因子分上高于肝型组(P<0.05)。所有患者MPAI量表中失控性因子分与BIS-11-C量表中的注意力冲动性因子分(r=0.499,P=0.001)、运动冲动性因子分(r=0.553,P=0.001)、无计划冲动性因子分(r=0.535,P=0.001)、冲动控制总分(r=0.653,P=0.001)正相关。线性回归分析显示注意力冲动性因子分与额叶病变(B=-1.634,P=0.018)相关联,失控性因子分与额叶病变(B=-3.609,P=0.023)相关联,戒断性因子分与丘脑病变(B=-5.047,P=0.007)、额叶病变(B=-2.204,P=0.024)相关联,逃避性因子分与顶叶病变(B=-1.867,P=0.032)相关联,低效性因子分与壳核病变(B=-1.789,P=0.016)、额叶病变(B=-1.592,P=0.044)相关联。结论脑型WD患者较肝型有更高的数字成瘾倾向,数字成瘾倾向与冲动性相关。WD患者的数字成瘾倾向可能与壳核、丘脑、额叶等多个脑区病变引起的冲动控制障碍有关。展开更多
BACKGROUND Wilson disease(WD)is the most common genetic metabolic liver disease.Some studies have shown that comorbidities may have important effects on WD.Data on hepatitis B virus(HBV)infection in patients with WD a...BACKGROUND Wilson disease(WD)is the most common genetic metabolic liver disease.Some studies have shown that comorbidities may have important effects on WD.Data on hepatitis B virus(HBV)infection in patients with WD are limited.AIM To investigate the prevalence and clinical impact of HBV infection in patients with WD.METHODS The clinical data of patients with WD were analyzed retrospectively,and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD.RESULTS Among a total of 915 WD patients recruited,the total prevalence of current and previous HBV infection was 2.1%[95%confidence interval(CI):1.2%-3.0%]and 9.2%(95%CI:7.3%-11.1%),respectively.The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B(CHB)infection.The diagnosis of WD was missed in all but two patients with CHB infection.The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo,which was significantly longer than that in patients with isolated WD(10.5 mo).The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD(63.1%vs 19.3%,P=0.000 and 36.8%vs 4.1%,P<0.001,respectively).Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection[odds ratio(OR)=7.748;95%CI:2.890-20.774;P=0.000)]or previous HBV infection(OR=5.525;95%CI:3.159-8.739;P=0.000)than in patients with isolated WD.CONCLUSION The total prevalence of current HBV infection in patients with WD was 2.1%.The diagnosis of WD in CHB patients is usually missed.HBV infection is an independent risk factor for severe liver disease in WD patients.The diagnosis of WD should be ruled out in some patients with CHB infection.展开更多
Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q.This leads to copper deposition in various organs,most importantly in the liver and brain.The genetic mutations are ...Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q.This leads to copper deposition in various organs,most importantly in the liver and brain.The genetic mutations are vast,well reported in the West but poorly documented in developing countries.Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians.Diagnostic scoring systems are not fool-proof.The availability and affordability of chelators in developing countries impact the drug compliance of patients.While D-penicillamine is a potent drug,its side effects lead to drug discontinuation.Trientine is cost-prohibitive in developing countries.There is no single test to assess the adequacy of chelation.Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool.In the presence of cirrhosis,hypersplenism clouds the assessment of myelosuppression of drugs.Similarly,it may be difficult to distinguish disease tubulopathy from druginduced glomerulonephritis.Neurological worsening due to chelators may appear similar to disease progression.Presentation as fulminant hepatic failure requires rapid workup.There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices.This review addresses the challenges and clinical dilemmas faced at beside in developing countries.展开更多
文摘BACKGROUND Wilson disease(WD)is a progressive,potentially fatal degenerative disease affecting the liver and central nervous system.Given its low prevalence,collecting data on large cohorts of patients with WD is challenging.Comprehensive insur-ance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare diseases.AIM To describe patients with WD in the United States,their treatment and clinical outcome,using a large insurance claims database.METHODS This retrospective,longitudinal study was performed in the Clarivate Real-World Data Product database.All patients with≥2 claims associated with an Interna-tional Classification of Diseases 10(ICD-10)diagnostic code for WD(E83.01)between 2016 and 2021 were included and followed until death or study end.Patients were divided into two groups by whether or not they were documented to have received a specific treatment for WD.Clinical manifestations,hospital-isations,liver transplantation and death were documented.RESULTS Overall,5376 patients with an ICD-10 diagnostic code for WD were identified.The mean age at inclusion was 41.2 years and 52.0%were men.A specific WD treatment was documented for 885 patients(15.1%),although the number of patients taking zinc salts may be underestimated due to over the counter purchase.At inclusion,the mean age of patients with a documented treatment was 36.6±17.8 years vs 42.2±19.6 years in those without a documented treatment.During follow-up,273 patients(5.1%)died.Compared with the American general population,the standardised mortality ratio was 2.19.The proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0%and the mean age at death 52.7 years.CONCLUSION Patients treated for WD in the United States had an excess early mortality compared with the American population.These findings indicate that there is a significant unmet need for effective treatment for WD in the United States.
文摘目的探讨Wilson病(Wilson disease,WD)患者冲动性对数字成瘾倾向的影响及其相关因素。方法纳入66例WD患者为研究对象,根据临床表现分为脑型组42例、肝型组24例。采用网络成瘾量表(internet addiction test,IAT)评估患者网络成瘾倾向,总分>50分界定为具有网络成瘾倾向;使用Barratt冲动量表中文版(the Chinese version of the Barratt impulsiveness scale,11version,BIS-11-C)评估患者冲动性;手机依赖量表(mobile phone addiction index,MPAI)评估对手机使用的依赖程度;通过颅脑MRI检查患者病变脑区的部位和累计频次。结果66例WD患者中有数字成瘾倾向者45例(68.2%),其中脑型组中35例(53.0%)、肝型组中10例(15.2%),两组成瘾倾向者比例差异有统计学意义(P=0.001)。脑型组患者在BIS-11-C、MPAI量表多项因子分上高于肝型组(P<0.05)。所有患者MPAI量表中失控性因子分与BIS-11-C量表中的注意力冲动性因子分(r=0.499,P=0.001)、运动冲动性因子分(r=0.553,P=0.001)、无计划冲动性因子分(r=0.535,P=0.001)、冲动控制总分(r=0.653,P=0.001)正相关。线性回归分析显示注意力冲动性因子分与额叶病变(B=-1.634,P=0.018)相关联,失控性因子分与额叶病变(B=-3.609,P=0.023)相关联,戒断性因子分与丘脑病变(B=-5.047,P=0.007)、额叶病变(B=-2.204,P=0.024)相关联,逃避性因子分与顶叶病变(B=-1.867,P=0.032)相关联,低效性因子分与壳核病变(B=-1.789,P=0.016)、额叶病变(B=-1.592,P=0.044)相关联。结论脑型WD患者较肝型有更高的数字成瘾倾向,数字成瘾倾向与冲动性相关。WD患者的数字成瘾倾向可能与壳核、丘脑、额叶等多个脑区病变引起的冲动控制障碍有关。
文摘BACKGROUND Wilson disease(WD)is the most common genetic metabolic liver disease.Some studies have shown that comorbidities may have important effects on WD.Data on hepatitis B virus(HBV)infection in patients with WD are limited.AIM To investigate the prevalence and clinical impact of HBV infection in patients with WD.METHODS The clinical data of patients with WD were analyzed retrospectively,and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD.RESULTS Among a total of 915 WD patients recruited,the total prevalence of current and previous HBV infection was 2.1%[95%confidence interval(CI):1.2%-3.0%]and 9.2%(95%CI:7.3%-11.1%),respectively.The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B(CHB)infection.The diagnosis of WD was missed in all but two patients with CHB infection.The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo,which was significantly longer than that in patients with isolated WD(10.5 mo).The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD(63.1%vs 19.3%,P=0.000 and 36.8%vs 4.1%,P<0.001,respectively).Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection[odds ratio(OR)=7.748;95%CI:2.890-20.774;P=0.000)]or previous HBV infection(OR=5.525;95%CI:3.159-8.739;P=0.000)than in patients with isolated WD.CONCLUSION The total prevalence of current HBV infection in patients with WD was 2.1%.The diagnosis of WD in CHB patients is usually missed.HBV infection is an independent risk factor for severe liver disease in WD patients.The diagnosis of WD should be ruled out in some patients with CHB infection.
文摘Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q.This leads to copper deposition in various organs,most importantly in the liver and brain.The genetic mutations are vast,well reported in the West but poorly documented in developing countries.Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians.Diagnostic scoring systems are not fool-proof.The availability and affordability of chelators in developing countries impact the drug compliance of patients.While D-penicillamine is a potent drug,its side effects lead to drug discontinuation.Trientine is cost-prohibitive in developing countries.There is no single test to assess the adequacy of chelation.Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool.In the presence of cirrhosis,hypersplenism clouds the assessment of myelosuppression of drugs.Similarly,it may be difficult to distinguish disease tubulopathy from druginduced glomerulonephritis.Neurological worsening due to chelators may appear similar to disease progression.Presentation as fulminant hepatic failure requires rapid workup.There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices.This review addresses the challenges and clinical dilemmas faced at beside in developing countries.
