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

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

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

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

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

UPDATE OF THE BRAZILIAN SOCIETY OF HEPATOLOGY RECOMMENDATIONS FOR DIAGNOSIS AND MANAGEMENT OF AUTOIMMUNE DISEASES OF THE LIVER

ABSTRACT New data concerning the management of autoimmune liver diseases have emerged since the last single-topic meeting sponsored by the Brazilian Society of Hepatology to draw recommendations about the diagnosis and treatment of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), overlap syndromes of AIH, PBC and PSC and specific complications and topics concerning AIH and cholestatic liver diseases. This manuscript updates those previous recommendations according to the best evidence available in the literature up to now. The same panel of experts that took part in the first consensus document reviewed all recommendations, which were subsequently scrutinized by all members of the Brazilian Society of Hepatology using a web-based approach. The new recommendations are presented herein. RESUMO Desde a publicação em 2015 das recomendações da Sociedade Brasileira de Hepatologia sobre a prevenção e tratamento de doenças hepáticas autoimunes, novos dados baseados em evidências científicas foram publicados na literatura, mudando o diagnóstico e tratamento da hepatite autoimune (HAI), colangite biliar primária (CBP), colangite esclerosante primária (CEP), síndromes de sobreposição de HAI, CBP e CEP e o manejo de complicações específicas além de outros tópicos relativos à HAI e doenças hepáticas colestáticas. Este manuscrito atualiza as recomendações anteriores de acordo com as melhores evidências disponíveis na literatura até o momento. O mesmo painel de experts que participou da primeira diretriz revisou todas as recomendações de acordo com os dados publicados na literatura e elaborou um manuscrito submetido subsequentemente à apreciação e revisão de todos os membros da Sociedade Brasileira de Hepatologia via homepage da sociedade. As recomendações finais atualizadas foram condensadas no presente documento

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

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 (x ULN) among responders versus 5.05 +/- 3.08 x 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

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

Hepatocellular carcinoma recurrence after liver transplantation in a brazilian multicenter study : clinical profile and prognostic factors of survival

Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified alpha-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis3191148115