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Conflict of interest: No Introduction and Objectives: Wilson's disease (WD) is a rare genetic disease presenting more than 900 mutations in the ATP7B gene. The knowledge of the regional distribution of these mutations can improve the diagnosis of WD. We aimed to evaluate the frequency of ATP7B mutations in a WD Brazilian cohort and the association with disease phenotypes. Patients / Materials and Methods: We performed molecular analysis by NGS of the 21 exons of ATP7B (Mendelics Genomic Analysis Laboratory) in patients with diagnosis of WD and in first-degree relatives undergoing WD investigation, followed in a single hepatology center. Demographic data and predominant type of WD presentation were assessed. Results and Discussion: 28 patients were included (60% female; mean age 25 ± 13 years): 25 had an established diagnosis of WD and 3 were heterozygous relatives without disease. The phenotypes of WD were as follows: 15/25 (60%) with exclusively hepatic manifestation, 8/25 (32%) combination of hepatic and neurological, 1/25 (4.0%) isolated neurological manifestations and 1/25 (4.0%) were pre-symptomatic. We identified 17 ATP7B gene distinct mutations. The pathogenic variants c.3402delC, c.2123T>C and c.3818C>T presented the highest allele frequency, respectively, 25.5%, 15.7% and 15.7%. The majority (80.0%) presented the mutation in compound heterozygosity, 12.0% ​​in homozygosity and 8.0% in simple heterozygosity. The c.2145C>T, c.1552T>C and c.3188C>T variants were considered of undetermined significance; c.2072G>T and c.3071_3072delTG variants were considered probably pathogenic. Regarding the disease phenotype, patients with mutations c.3402delC CG>C and c.2123T>C presented equal distribution of isolated hepatic or hepatic plus neurological phenotype, while c.3818C>T mutation was associated with predominantly hepatic phenotype. Presence of exon 2 deletion was associated with severe neurological manifestations. Conclusions: The mutations c.3402delC, c.2123T>C and c.3818C>T were the most prevalent. The c.2145C>T and c.3188C>T variants, considered of undetermined significance, were found in confirmed cases of WD. An important heterogeneity of the ATP7B genotype associated with variation in phenotypic presentation was observed.

Conflict of interest: No Introduction and Objectives: Wilson's disease (WD) is a rare autosomal recessive disease leading to impairment in copper excretion and subsequent accumulation primarily in the liver and brain. Long-term survival appears to be similar to that of the general population, depending on early diagnosis and treatment. However, studies evaluating WD survival are scarce. We aimed to evaluate the long-term survival of a cohort of WD patients followed at a single Hepatology Center in Brazil. Patients / Materials and Methods: Demographic characteristics, age at diagnosis, type of manifestation (isolated hepatic, isolated neuropsychiatric or associated hepatic and neuropsychiatric) of WD patients, followed between 1999 and 2023, were evaluated. The average survival and its relationship with the predominant disease phenotype were determined. Results and Discussion: 34 patients were evaluated, 53% female, mean age at diagnosis 21 ± 9 years (6 to 42), disease duration of 11 ± 7 years (1 to 25) until outcome. The majority (47%) had the isolated hepatic manifestation, 38% hepatic neuropsychiatric manifestations and 15% isolated neuropsychiatric disorder. The overall population mortality rate was 36%. The mean age at the time of death was 33 ± 12 years (11 to 55). The estimated average survival at 5 years was 85%, at 10 years 70% and at 20 years 40%, from diagnosis. There was a tendency towards lower survival in patients who presented neuropsychiatric manifestations, either alone or in association with liver disease, compared to patients with isolated liver manifestations (50% vs. 80%; p= 0.07). There was no difference in survival curves according to gender (p=0.82) or considering the age at onset of the disease above or below 20 years (p=0.54). Conclusions: Despite being potentially treatable, WD still presents high mortality, affecting young patients, whose survival rate is greatly reduced. WD patients with neuropsychiatric symptoms had worse survival. These data highlight the need for earlier diagnosis and easier access to treatment.

Conflict of interest: No Introduction and Objectives: Liver stiffness (LS) is increased in fibrosis related to chronic liver diseases. Nevertheless, other factors such as liver inflammation, congestion and intrahepatic deposits may also affect hepatic elasticity. We hypothesized that Wilson's disease (WD) intrahepatic copper accumulation can lead to an increase in LS. The aim of this study is to assess the changes in LS during treatment of patients with different presentations of WD. Patients / Materials and Methods: We included patients with confirmed diagnosis of WD (Leipzig score ≥4) under regular use of chelating agents or zinc salts, between 2014 and 2024. Patients who have undergone at least two transient hepatic elastography (THE; Fibroscan, ECHOSENS) during clinical follow-up, were included. The minimum interval between each elastography was one year. Patients submitted to liver transplantation were excluded. Variations in liver stiffness between the last and first THE, the anticopper therapy used, and the main WD manifestations, were evaluated. Results and Discussion: Thirteen patients were included: mean age of 28.8 ± 9.9 years; 54% female. Seven (54%) patients presented predominantly neurologic manifestation and six (46%) hepatic manifestations; 92% used chelating agents. The mean initial LS was 12.2 ± 14.8 kPa (median 7.5 kPa; ranging from 3.8 to 59.3), decreasing during treatment to 7.7 ± 4.6 kPa (median 6.3 kPa; ranging from 3.9 to 18.9) at a mean follow-up interval of 4.9 ± 2.8 years (ranging from 1 to 10) (p < 0.0001). Eight (61%) patients observed a median reduction of 2.3 kPa and five presented a median elevation of 0.3 kPa. There was no difference in LS variations according to clinical presentation of WD (p=0.387). Conclusions: In patients with WD, LS decreased in most patients during chelating therapy. Intrahepatic copper deposit might influence higher values of LS before anticopper therapy, suggesting the possibility of using THE to evaluate hepatic copper accumulation and to monitor WD treatment.

Conflict of interest: No Introduction and Objectives: Liver biopsy is considered the gold standard to define fibrosis stage and inflammation degree in Autoimmune Hepatitis (AIH). Noninvasive methods have been utilized for these purposes, However, the respective accuracies in different populations have not been clarified. AIMS: Investigate the performance of TE and APRI and of serum IgG and γ-glob levels in defining liver fibrosis and inflammation degree, respectively, in a group of patients with AIH. Patients / Materials and Methods: Prospective study involving patients with AIH who underwent liver biopsy (classified by Metavir and Ishak) and TE (FibroScan, Echosens 502), with a maximum interval of 6 months between the two procedures. Laboratory parameters for APRI, IgG and γ-glob were obtained within a maximum interval of 3 months from the biopsy. The performances were compared with liver biopsies using ROC curves. Results and Discussion: 63 patients with AIH were included (88% female; mean age 43 ± 18 years), platelets levels: 214.524 ±72.121/µL. Medians: IgG:1530, APRI: 0.4 and TE: 8.8 kPA. Liver fragments had ≥ 8 complete portal spaces. Thirty-four patients (54%) had advanced fibrosis (F≥3 METAVIR) and 67% had inflammation A≤1 by METAVIR and A

Background and Aims: Azathioprine (AZA) and prednisone (PD) are the standard treatment (ST) for the onset or relapse of autoimmune hepatitis (AIH). Antimalarials were effective for maintenance of remission of AIH after immunosuppression withdrawal. Our aim is to describe a series of patients who relapsed after antimalarial withdrawal and achieved biochemical remission after reintroduction of chloroquine in monotherapy. Methods: Eight patients received chloroquine diphosphate (DCQ) 250mg/d or hydroxichloroquine (HCQ) 400-800mg/d in monotherapy for biochemical remission after relapse. The schedule is described below: histological remission (HR) with ST → ST withdrawal and antimalarial use for maintenance of remission for 1-3y → antimalarial withdrawal → relapse of AIH → reintroduction of antimalarial instead of ST, at the request of patient due to corticosteroids side effects (SE). Four out of 8 patients underwent liver biopsy to evaluate HR after at least 18mo of biochemical remission. Results: Mean age at diagnosis of AIH of 36.2 ± 20.4y; 6 type-1, 2 anti-SLA/LP (5 reactive in 7 tested); 3 with cirrhosis at diagnosis. Mean doses of AZA/PD at HR were, respectively, 84.4 ± 18.6 and 9.4 ± 2.2mg/d. Mean interval between antimalarial withdrawal and relapse was 20.5 ± 34.1mo. Mean ALT at relapse was 139.7 ± 54.2 U/L. Three patients received DCQ and 5 HCQ. During HCQ intake 1 patient needed further adjustment of drug to 800 mg/d for 15 days due to worsening of ALT from 130 to 246 U/L, with subsequent reduction to the initial dose. Seven patients achieved biochemical remission, in a mean time of 14.2 ± 19.9mo; 3/4 had histological remission. The drug was well tolerated and there were no serious SE. Conclusions: CQ monotherapy was safe and effective for induction of remission in this subgroup of AIH. This finding raises arguments to include this drug as an option for treatment of AIH, not necessarily in monotherapy.

Introduction and objectives: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. Materials and methods: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). Results: 3939 patients (60% males, mean age 58 ± 10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. Conclusion: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries.