Hepatobiliary disease after bone marrow transplant: A cross-sectional study of 377 patients.

BACKGROUND: Bone marrow transplantation (BMT) is a standard treatment for several haematologic conditions. Following BMT, patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischaemic hepatitis, and fulminant hepatitis. AIMS: To evaluate the frequency, clinical characteristics, and outcomes of patients with hepatobiliary alterations associated with BMT in a tertiary referral centre. METHODS: This was a cross-sectional study with data collected from the medical records of patients undergoing BMT between January 2017 and June 2022. We diagnosed hepatobiliary complications based on established criteria. RESULTS: We included 377 patients; 55.7% had hepatobiliary complications. Female gender, pre-BMT hepatobiliary alteration, and haploidentical allogeneic transplantation were associated with increased risk with odds ratios (OR) of 1.8 (p = 0.005), 1.72 (p = 0.013) and 3.25 (p = 0.003), respectively. Patients with hepatobiliary complications spent longer in the hospital than those without (27.7 × 19.3 days, respectively; p < 0.001). Among 210 patients with hepatobiliary complications, 28 died compared to 5 of 167 without complications (OR 4.98; p = 0.001). CONCLUSIONS: Hepatobiliary complications are frequent in patients undergoing BMT. There is a greater risk of their occurrence in women, people with pre-BMT liver alterations, and in haploidentical transplants. The occurrence of these complications increases the length of stay and is associated with a higher risk of death.

Efficacy of silymarin in patients with non-alcoholic fatty liver disease - the Siliver trial: a study protocol for a randomized controlled clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases globally. Pharmacological treatments for NAFLD are still limited. Silymarin, a compound extracted from Silybum marianum, is an herbal supplement traditionally used in folk medicine for liver disorders. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the efficacy of silymarin supplementation in the adjuvant treatment of NAFLD in adult patients. METHOD: This is a randomized double-blind placebo-controlled clinical trial recruiting adult NAFLD patients in therapy on an outpatient basis. Participants are randomized to an intervention (I) or control (C) group. Both groups receive identical capsules and are followed for 12 weeks. I receives 700mg of silymarin + 8mg vitamin E + 50mg phosphatidylcholine daily, while C receives 700mg maltodextrin + 8mg vitamin E + 50mg phosphatidylcholine daily. Patients undergo a computerized tomography (CT) scan and blood tests at the beginning and end of the study. Monthly face-to-face consultations and weekly telephone contact are carried out for all participants. The primary outcome assessed will be change in NAFLD stage, if any, assessed by the difference in attenuation coefficient between liver and spleen, obtained by upper abdomen CT. DISCUSSION: The results of this study may provide a valuable opinion on whether silymarin can be used as adjuvant therapy for the management or treatment of NAFLD. The data presented on the efficacy and safety of silymarin may provide more foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION: This study has been approved by the Research Ethics Committee of the Professor Edgard Santos University Hospital Complex, Salvador BA, Brazil, under protocol 2.635.954. The study is carried out according to guidelines and regulatory standards for research involving humans, as set out in Brazilian legislation. Trial registration - ClinicalTrials.gov : NCT03749070. November 21, 2018.

Hepatobiliary disease after bone marrow transplant.

INTRODUCTION: Bone marrow transplantation (BMT) is the standard treatment for several hematologic pathologies. Post-BMT patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischemic and fulminant hepatitis, among others. AREA COVERED: Defining the etiology of hepatobiliary injury is challenging due to the overlapping symptoms. Thus, it is necessary to be aware of and understand the clinical characteristics of these hepatobiliary complications and provide adequate management with possible better outcomes. We reviewed the scientific literature focused on early hepatobiliary complications associated with BMT. We searched the PubMed database using the following descriptors: hepatic complications, drug-induced liver disease, graft-versus-host disease, cholestasis, sepsis, sinusoidal obstruction syndrome, cytomegalovirus, viral hepatitis, bone marrow transplantation, and hematopoietic stem cell transplantation. EXPERT OPINION: Post-BMT hepatobiliary complications comprise several differential diagnoses and are challenges for the hepatologist's clinical practice. When evaluating these patients, it is necessary to consider the temporality between the use of certain medications, the increase in liver enzymes, and the presence of infection, in addition to applying diagnostic criteria and complementary tests for a specific diagnosis.

RISK FACTORS FOR HEPATOCELLULAR CARCINOMA IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE.

Non-alcoholic fatty liver disease is growing in worldwide prevalence and thus, is expected to have a higher number of NAFLD-related hepatocellular carcinoma (HCC) in the following years. This review describes the risk factors associated with HCC in NAFLD-patients. The presence of liver cirrhosis is the preponderant one. Male gender, PNPLA3 variants, diabetes, and obesity also appear to predispose to the development of HCC, even in non-cirrhotic subjects. Thus far, intensive lifestyle modifications, including glycemic control, and obesity treatment, are effective therapies for NAFLD/ non-alcoholic steatohepatitis and, therefore, probably, also for HCC. Some drugs that aimed at decreasing inflammatory activity and fibrosis, as well as obesity, were studied. Other data have suggested the possibility of HCC chemoprevention. So far, however, there is no definitive evidence for the routine utilization of these drugs. We hope, in the future, to be able to profile patients at higher risk of NAFLD-HCC and outline strategies for early diagnosis and prevention.

Fatores de risco para carcinoma hepatocelular em pacientes com doença gordurosa não alcóolica do fígado / Risk factors for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease

ABSTRACT Non-alcoholic fatty liver disease is growing in worldwide prevalence and thus, is expected to have a higher number of NAFLD-related hepatocellular carcinoma (HCC) in the following years. This review describes the risk factors associated with HCC in NAFLD-patients. The presence of liver cirrhosis is the preponderant one. Male gender, PNPLA3 variants, diabetes, and obesity also appear to predispose to the development of HCC, even in non-cirrhotic subjects. Thus far, intensive lifestyle modifications, including glycemic control, and obesity treatment, are effective therapies for NAFLD/ non-alcoholic steatohepatitis and, therefore, probably, also for HCC. Some drugs that aimed at decreasing inflammatory activity and fibrosis, as well as obesity, were studied. Other data have suggested the possibility of HCC chemoprevention. So far, however, there is no definitive evidence for the routine utilization of these drugs. We hope, in the future, to be able to profile patients at higher risk of NAFLD-HCC and outline strategies for early diagnosis and prevention.

RESUMO A doença metabólica e doença hepática gordurosa metabólica estão aumentando a prevalência mundial e, portanto, espera-se um número maior de carcinoma hepatocelular (CHC) relacionado à doença hepática gordurosa não alcóolica (DHGNA) nos próximos anos. Esta revisão descreve os fatores de risco associados ao CHC em pacientes com DHGNA. A presença de cirrose hepática é a preponderante. Sexo masculino, variantes do gene PNPLA3, diabetes e obesidade também parecem predispor ao desenvolvimento de CHC, mesmo em indivíduos não cirróticos. Até agora, modificações significativas no estilo de vida, incluindo controle glicêmico e tratamento da obesidade, são terapias eficazes para DHGNA/ Esteatohepatite não-alcoolica e, portanto, provavelmente, também para CHC. Alguns medicamentos que propunham-se diminuir a atividade inflamatória e fibrose, bem como a obesidade, foram estudados. Outros dados sugeriram a possibilidade de quimioprevenção do CHC. Até o momento, no entanto, não há evidências definitivas para o uso rotineiro desses medicamentos. Esperamos, no futuro, poder traçar o perfil de pacientes com maior risco de DHGNA-CHC e traçar estratégias para diagnóstico precoce e prevenção.

Overweight and abdominal fat are associated with normal bone mineral density in patients with ulcerative colitis.

BACKGROUND: Low bone mineral density (BMD) is common in patients with inflammatory bowel disease. However, nutritional risk factors for low BMD in the ulcerative colitis (UC) population are still poorly understood. AIM: To investigate the association of anthropometric indicators and body composition with BMD in patients with UC. METHODS: This is a cross-sectional study on adult UC patients of both genders who were followed on an outpatient basis. A control group consisting of healthy volunteers, family members, and close people was also included. The nutritional indicators evaluated were body mass index (BMI), total body mass (TBM), waist circumference (WC), body fat in kg (BFkg), body fat in percentage (BF%), trunk BF (TBF), and also lean mass. Body composition and BMD assessments were performed by dual-energy X-ray absorptiometry. RESULTS: The sociodemographic characteristics of patients with UC (n = 68) were similar to those of healthy volunteers (n = 66) (P > 0.05). Most patients (97.0%) were in remission of the disease, 58.8% were eutrophic, 33.8% were overweight, 39.0% had high WC, and 67.6% had excess BF%. However, mean BMI, WC, BFkg, and TBF of UC patients were lower when compared to those of the control group (P < 0.05). Reduced BMD was present in 41.2% of patients with UC (38.2% with osteopenia and 2.9% with osteoporosis) and 3.0% in the control group (P < 0.001). UC patients with low BMD had lower BMI, TBM, and BFkg values than those with normal BMD (P < 0.05). Male patients were more likely to have low BMD (prevalence ratio [PR] = 1.86; 95% confidence interval [CI]: 1.07-3.26). Those with excess weight (PR = 0.43; 95%CI: 0.19-0.97) and high WC (PR = 0.44; 95%CI: 0.21-0.94) were less likely to have low BMD. CONCLUSION: Patients with UC in remission have a high prevalence of metabolic bone diseases. Body fat appears to protect against the development of low BMD in these patients.

African genetic ancestry is associated with lower frequency of PNPLA3 G allele in non-alcoholic fatty liver in an admixed population.

INTRODUCTION AND OBJECTIVES: PNPLA3 (rs738409) and TM6SF2 (rs58542926) variants, interindividual and ethnic differences may be risk factors for non-alcoholic fatty liver disease (NAFLD). The PNPLA3 G allele is associated with worse NAFLD evolution in Hispanics and Caucasians. TM6SF2 is associated with hypertriglyceridemia, NAFLD, and cardiovascular disease. We aimed to evaluate the association between genetic ancestry by Ancestry Informative Markers (AIM), PNPLA3 and TM6SF2 polymorphisms in patients with biopsy-proven NAFLD in an admixed population. METHODS: We included adults with biopsy-proven NAFLD and excluded patients with the presence of other chronic liver disease, alcohol intake >100g/week, HIV, drug-induced fatty liver disease, or liver transplantation. We classified NAFLD using the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) histological scoring system. The PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) genotyping were performed by RT-PCR. Genetic ancestry was determined using 46 insertion-deletion AIM; α<0.05 was considered significant. RESULTS: A total of 248 patients with NAFLD were enrolled [34 with simple steatosis (NAFL); 214 with NASH]. Overall, we detected a greater European ancestry contribution (0.645), followed by African (0.173), Amerindian (0.095), and East Asian (0.087) ancestry contribution, without differences between NAFL and NASH patients. However, we found a higher African genetic ancestry contribution among patients with NAFL who had the PNPLA3 C/C genotype than those with the G allele (0.216 ± 0.205 versus 0.105 ± 0.101, respectively; p=0.047). Ancestry contributions did not differ among TM6SF2 genotypes. CONCLUSION: Among NAFL patients, greater African genetic ancestry was associated to a lower frequency of the PNPLA3 G allele, demonstrating a possible NASH ancestry-related protective factor.

BETTER LIVING DONOR LIVER TRANSPLANTATION PATIENT SURVIVAL COMPARED TO DECEASED DONOR - A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Deceased donor liver transplantation (DDLT) is the first choice, but living donor transplantation (LDLT) is an alternative to be considered in special situations, such as lack of donated organs and emergencies. So far, there is no consensus on which transplantation method provides better survival and fewer complications, which is still an open point for discussion. METHODS: This meta-analysis compared the 1, 3, and 5-year patient and graft survival rates of LDLT and DDLT. We included studies published from April-2009 to June-2021 and adopted the generic model of the inverse of variance for the random effect of hazard ratios. The adequacy of the studies was determined using the Newcastle-Ottawa Scale - NOS (WELLS). RESULTS: For patient survival analysis, we included a total of 32,258 subjects. We found a statistically significant better survival for the LDLT group at 1, 3 and 5 years, respectively: 1.35 HR (95%CI 1.10-1.66, P=0.005), 1.26 HR (95%CI 1.09-1.46, P=0.002) and 1.27 HR (95%CI 1.09-1.48, P=0.002). Our meta-analysis evaluated a total of 21,276 grafts. In the overall analysis, the 1-year survival was improved in favor of the LDLT group (1.36 HR, 95%CI 1.16-1.60, P<0.0001), while the 3-year survival (1.13 HR, 95%CI 0.96-1.33, P<0.13), and 5 (0.99 HR, 95%CI 0.74-1.33, P<0.96), did not differ significantly. CONCLUSION: This metanalysis detected a statistically significant greater 1-, 3- and 5-years patient survival favoring LDLT compared to DDLT as well as a statistically significant difference better 1-year graft survival favoring the LDLT group.

Sobrevida de pacientes submetidos ao transplante hepático com enxerto de doador vivo é melhor em comparação com doador falecido — uma revisão sistemática e meta-análise / Better living donor liver transplantation patient survival compared to deceased donor — a systematic review and meta-analysis

ABSTRACT Background Deceased donor liver transplantation (DDLT) is the first choice, but living donor transplantation (LDLT) is an alternative to be considered in special situations, such as lack of donated organs and emergencies. So far, there is no consensus on which transplantation method provides better survival and fewer complications, which is still an open point for discussion. Methods This meta-analysis compared the 1, 3, and 5-year patient and graft survival rates of LDLT and DDLT. We included studies published from April-2009 to June-2021 and adopted the generic model of the inverse of variance for the random effect of hazard ratios. The adequacy of the studies was determined using the Newcastle-Ottawa Scale — NOS (WELLS). Results For patient survival analysis, we included a total of 32,258 subjects. We found a statistically significant better survival for the LDLT group at 1, 3 and 5 years, respectively: 1.35 HR (95%CI 1.10—1.66, P=0.005), 1.26 HR (95%CI 1.09—1.46, P=0.002) and 1.27 HR (95%CI 1.09—1.48, P=0.002). Our meta-analysis evaluated a total of 21,276 grafts. In the overall analysis, the 1-year survival was improved in favor of the LDLT group (1.36 HR, 95%CI 1.16—1.60, P<0.0001), while the 3-year survival (1.13 HR, 95%CI 0.96—1.33, P<0.13), and 5 (0.99 HR, 95%CI 0.74—1.33, P<0.96), did not differ significantly. Conclusion This metanalysis detected a statistically significant greater 1-, 3- and 5-years patient survival favoring LDLT compared to DDLT as well as a statistically significant difference better 1-year graft survival favoring the LDLT group.

RESUMO Contexto O transplante de fígado com doador falecido é a primeira escolha, mas o transplante de doador vivo é uma alternativa a ser considerada em situações especiais, como falta de órgãos doados e emergências. Até o momento, não há consenso sobre qual método de transplante proporciona melhor sobrevida e menos complicações, sendo, ainda, um ponto em aberto para discussão. Métodos Esta meta-análise comparou as taxas de sobrevida de pacientes e enxertos de 1, 3 e 5 anos de transplante de doador vivo e transplante de fígado com doador falecido. Incluímos estudos publicados de abril de 2009 a junho de 2021 e adotamos o modelo genérico do inverso da variância para o efeito aleatório das razões de risco. A adequação dos estudos foi determinada por meio da Escala de Newcastle-Ottawa — NOS (WELLS). Resultados Para análise de sobrevida do paciente, incluímos um total de 32.258 indivíduos. Encontramos uma melhor sobrevida estatisticamente significativa para o grupo de transplante de fígado de doador vivo em 1, 3 e 5 anos, respectivamente: 1,35 HR (IC95% 1,10—1,66, P=0,005), 1,26 HR (IC95% 1,09—1,46, P=0,002) e 1,27 HR (IC95% 1,09—1,48, P=0,002). Nossa meta-análise avaliou um total de 21.276 enxertos. Na análise geral, a sobrevida em 1 ano foi melhorada em favor do grupo de transplante de doador vivo (1,36 HR, IC95% 1,16—1,60, P<0,0001), enquanto a sobrevida em 3 anos (1,13 HR, IC95% 0,96—1,33, P<0,13) e 5 (0,99 HR, IC95% 0,74—1,33, P<0,96), não diferiram significativamente. Conclusão Esta meta-análise detectou uma sobrevida estatisticamente significativa maior do paciente em 1, 3 e 5 anos favorecendo o transplante de doador vivo em comparação com o transplante de fígado com doador falecido, bem como uma diferença estatisticamente significativa melhor na sobrevida do enxerto em 1 ano favorecendo o grupo de transplante de doador vivo.

Endoscopic and Histopathological Findings of the Esophagus, Stomach, and Duodenum in Patients with Crohn's Disease from a Reference Center in Bahia, Brazil.

(1) The aim of the present study was to describe the endoscopic and histopathological findings in the esophagus, stomach, and duodenum in patients with Crohn's disease. (2) Methods: This was a cross-sectional study that included patients receiving treatment from the inflammatory bowel disease outpatient clinic. Esophagogastroduodenoscopies with biopsies of the stomach and proximal duodenum were performed. Presence of Helicobacter pylori bacteria was assessed by Giemsa staining. (3) Results: We included 58 patients. Erosive esophagitis was identified in 25 patients (43.1%), gastritis was diagnosed in 32 patients (55.2%) and erosive duodenitis was found in eight (13.8%). The most frequent histopathological finding in the H. pylori-positive group was increased inflammatory activity in the gastric body and antrum, with a predominance of mononuclear and polymorphonuclear cells. In turn, the most frequent finding in the H. pylori-negative group was chronic inflammation with predominance of mononuclear cells. Focally enhanced gastritis was identified in four patients (6.9%), all of whom were negative for H. pylori. Granulomas were not observed. H. pylori infection was present in 19 patients (32.8%). (4) Conclusions: Nonspecific endoscopic and histological findings were frequent in patients with Crohn's disease. Focally enhanced gastritis was uncommon and observed only in H. pylori-negative patients. The time from the diagnosis, patient age, and therapy in use may have influenced the nondetection of epithelioid granuloma.

Sweet syndrome as a paraneoplastic manifestation of cholangiocarcinoma: A case report.

BACKGROUND: Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, is a rare skin disorder that may be associated with cancer. CASE SUMMARY: A 58-year-old female presented with a cholestatic syndrome and significant weight loss three months before admission. Five months earlier, she had abruptly developed skin lesions with erythematous papules that evolved to erythematous blisters. Clinical evaluation and laboratory tests confirmed hepatic cholangiocarcinoma. Skin lesions histopathological findings showed neutrophilic dermatosis, massive edema, fibrin, necrosis, and elastosis. These results, in association with the macroscopic aspects of the findings, led to the diagnosis of paraneoplastic Sweet's syndrome due to cholangiocarcinoma. As staging was consistent with an advanced tumor without a cure perspective, we opted to perform percutaneous biliary drainage, and subsequently, palliative care. Eventually, after a few weeks, the patient died. CONCLUSION: In conclusion, the diagnosis of the underlying disease-causing Sweet's syndrome must be accurate, and patients need to be followed-up, as neoplasia such as cholangiocarcinoma may be a later manifestation.

Epidemiological profile of alcoholic liver disease hospital admissions in a Latin American country over a 10-year period.

BACKGROUND: Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. AIM: To describe the epidemiological profile and mortality rates of patients with ALD admitted to public hospitals in different regions of Brazil from 2006 to 2015. METHODS: This is a descriptive study that evaluated aggregate data from the five Brazilian geographic regions. RESULTS: A total of 160093 public hospitalizations for ALD were registered. There was a 34.07% increase in the total number of admissions over 10 years, from 12879 in 2006 to 17267 in 2015. The region with the highest proportion (49.01%) of ALD hospitalizations was Southeast (n = 78463). The North region had the lowest absolute number of patients throughout the study period, corresponding to 3.9% of the total (n = 6242). There was a 24.72% increase in the total number of ALD deaths between 2006 and 2015. We found that the age group between 50 and 59 years had the highest proportion of both hospitalizations and deaths: 28.94% (n = 46329) of total hospital admissions and 29.43% (n = 28864) of all deaths. Men were more frequently hospitalized than women and had the highest proportions of deaths in all regions. Mortality coefficient rates increased over the years, and simple linear regression analysis indicated a statistically significant upward trend in this mortality (R² = 0.744). CONCLUSION: Our study provides a landscape of the epidemiological profile of public hospital admissions due to ALD in Brazil. We detected an increase in the total number of admissions and deaths due to ALD over 10 years.

Factors Associated with Insulin Resistance in Patients with Chronic HCV Genotype 1 Infection without Obesity or Type 2 Diabetes.

OBJECTIVE: To investigate the prevalence of insulin resistance (IR) and its association with clinical parameters in patients with hepatitis C virus (HCV) genotype 1 without obesity or type 2 diabetes. METHODS: One hundred and twenty-seven HCV-infected patients admitted to the Nutrition and Hepatology Clinic were included. Statistical analysis was performed using the Mann-Whitney test, Fisher's exact test, and Poisson regression analysis. RESULTS: The prevalence of IR (homeostasis model assessment [HOMA]-IR ≥ 3.0) was 37.0%. The independent predictors for IR included the following: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.5 times the upper normal limit (odds ratio [PR] = 2.06, 95% CI, 1.16-3.66; PR = 2.32, 95% CI, 1.26-4.49, respectively); gamma glutamyl transferase (γGT) ≥ 85 U/L (PR = 2.09, 95% CI, 1.12-4.12); increased waist circumference (PR = 2.24, 95% CI, 1.25-4.17); increased waist : hip ratio (PR = 2.24, 95% CI, 1.11-5.17); increased body fat percentage (PR = 2.21, 95% CI, 1.01-5.79); overweight (PR = 2.54, 95% CI, 1.40-4.82); and metabolic syndrome (PR = 3.05, 95% CI, 1.69-5.44). High ALT levels and anthropometric parameters remained in the model of multivariate regression analysis. CONCLUSIONS: Our findings showed a significantly high prevalence of insulin resistance in nondiabetic, nonobese patients with hepatitis C genotype 1. High ALT levels and anthropometric parameters were significantly associated with IR after multivariate regression analysis. Our data show the importance of monitoring IR, weight, and body composition in patients with chronic hepatitis C. Nutritional management seems to be important in the control of comorbidities related to excess weight and the enhancement of therapeutic responses.

Diagnosis and treatment of benign liver nodules: Brazilian Society of Hepatology (SBH) recommendations

ABSTRACT Space-occupying lessions of the liver may be cystic or solid. Ultrasonography is an extremely useful method for initial screening, and suffices for diagnosis of simple hepatic cysts. Complex cysts and solid masses require computed tomography or magnetic resonance imaging for confirmation. Wide surgical excision is indicated in cystadenoma or cystadenocarcinoma. Clinical and epidemiological data are important, as nodules in noncirrhotic livers are more likely to be benign. Hemangiomas, the most common benign tumors, require no follow-up after diagnostic confirmation if they are small and asymptomatic. Patients with giant, symptomatic hemangiomas or compression of adjacent structures should be referred to hepatobiliary centers for potential surgery. The genetic heterogeneity of hepatocellular adenoms and their epidemiology and prognosis prompted classification of these tumors into four subtypes based on histology and immunohistochemistry. The major complications of hepatocellular adenoms are rupture with bleeding and malignant transformation. Rupture occurs in approximately 30% of cases. The main risk factors are tumors size >5 cm and inflammatory subtype. Hepatocellular adenoms may enlarge during pregnancy due to marked hormonal stimulation. As oral contraceptive pills and anabolic steroids have associated with hepatocellular adenoms growth, particularly of the hepatocyte nuclear factor-1 alfa subtype, these drugs should be discontinued. Focal nodular hyperplasia is the second most common benign tumor of hte liver. It is most frequent in women aged 20 to 60, and 70% to 90% of cases are asymptomatic. In the adsence of a central scar and/or other hallmarks of Focal nodular hyperplasia, with uncertainty between this diagnosis and hepatocellular adenoma, liver-specific contrast agentes are indicated.

RESUMO As lesões que ocupam espaço no fígado podem ser císticas ou sólidas. A ultrassonografia é extremamente útil como rastreamento inicial, bastando como método diagnósticos em casos de cistos simples. Em cistos complexos e em nódulos sólidos é necessária a complementação diagnóstica com tomografia computadorizada ou ressonância magnética. Em casos de cistadenoma ou cistadenocarcinoma, a ampla retirada cirúrgica está indicada. Dados clínico-epidemiológicos são importantes, já que nódulos em fígados não-cirróticos têm maiores probabilidades de serem benignos. Para os hemangiomas, tumores benignos mais frequentes, após a confirmação diagnóstica não existe necessidade de acompanhamento sistemático quando os nódulos são pequenos e assintomáticos. Hemangiomas gigantes sintomáticos ou comprimindo órgãos vizinhos devem ser encaminhados a centros de referência para avaliação de intervenção cirúrgica. A heterogeneidade genética nos adenomas hepatocelulares bem como características epidemiológicas e prognósticas motivou sua classificação em quatro subtipos, com base em achados histológicos e de imunohistoquímica. As principais complicações que ocorrem com o adenomas hepatocelulares são ruptura com hemorragia e transformação carcinomatosa. A primeira ocorre em cerca de 30% dos casos e o principal fator de risco para esta complicação são tumores maiores do que 5 cm, do subtipo hiperplasia nodular focal 1A, esses medicamentos devem ser suspensos. A hiperplasia nodular focal é o segundo tumor benigno mais frequente, mais comum nas mulheres entre 20 e 60 anos, sendo assintomáticos em 70% a 90% dos casos. Na ausência de lesão cicatricial central e/ou outros sinais sugestivos de hiperplasi nodular focal, havendo dúvida diagnóstica com adenoma hepatocelular, o uso de contraste hepatespecíficos está indicado.

Risk factors for osteoporosis in inflammatory bowel disease patients.

Inflammatory bowel disease (IBD) patients exhibit higher risk for bone loss than the general population. The chronic inflammation causes a reduction in bone mineral density (BMD), which leads to osteopenia and osteoporosis. This article reviewed each risk factor for osteoporosis in IBD patients. Inflammation is one of the factors that contribute to osteoporosis in IBD patients, and the main system that is involved in bone loss is likely RANK/RANKL/osteoprotegerin. Smoking is a risk factor for bone loss and fractures, and many mechanisms have been proposed to explain this loss. Body composition also interferes in bone metabolism and increasing muscle mass may positively affect BMD. IBD patients frequently use corticosteroids, which stimulates osteoclastogenesis. IBD patients are also associated with vitamin D deficiency, which contributes to bone loss. However, infliximab therapy is associated with improvements in bone metabolism, but it is not clear whether the effects are because of inflammation improvement or infliximab use. Ulcerative colitis patients with proctocolectomy and ileal pouches and Crohn's disease patients with ostomy are also at risk for bone loss, and these patients should be closely monitored.

The Demographic and Clinical Characteristics of Ulcerative Colitis in a Northeast Brazilian Population.

INTRODUCTION: The purpose of this study was to describe the clinical and demographic characteristics of UC in Bahia, a Brazilian state, and to identify the variables associated with extensive colitis, steroid therapy, immunosuppression, and colectomy. METHODS: In this cross-sectional study UC patients were interviewed, and additional information was collected from the medical records. Descriptive statistics and multivariate Poisson regression analysis were used. RESULTS: This study included 267 individuals, the mean age of whom was 39.4 years at diagnosis. There was a predominance of females and left-side colitis. Extensive colitis was positively associated with male gender, diarrhea, weight loss, and a younger age at diagnosis. In contrast, active smoking and a family history of IBD were negatively associated with extensive colitis. Positive associations were observed between steroid therapy and diarrhea, weight loss, urban patients, extraintestinal manifestations (EIMs), and hospitalization. Younger age and weight loss at diagnosis, a family history of IBD, extensive colitis, EIMs, hospitalization, and steroid therapy were all positively associated with immunosuppression. In contrast, Caucasian individuals, smokers, patients with rectal bleeding, and rural patients areas were all observed to have a decreased likelihood of immunosuppression. CONCLUSIONS: Our results corroborate the association between higher prevalence of extensive colitis and younger age at diagnosis. An association between steroid therapy and clinical presentation at diagnosis was observed. The observation that white individuals and rural patients use less immunosuppressive drugs highlights the need to study the influence of environmental and genetic factors on the behavior of UC in this population.

Predictive factors associated with hepatitis C antiviral therapy response.

Hepatitis C virus (HCV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000s, dual therapy using a combination of pegylated interferon plus ribavirin (PR) became the standard of care for HCV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HCV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors (boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response (SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis C treatment has been rapidly changing with the development of new therapies and other developments. Currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs.

Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal.

AIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P < 0.05). RESULTS: In the Brazilian sample, NASH was significantly more frequent among the elderly patients with diabetes (NASH 56 ± 1.1 years old vs S. Steatosis 51 ± 1.5 years old, P = 3.7 x 10(-9)), dyslipidemia (NASH 63% vs S. Steatosis 37%, P = 0.009), higher fasting glucose levels (NASH 124 ± 5.2 vs S. Steatosis 106 ± 5.3, P = 0.001) and Homeostatic Model of Assessment index > 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups. CONCLUSION: There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.

Diagnosis and treatment of benign liver nodules: Brazilian Society of Hepatology (SBH) recommendations.

Space-occupying lesions of the liver may be cystic or solid. Ultrasonography is an extremely useful method for initial screening, and suffices for diagnosis of simple hepatic cysts. Complex cysts and solid masses require computed tomography or magnetic resonance imaging for confirmation. Wide surgical excision is indicated in cystadenoma or cystadenocarcinoma. Clinical and epidemiological data are important, as nodules in noncirrhotic livers are more likely to be benign. Hemangiomas, the most common benign tumors, require no follow-up after diagnostic confirmation if they are small and asymptomatic. Patients with giant, symptomatic hemangiomas or compression of adjacent structures should be referred to hepatobiliary centers for potential surgery. The genetic heterogeneity of hepatocellular adenomas and their epidemiology and prognosis prompted classification of these tumors into four subtypes based on histology and immunohistochemistry. The major complications of hepatocellular adenomas are rupture with bleeding and malignant transformation. Rupture occurs in approximately 30% of cases. The main risk factors are tumors size >5 cm and inflammatory subtype. Hepatocellular adenomas may enlarge during pregnancy due to marked hormonal stimulation. As oral contraceptive pills and anabolic steroids have associated with hepatocellular adenomas growth, particularly of the hepatocyte nuclear factor-1alfa subtype, these drugs should be discontinued. Focal nodular hyperplasia is the second most common benign tumor of the liver. It is most frequent in women aged 20 to 60, and 70% to 90% of cases are asymptomatic. In the absence of a central scar and/or other hallmarks of Focal nodular hyperplasia, with uncertainty between this diagnosis and hepatocellular adenoma, liver-specific contrast agents are indicated.