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Background Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations.

Background. Primary sclerosing cholangitis (PSC) is associated with a broad phenotypic spectrum in different populations from diverse ethnic and racial backgrounds. This study aimed to describe the clinical characteristics and outcomes of PSC in a multicenter cohort of patients from Brazil. Methods. Data from the Brazilian Cholestasis Study Group were retrospectively reviewed to assess demographic information and clinical characteristics of PSC, as well as the outcomes, such as transplantation-free survival. Results. This cohort included 210 patients. After excluding 33 (15.7%) patients with PSC and overlap syndrome of autoimmune hepatitis, 177 (97 males, median age 33 (21–42) years) with clear-cut PSC were eligible for this study. Most of the patients (n = 139, 78.5%) were symptomatic, and 104 (58.7%) had advanced PSC at the time of diagnosis. Concurrent inflammatory bowel disease was observed in 78 (58.6%) of the investigated patients (n = 133), and most of them had ulcerative colitis (n = 61, 78.2%). The 1- and 5-year survival free of liver transplantation or death were 92.3 ± 2.1% and 66.9 ± 4.2%, respectively, and baseline advanced PSC, pruritus, and elevated bilirubin levels were independent risk factors for the composite adverse outcome. Females were significantly older and had lower bilirubin levels than males at baseline, but survival was not associated with sex. Approximately 12.4% (n = 22) of patients with PSC died, and 32.8% (n = 58) underwent liver transplantation at a median follow-up time of 5.3 and 3.2 years. Conclusion. Multiethnic Brazilian PSC patients exhibited a less pronounced male predominance and a lower frequency of inflammatory bowel disease than Caucasians. Adverse outcomes were more frequent, probably due to advanced disease at baseline.

Portal vein aneurysm is a rare medical entity that can be caused by chronic hepatic diseases with portal hypertension. We describe a 45-year-old man with variceal bleeding from hepatosplenic schistosomiasis and an incidentally found intrahepatic aneurysm. Diagnosis was confirmed with non-invasive imaging exams, arteriography and liver biopsy. Following splenectomy, the aneurysm diameter decreased substantially.

BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 ± 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.

Although the prevalence of autoimmune hepatitis in first-degree relatives is small, the relationship between genetic markers, especially human leucocyte antigens (HLA), and susceptibility to this disease, has been studied for over three decades. The genetic susceptibility to AIH is believed to be different in the two subtypes of the disease, AIH type 1 and AIH type 2. Type 1 AIH has anti-smooth muscle and anti-nuclear antibodies as its main markers, while those of type 2 AIH are the anti-liver/kidney microsome type 1 and anti-liver cytosol type 1 antibodies. The anti-soluble liver antigen/liver-pancreas antibodies, which, in addition to being present in both subtypes, mark an important number of patients without serological markers. Therefore, a third type of disease is questionable. The vast majority of immunogenetic studies compare the differences between the two main types and make no difference between which antibodies are present to define the subtype. This review seeks to analyze what was most important published in the AIH in this context, trying to relate the HLA alleles according to the AIH marker autoantibodies.

BACKGROUND: Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES: Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. METHODS: An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. RESULTS: Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. CONCLUSIONS: Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients

OBJECTIVE: Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. METHODS: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. RESULTS: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. CONCLUSION: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.

Conflict of interest: No Introduction and Objectives: Primary biliary cholangitis (PBC) may present differently depending on various factors such as ethnicity and genetic background. Latin America has a highly admixed population with a unique genetic diversity compared to other regions of the world. However, there is limited information available on the presentation and epidemiology of PBC in this region. This study aims to address the epidemiology of PBC in Latin America. Patients / Materials and Methods: Ongoing retrospective, international, multicentric cohort study sponsored by ALEH that enrolls PBC patients from different countries in Latin America. Results and Discussion: Data were accrued on 231 patients [Brazil (52%), Argentina (27.4%), Chile (10.8%), Costa Rica (4.5%), Cuba (3.6%), and Mexico (0.9%)], 92.1% female (mean age at diagnosis 50.5 years), 25.6% with cirrhosis at baseline. Overlap with autoimmune hepatitis was reported in 16.0% of cases. Most patients were symptomatic (67.9%) at diagnosis, with fatigue (41.9%) and pruritus (40.5%) being the main symptoms. Anti-mitochondrial antibodies (AMA) were positive in 70.8% and antinuclear antibodies (ANA) in 60.6%. Hashimoto thyroiditis (23.7%) and Sjogren syndrome (9.1%) were the most common extrahepatic autoimmune diseases associated with PBC. Mean baseline alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and bilirubin levels were 445.9 (± 407), 89.8 (± 137.2), 37.6 (± 8.9) U/L, and 1.6 (± 3.1) mg/dL, respectively. Almost all patients (99.1%) were treated with ursodeoxycholic acid (UDCA). 67.4% achieved adequate response to UDCA according to the Toronto criteria and 32% normalized alkaline phosphatase at 12 months. Only 19.9% received second-line therapy, all with fibrates (89.1% bezafibrate, 8.7% ciprofibrate, 4.3% fenofibrate). Of the patients, 9% died, with 33% of deaths being liver-related, while 6% underwent liver transplantation. Hepatocellular carcinoma was diagnosed in 1.7% of patients. Conclusions: In this unprecedented study, the epidemiology of PBC in Latin America appears similar to that in other parts of the world. However, lower rates of AMA positivity were observed, and most patients were still diagnosed with symptomatic disease. Second-line therapy options were limited to the availability of fibrates only.

Conflict of interest: Yes, Ultragenyx has provided 25 kits for copper panel genotyping by NGS at Mendelics laboratory Introduction and Objectives: Wilson disease (WD) is an autosomal recessive disorder caused by a defect in the ATP7B protein, leading to copper overload. ATP7B genotyping has been performed by Sanger method, but NGS techniques have recently become available. Our aim was to analyze the impact of Sanger direct sequencing and NGS in the diagnosis of WD. Patients / Materials and Methods: A series of 287 WD patients included 160 individuals who provided DNA after informed consent. All patients met ≥4 points of the European WD scoring system. DNA for Sanger sequencing was extracted from peripheral leukocytes and for NGS from oral cells using a buccal swab. ATP7B mutations were identified in 135 patients by Sanger sequencing only, in 17 by NGS and in 8 by both methods. Sanger sequencing was performed as previously published (Deguti et al, 2004). In targeted NGS using a ''copper panel'' (Laboratório Mendelics), libraries were prepared with Illumina DNA with enrichment, target regions were captured using specific probes (Twist Biosciences v.3) for all exons/intronic regions, and variants and indels were identified using GATL v4 program and CNVs using ExomeDepth. Results and Discussion: Of the 320 alleles analyzed, the most frequent mutations were p.A1135fs (26.7%), L708P (15.8%), p.H1069Q (5.3%) and p.M645R (3.1%).The remaining 49.1% of alleles had 38 distinct disease-causing mutations, each with a frequency of

Conflict of interest: No Introduction and Objectives: Wilson disease (WD) is an inherited disease that mainly affects the liver and brain due to copper overload. Pregnancy in WD is a challenging situation. Our aim was to analyze the clinical aspects and outcomes of pregnancies in WD. Patients / Materials and Methods: In a series of 289 WD cases (1963-2024), we reviewed the medical records of 123 women, 26 of whom became pregnant at least once (1-5). A total of 52 pregnancies were recorded, but 3 were excluded because data on the conceptus were missing. Pregnancy outcomes were correlated with disease severity and anti-copper medication. Hepatic and/or neuropsychiatric manifestations were categorized as 1) asymptomatic/mild or 2) moderate/severe. Pregnancy outcomes were considered 1) successful if the preterm/term infant survived the neonatal period or 2) unsuccessful if there was a miscarriage/fetal demise/perinatal death. Drug regimen during pregnancy were 1) penicillamine (DPA), 2) zinc (Zn) or 3) DPA/Zn if the patient had switched therapy for any reason. Statistical analysis was carried out using Fisher´s test, with significance level at p

Conflict of interest: No Introduction and Objectives: Autoimmune hepatitis (AIH) is a rare disease characterized by a destructive immune response to hepatocytes in the absence of an identified causative agent. The epidemiology of AIH in Latin America is largely unknown. This study aims to address the epidemiology of AIH in Latin America. Patients / Materials and Methods: This ongoing retrospective, international, multicentric cohort study, sponsored by ALEH, enrolls AIH patients from different countries in Latin America. Results and Discussion: Data were accrued on 200 patients [Brazil (36.3%), Argentina (22.3%), Chile (21.8%), Cuba (7.3%), Costa Rica (5.2%), Ecuador (5.2%), and Mexico (2.1%)], 85.9% female, with a mean age at AIH diagnosis of 43.8 years. The most common form of disease presentation was chronic asymptomatic elevation of liver enzymes (40.9%), while acute severe hepatitis and fulminant hepatitis were observed in 7.2% and 2.8% of cases, respectively. Cirrhosis was present in 39% of patients at diagnosis. AIH type 1 was diagnosed in 93.7%, type 2 in 1.6%, while 4.8% were seronegative. Overlap with primary biliary cholangitis and primary sclerosing cholangitis was reported in 5.7% and 2.9% of cases, respectively. Most patients were symptomatic (66.8%) at diagnosis, with jaundice (42.4%) and asthenia (28.3%) being the main symptoms. Hashimoto thyroiditis (11.4%) and lupus (4.9%) were the most common extrahepatic autoimmune diseases associated with AIH. Prednisone was prescribed to 86%, azathioprine to 81%, and mycophenolate to 8% of patients as first-line treatments. Complete biochemical response after the first 12 months of treatment was achieved by 66.9% of patients. Mycophenolate (60%) was the preferred option for second-line therapy, which was prescribed to 10.7% of the individuals. Of the patients, 10.5% died, while 1.5% underwent liver transplantation. Hepatocellular carcinoma was diagnosed in 1.1% of patients. Conclusions: Our unprecedented data shed light on AIH epidemiology and management in Latin America.

Conflict of interest: Yes, This work was supported by Brazilian Society of Hepatology and Instituto Brasileiro do Fígado - IBRAFIG. Introduction and Objectives: Previous studies have identified risk factors associated with recurrent primary sclerosing cholangitis (rPSC) after liver transplantation (LT) in Caucasians. There is paucity of data regarding rPSC in multiethnic Latin patients. Objectives: To investigate rPSC frequency and its associated risk factors in a highly admixed population from Brazil. Patients / Materials and Methods: The Brazilian Cholestasis Study Group database was retrospectively reviewed for including primary sclerosing cholangitis (PSC) patients who underwent LT. Primary outcome was rPSC. Results and Discussion: A total of 96 patients were included, 60% males, mean age 32 ± 13 years. After a follow-up of 90 months (interquartile range 39-154), rPSC occurred in 29 (30%) of the participants. There were no statistically significant associations between rPSC and age, gender, concurrent or de novo inflammatory bowel disease, MELD score at the time of LT or allograft rejection. The only factor associated with an increased risk of disease recurrence was time after LT. Conclusions: In Brazilian PSC patients who underwent LT, one-third had rPSC. Longer time after LT was associated with rPSC diagnosis.

Conflict of interest: No Introduction and Objectives: Primary biliary cholangitis is a chronic and progressive autoimmune liver disease, whose prognosis can be improved by normalizing alkaline phosphatase and bilirubin. While ursodeoxycholic acid (UDCA) is first line standard of care, approximately 40% of patients exhibit incomplete response. We aimed to identify prognostic markers for deep response to UDCA therapy at presentation. Patients / Materials and Methods: Data from the Brazilian Cholestasis Study Group cohort were analyzed retrospectively. Patients were assessed for deep response (defined as normalization of alkaline phosphatase and bilirubin) after 1 year of UDCA treatment. With the purpose of selecting the set of relevant variables related to the deep response for a parsimonious multivariate model, we applied the Varrank algorithm. Additionally, the performance of the UDCA response score in predicting deep response was evaluated. Results and Discussion: A total of 297 patients were analyzed, with 57.2% achieving an adequate response according to the Toronto criteria, while 22.9% reached deep response. Cirrhosis (OR 0.460; 95% CI 0.225-0.942; p=0.034) and elevated baseline alkaline phosphatase levels (OR 0.629; 95% CI 0.513-0.770; p

Abstract Background and Aim The aim was to analyze the concordance of liver stiffness measurement (LSM) either by transient elastography (TE) or ARFI with liver biopsy in autoimmune hepatitis (AIH) patients with biochemical remission and to identify those with histological remission. Liver biopsy is still the golden standard for AIH diagnosis. However, it is an invasive procedure and these patients, most of the time, require many biopsies, so it would be valuable to search for noninvasive method that could select all these patients and keep under observation. Methods Thirty‐three patients with AIH were submitted for liver biopsy to evaluate histological remission after at least 18 months of normal aminotransferases. The efficiency of LSM and fibrosis stages was tested by a receiver operating characteristic curve analysis (AUROC). Results One patient (3%) was F0, 6 (18.2%) were F1, 8 (24.2%) were F2, 10 (30.3%) were F3, and 8 (24.2%) were F4, according to METAVIR. Thirteen of thirty‐three (39.4%) patients did not achieve histological remission. AUROC for F4 stage was 0.83 (IC: 0.76–0.99) for TE and 0.78 (IC: 0.65–0.95) for ARFI. Optimal LSM cutoff values were 12.3 kPa (Se = 87.5%, Sp = 88%) for TE and 1.65 m/s (Se = 87.5%, Sp = 76%) for ARFI. The tests were unable to differentiate patients with histological activity from those in histological remission (P

Introduction and objectives: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. Materials and methods: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. Results: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p=

Introduction and Objectives: Primary sclerosing cholangitis (PSC) is a cholestatic disease that commonly affects young males with inflammatory bowel disease (IBD). There is no efficient medical treatment, being orthotopic liver transplantation (OLT) the only curative treatment recommended in decompensated cirrhosis, intractable pruritus and recurrent cholangitis. Objectives: Describe clinical, laboratory and histological findings in patients with PSC-IBD of a quaternary hospital and identify prognostic factors for OLT. Materials and Methods: Review of patients’ medical records with PSC-IBD followed from 01/2000 to 05/2022, excluding cases with insufficient data. Results: Among 73 patients, 57% were male; the mean age during PSC diagnosis was 34,2±14,3 years, with a follow-up period of 8,8±5.4 years, 85% of those presenting ulcerative colitis. During diagnosis, 93% were symptomatic, usually presenting with pruritus and fatigue. A liver biopsy was performed in 30 patients, and 60% of those revealed F3/4. 4 patients presented dominant strictures (DS) and 68 were treated with ursodeoxycholic acid (UDCA) 16mg/kg/d. 16 (21.9%) underwent OLT in a period of 6.3±4,5 years after diagnosis; the main indication was decompensated cirrhosis. Ten patients had cancer, and the two most frequent were colorectal carcinoma and cholangiocarcinoma. 13 patients died; from those, four were transplanted and six died of infection. Between patients with and without OLT, there were no significant differences in age during diagnosis, type of IBD, comorbidities, presence of symptoms during diagnosis, histological fibrosis, or presence of DS. The OLT group had higher levels of bilirubin (3 × 0,8mg/dL;p

Introduction and Objectives: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aimed to assess potential risk factors associated with cancer development in PBC and AIH/PBC patients. Materials and Methods: The Brazilian Cholestasis Study Group database was reviewed and analyzed. Results: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, and 87 cancers were identified in 79 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5%, p=

Abstract Background Health care costs are growing faster than the rest of the global economy, according to the World Health Organization (WHO). Countries’ health expenditures include paying for general medicine, diagnostic procedures, hospitalizations and surgeries, as well as medications and prescribed treatment. Primary biliary cholangitis (PBC) is a rare autoimmune liver disease and the first line available treatment is ursodeoxycholic acid (UDCA), however, direct and indirect treatment costs are expensive. Main aim of this trial was to assess if the therapeutic efficacy of UDCA manufactured by the university hospital is equivalent to that of standard UDCA and treatment cost reduction in patients with PBC. Methods It is a prospective, interventional, randomized, and crossover study in patients diagnosed with PBC. UDCA 300 mg tablets and capsules were developed and manufactured by the university hospital. Thirty patients under treatment with standard UDCA, in stable doses were randomized in sequence A and B, 15 patients in each arm. The groups were treated for 12 weeks and after, the UDCA formulation was changed, following for another 12 weeks of continuous therapy (tablets and capsules / capsules and tablets). Laboratory tests were performed at time T0 (beginning of treatment), T1 (at the 12 week-therapy, before the crossing-over) and T2 (end of treatment). The evaluation was done by comparing the hepatic parameters ALP, GGT, ALT, AST and total bilirubin, also considering the adverse events. The comparison of costs was based on price of the manufactured UDCA and standard UDCA price of the hospital. Results Hospital reduced 66.1% the PBC treatment costs using manufactured UDCA. There were no differences in the biochemical parameters between sequence (A and B) and tablets or capsules of UDCA formulations applied in the treatment of PBC. Conclusions The study showed that there was no significant difference between manufactured UDCA (capsule and tablet) and standard UDCA. Hospital reduced the PBC treatment costs using the manufactured UDCA by the university hospital. Trial registration ClinicalTrials.gov: NCT03489889 retrospectively registered on January 12th, 2018; Ethics Committee approved the study (ID: 1.790.088) on October 25th, 2016.

Aim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC.Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria.Results: In total, 27 patients (100% women, mean age 48.9 ± 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39–76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria.Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients.

Introduction and objectives: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. Material and methods: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. Results: 562 patients (95% females, mean age 51 ± 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 ± 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histological stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates.Conclusions: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Caucasians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization.

Background and Aims: Hepatocellular carcinoma (HCC) occurrence is rare in autoimmune hepatitis (AIH) and data about its characteristics are still scarce. The aims of this study were to describe HCC prevalence and risks factors in AIH patients in a tertiary referral hospital. Methods: Retrospective cohort of AIH patients followed from 2003 to 2019. The hazard ratios (HR) and their respective 95% confidence intervals (95%CI) were estimated using simple Cox regression. A multivariate regression model was fitted using relevant covariates for HCC occurrence. Results: Among 355 AIH patients, 84.5% were female, 85% AIH-1, 65% with cirrhosis and mean age at AIH diagnosis of 27±18yr. Sixteen cases of HCC were diagnosed (4.5%), all of them in cirrhotic patients, 81.3% female, mean age of 49±20yr, 83% overweight (BMI 34±5kg/m2) and 3 with associated steatohepatitis. The pooled incidence rate for HCC was 3.2 per 100 patient-years. The pooled incidence of HCC in patients with cirrhosis at AIH diagnosis was 4.5 per 100 patient-years. The median time between AIH diagnosis and HCC was 9 years (1-42). At univariate analysis the factors associated with HCC risk were age at diagnosis of AIH (HR,1.05; 95%CI,1.02-1.08; p

Background and Aims: Clinical course of Covid-19 is not yet established in autoimmune hepatitis (AIH). About 25% of our 400 AIH-outpatients from various states in Brazil are using hydrochloroquine (HCQ) for maintenance or treatment with corticosteroids and immunosuppressants (IS). The aim is to describe the clinical features and outcomes of COVID-19 in patients with AIH. Methods: The diagnosis of COVID was confirmed by positive PCR of nasal swab and/or by serological tests. The diagnosis and treatment of COVID was not always made in our service. Results: 33 patients, 85% female, 41±13yr; 88% AIH-1; 54.6% with advanced fibrosis (F3/F4); 81.8% with comorbidities (17 overweight/obesity [BMI 31.8±5.4], 10 arterial hypertension, 8 diabetes, 2 systemic lupus erythematosus [SLE, with renal failure], 1 celiac disease and malnutrition). The most frequent symptoms were cough (20), headache (19), anosmia and myalgia (18), diarrhea (17) and dyspnea (11). IS at infection was 14 azathioprine(AZA)+prednisone(PD), 2 AZA+PD+cyclosporine, 3 Mycophenolate+PD. HCQ was used for maintenance (6) or as a complement of IS (5). Five hospitalized patients received oxygen supplementation (1 endotracheal intubation); 1 was pregnant and 1 received methylprednisolone pulse+immunoglobulin to treat SLE immediately before COVID; 3 were under double IS and 2 HCQ. 23 received antibiotics (19 azithromycin). In 10 patients (9 with normal liver enzymes before COVID) there were IS adjustments: IS withdrawal and increase of PD dosage (6), increase PD dosage (2), IS withdrawal and HCQ prescription (1), AZA withdrawal+decrease PD dose (1). Six of the 10 patients had slight increase of liver enzymes, none liver decompensation. One patient died, with celiac disease who acquired COVID during hospitalization for lymphoma investigation. Conclusions: It appears that patients under IS for AIH and COVID-19 show outcomes similar to that of non-immunosuppressed population. HCQ does not appear to have a positive impact on preventing or progressing the disease.

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient’s 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profile

BACKGROUND: Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). AIMS: To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. PATIENTS AND METHODS: Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A®. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. RESULTS: In our cohort, nine (47%) patients were homozygous for the C282Y mutation, two (11%) were heterozygous for the H63D mutation, and one each (5%) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. CONCLUSIONS: One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.

O estudo ultra-sonográfico de 33 pacientes com degeneração hepatolenticular revelou as seguintes alterações princpais: desordens da ecotextura hepática (29 casos), alterações das dimensões esplénicas (21), contração do fígado (10), colelitíase (8), hepatomegalia e ascite (1). As desordens da ecotextura hepática se apresentaram sob diversas formas, desde leves até graves alterações da ecogênese hepática, associadas com distorções anatômicas do fígado, tais como modificações do perfil e redução das dimensões. A contração hepática sempre se acompanhou de esplenomegalia. A raridade da hepatomegalia pode ser explicada pelo fato de que a ultra-sonografia foi realizada após o início do tratamento com penicilamina, ou por outros fatores ainda desconhecidos, como a possibilidade de que o cobre possua uma ação fibrogênica maior do que a de outros agentes hepatotóxicos. A colelitíase foi muito freqüente no sexo teminino (6 de 13 pacientes) e sua incidência tendeu a crescer com a idade. Quanto aos doentes do sexo masculino, não se notou aumento da incidência em relação à freqüência na população geral. Os dois únicos pacientes do sexo masculino eram jovens, fato raramente observado nos homens normais.

ABSTRACT New data concerning the management of autoimmune liver diseases have emerged since the last single-topic meeting sponsored by the Brazilian Society of Hepatology to draw recommendations about the diagnosis and treatment of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), overlap syndromes of AIH, PBC and PSC and specific complications and topics concerning AIH and cholestatic liver diseases. This manuscript updates those previous recommendations according to the best evidence available in the literature up to now. The same panel of experts that took part in the first consensus document reviewed all recommendations, which were subsequently scrutinized by all members of the Brazilian Society of Hepatology using a web-based approach. The new recommendations are presented herein.

ABSTRACT In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.

OBJECTIVES: To determine the frequency of the antineutrophil cytoplasmic antibodies (ANCA), antiproteinase-3 and antimyeloperoxidase, in primary sclerosing cholangitis (PSC) with or without inflammatory bowel disease (IBD+ or IBD-) and in different types of autoimmune hepatitis (AIH). Additionally, to verify the agreement between ANCA patterns by indirect immunofluorescence and their antigenic specificities by ELISA. METHODS: For this study, 249 patients were enrolled (42 PSC/IBD+; 33 PSC/IBD-; 31 AIH type-1; 30 AIH type-2; 31 AIH type-3; 52 primary biliary cirrhosis; 30 healthy controls) whose serum samples were tested for ANCA autoantibodies. RESULTS: There were fewer female subjects in the PSC/IBD- group (p=0.034). Atypical perinuclear-ANCA was detected more frequently in PSC/IBD+ patients than in PSC/IBD- patients (p=0.005), and was significantly more frequent in type-1 (p