Clinical, biochemical and histological features related to treatment response and prognosis in autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, and transplant-free survival are not well established. This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. MATERIALS AND METHODS: This retrospective cohort study included 101 patients with AIH treated with immunosuppressants and followed at the Federal University of Minas Gerais, Brazil, from 1990 to 2018. Pretreatment data such as clinical profiles, laboratory, and histological exams were analyzed regarding biochemical response at one year, histological remission, relapse, and death/transplantation rates. RESULTS: Cirrhosis was present in 59 % of cases at diagnosis. One-year biochemical remission was observed in 55.7 % of the patients and was found to be a protective factor for liver transplant. Overall survival was 89 %. Patients with ascites at disease onset showed a higher aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio and elevated Model of end-stage liver disease (MELD) score. The presence of ascites was significantly associated with a 20-fold increase in mortality rate. CONCLUSIONS: AIH has a severe clinical phenotype in Brazilians, with high rates of cirrhosis and low remission rates. Early diagnosis and treatment are essential for achieving remission and reducing complications. The presence of ascites is significantly associated with mortality, emphasizing the importance of monitoring and prompt intervention. This study also stresses the need for further research on AIH in Latin America.

A new and simple score to predict adequate and deep response to ursodeoxycholic acid in patients with primary biliary cholangitis: the ALP-A score.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA. METHODS: A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed. RESULTS: ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855). CONCLUSION: ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.

Dietary pattern in women with polycystic ovary syndrome with and without associated non-alcoholic fatty liver disease: A cross-sectional study.

INTRODUCTION: Women with Polycystic Ovary Syndrome (PCOS) have a higher prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) than the general population. PCOS and NAFLD have common metabolic risk factors, however, the role of diet in NAFLD development is still uncertain in PCOS women. OBJECTIVE: To evaluate and compare the dietary patterns and nutritional intake in patients with PCOS with and without NAFLD. METHOD: Cross-sectional study that included patients with PCOS diagnosed according to Rotterdam criteria. All participants were submitted to abdominal ultrasound to investigate liver steatosis. Dietary profile was assessed by 24-hour food recall (24hR), and Food Frequency Questionnaire (FFQ). Diet quality was assessed by the Healthy Eating Index (HEI) adapted for the Brazilian population. Physical activity practice was also assessed. RESULTS: 87 participants were included (average age 35.2 ± 5.7 years), among whom, 67 (77%) had NAFLD. The group with PCOS and NAFLD presented higher body mass index (BMI) (34.9 ± 4.5 vs. 30.4 ± 4.9 kg/m2; p = 0.001), Waist Circumference (WC) (103 [97‒113] vs. 95 [87.5‒100] cm; p < 0.001) and were considered physically active less frequently than those without NAFLD (34.3% vs. 60%; p = 0.04). Food intake and dietary patterns assessed by 24hR, FFQ and HEI presented no difference between the groups. CONCLUSIONS: PCOS women with coexistent NAFLD had higher BMI, WC and were less physically active than those without NAFLD. Dietary evaluation showed that PCOS women with NAFLD had no significant difference in macro and micronutrients or food group intake and diet quality in comparison to those without NAFLD.

Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome.

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= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis.

BACKGROUND: Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. AIMS: This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. METHODS: Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. RESULTS: 206 patients with PBC (96.6% women; mean age 54 ± 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 ± 1.95 times the upper limit of normal (× ULN) among responders versus 5.05 ± 3.08 × ULN in non-responders (p < 0.001). CONCLUSIONS: After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.

Dietary pattern in women with polycystic ovary syndrome with and without associated non-alcoholic fatty liver disease: A cross-sectional study

Abstract Introduction Women with Polycystic Ovary Syndrome (PCOS) have a higher prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) than the general population. PCOS and NAFLD have common metabolic risk factors, however, the role of diet in NAFLD development is still uncertain in PCOS women. Objective To evaluate and compare the dietary patterns and nutritional intake in patients with PCOS with and without NAFLD. Method Cross-sectional study that included patients with PCOS diagnosed according to Rotterdam criteria. All participants were submitted to abdominal ultrasound to investigate liver steatosis. Dietary profile was assessed by 24-hour food recall (24hR), and Food Frequency Questionnaire (FFQ). Diet quality was assessed by the Healthy Eating Index (HEI) adapted for the Brazilian population. Physical activity practice was also assessed. Results 87 participants were included (average age 35.2 ± 5.7 years), among whom, 67 (77%) had NAFLD. The group with PCOS and NAFLD presented higher body mass index (BMI) (34.9 ± 4.5 vs. 30.4 ± 4.9 kg/m2; p = 0.001), Waist Circumference (WC) (103 [97‒113] vs. 95 [87.5‒100] cm; p < 0.001) and were considered physically active less frequently than those without NAFLD (34.3% vs. 60%; p = 0.04). Food intake and dietary patterns assessed by 24hR, FFQ and HEI presented no difference between the groups. Conclusions PCOS women with coexistent NAFLD had higher BMI, WC and were less physically active than those without NAFLD. Dietary evaluation showed that PCOS women with NAFLD had no significant difference in macro and micronutrients or food group intake and diet quality in comparison to those without NAFLD.

Autoimmune hepatitis presenting with peripheral eosinophilia: Case report and literature review.

Acute hepatitis presenting with blood eosinophilia are scarcely reported. Different clinical courses of autoimmune hepatitis (AIH) have been associated with acute hepatitis with eosinophilia, however it is still unclear if the latter is a common manifestation of different autoimmune diseases, part of a similar spectrum of eosinophil-associated liver injury or even a trigger to AIH. We report a case of a 32 years old woman who presented with subacute hepatitis, peripheral eosinophilia, hypergammaglobulinemia and liver biopsy suggestive of AIH. The role of eosinophils in autoimmune liver diseases deserves further studies in order to clarify its physiopathology aspects.

COLONOSCOPY FINDINGS IN LIVER TRANSPLANTATION CANDIDATES.

BACKGROUND: Mandatory colonoscopy in liver transplantation (LT) candidates is recommended but still controversial. OBJECTIVE: To investigate the frequency of colonoscopy lesions in order to support colorectal cancer (CRC) screening in a real-world pre-LT cohort. METHODS: Retrospective study conducted at a single-center included 632 subjects who underwent pre-transplantation colonoscopy. RESULTS: Median age was 56.9 years (yr.) old (82.3% were ≥50 yr.). Primary sclerosing cholangitis (PSC) occurred in 4.6%. Colonoscopy was abnormal in 438 (69.3%) by detection of polyps (37.7%), vascular changes (29.9%), diverticulosis (18.4%), inflammatory bowel disease features (5.2%) and CRC (0.6%). Histology was available in 66.8% of polyps: hyperplastic (47.8%), low-grade dysplasia (56.6%) and high-grade dysplasia (3.8%). High-risk adenomas occurred in 8.2% of the 594 subjects evaluated. Individuals ≥50 yr. were more likely to present abnormal colonoscopy and polyps. High-grade dysplasia and CRC were only found in individuals ≥50 yr. Patients with high-risk adenomas were more likely to be ≥50 yr.: there was no association between high-risk adenomas detection and liver disease etiology or PSC diagnosis. CONCLUSION: Most LT candidates presented abnormal colonoscopy examination, especially by polyps presence. All cases of high-grade dysplasia and CRC occurred in patients ≥50 yr., regardless of disease etiology.

Achados da colonoscopia em candidatos a transplante hepático / Colonoscopy findings in liver transplantation candidates

ABSTRACT Background Mandatory colonoscopy in liver transplantation (LT) candidates is recommended but still controversial. Objective To investigate the frequency of colonoscopy lesions in order to support colorectal cancer (CRC) screening in a real-world pre-LT cohort. Methods Retrospective study conducted at a single-center included 632 subjects who underwent pre-transplantation colonoscopy. Results Median age was 56.9 years (yr.) old (82.3% were ≥50 yr.). Primary sclerosing cholangitis (PSC) occurred in 4.6%. Colonoscopy was abnormal in 438 (69.3%) by detection of polyps (37.7%), vascular changes (29.9%), diverticulosis (18.4%), inflammatory bowel disease features (5.2%) and CRC (0.6%). Histology was available in 66.8% of polyps: hyperplastic (47.8%), low-grade dysplasia (56.6%) and high-grade dysplasia (3.8%). High-risk adenomas occurred in 8.2% of the 594 subjects evaluated. Individuals ≥50 yr. were more likely to present abnormal colonoscopy and polyps. High-grade dysplasia and CRC were only found in individuals ≥50 yr. Patients with high-risk adenomas were more likely to be ≥50 yr.: there was no association between high-risk adenomas detection and liver disease etiology or PSC diagnosis. Conclusion Most LT candidates presented abnormal colonoscopy examination, especially by polyps presence. All cases of high-grade dysplasia and CRC occurred in patients ≥50 yr., regardless of disease etiology.

RESUMO Contexto Colonoscopia mandatória em candidatos a transplante hepático (TH) é recomendada, mas ainda é controversa. Objetivo Investigar a frequência de lesões detectadas pela colonoscopia para endossar o screening de câncer colorretal (CCR) em uma coorte pré-TH de mundo real. Métodos Estudo retrospectivo conduzido em um centro único que incluiu 632 indivíduos submetidos a colonoscopia pré-TH. Resultados Idade mediana foi 56.9 anos (82,3% eram ≥50 anos). Colangite esclerosante primária (CEP) estava presente em 4.6%. Colonoscopia foi anormal em 438 (69,3%) por: detecção de pólipos (37,7%), alterações vasculares (29,9%), diverticulose (18,4%), características de doença inflamatória intestinal (5,2%) e CCR (0,6%). Histologia estava disponível em 66,8% dos pólipos: hiperplásicos (47,8%), displasia de baixo grau (56,6%) e displasia de alto grau (3,8%). Adenomas de alto risco ocorreram em 8,2% dos 594 indivíduos avaliados. Indivíduos ≥50 anos eram mais prováveis de apresentar colonoscopia anormal e pólipos. Displasia de alto grau e CCR foram encontrados somente em indivíduos ≥50 anos. Pacientes com adenoma de alto risco eram mais prováveis de ter ≥50 anos: não houve associação entre a detecção de adenomas de alto risco e a etiologia da hepatopatia ou o diagnóstico de CEP. Conclusão A maioria dos candidatos a TH apresentaram achados anormais na colonoscopia, principalmente pela presença de pólipos. Todos os casos de displasia de alto grau e CCR ocorreram em pacientes ≥50 anos, independente da etiologia da hepatopatia.

High prevalence of functional dyspepsia in nonalcoholic fatty liver disease: a cross-sectional study

Abstract BACKGROUND: Gastrointestinal (GI) symptoms are frequent complaints from individuals with nonalcoholic fatty liver disease (NAFLD). Dyspepsia is a universal clinical symptom and is among the most common GI complaints observed in the general population, but its prevalence in the population with NAFLD has not been previously investigated. OBJECTIVE: To compare the prevalence of functional dyspepsia (FD) between patients with NAFLD and controls without liver disease. DESIGN AND SETTING: Cross-sectional study at the Outpatient Liver Clinic, University Hospital, Belo Horizonte, Brazil. METHODS: We included 96 NAFLD patients and 105 controls without liver disease. All participants were assessed for GI symptoms in accordance with the Rome III criteria. Evaluation methods included a questionnaire for FD (validated in Brazil), laboratory tests and upper GI endoscopy. RESULTS: Mean age and sex were similar between the groups. The NAFLD group presented higher frequency of proton-pump inhibitor usage (31.3% vs 4.8%; P < 0.001) and prevalence of FD (25.0% versus 12.4%; P = 0.021). The symptom frequencies were as follows: postprandial distress, 22.9% versus 11.4% (P = 0.030); postprandial fullness, 18.8% versus 10.5% (P = 0.095); early satiation, 8.3% versus 5.7% (P = 0.466); and epigastric pain or burning, 18.8% versus 5.7% (P = 0.004), in NAFLD patients and controls, respectively. Multivariate analysis demonstrated that female sex (odds ratio, OR 6.97; 95% confidence interval, CI: 1.51-32.12; P = 0.013) and NAFLD diagnosis (OR 2.45; 95% CI: 1.14-5.27; P = 0.021) were independently associated with FD occurrence. CONCLUSION: FD occurs more frequently in individuals with NAFLD than in controls without hepatic disease.

Carvedilol as secondary prophylaxis for variceal bleeding in hepatosplenic schistosomiasis.

BACKGROUND: Upper variceal bleeding (UVB) is a possible complication of portal hypertension secondary to hepatosplenic schistosomiasis (HSS). Propranolol is a non-selective beta-blocker used as secondary prophylaxis for UVB, but no previous studies have addressed carvedilol effects in rebleeding prevention. METHODS: A retrospective exploratory study of 57 patients with chronic HSS and index UVB treated with endoscopic variceal ligation and propranolol or carvedilol was conducted. The primary outcome was UVB-free time in the first 12 mo after the initial bleeding episode. RESULTS: Propranolol was used for secondary UVB prophylaxis in 43 (75.4%) participants (median dose 80 [interquartile range - IQR 60-80] mg/d) and carvedilol in 14 (24.6%) participants (median dose 12.5 [IQR 7.9-25.0] mg/d). During a 12-mo follow-up, rebleeding was observed in 13 (22.8%) patients, 9 (20.9%) of those treated with propranolol and 4 (28.6%) treated with carvedilol (p=0.715). Mean time from the beginning of drug prophylaxis to rebleeding was 6±3 mo and there was no difference between that for propranolol vs carvedilol subgroups. Portal vein thrombosis did not influence the bleeding recurrence in either subgroup. CONCLUSION: Carvedilol may be equally effective as propranolol in preventing secondary UVB in HSS at 12-mo follow-up.

High prevalence of functional dyspepsia in nonalcoholic fatty liver disease: a cross-sectional study.

BACKGROUND: Gastrointestinal (GI) symptoms are frequent complaints from individuals with nonalcoholic fatty liver disease (NAFLD). Dyspepsia is a universal clinical symptom and is among the most common GI complaints observed in the general population, but its prevalence in the population with NAFLD has not been previously investigated. OBJECTIVE: To compare the prevalence of functional dyspepsia (FD) between patients with NAFLD and controls without liver disease. DESIGN AND SETTING: Cross-sectional study at the Outpatient Liver Clinic, University Hospital, Belo Horizonte, Brazil. METHODS: We included 96 NAFLD patients and 105 controls without liver disease. All participants were assessed for GI symptoms in accordance with the Rome III criteria. Evaluation methods included a questionnaire for FD (validated in Brazil), laboratory tests and upper GI endoscopy. RESULTS: Mean age and sex were similar between the groups. The NAFLD group presented higher frequency of proton-pump inhibitor usage (31.3% vs 4.8%; P < 0.001) and prevalence of FD (25.0% versus 12.4%; P = 0.021). The symptom frequencies were as follows: postprandial distress, 22.9% versus 11.4% (P = 0.030); postprandial fullness, 18.8% versus 10.5% (P = 0.095); early satiation, 8.3% versus 5.7% (P = 0.466); and epigastric pain or burning, 18.8% versus 5.7% (P = 0.004), in NAFLD patients and controls, respectively. Multivariate analysis demonstrated that female sex (odds ratio, OR 6.97; 95% confidence interval, CI: 1.51-32.12; P = 0.013) and NAFLD diagnosis (OR 2.45; 95% CI: 1.14-5.27; P = 0.021) were independently associated with FD occurrence. CONCLUSION: FD occurs more frequently in individuals with NAFLD than in controls without hepatic disease.

Noninvasive predictors of esophageal varices in patients with hepatosplenic schistosomiasis mansoni.

BACKGROUND: No previous study have evaluated transient elastography for predicting esophageal varices in hepatosplenic schistosomiasis. AIM: To investigate noninvasive methods of predicting esophageal varices in patients with hepatosplenic schistosomiasis mansoni. METHODS: Cross-sectional multicentric study included 51 patients with hepatosplenic schistosomiasis. Patients underwent ultrasonography-dopplerfluxometry, upper endoscopy, complete blood cell count and transient elastography (Fibroscan®) for liver and spleen stiffness measurement (LSM and SSM). Noninvasive scores previously established for cirrhotic population were studied: platelet count to spleen diameter ratio (PSR), LSM-spleen diameter to platelet ratio score (LSPS) and varices risk score (VRS). We proposed a version of LSPS and VRS by replacing LSM with SSM and named them SSPS and modified-VRS, respectively. RESULTS: Esophageal varices were detected in 42 (82.4%) subjects. Individuals with varices presented higher SSM (73.5 vs 36.3 Kpa, p = 0.001), splenic vein diameter (10.8 vs 8.0 mm, p = 0.017), SSPS (18.7 vs 6.7, p = 0.003) and modified-VRS (4.0 vs 1.4, p = 0.013), besides lower PSR (332 vs 542, p = 0.038), than those without varices. SSPS was independently associated with varices presence (OR=1.19, 95%CI 1.03-1.37, p = 0.020) after multivariate analysis. In a model excluding noninvasive scores, SSM was independently associated with varices diagnosis (OR=1.09, 95%CI 1.03-1.16, p = 0.004). AUROC was 0.856 (95%CI 0.752-0.961, p = 0.001) for SSM and 0.816 (95%CI 0.699-0.932, p = 0.003) for SSPS (p = 0.551). CONCLUSIONS: Spleen-related variables were predictors of esophageal varices: SSM, splenic vein diameter, SSPS, modified-VRS and PSR. Multivariate models indicated that SSM and SSPS are useful tools for predicting varices in non-cirrhotic portal hypertension by hepatosplenic schistosomiasis and may be used in clinical practice.

Anti-mitochondrial Antibody-Negative Primary Biliary Cholangitis Is Part of the Same Spectrum of Classical Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease in which anti-mitochondrial antibodies (AMA) are the diagnostic hallmark. Whether AMA-negative PBC patients represent a different phenotype of disease is highly debated. AIMS: The purpose of our study was to compare AMA-positive and AMA-negative PBC patients in a large non-white admixed Brazilian cohort. METHODS: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian PBC patients, stratifying data according to AMA status. RESULTS: A total of 464 subjects (95.4% females, mean age 56 ± 5 years) with PBC were included. Three hundred and eighty-four (83%) subjects were AMA-positive, whereas 80 (17%) had AMA-negative PBC. Subjects with AMA-negative PBC were significantly younger (52.2 ± 14 vs. 59.6 ± 11 years, p = 0.001) and had their first symptom at an earlier age (43.2 ± 13 vs. 49.5 ± 12 years, p = 0.005). Frequency of type 2 diabetes was significantly increased in subjects with AMA-negative PBC (22.5% vs. 12.2%, p = 0.03). Lower IgM (272.2 ± 183 vs. 383.2 ± 378 mg/dL, p = 0.01) and triglycerides (107.6 ± 59.8 vs.129.3 ± 75.7 mg/dL, p = 0.025) and higher bilirubin (3.8 ± 13.5 vs. 1.8 ± 3.4 mg/dL, p = 0.02) levels were also observed in this subgroup. Response to ursodeoxycholic acid varied from 40.5 to 63.3% in AMA-positive and 34 to 62.3% in AMA-negative individuals, according to different response criteria. Outcomes such as development of liver-related complications, death and requirement for liver transplantation were similar in both groups. CONCLUSIONS: AMA-negative PBC patients are similar to their AMA-positive counterparts with subtle differences observed in clinical and laboratory features.

Pregnancy Outcomes in Wilson's Disease Women: Single-Center Case Series.

OBJECTIVES: To evaluate and compare pregnancy outcomes in women with Wilson's disease (WD) undergoing different therapies during pregnancy. MATERIAL AND METHODS: Retrospective review of medication in WD patients during pregnancy and the outcomes. RESULTS: Of 26 pregnancies, zinc was used in 14 (53.8%), D-penicillamine in 4 (15.4%) patients, and 8 (30.8%) were untreated. Spontaneous abortion was observed in 8 (30.8%) pregnancies - untreated patients (4/8 pregnancies), zinc (2/14 pregnancies) and D-penicillamine (2/4 pregnancies) -, healthy outcome in 12 (46.1%) and birth defects in 6 (23.1%). All cases of birth defects occurred in patients using zinc therapy (6/14 pregnancies). CONCLUSIONS: A remarkably high frequency of fetal complications shed lights on the potentially harmful effect of WD drugs during childbearing age. Zinc's safety profile may have to be better evaluated during pregnancy, as all of birth defects occurred with zinc therapy.

Clinical features and treatment outcomes of primary biliary cholangitis in a highly admixed population.

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.

Clinical Features and Outcomes of Primary Sclerosing Cholangitis in the Highly Admixed Brazilian Population.

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.

A cost of illness comparison for toxigenic Clostridioides difficile diagnosis algorithms in developing countries.

BACKGROUND: Availability of several commercial tests with different Clostridioides difficile targets contributes to uncertainty and controversies around the optimal diagnostic algorithm. While numerous studies have estimated the financial impact of C. difficile infection, models to guide testing strategies decisions in developing countries, where economic value significantly impacts clinical practice, are currently not available. AIM: To determine the cost of illness of different C. difficile infection (CDI) diagnostic strategies in developing countries. METHODS: Cost-comparison analysis was performed to compare eleven different algorithms of CDI diagnosis. The basis of calculation was a hypothetical cohort of 1000 adult inpatients suspected of CDI. We analyzed turnaround time of test results (i.e., time from taking sample to results emission), test performance (i.e., sensitivity and specificity) and testing costs. Patients were divided in true positive, false positive, true negative and false negative in order to integrate test performance and economics effects. Additional medical costs were calculated: costs of hygiene, medication, length of stay and intensive care unit costs, based on a Brazilian University Hospital costs. CDI prevalence was considered 22.64%. FINDINGS: From laboratory-assisted tests, simultaneous glutamate dehydrogenase (GDH) and toxin A/B rapid immunoassay arbitrated by nucleic acid amplification test (NAAT) presented the lowest cost of illness (450,038.70 USD), whereas standalone NAAT had the highest (523,709.55 USD). Empirical diagnosis only presented the highest overall cost (809,605.44 USD). CONCLUSION: The two-step algorithm with simultaneous GDH and toxin A/B rapid immunoassay arbitrated by NAAT seems to be the best strategy for CDI diagnosis in developing countries.

Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study.

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.

PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide, with significant morbidity associated with nonalcoholic steatohepatitis (NASH). Genome-wide association studies demonstrated that the variants rs738409 C/G in the PNPLA3 and rs58542926 C/T in the TM6SF2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAFLD progression. AIM: To investigate PNPLA3 and TM6SF2 genotype frequency and their association with NAFLD development and progression in Brazilian patients. METHODS: This cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in Brazil. The case patients (n = 148) were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver disease. According to the clinical protocol, patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis (n = 65). Steatohepatitis was confirmed in 54 patients. Individuals who did not have biopsy indication or NASH on histology were considered to have simple steatosis (n = 94). The control group (n = 137) was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical tests. All individuals underwent PNPLA3 and TM6SF2 genotype analysis. RESULTS: PNPLA3 CC, CG and GG genotype frequencies were 37%, 44% and 19%, respectively, in NAFLD patients and were 58%, 31% and 10% in controls (P < 0.001). In a model adjusted for gender, age, body mass index and type 2 diabetes mellitus, the G allele increased the chance of NAFLD (OR = 1.69, 95%CI: 1.21-2.36, P = 0.002) and NASH (OR = 3.50, 95%CI: 1.84-6.64, P < 0.001). The chance of NASH was even higher with GG homozygosis (OR = 5.53, 95%CI: 2.04-14.92, P = 0.001). No association was found between G allele and the features of metabolic syndrome. In histological assessment, PNPLA3 genotype was not associated with steatosis grade, although GG homozygosis increased the chance of significant NASH activity (OR = 17.11, 95%CI: 1.87-156.25, P = 0.01) and fibrosis (OR = 7.42, 95%CI: 1.55-34.47, P = 0.01) in the same adjusted model. TM6SF2 CC, CT and TT genotype frequencies were 83%, 15% and 0.7%, respectively, in NAFLD patients and were 84%, 16% and 0.7% in controls (P = 0.78). The T allele presence was not associated with NAFLD or NASH, and was not associated with histological features. CONCLUSION: PNPLA3 may be involved in susceptibility and progression of NAFLD and NASH in the Brazilian population. More advanced histological liver disease was associated with the G allele. The TM6SF2 genetic variants were not associated with NAFLD susceptibility and progressive histological forms in the population studied, but further studies are required to confirm these findings.