The role and evolution of partial splenic embolization over three decades: A multicentric retrospective single cohort study of 90 patients from French nationwide experience.

BACKGROUND: Partial splenic embolization (PSE) has been proposed to treat the consequences of hypersplenism in the context of portal hypertension, especially thrombocytopenia. However, a high morbidity/mortality rate has made this technique unpopular. We conducted a multicenter retrospective nationwide French study to reevaluate efficacy and tolerance. METHODS: All consecutive patients who underwent PSE for hypersplenism and portal hypertension in 7 tertiary liver centers between 1998 and 2023 were included. RESULTS: The study population consisted of 91 procedures in 90 patients, with a median age of 55.5 years [range 18-83]. The main cause of portal hypertension was cirrhosis (84.6 %). The main indications for PSE were (1) an indication of medical treatment or radiological/surgical procedure in the context a severe thrombocytopenia (59.3 %), (2) a chronic hemorrhagic disorder associated with a severe thrombocytopenia (18.7 %), and (3) a chronic pain associated with a major splenomegaly (9.9 %). PSE was associated with a transjugular intrahepatic portosystemic shunt in 20 cases. Median follow-up after PSE was 41.9 months [0.5-270.5]. Platelet count increased from a median of 48.0 G/L [IQR 37.0; 60.0] to 100.0 G/L [75.0; 148]. Forty-eight patients (52.7 %) had complications after PSE; 25 cases were considered severe (including 7 deaths). A Child-Pugh B-C score (p < 0.02) was significantly associated with all complications, a history of portal vein thrombosis (p < 0.01), and the absence of prophylactic antibiotherapy (p < 0.05) with severe complications. CONCLUSION: Our results strongly confirm that PSE is very effective, for a long time, although a quarter of the patients experienced severe complications. Improved patient selection (exclusion of patients with portal vein thrombosis and decompensated cirrhosis) and systematic prophylactic antibiotherapy could reduce morbidity and early mortality in the future.

Phenotype and molecular characterization of Wilson's disease in Morocco.

BACKGROUND AND STUDY AIMS: In Morocco the prevalence of Wilson disease (WD) and the spectrum of mutations are not known. The aim of the present study was to estimate the prevalence of WD in Morocco, to evaluate the phenotype among a large cohort of WD patients, and to characterize ATP7B variants in a subgroup of WD patients. PATIENTS AND METHODS: We collected data from 226 patients admitted to five university hospital centers in Morocco between 2008 and 2020. The diagnosis was based on clinical manifestations, function tests and biochemical parameters. The genotype was characterized in 18 families diagnosed at the University Hospital Center of Marrakesh, by next generation sequencing. RESULTS: The mean annual prevalence in Morocco was 3.88 per 100,000 and the allele frequency was 0.15 %. Among the 226 patients included (121 males and 105 females), 196 were referred for a hepatic or neurological involvement and 30 were asymptomatic. The mean age at diagnosis was 13 ± 5.1 years (range: 5 - 42 years). Consanguinity was found in 63.3 % of patients. The mean duration of illness was 2.8 ± 1.9 years. Kayser-Fleischer rings were found in 131 (67.9 %) of 193 patients. Among the 196 symptomatic patients, 141/159 (88.7 %) had low serum ceruloplasmin (<0.2 g/L) and a high 24-hours urinary copper (>100 µg/day) was found in 173/182 (95.1 %) patients. The initial treatment was D-penicillamine in 207 patients, zinc acetate in five, zinc sulfate in five, and nine patients were not treated; 60/207 (29 %) patients have stopped treatment. A total of 72 patients died; the mortality rate was 31.9 %. Eight different ATP7B variants were identified among the 18 patients studied, of which two were novel (p.Cys1104Arg and p.Gln1277Hisfs*52), and six previously published (p.Gln289Ter, p.Cys305Ter, p.Thr1232Pro, p.Lys1020Arg, p.Glu583ArgfsTer25 and c.51+4A>T). All informative patients were homozygous for the disease-causing mutation. CONCLUSION: In Morocco, a high prevalence due to consanguinity and a high mortality rate due to the difficulty of diagnosis and lack of treatment were observed in WD patients. NGS sequencing identified new ATP7B variants in WD patients from Morocco.

Autoimmune hepatitis recurrence after liver transplantation: "Les jeux sont faits".

Autoimmune hepatitis (AIH) may recur after liver transplantation (LT). The aims of this study were to evaluate the incidence and risk factors for recurrent autoimmune hepatitis (rAIH). A multicenter retrospective French nationwide study, including all patients aged ≥16 transplanted for AIH, with at least 1 liver biopsy 1 year after LT, was conducted between 1985 and 2018. Risk factors for rAIH were identified using a multivariate Cox regression model. Three hundred and forty-four patients were included (78.8% women) with a median age at LT of 43.6 years. Seventy-six patients (22.1%) developed recurrence in a median time of 53.6 months (IQR, 14.1-93.2). Actuarial risk for developing rAIH was 41.3% 20 years after LT. In multivariate analysis, the strongest risk factor for rAIH was cytomegalovirus D+/R- mismatch status (HR=2.0; 95% CI: 1.1-3.6; p =0.03), followed by associated autoimmune condition. Twenty-one patients (27.6% of rAIH patients) developed liver graft cirrhosis after rAIH. Independent risk factors for these severe forms of rAIH were young age at LT, IgG levels >20.7 g/L, and LT in the context of (sub)fulminant hepatitis. Immunosuppression, especially long-term maintenance of corticosteroid therapy, was not significantly associated with rAIH. Recurrence of AIH after LT is frequent and may lead to graft loss. Recurrence is more frequent in young patients with active disease at the time of LT, yet systematic corticosteroid therapy does not prevent it.

Dual alcohol and metabolic-related liver disease: Results from a population of liver transplant patients.

BACKGROUND & AIMS: If alcohol-related liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are now the two main indications for liver transplantation (LT), it has been recognized that both conditions can coexist in varying degrees and the concept of dual-aetiology fatty liver disease (DAFLD) has been proposed. This retrospective study aimed to evaluate, in a cohort of patients transplanted for ALD and NAFLD, the prevalence of DAFLD before LT and the impact on liver graft outcome. METHODS: From 1990 to 2010, all patients who underwent LT for the so-called ALD or NAFLD in our centre were included. Before LT, DAFLD was defined as patients with a history of excessive alcohol consumption and obesity associated with either diabetes or hypertension. Before LT, patients were separated into three groups: DAFLD, ALD, and NAFLD. Fatty liver graft disease was classified according to the FLIP algorithm. RESULTS: Out of 907, adult LT recipients were identified: 33 DAFLD patients, 333 ALD patients, and 24 NAFLD patients. After LT, ALD patients experienced significantly more alcohol relapse than DAFLD patients, who had twice more post-LT metabolic syndrome. Out of 926, post-LT biopsies, DAFLD patients had significantly more fatty liver graft disease due to metabolic syndrome features than ALD patients. CONCLUSION: Our results support that DAFLD recently emerged as an indication of LT. In the future, this particular population needs to be identified as a specific entity since post-LT outcome on the graft is different from ALD and more similar to NAFLD patients.

Histological features of liver disease development in the Atp7b-/- mouse: a model of Wilson's disease.

AIMS: Wilson's disease (WD) is caused by mutations in the ATP7B gene, resulting in copper accumulation and toxicity in liver and brain tissues. Due to the initial asymptomatic liver involvement, the progression of liver injuries in WD stays primarily unknown. Atp7b-/- knockout mice have been shown to be an appropriate model of WD for liver involvement. METHODS: A total of 138 Atp7b-/- mice were included and separated into five groups according to age as follows: 6, 20, 39 and 50 weeks without treatment, and 50 weeks with copper chelator treatment from 39 to 50 weeks of age and compared with 101 wild-type (WT) mice at the same stages. The evolution of histological liver lesions was analysed and compared between groups. RESULTS: Significant changes were observed in Atp7b-/- mice compared with WT. Copper deposits in hepatocytes appeared as early as 6 weeks but no significant increase over time was observed. Inflammation appeared as early as 6 weeks and progressed henceforth. Lobular and periportal acidophilic bodies appeared after 20 weeks. Significant atypia was also observed at 20 weeks and increased over time to reach a severe stage at 39 weeks. Fibrosis also became apparent at 20 weeks, progressing subsequently to precirrhotic stages at 50 weeks. Copper content, inflammation and fibrosis scores were significantly reduced in the treated group. No bile duct lesions or dysplastic changes were noted. CONCLUSIONS: Copper accumulation leads to progressive changes in Atp7b-/- mice regarding inflammation, fibrosis and atypia. The severity of liver damage is lessened by chelation therapy.

Determinants of early surgical complications after pediatric liver transplantation: A single center/single surgeon experience over 20 years.

BACKGROUND: The risk of early surgical complications of liver transplantation (LT) is higher in children when compared with adults. The aims of the present retrospective study from a single center cohort/single surgeon were to identify the predictive factors for surgical complications after pediatric LT. METHODS: All children receiving a first LT from October 1990 to October 2010 in our center were included. RESULTS: Included 151 children (boys 55.0%), with a mean age of 4.8 ± 4.8 years, and a mean weight of 17.9 ± 14.4 kg. Thirty-seven patients were transplanted within the first year, and 59 patients had a body weight below 10 kg. The main initial liver disease was biliary atresia (49.0%). Living donor LT was performed in 39 cases (25.8%), cadaveric whole liver LT in 50 cases (33.1%), and cadaveric partial liver LT in 62 cases (41.1%). Early surgical complications included reoperation (37.8%), vascular complications (8.6%), i.e. arterial (3.3%) or portal thrombosis/stenosis (7.3%) within the first month, and biliary complications in the first 90 days occurred in 22.5% of the cases. The main indications for surgical revision were abdominal bleeding, treatment of a biliary complication, and bowel perforation. Multivariate analysis disclosed that only graft type (split and moreover from a living donor) was significantly and independently associated with the occurrence of biliary complication, and that indication for LT, period, graft type, and operative time were significantly and independently associated with the necessity of surgical revision. CONCLUSION: Our results emphasize that surgical complications are frequent and strongly depend on patient/graft characteristics.

Evaluation of vitamin B6 supplementation in Wilson's disease patients treated with D-penicillamine.

INTRODUCTION: Wilson's disease (WD) is a copper metabolism disorder characterised by a progressive accumulation of this metal mainly in the liver and the brain. Treatment is based on the removal of copper operated by the chelators, among which, D-penicillamine (DP) is prescribed as a first-line treatment in most situations. There is some evidence in linking the use of DP with a risk of vitamin B6; therefore, vitamin supplementation is sometimes recommended, although non-consensually. The objective of our study was to evaluate the level of vitamin B6 in WD patients treated with DP with and without associated supplementation. METHODOLOGY: All WD patients followed at the National Reference Centre for WD in Lyon between January 2019 and December 2020 treated with DP for more than 1 year were included and separated in two groups according to vitamin B6 supplementation. The level of vitamin B6 was measured by the determination of pyridoxal phosphate (PLP). RESULTS: A total of 37 patients were included. Average age of 23.3±14.8 years, 15 patients with <18 years. Median duration of treatment was 51 (55.8) months. 15 patients were under vitamin B6 supplementation and 22 had interrupted it for more than 1 year. The median PLP level was significantly higher in the group with supplementation, 137.2 (86.7) nmol/L vs 64.9 (30.8) nmol/(p<0.01). No patient had a PLP level<35 nmol/L. CONCLUSION: Long-term stable WD patients under DP treatment probably do not need vitamin B6 supplementation.

Alpha1-antitrypsin deficiency: An updated review.

Alpha1-antitrypsin deficiency (AATD) is a rare autosomal recessive disease associated with the homozygous Z variant of the SERPINA1 gene. Clinical expression of AATD, reported 60 years ago associate a severe deficiency, pulmonary emphysema and/or liver fibrosis. Pulmonary emphysema is due to the severe alpha1-antitrypsin deficiency of the ZZ homozygous status and is favored by smoking. Liver fibrosis is due to the ZZ homozygous status and is favored by obesity and excessive chronic alcohol intake, with a risk of liver cancer. Diagnosis is based on serum level and either isoelectric focusing determination of the biochemical phenotype or PCR detection of some variants. SERPINA1 gene sequencing is necessary in case of discrepancies between the results of these tests. No treatment is available for the liver disease in AATD. Although no specific trial has been performed, COPD in AATD should be treated as per COPD recommendations. Based on a randomized clinical trial, augmentation therapy is indicated in non-smoking adults less than 70 years of age with emphysema at chest CT, confirmed homozygous AATD, and FEV1 between 35% and 70% of predicted. In contrast Z heterozygosis (MZ or SZ) brings a risk of lung or liver disease only in association with further risk factors. Early detection, in all patients with COPD and chronic liver disease, is critical for the correct information of Z variant carriers. News ways of correcting the liver production of alpha1-antitrypsin will modify the care of AATD patients.

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH). METHODS: A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded. RESULTS: The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4-53.8). Median follow-up was 87.0 months (IQR, 43.5-168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4-6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2-5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5-5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4-6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2-3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0-3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2-3.5; p = 0.006) complications. CONCLUSION: Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.

Wilson Disease and Alpha1-Antitrypsin Deficiency: A Review of Non-Invasive Diagnostic Tests.

Wilson disease and alpha1-antitrypsin deficiency are two rare genetic diseases that may impact predominantly the liver and/or the brain, and the liver and/or the lung, respectively. The early diagnosis of these diseases is important in order to initiate a specific treatment, when available, ideally before irreversible organ damage, but also to initiate family screening. This review focuses on the non-invasive diagnostic tests available for clinicians in both diseases. These tests are crucial at diagnosis to reduce the potential diagnostic delay and assess organ involvement. They also play a pivotal role during follow-up to monitor disease progression and evaluate treatment efficacy of current or emerging therapies.

Diagnosis and Outcomes of Late-Onset Wilson's Disease: A National Registry-Based Study.

BACKGROUND: Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late-onset forms. OBJECTIVE: The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late-onset WD. METHODS: Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow-up. RESULTS: Forty-five patients were identified (median age: 49, range: 40-64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser-Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24-h urinary copper excretion was normal in 33% of patients at diagnosis. CONCLUSIONS: In the FWDR, late-onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long-lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Liver transplantation for autoimmune hepatitis: Pre-transplant does not predict the early post-transplant outcome.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a rare indication (<5%) for liver transplantation (LT). The aim of this study was to describe the early outcome after LT for AIH. METHODS: A multicenter retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Occurrences of biliary and vascular complications, rejection, sepsis, retransplantation and death were collected during the first year after LT. RESULTS: A total of 344 patients (78.8% of women, 17.0% of (sub)fulminant hepatitis and 19.2% of chronic liver diseases transplanted in the context of acute-on-chronic liver failure [ACLF]) were included, with a median age at LT of 43.6 years. Acute rejection, sepsis, biliary and vascular complications occurred in respectively 23.5%, 44.2%, 25.3% and 17.4% of patients during the first year after LT. One-year graft and patient survivals were 84.3% and 88.0% respectively. The main cause of early death was sepsis. Pre-LT immunosuppression was not associated with an increased risk for early infections or surgical complications. Significant risk factors for septic events were LT in the context of (sub)fulminant hepatitis or ACLF, acute kidney injury at the time of LT (AKI) and occurrence of biliary complications after LT. AKI was the only independent factor associated with graft (HR = 2.5; 95% CI: 1.1-5.4; p = .02) and patient survivals (HR = 2.6; 95% CI: 1.0-6.5; p = .04). CONCLUSION: Early prognosis is good after LT for AIH and is not impacted by pre-LT immunosuppression but by the presence of AKI at the time of LT.

Antineoplastic chemotherapy and immunosuppression in liver transplant recipients: Squaring the circle?

BACKGROUND: Malignancies are a major cause of late death after liver transplantation (LT). In LT recipients presenting a malignancy, antineoplastic chemotherapy is central part of the therapeutic arsenal, but management of both immunosuppressive and antineoplastic chemotherapy can be very challenging. The aim of the present retrospective study was to describe a recent single center cohort of LT recipients treated with antineoplastic cytotoxic chemotherapy. METHODS: All LT recipients who received antineoplastic chemotherapy in our center between 2005 and 2021 were included. RESULTS: The study population included 72 antineoplastic chemotherapy courses in 69 patients. There was a majority of men (81.9%); median age at LT was 54.9 (range 1-68) and was 63.0 (18-79) at the diagnosis of malignancy. Lung carcinomas (23.6%), head and neck carcinomas (20.8%), lymphomas (16.7%), and recurrent hepatocellular carcinoma (HCC) (8.3%) were the most frequent malignancies. Neoadjuvant (30.6%), adjuvant (12.5%) or palliative (54.2%) chemotherapy was performed. Immunosuppressive regimen was modified from a calcineurin inhibitor (CNI)-based to an everolimus-based regimen (63.5% of CNI discontinuation). Median survival after diagnosis of malignancy was 22.5 months and 5-year survival was 30.1%. Chemotherapy regimen was considered optimal in 81.9% of the cases. Multivariate analysis disclosed that non-PTLD N+ stage malignancy (HR = 5.52 95%CI [1.40;21.69], p = .014), non-PTLD M+ stage malignancy (HR = 10.55 95%CI [3.20;34.73], p = .0001), and suboptimal chemotherapy (HR = 2.73 95%CI [1.34;5.56], p = .005) were significantly associated with poorer prognosis. No rejection episode occurred during chemotherapy. CONCLUSIONS: The present study is the first one focused on antineoplastic chemotherapy in LT recipients. Our results suggest that immunosuppressive drugs and antineoplastic chemotherapy can be managed satisfactorily in most cases but this needs confirmation from larger cohorts.

Long-Term Urinary Copper Excretion and Exchangeable Copper in Children With Wilson Disease Under Chelation Therapy.

OBJECTIVES: Determining 24-hour urinary copper excretion (UCE) levels is useful for diagnosing Wilson's disease (WD) and for treatment monitoring. Exchangeable copper (ExC) is a novel potential marker, but its long-term changes have never been described in patients under chelation therapy. Our aim was to describe the long-term changes in ExC levels compared to UCE levels in symptomatic WD pediatric patients under chelation therapy. METHODS: A retrospective, descriptive, and analytical study including all patients under 18 years of age, diagnosed between 2006 and 2020, and treated with chelation therapy was conducted at the National Reference Center for WD in Lyon. Ceruloplasmin levels, serum copper, 24 h-UCE, ExC, and liver enzymes at diagnosis and during follow-up were analyzed. RESULTS: Our study included 36 patients, predominantly with hepatic form of WD (n = 31). The median [interquartile range (IQR)] age at diagnosis was 10.5 (8.4-13.1) years, and the median (IQR) follow-up duration was 6.3 (3.3-8.8) years. At diagnosis, the median (IQR) ExC value was 1.01 (0.60-1.52) µmol/L. There was a significant decrease during the first year of chelation treatment ( P = 0.0008), then a stabilization. The median (IQR) ExC values was 0.38 (0.22-0.63) µmol/L at 12-18 months and 0.43 (0.31-0.54) µmol/L at 5 years of chelation treatment ( P = 0.4057). Similarly, there was a significant decrease in 24-hour UCE ( P < 0.001) during the first year of chelation treatment, then a stabilization. CONCLUSIONS: Our study showed a significant decrease in ExC and 24-hour UCE levels during the first year of follow-up; The dynamics of both biomarkers were similar along the follow-up, demonstrating their usefulness in clinical practice for monitoring WD.

Prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis.

BACKGROUND AND AIMS: Recurrent liver/biliary sepsis are rare and can occur in different situations. Curative treatment of acute septic episodes is based on antibiotics. Nevertheless, recurrent sepsis can be life-threatening, and the treatment of the underlying disease could be complex, and eventually not possible. The aim of the present study was to report our experience on prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in a large cohort of patients with long follow-up. METHODS: All patients who received a prophylactic sequential antibiotic therapy for recurrent liver/biliary sepsis in our institution from 2005 to 2020 were included. Prophylactic sequential antibiotic therapy was based on per os antibiotics with expected antibacterial activity on digestive bacteria, mainly Gram-negative bacilli. The primary end-point was the reduction of the number of septic episodes to 1 or less episode per year, and not severe (not requiring hospitalization). RESULTS: Were included 33 adult patients and the main initial disease/condition leading to prophylaxis was history of hepaticojejunostomy (78.8%). The majority of septic episodes required hospitalization (57.6%). First line prophylactic sequential antibiotic therapy was weekly ciprofloxacin in all cases. First line therapy was successful in the long-term in 19 patients (57.6%), with a median follow-up of 92 months (range: 25-206). Global efficacy (first-second-third lines) was 28/33 (84.8%). CONCLUSIONS: The results of the present study with very long follow-up suggest that prophylactic sequential antibiotic therapy can successfully prevent recurrent liver/biliary sepsis with good tolerance.

Maintenance therapy simplification using a single daily dose: A preliminary real-life feasibility study in patients with Wilson disease.

BACKGROUND: Single daily dose (SDD) is a good way to improve adherence by simplifying treatment. Efficacy data concerning patients with Wilson disease (WD) taking an SDD are lacking. AIM: To report the effectiveness of the use of SDD for the treatment of WD. METHODS: This retrospective study included WD patients followed in the French National Network who received an SDD in maintenance phase. The treatment failure was defined as a composite criterion with the occurrence of at least one of the following criterion: death, transplantation, increase of transaminases >2xULN, hepatic decompensation, neurological aggravation, severe side effects related to treatment, and/or discontinuation of treatment. RESULTS: A total of 26 patients received an SDD (D-penicillamine=13, trientine=8, zinc=5) after a median interval of 152 months after diagnosis. After one year, two patients had treatment failure: transaminitis in one, continuation of neurological deterioration in the other related to a poor compliance. After a median duration of 41 months on SDD, 3 other patients had treatment failure (transaminitis=2, treatment discontinuation=1). There was no death, no liver transplantation, no hepatic decompensation, and no severe side effects related to treatment during the follow-up. Moreover, transaminases and serum exchangeable copper were not significantly different 1 year post-switch and at last follow-up compared to baseline. CONCLUSIONS: Maintenance therapy simplification through the use of an SDD could be considered in some WD patients. In this pilot study, SDD was effective in 21/26 patients (81%) without any concern regarding safety.

Non-invasive diagnosis and follow-up of rare genetic liver diseases.

Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease and alpha-1 antitrypsin deficiency must be investigated in any patient with unexplained liver disease. Cystic fibrosis screening of new-borns is now implemented in most high-prevalence countries. The diagnosis of these diseases can be strongly suggested with specific non-invasive tests. Molecular analysis gene for these diseases is long and tedious but is recommended to confirm the diagnosis and help for the family screening. Liver biopsy is not systematic and is discussed when it helps diagnosis. Currently, for these three diseases, non-invasive fibrosis markers could identify patients with risk of cirrhosis and complications. Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease, must be investigated in any patient with unexplained liver disease and/or unexplained neurological or neuropsychiatric disorders. The diagnosis is based on a combination of clinical, biological features, including copper balance. The exchangeable copper/total copper ratio is a new sensible and specific biological marker, useful for the diagnosis of the disease. Timely diagnosis and treatment will prevent serious complications from the disease. Neurological evaluation and familial screening are essential in patients with Wilson's disease.

Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation. RESULTS: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM. CONCLUSION: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.