Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso).

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusion: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Metabolomics in chronic hepatitis C: Decoding fibrosis grading and underlying pathways.

BACKGROUND: Chronic Hepatitis C (CHC) affects 71 million people globally and leads to liver issues such as fibrosis, cirrhosis, cancer, and death. A better understanding and prognosis of liver involvement are vital to reduce morbidity and mortality. The accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting outcomes. Tests used to grade fibrosis include histological analysis and imaging but have limitations. Blood markers such as molecular biomarkers can offer valuable insights into fibrosis. AIM: To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the disease. METHODS: Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1 (n = 13), F2 (n = 12), F3 (n = 6), and F4 (n = 15). To ensure that the identified biomarkers were exclusive to liver lesions (CHC fibrosis), healthy volunteer participants (n = 50) were also included. An untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database verification. Statistical analyses were performed to identify differential biomarkers among groups. RESULTS: Six differential metabolites were identified in each grade of fibrosis. This six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis; thus, they showed greater efficiency in discriminating grades. CONCLUSION: This study suggests that some of the observed biomarkers, once validated, have the potential to be applied as prognostic biomarkers. Furthermore, it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.

Economic evaluation of non-invasive liver tests for the diagnosis of liver fibrosis in chronic liver diseases: a systematic review protocol.

OBJECTIVE: The objective of this review is to determine the costs and benefits of non-invasive liver tests versus liver biopsy in patients with chronic liver diseases. INTRODUCTION: Hepatic diseases can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. In the past, liver biopsy was the only option for diagnosing fibrosis degree; however, it is an invasive procedure that depends on the sample size to be able to deliver an accurate diagnosis. In recent years, non-invasive liver tests have been increasingly used to estimate liver fibrosis degree, however, there is a lack of economic assessments of technology implementation outcomes. INCLUSION CRITERIA: This review will include partial (cost studies) and complete economic evaluation studies on hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease that compare non-invasive liver tests with liver biopsies. Studies published in English, French, Spanish, German, Italian, or Portuguese will be included. No date limits will be applied to the search. METHODS: This review will identify published and unpublished studies. Published studies will be identified using MEDLINE (PubMed), Cochrane Library (CENTRAL), Embase (Elsevier), Web of Science, Scopus, and LILACS. Sources of unpublished studies and gray literature will include sources from health technology assessment agencies, clinical practice guidelines, regulatory approvals, advisories and warnings, and clinical trial registries, as well as Google Scholar. Two independent reviewers will screen and assess studies, and extract and critically appraise the data. Data extracted from the included studies will be analyzed and summarized to address the review objective using narratives, tables, and the JBI dominance ranking matrix. REVIEW REGISTRATION: PROSPERO CRD42023404278.

Hepatic epithelioid hemangioendothelioma: how fast does it grow and which findings could have prevented diagnostic delay?-a case report.

Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare neoplastic disease of varied presentation and unspecific radiological signs in the early stages. The diagnostic delay can lead to metastatic disease, thus increasing the tumor burden and reducing the treatment options. HEHE is usually deemed a slow-growing tumor, but its speed of growth is poorly reported and still unknown. Case Description: In this case report, we documented a HEHE diagnosed in a young woman who had complaints of abdominal pain, weight loss and bloating for a long time. The typical findings observed in histological studies were not promptly recognized in the histological analyzes, even after two laparoscopic-guided liver biopsies, delaying the diagnosis until extrahepatic tumor spreading. Findings observed in computed tomography, magnetic resonance imaging and histological studies are presented. The coalescence of nodules and the rising of giant masses, occupying large parts of the liver in a specific time span, were registered and quantified. As opposed to prior reports, the results show that hepatic HEHE can grow rapidly, reinforcing the need of early diagnosis, thus avoiding the complications presented herein. Conclusions: The findings observed via radiological and histological imaging that could have avoided the diagnosis delay are depicted and discussed, showing that HEHE can rise faster than previously documented.

HLA-DRB1 Polymorphisms and Rheumatologic Manifestations in Chronic Hepatitis C.

BACKGROUND/AIMS: Hepatitis C has been associated with rheumatologic manifestations (HCV-related RM). Clinically, HCV-related RM may be indistinguishable from the symptoms that occur in diffuse connective tissue diseases (DCTD-related RM), making the differential diagnosis difficult. Host genetic factors, such as the Human Leukocyte Antigens (HLA) polymorphisms were associated with HCV infection, however, there are no studies that discriminate between HCVrelated RM and DCTD-related RM. This study focused on verifying associations between HLADRB1 and RM in patients with chronic hepatitis C, aiming to distinguish between DCTD-related RM and HCV-related RM. METHODS: The participants were 152 individuals, of both sexes, aged between 18 and 80 years, and affected by chronic hepatitis C. The patients underwent rheumatologic physical examination and HLA-class II (HLA-DRB1) typing was performed by PCR-SSO (Polymerase Chain Reactionsequence Specific Oligonucleotides). RESULTS: A significant number of patients with rheumatologic complaints (73%) not attributed to other causes was observed. DRB1*08 allele seems to confer protection against RM in chronic hepatitis C. There is no susceptibility association between HLA-DRB1 alleles and RM. CONCLUSION: The absence of association between HLA-DRB1 and the rheumatologic manifestations studied suggests that the pathophysiological pathways of DCTD-related RM and HCV-related RM are distinct.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents.

BACKGROUND AND AIMS: Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. PATIENTS AND METHODS: Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. RESULTS: As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. CONCLUSION: The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.

Factors associated with hepatitis C treatment adherence: an integrative review. / Fatores associados à adesão ao tratamento da hepatite C: revisão integrativa.

This integrative review examined factors associated with hepatitis C treatment adherence. The articles included were published in English, Spanish and Portuguese in the Lilacs, Medline, PsycINFO, Web of Science, Scopus and CINAHL databases, between 2000 and 2019. Initially, 540 publications were found and, after applying the study inclusion criteria, 22 articles were selected. Percentage non-adherence to treatment ranged from 12% to 32%. The variables identified as facilitating adherence were: receiving treatment for psychiatric disorders identified during treatment; knowing about medications and disease; receiving less complex treatment with greater likelihood of cure; fewer adverse events; social support; doctor-patient communication; and/or being in relationships. Barriers to adherence identified were: presence of depressive symptoms and other mental disorders; abuse of alcohol and psychoactive substances; education; age; ethnicity; unemployment; not having a steady partner; stigma; distance from health services; and the complexity and adverse effects of treatment. This review identified gaps in research on adherence.

Esta revisão integrativa propôs-se a analisar na literatura da área estudos sobre fatores associados à adesão ao tratamento da hepatite C. Foram pesquisados artigos, publicados em inglês, espanhol e português, nas bases de dados Lilacs, Medline, PsycINFO, Web of Science, Scopus e CINAHL, entre os anos 2000 a 2019. Foram obtidas, inicialmente, 540 publicações e, posteriormente, aplicando-se os critérios de inclusão estabelecidos, foram selecionados 22 artigos. Constatou-se nos artigos analisados que a porcentagem de não adesão ao tratamento variou de 12% a 32%. Foram identificados como facilitadores da adesão: receber tratamento para transtornos psiquiátricos identificados durante o tratamento, ter conhecimento sobre os medicamentos e doença, receber tratamento menos complexo e com maior possibilidade de cura, apresentar menor número de eventos adversos, ter apoio social e bom vínculo com o médico. Foram identificadas como barreiras à adesão: presença de sintomas depressivos e de outros transtornos mentais, uso abusivo de álcool e substâncias psicoativas, baixa escolaridade, idade (ser mais jovem); etnia (afro-americanos), desemprego, não ter parceiro fixo, relatar estigma, distância do serviço de saúde, complexidade e eventos adversos do tratamento. Foram também identificadas lacunas nas pesquisas sobre adesão.

Fatores associados à adesão ao tratamento da hepatite C: revisão integrativa / Factors associated with hepatitis C treatment adherence: an integrative review

Resumo Esta revisão integrativa propôs-se a analisar na literatura da área estudos sobre fatores associados à adesão ao tratamento da hepatite C. Foram pesquisados artigos, publicados em inglês, espanhol e português, nas bases de dados Lilacs, Medline, PsycINFO, Web of Science, Scopus e CINAHL, entre os anos 2000 a 2019. Foram obtidas, inicialmente, 540 publicações e, posteriormente, aplicando-se os critérios de inclusão estabelecidos, foram selecionados 22 artigos. Constatou-se nos artigos analisados que a porcentagem de não adesão ao tratamento variou de 12% a 32%. Foram identificados como facilitadores da adesão: receber tratamento para transtornos psiquiátricos identificados durante o tratamento, ter conhecimento sobre os medicamentos e doença, receber tratamento menos complexo e com maior possibilidade de cura, apresentar menor número de eventos adversos, ter apoio social e bom vínculo com o médico. Foram identificadas como barreiras à adesão: presença de sintomas depressivos e de outros transtornos mentais, uso abusivo de álcool e substâncias psicoativas, baixa escolaridade, idade (ser mais jovem); etnia (afro-americanos), desemprego, não ter parceiro fixo, relatar estigma, distância do serviço de saúde, complexidade e eventos adversos do tratamento. Foram também identificadas lacunas nas pesquisas sobre adesão.

Abstract This integrative review examined factors associated with hepatitis C treatment adherence. The articles included were published in English, Spanish and Portuguese in the Lilacs, Medline, PsycINFO, Web of Science, Scopus and CINAHL databases, between 2000 and 2019. Initially, 540 publications were found and, after applying the study inclusion criteria, 22 articles were selected. Percentage non-adherence to treatment ranged from 12% to 32%. The variables identified as facilitating adherence were: receiving treatment for psychiatric disorders identified during treatment; knowing about medications and disease; receiving less complex treatment with greater likelihood of cure; fewer adverse events; social support; doctor-patient communication; and/or being in relationships. Barriers to adherence identified were: presence of depressive symptoms and other mental disorders; abuse of alcohol and psychoactive substances; education; age; ethnicity; unemployment; not having a steady partner; stigma; distance from health services; and the complexity and adverse effects of treatment. This review identified gaps in research on adherence.

Cirrhosis regression after SVR with indirect methods of fibrosis analysis: How far is it real?

Hepatitis C virus has infected over 71 million people worldwide, and it is the main cause of cirrhosis in the western world. Currently, the treatment involves direct-acting antiviral agents (DAAs) and its main goal is to achieve sustained virologic response (SVR). The aim of this study was to evaluate the impact of SVR using DAAs in the improvement of liver fibrosis using scores evaluation by indirect method, liver function, and inflammation indirect biomarkers. Patients with cirrhosis with SVR after treatment (n = 104) were evaluated using liver function scores, indirect fibrosis methods, alpha-fetoprotein, and ferritin at t-base and t-SVR. Statistically significant positive results in all parameters were observed: 54 patients were classified as 5 in the CP score in t-base, and 77 in t-SVR; a significant decrease was observed in MELD score, alpha-fetoprotein, ferritin, APRI, FIB-4 and liver stiffness in liver elastography. We did not observe difference in the liver function scores between regressors and non-regressors of liver stiffness, as well as in indirect inflammation biomarkers. The measurements of fibrosis using the indirect methods have significantly decreased in patients with cirrhosis treated who achieved SVR associated with decreased indirect inflammation biomarkers and improved liver function scores.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents

ABSTRACT Background and aims: Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. Patients and methods: Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. Results: As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. Conclusion: The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.

Inflammation response and liver stiffness: predictive model of regression of hepatic stiffness after sustained virological response in cirrhotics patients with chronic hepatitis C.

Cirrhotic patients with chronic hepatitis C should be monitored for the evaluation of liver function and screening of hepatocellular carcinoma even after sustained virological response (SVR). The stage of inflammatory resolution and regression of fibrosis is likely to happen, once treatment and viral clearance are achieved. However, liver examinations by elastography show that 30-40% of patients do not exhibit a reduction of liver stiffness. This work was a cohort study in cirrhotic patients whose purpose was to identify immunological factors involved in the regression of liver stiffness in chronic hepatitis C and characterize possible serum biomarkers with prognostic value. The sample universe consisted of 31 cirrhotic patients who underwent leukocyte immunophenotyping, quantification of cytokines/chemokines and metalloproteinase inhibitors in the pretreatment (M1) and in the evaluation of SVR (M2). After exclusion criteria application, 16 patients included were once more evaluated in M3 (like M1) and classified into regressors (R) or non-regressors (NR), decrease or not ≥ 25% stiffness, respectively. The results from ROC curve, machine learning (ML) and linear discriminant analysis showed that TCD4 + lymphocytes (absolute) are the most important biomarkers for the prediction of the regression (AUC = 0.90). NR patients presented levels less than R of liver stiffness since baseline, whereas NK cells were increased in NR. Therefore, it was concluded that there is a difference in the profile of circulating immune cells in R and NR, thus allowing the development of a predictive model of regression of liver stiffness after SVR. These findings should be validated in greater numbers of patients.

Mixed and disseminated paracoccidioidomycosis after liver transplantation: Case report.

Paracoccidioidomycosis (PCM) is a systemic granulomatous fungal infection rarely associated with solid organ transplantation. We report the second case of PCM in an adult after liver transplantation. A 47-year-old woman who had undergone liver transplantation was hospitalized for flu-like symptoms and multiple erythematous ulcerated skin papules. There was lymphadenopathy, pulmonary compromise, and quickly progression to septic shock. PCM was confirmed by skin biopsy and serologic tests, and a satisfactory response to amphotericin B was achieved.

Efficacy and safety of glecaprevir/pibrentasvir in treatment-naïve adults with chronic hepatitis C virus genotypes 1-6 in Brazil.

INTRODUCTION AND OBJECTIVES: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. PATIENTS AND METHODS: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1-6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. RESULTS: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0-99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. CONCLUSIONS: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03219216.

New LncRNAs in Chronic Hepatitis C progression: from fibrosis to hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world, and about 80% of the cases are associated with hepatitis B or C. Genetic and epigenetic alterations are accumulated over decades of chronic injury and may affect the functioning of tumor suppressor genes and protooncogenes. Studies have evidenced the role of Long non-coding RNAs (LncRNA) with oncogenic or tumor suppressor activities, suggesting a great potential in the treatment, diagnosis or indicator of prognosis in cancer. In this context, the aim of this study was to evaluate the global expression profile lncRNA in hepatic tissue samples with different stages of fibrosis associated with chronic hepatitis C, HCC and normal liver, in order to identify new lncRNAs that could contribute to study the progression of hepatic fibrosis to HCC associated with chronic hepatitis C. RNA-Seq was performed on Illumina NextSeq platform to identify lncRNAs expressed differently in 15 patients with chronic hepatitis C, three patients with HCC and three normal liver specimens. When the pathological tissues (fibrosis and carcinoma) were compared to normal hepatic tissue, were identified 2, 6 e 34 differentially expressed lncRNAs in moderate fibrosis, advanced fibrosis and HCC, respectively. The carcinoma group had the highest proportion of differentially expressed lncRNA (34) and of these, 29 were exclusive in this type of tissue. A heat map of the deregulated lncRNA revealed different expression patterns along the progression of fibrosis to HCC. The results showed the deregulation of some lncRNA already classified as tumor suppressors in HCC and other cancers, as well as some unpublished lncRNA whose function is unknown. Some of these lncRNAs are dysregulated since the early stages of liver injury in patients with hepatitis C, others overexpressed only in tumor tissue, indicating themselves as candidates of markers of fibrosis progression or tumor, with potential clinical applications in prognosis as well as a therapeutic target. Although there are already studies on lncRNA in hepatocellular carcinoma, this is the first study conducted in samples exclusively of HCV-related liver and HCV HCC.

Human platelet antigen-3 polymorphism as a risk factor for rheumatological manifestations in hepatitis C.

INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.

Human platelet antigen-3 polymorphism as a risk factor for rheumatological manifestations in hepatitis C

Abstract INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.

Safety and efficacy of risedronate for patients with esophageal varices and liver cirrhosis: a non-randomized clinical trial.

Despite the high prevalence of osteoporosis in liver cirrhosis, the indication of bisphosphonates for patients with esophageal varices has been avoided due to risk of digestive mucosal damage. Therefore, this study aimed to evaluate the safety profile of risedronate treatment for patients with osteoporosis, liver cirrhosis and esophageal varices with low risk of bleeding. A total of 120 patients were allocated into two groups according to their bone mineral density measured by dual-energy X-ray absorptiometry. In the intervention group, 57 subjects with osteoporosis received oral risedronate at 35 mg weekly plus daily calcium and vitamin D supplementation. In the control group, 63 subjects with osteopenia received only calcium and vitamin D. The groups received the treatment for one year and underwent surveillance endoscopies at six and 12 months, as well as a control dual-energy X-ray absorptiometry after a 12-month follow-up. The study received Institutional Review Board approval. The groups had not only comparable Model for End-stage Liver Disease score and esophageal varices degree, but also similar incidence of digestive adverse effects. A significant improvement was achieved in the intervention group in the lumbar spine T score (p < 0.001). The results suggest that risedronate may be safely used in liver cirrhosis and esophageal varices with low bleeding risk under endoscopic surveillance, thus allowing bone mass recovery.

Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil.

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.

Influence of the HIV GWG variant in the HIV infection progression in mono and HCV coinfected patients.

The HIV subtype B is the most frequent in Brazil. The HIV subtype B' codes the amino acids glicine-tryptophan-glicine (GWG) instead of glicine-proline-glicine on the tip of gp120 V3 loop. This variant was associated to a slower HIV progression in mono-infected patients; however, there is no information in coinfected patients. This study evaluated the infection progression of HIV variant B' on the hepatitis C virus presence. RNA isolated from plasma of the 601 infected patients were used to human immunodeficiency virus (HIV) subtyping and to classify the virus according their syncytium-inducing ability. The HIV infection progression was evaluated by clinical and laboratorial data. The results showed a significant association between HIV B' variant and CD4 count and time of AIDS in HIV mono-infected patients. Notwithstanding the fact that we did not find a direct association between GWG variant and AIDS and in HIV coinfected patients no mitigating effect due to GWG presence was found. We did observe that the association between GWG variant and CD4 counts is lost in coinfected patients. This is first work showing influence of the HIV GWG variant in coinfected patients. Nevertheless, the presence of the GWG variant can indicate a better prognostic in the mono-infected patients.