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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.

Introduction and objectives: The agreement of elastography techniques in chronic Hepatitis B (CHB) needs evaluation. We aimed to evaluate, in CHB, the agreement between transient elastography (TE) and two-dimensional shear wave elastography (2D-SWE), analyzing the factors related to the disagreement of measures. Materials and methods: CHB patients underwent liver stiffness measures with both TE and 2D-SWE on the same day. For concordance analysis, we defined liver fibrosis as F0/1 vs. F ≥ 2, F0/1-F2 vs. F ≥ 3 and F0/1-F2-F3 vs. F4 for both methods. Logistic regression analysis was used to identify the variables independently associated with the disagreement between methods. RESULTS: A total of 150 patients were enrolled. Liver fibrosis categorization according to TE was: F0-F1 = 73 (50.4%), F ≥ 2 = 40 (27.6%), F ≥ 3 = 21 (14.5%) and F4 = 11 (7.6%), and according to 2D-SWE was: F0/F1 = 113 (77.9%), F ≥ 2 = 32 (22.1%), F≥ 3 = 25 (17.2%) and F4 = 11 (7.6%). It was observed that 20.0% of the sample had steatosis (CAP≥ 275 dB/m). TE and SD-SWE estimated equal fibrosis stages in 79.3% of cases. Spearman's correlation coefficient was 0.71 (p < 0.01). Kappa values for F ≥ 2, F ≥ 3 and F = 4 were: 0.78, p < 0.001; 0.73, p < 0.001; and 0.64, p < 0.001, respectively. Diabetes mellitus (DM) (OR 5.04; 95%CI: 1.89–13.3; p < 0.001) and antiviral treatment (OR 6.79; 95%CI: 2.33–19.83; p < 0.001) were independently associated with discordance between both methods. Conclusions: In CHB, there is strong correlation and good agreement between TE and 2D-SWE in identifying fibrosis stages. Diabetes mellitus and antiviral therapy may impact the agreement of stiffness measures obtained with these elastographic methods.

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p

Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.

In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum samples; however, oral fluid collection for detection of HBV DNA has not yet been explored, despite the availability of collection devices. Serum and oral fluid samples from 45 hepatitis B core antibody (anti-HBc)-positive patients were collected for the amplification of the HBV polymerase gene. HBV DNA was detected in five serum and four oral fluid samples (the detection limit for oral fluid was 1.656 log IU/mL in paired serum). In conclusion, simple methodologies of sample collection and in-house polymerase chain reaction (PCR) allowed detection of HBV DNA, and these could be used to improve the diagnosis of OBI, especially in locations with limited resources.

Introduction and Objectives: The Choosing Wisely (CW) initiative aims to improve daily practice supported by evidence concerning unnecessary medical tests, procedures, and treatments. This philosophy is essential in managing viral hepatitis (VH), which primary care physicians increasingly carry out. It is also essential to achieving disease elimination. Thus, the aim of our study was to propose evidence-based CW recommendations in VH. Materials and Methods: The Brazilian Society of Hepatology (SBH) formed a panel of experts in VH who selected evidence-based CW recommendations, which were subsequently scrutinized and ranked by all members of SBH using a web-based approach. Results: Five recommendations were chosen in order of importance: 1) do not order anti-HCV testing after achieving sustained virological response; 2) do not request serial HCV viral load to evaluate HCV progression, 3) do not add ribavirin to direct-acting antivirals in non-cirrhotic, naïve HCV patients; 4) do not screen for hepatocellular carcinoma in HCV patients with none to moderate fibrosis (≤ F2); 5) do not request anti-HBs after HBV vaccination, except for children born to HBV-infected mothers, hemodialysis patients, healthcare professionals, people who have had sexual contact with chronic HBV carriers, HIV-positive persons and immunocompromised individuals (hematopoietic stem-cell transplant recipients or persons receiving chemotherapy). Conclusions: CW recommendations may help general practitioners adopt a more rational and cost-effective approach in managing patients with VH in Brazil and Latin America, leading to lesser waste or harm to patients.

Introduction: Choosing wisely (CW) initiative aims to improve daily practice supported by evidence avoiding unnecessary medical tests, procedures, and treatments. This philosophy is of utmost importance in managing viral hepatitis (VH), increasingly carried out by primary care physicians. Objective: To propose evidence-based CW recommendations in VH. Methods: The Brazilian Society of Hepatology (SBH) selected a panel of experts in VH who selected evidence-based CW recommendations, which were subsequently scrutinized and ranked by all members of SBH using a web-based approach. Results: Eight recommendations were chosen in order of importance, including 1) Do not order anti-HCV testing after achieving sustained virological response; 2) Do not request serial HCV viral load to evaluate HCV progression, 3) Do not add ribavirin to direct-acting antivirals in non-cirrhotic, naïve HCV patients; 4) Do not screen for hepatocellular carcinoma in HCV patients with none to moderate fibrosis; 5) Do not request anti-HBs after HBV vaccination, except for children born to HBV-infected mothers, hemodialysis patients, healthcare professionals, sexual contacts of chronic HBV carriers, HIV-positive persons and immunocompromised individuals (hematopoietic stem-cell transplant recipients or persons receiving chemotherapy); 6) Do not order complete HBV serology for screening HBV infection; 7) Do not order complete HBV serology for evaluation of acute hepatitis B; 8) Do not treat chronic hepatitis B based on a single ALT and viral load results, except in cirrhotic patients. Conclusion: These recommendations defined by SBH may help general practitioners adopt a more rational and cost-effective approach to handling VH cases in Brazil.

In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area.

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.