Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic fail...Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.展开更多
Wilson’s disease(WD)is an autosomal recessive inherited disorder of hepatic copper metabolism.WD can be present in different clinical conditions,with the most common ones being liver disease and neuropsychiatric dist...Wilson’s disease(WD)is an autosomal recessive inherited disorder of hepatic copper metabolism.WD can be present in different clinical conditions,with the most common ones being liver disease and neuropsychiatric disturbances.Most cases present symptoms at<40years of age.However,few reports exist in the literature on patients in whom the disease presented beyond this age.In this report,we present a case of late onset fulminant WD in a 58-year-old patient in whom the diagnosis was established clinically,by genetic analysis of the ATP7B gene disclosing rare mutations(G1099S and c.1707+3ins T)as well as by high hepatic copper content.We also reviewed the relevant literature.The diagnosis of WD with late onset presentation is easily overlooked.The diagnostic features and the geneticbackground in patients with late onset WD are not different from those in patients with early onset WD,except for the age.Effective treatments for this disorder that can be fatal are available and will prevent or reverse many manifestations if the disease is discovered early.展开更多
BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine trea...BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine treatment leading to decompensation of liver cirrhosis.CASE SUMMARY A healthy 51-year-old woman was diagnosed with liver cirrhosis due to decompensation with ascites.Etiologic evaluation raised suspicion of hereditary hemochromatosis because of compound heterozygosity HFE p.C282Y/p.H63D,and phlebotomy was started.Re-evaluation showed low ceruloplasmin,increased urinary copper excretion and the presence of Kayser-Fleischer rings.WD was confirmed by genetic analysis.Because of decompensated cirrhosis,she was referred for liver transplant evaluation.Simultaneously,treatment with trientine was initiated.Liver function initially stabilized,and the patient was not accepted for a liver transplant.Shortly after this,she developed severe hemorrhagic colitis,most probably a side effect of trientine.During that episode,she decompensated with hepatic encephalopathy.Because of a second decompensating event,she was accepted for liver transplantation,and an uneventful transplantation was carried out after clinical improvement of colitis.CONCLUSION Despite WD being a rare disorder,it is important to consider because it can present with a plethora of symptoms from childhood to an elderly age.Colitis should be recognized as a serious adverse drug reaction to trientine treatment that can result in decompensated liver disease.展开更多
Summary: To investigate the changes in neurological symptoms and signs, as well as serum copper, serum ceruloplasmin after hepatic transplantation in patients with Wilson’s disease, neurological symptoms and signs, s...Summary: To investigate the changes in neurological symptoms and signs, as well as serum copper, serum ceruloplasmin after hepatic transplantation in patients with Wilson’s disease, neurological symptoms and signs, serum copper, serum ceruloplasmin before and after hepatic transplantation in 18 patients with Wilson’s disease were observed, and those changes were followed up in 20 non-operative controls treated with penicillamine. Our results showed that the neurological symptoms and signs, serum copper and serum ceruloplasmin were improved in the operative group but deteriorated in the non-operative control group. Our study showed that hepatic transplantation is better than penicillamine in the treatment of Wilson’s disease.展开更多
Background and aims:There is currently no single model for predicting Wilson's disease(WD).We aimed to create a nomogram using daily clinical parameters to improve the accuracy of WD diagnosis in patients with abn...Background and aims:There is currently no single model for predicting Wilson's disease(WD).We aimed to create a nomogram using daily clinical parameters to improve the accuracy of WD diagnosis in patients with abnormal liver function.Methods:Between July 2016 and December 2020,we identified 90 WD patients with abnormal liver function who had homozygous or compound heterozygous mutations in the ATP7B gene.The control group included 128 patients with similar liver function but no WD during the same time period.To create a nomogram,we screened potential predictive variables using the least absolute shrinkage and selection operator model and multivariate logistic regression.Results:We developed a nomogram for screening for WD based on six predictive factors:serum copper,direct bilirubin,uric acid,cholinesterase,prealbumin,and reticulocyte percentage.In the training cohort,the area under curve(AUC)of the nomogram reached 0.967(95%confidence interval(CI)0.946e0.988),while the area under the precision-recall curve was 0.961.Based on the optimal cutpoint of 213.55,our nomogram performed well,with a sensitivity of 96%and a specificity of 87%.In the validation cohort,the AUC of the nomogram was as high as 0.991(95%CI 0.970e1.000).Conclusions:We developed a nomogram that can predict the risk of WD prior to the detection of serum ceruloplasmin or urinary copper,greatly increasing screening efficiency for patients with abnormal liver function.展开更多
OBJECTIVE: To evaluate the efficacy and safety of gandouling plus sodium dimercaptosulphonate(DMPS) on neurological Wilson's disease(WD) in patients.METHODS: We retrospectively evaluated the clinical records of 12...OBJECTIVE: To evaluate the efficacy and safety of gandouling plus sodium dimercaptosulphonate(DMPS) on neurological Wilson's disease(WD) in patients.METHODS: We retrospectively evaluated the clinical records of 125 WD patients with neurological syndromes who were treated with gandouling plus sodium DMPS or DMPS used alone. All patients had a history of neurological deterioration during their diseases courses. The clinical efficacies, adverse reactions, and results of the various hematological and biochemical investigations were recorded for statistical analysis.RESULTS: 92.30%(60 patients) of the WD patients treated with the combined therapy experienced an improved or stable neurological condition paral-leled by a significantly improved GAS score. Meanwhile, the WBC and PLT counts stabilized, liver function and renal function were improved or remained stable. The combined therapy also obviously promoted the 24-h urinary copper excretion. In particular, only 30.76% of the WD patients experienced mild adverse reactions, including neurological deterioration in 5 patients(7.69%), hepatic worsening in 1 subject(1.89%), which was less frequently than those in the control group treated with DMPS only.CONCLUSION: Our findings indicate that the safety and efficacy of gandou-ling plus DMPS is superior to those of DMPS used alone in the WD patients with neurological symptoms.展开更多
We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy(FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino ...We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy(FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the firststage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava(IVC). The orifices of the left, middle, and right hepatic veins were reconstructed using an iliac vein patch and then anastomosed to the right side of the IVC. Thirty days later, a second domino liver graft was implanted. The second domino graft was from a 3-yearold female child with an ornithine carbamyl enzyme defect, and it replaced the residual native liver(left lobe). To balance the function and blood flow between the two grafts, a percutaneous transcatheter selective portal vein embolization was performed, and "the left portal vein" of the first graft was blocked 9 mo after the second transplantation. The liver function indices, blood ammonia, and 24-h urinary copper levels were normal at the end of a 3-year follow-up. These two domino donor grafts from donors with different metabolic disorders restored normal liver function. Our experience demonstrated a new approach for resolving metabolic disorders with domino grafts and utilizing explanted livers from children.展开更多
Background: Medical therapy is rarely effective inpatients with fulminant Wilson's disease (FWD). Livertransplantation is limited by the lack of donor liver inmost patients with FWD at the time of diagnosis. NewWi...Background: Medical therapy is rarely effective inpatients with fulminant Wilson's disease (FWD). Livertransplantation is limited by the lack of donor liver inmost patients with FWD at the time of diagnosis. NewWilson's index, model for end-stage liver disease (MELD)and Child-Pugh score are useful tools for decisionmakingof liver transplantation;however, none of them isan independent decisive tool. It is worthwhile to explorea more effective and practical therapeutic strategy andreevaluate the prediction systems for patients with FWD.Methods: Nine patients with FWD associated withhemolytic crisis and fulminant hepatic failure (FHF) wereinvestigated. The clinical presentation, prognostic scoreand medical therapies of the patients were analyzed.Results: In 7 of the 9 patients with FWD who receivedthe comprehensive therapy of corticosteroid, copperchelatingagent (dimercaptopropansulfonate sodium)and therapeutic plasma exchange (TPE), 6 patientsrecovered from FHF. The remaining one had beenimproved through the comprehensive therapy but died ofsepticemia 51 days later. Two patients with spontaneousbacterial peritonitis (SBP) died from liver failure inthree or five hospital days without plasma exchangeor chelating therapy. All of the 9 patients with FWDpresented with acute hepatic failure, severe jaundice andmild to severe hemolytic anemia. No marked differencein the incidence of severe hemolytic anemia was detectedbetween the survival and deceased groups. However,the incidence and the degree of hepatic encephalopathy(HE) in the non-survival group were higher than thosein the survival group. Unlike the deceased group, thesurvival group had no complications induced by bacterialinfection. Compared to new Wilson's index, Child-Pughscore and MELD score, the variation of prothrombinactivity (PTA) between the survival and deceased groupswas more evident.Conclusions: For patients with FWD, the episodeof severe hepatic encephalopathy or/and spontaneousbacterial peritonitis indicates worse prognosis, andPTA is a recommendable predictor. An emergent livertransplantation should be considered for patients whosePTA is below 20%, or for those with severe HE or/and SBP. The comprehensive therapy of corticosteroid,copper-chelating agent and TPE is effective for patientswithout SBP and whose PTA is higher than 20%.展开更多
文摘Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.
文摘Wilson’s disease(WD)is an autosomal recessive inherited disorder of hepatic copper metabolism.WD can be present in different clinical conditions,with the most common ones being liver disease and neuropsychiatric disturbances.Most cases present symptoms at<40years of age.However,few reports exist in the literature on patients in whom the disease presented beyond this age.In this report,we present a case of late onset fulminant WD in a 58-year-old patient in whom the diagnosis was established clinically,by genetic analysis of the ATP7B gene disclosing rare mutations(G1099S and c.1707+3ins T)as well as by high hepatic copper content.We also reviewed the relevant literature.The diagnosis of WD with late onset presentation is easily overlooked.The diagnostic features and the geneticbackground in patients with late onset WD are not different from those in patients with early onset WD,except for the age.Effective treatments for this disorder that can be fatal are available and will prevent or reverse many manifestations if the disease is discovered early.
文摘BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine treatment leading to decompensation of liver cirrhosis.CASE SUMMARY A healthy 51-year-old woman was diagnosed with liver cirrhosis due to decompensation with ascites.Etiologic evaluation raised suspicion of hereditary hemochromatosis because of compound heterozygosity HFE p.C282Y/p.H63D,and phlebotomy was started.Re-evaluation showed low ceruloplasmin,increased urinary copper excretion and the presence of Kayser-Fleischer rings.WD was confirmed by genetic analysis.Because of decompensated cirrhosis,she was referred for liver transplant evaluation.Simultaneously,treatment with trientine was initiated.Liver function initially stabilized,and the patient was not accepted for a liver transplant.Shortly after this,she developed severe hemorrhagic colitis,most probably a side effect of trientine.During that episode,she decompensated with hepatic encephalopathy.Because of a second decompensating event,she was accepted for liver transplantation,and an uneventful transplantation was carried out after clinical improvement of colitis.CONCLUSION Despite WD being a rare disorder,it is important to consider because it can present with a plethora of symptoms from childhood to an elderly age.Colitis should be recognized as a serious adverse drug reaction to trientine treatment that can result in decompensated liver disease.
文摘Summary: To investigate the changes in neurological symptoms and signs, as well as serum copper, serum ceruloplasmin after hepatic transplantation in patients with Wilson’s disease, neurological symptoms and signs, serum copper, serum ceruloplasmin before and after hepatic transplantation in 18 patients with Wilson’s disease were observed, and those changes were followed up in 20 non-operative controls treated with penicillamine. Our results showed that the neurological symptoms and signs, serum copper and serum ceruloplasmin were improved in the operative group but deteriorated in the non-operative control group. Our study showed that hepatic transplantation is better than penicillamine in the treatment of Wilson’s disease.
基金supported by the Science and Technology Planning Project of Guangdong Province,China(2019B020228001)National Key R&D Program of China(2018YFC1315400)5010 Project of Sun Yat-sen University(No.2018024).
文摘Background and aims:There is currently no single model for predicting Wilson's disease(WD).We aimed to create a nomogram using daily clinical parameters to improve the accuracy of WD diagnosis in patients with abnormal liver function.Methods:Between July 2016 and December 2020,we identified 90 WD patients with abnormal liver function who had homozygous or compound heterozygous mutations in the ATP7B gene.The control group included 128 patients with similar liver function but no WD during the same time period.To create a nomogram,we screened potential predictive variables using the least absolute shrinkage and selection operator model and multivariate logistic regression.Results:We developed a nomogram for screening for WD based on six predictive factors:serum copper,direct bilirubin,uric acid,cholinesterase,prealbumin,and reticulocyte percentage.In the training cohort,the area under curve(AUC)of the nomogram reached 0.967(95%confidence interval(CI)0.946e0.988),while the area under the precision-recall curve was 0.961.Based on the optimal cutpoint of 213.55,our nomogram performed well,with a sensitivity of 96%and a specificity of 87%.In the validation cohort,the AUC of the nomogram was as high as 0.991(95%CI 0.970e1.000).Conclusions:We developed a nomogram that can predict the risk of WD prior to the detection of serum ceruloplasmin or urinary copper,greatly increasing screening efficiency for patients with abnormal liver function.
基金Supported by National Natural Science Foundation of China(No.81673811,81473534,81774299)
文摘OBJECTIVE: To evaluate the efficacy and safety of gandouling plus sodium dimercaptosulphonate(DMPS) on neurological Wilson's disease(WD) in patients.METHODS: We retrospectively evaluated the clinical records of 125 WD patients with neurological syndromes who were treated with gandouling plus sodium DMPS or DMPS used alone. All patients had a history of neurological deterioration during their diseases courses. The clinical efficacies, adverse reactions, and results of the various hematological and biochemical investigations were recorded for statistical analysis.RESULTS: 92.30%(60 patients) of the WD patients treated with the combined therapy experienced an improved or stable neurological condition paral-leled by a significantly improved GAS score. Meanwhile, the WBC and PLT counts stabilized, liver function and renal function were improved or remained stable. The combined therapy also obviously promoted the 24-h urinary copper excretion. In particular, only 30.76% of the WD patients experienced mild adverse reactions, including neurological deterioration in 5 patients(7.69%), hepatic worsening in 1 subject(1.89%), which was less frequently than those in the control group treated with DMPS only.CONCLUSION: Our findings indicate that the safety and efficacy of gandou-ling plus DMPS is superior to those of DMPS used alone in the WD patients with neurological symptoms.
基金Supported by Capital Special Program for Health Research and Development,No.2016-1-2021National Key Technologies R&D Program,No.2015BAI13B09+1 种基金The Training Program of Academic Leaders in Beijing Health System,No.2014-2-002Beijing Municipal Administration of Hospitals Ascent Plan,No.DFL20150101
文摘We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy(FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the firststage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava(IVC). The orifices of the left, middle, and right hepatic veins were reconstructed using an iliac vein patch and then anastomosed to the right side of the IVC. Thirty days later, a second domino liver graft was implanted. The second domino graft was from a 3-yearold female child with an ornithine carbamyl enzyme defect, and it replaced the residual native liver(left lobe). To balance the function and blood flow between the two grafts, a percutaneous transcatheter selective portal vein embolization was performed, and "the left portal vein" of the first graft was blocked 9 mo after the second transplantation. The liver function indices, blood ammonia, and 24-h urinary copper levels were normal at the end of a 3-year follow-up. These two domino donor grafts from donors with different metabolic disorders restored normal liver function. Our experience demonstrated a new approach for resolving metabolic disorders with domino grafts and utilizing explanted livers from children.
基金supported by Hunan Province Scientifi c Fund of Department of Health(B2006-052)the Project of New Clinic Techniques of Central South University.
文摘Background: Medical therapy is rarely effective inpatients with fulminant Wilson's disease (FWD). Livertransplantation is limited by the lack of donor liver inmost patients with FWD at the time of diagnosis. NewWilson's index, model for end-stage liver disease (MELD)and Child-Pugh score are useful tools for decisionmakingof liver transplantation;however, none of them isan independent decisive tool. It is worthwhile to explorea more effective and practical therapeutic strategy andreevaluate the prediction systems for patients with FWD.Methods: Nine patients with FWD associated withhemolytic crisis and fulminant hepatic failure (FHF) wereinvestigated. The clinical presentation, prognostic scoreand medical therapies of the patients were analyzed.Results: In 7 of the 9 patients with FWD who receivedthe comprehensive therapy of corticosteroid, copperchelatingagent (dimercaptopropansulfonate sodium)and therapeutic plasma exchange (TPE), 6 patientsrecovered from FHF. The remaining one had beenimproved through the comprehensive therapy but died ofsepticemia 51 days later. Two patients with spontaneousbacterial peritonitis (SBP) died from liver failure inthree or five hospital days without plasma exchangeor chelating therapy. All of the 9 patients with FWDpresented with acute hepatic failure, severe jaundice andmild to severe hemolytic anemia. No marked differencein the incidence of severe hemolytic anemia was detectedbetween the survival and deceased groups. However,the incidence and the degree of hepatic encephalopathy(HE) in the non-survival group were higher than thosein the survival group. Unlike the deceased group, thesurvival group had no complications induced by bacterialinfection. Compared to new Wilson's index, Child-Pughscore and MELD score, the variation of prothrombinactivity (PTA) between the survival and deceased groupswas more evident.Conclusions: For patients with FWD, the episodeof severe hepatic encephalopathy or/and spontaneousbacterial peritonitis indicates worse prognosis, andPTA is a recommendable predictor. An emergent livertransplantation should be considered for patients whosePTA is below 20%, or for those with severe HE or/and SBP. The comprehensive therapy of corticosteroid,copper-chelating agent and TPE is effective for patientswithout SBP and whose PTA is higher than 20%.
